Current Oncology

29 pages, 747 KiB

Open AccessEditor’s ChoiceReview

Artificial Intelligence in Brain Tumor Imaging: A Step toward Personalized Medicine

by Maurizio Cè, Giovanni Irmici, Chiara Foschini, Giulia Maria Danesini, Lydia Viviana Falsitta, Maria Lina Serio, Andrea Fontana, Carlo Martinenghi, Giancarlo Oliva and Michaela Cellina

Curr. Oncol. 2023, 30(3), 2673-2701; https://doi.org/10.3390/curroncol30030203 - 22 Feb 2023

Cited by 52 | Viewed by 7894

Abstract

The application of artificial intelligence (AI) is accelerating the paradigm shift towards patient-tailored brain tumor management, achieving optimal onco-functional balance for each individual. AI-based models can positively impact different stages of the diagnostic and therapeutic process. Although the histological investigation will remain difficult [...] Read more.

The application of artificial intelligence (AI) is accelerating the paradigm shift towards patient-tailored brain tumor management, achieving optimal onco-functional balance for each individual. AI-based models can positively impact different stages of the diagnostic and therapeutic process. Although the histological investigation will remain difficult to replace, in the near future the radiomic approach will allow a complementary, repeatable and non-invasive characterization of the lesion, assisting oncologists and neurosurgeons in selecting the best therapeutic option and the correct molecular target in chemotherapy. AI-driven tools are already playing an important role in surgical planning, delimiting the extent of the lesion (segmentation) and its relationships with the brain structures, thus allowing precision brain surgery as radical as reasonably acceptable to preserve the quality of life. Finally, AI-assisted models allow the prediction of complications, recurrences and therapeutic response, suggesting the most appropriate follow-up. Looking to the future, AI-powered models promise to integrate biochemical and clinical data to stratify risk and direct patients to personalized screening protocols. Full article

(This article belongs to the Section Neuro-Oncology)

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26 pages, 899 KiB

Open AccessEditor’s ChoiceReview

Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse

by Parva Bhatt, Colin Kloock and Raymond Comenzo

Curr. Oncol. 2023, 30(2), 2322-2347; https://doi.org/10.3390/curroncol30020179 - 15 Feb 2023

Cited by 47 | Viewed by 11626

Abstract

Multiple myeloma remains an incurable disease with the usual disease course requiring induction therapy, autologous stem cell transplantation for eligible patients, and long-term maintenance. Risk stratification tools and cytogenetic alterations help inform individualized therapeutic choices for patients in hopes of achieving long-term remissions [...] Read more.

Multiple myeloma remains an incurable disease with the usual disease course requiring induction therapy, autologous stem cell transplantation for eligible patients, and long-term maintenance. Risk stratification tools and cytogenetic alterations help inform individualized therapeutic choices for patients in hopes of achieving long-term remissions with preserved quality of life. Unfortunately, relapses occur at different stages of the course of the disease owing to the biological heterogeneity of the disease. Addressing relapse can be complex and challenging as there are both therapy- and patient-related factors to consider. In this broad scoping review of available therapies in relapsed/refractory multiple myeloma (RRMM), we cover the pharmacologic mechanisms underlying active therapies such as immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), monoclonal antibodies (mAbs), traditional chemotherapy, and Venetoclax. We then review the clinical data supporting the use of these therapies, organized based on drug resistance/refractoriness, and the role of autologous stem cell transplant (ASCT). Approaches to special situations during relapse such as renal impairment and extramedullary disease are also covered. Lastly, we look towards the future by briefly reviewing the clinical data supporting the use of chimeric antigen receptor (CAR-T) therapy, bispecific T cell engagers (BITE), and Cereblon E3 Ligase Modulators (CELMoDs). Full article

(This article belongs to the Special Issue Current Treatment Strategies for Relapsed and Refractory Multiple Myeloma)

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10 pages, 987 KiB

Open AccessEditor’s ChoiceArticle

“Well, to Be Honest, I Don’t Have an Idea of What It Might Be”—A Qualitative Study on Knowledge and Awareness Regarding Nonmelanoma Skin Cancer

by Luisa Leonie Brokmeier, Katharina Diehl, Bianca Annika Spähn, Charlotte Jansen, Tobias Konkel, Wolfgang Uter and Tatiana Görig

Curr. Oncol. 2023, 30(2), 2290-2299; https://doi.org/10.3390/curroncol30020177 - 15 Feb 2023

Cited by 6 | Viewed by 3232

Abstract

Nonmelanoma skin cancer (NMSC) is the most common cancer type in Western industrialized countries. However, research into the knowledge and awareness in the general population regarding NMSC is still scarce. This qualitative study aims to fill this research gap. Face-to-face, semi-structured interviews with [...] Read more.

Nonmelanoma skin cancer (NMSC) is the most common cancer type in Western industrialized countries. However, research into the knowledge and awareness in the general population regarding NMSC is still scarce. This qualitative study aims to fill this research gap. Face-to-face, semi-structured interviews with 20 individuals aged 55–85 years were conducted between February and October 2020. Transcribed interviews were analyzed using qualitative content analysis. The term “white skin cancer”—the German colloquial term of NMSC—was well-known, but the incidence was underestimated. None of the participants could give a precise definition of NMSC, and various alterations in the skin were, partially wrongly, stated as potential signs for NMSC. As risk factors for NMSC, solar radiation, and fair skin type were mentioned most often. The perceived individual risk of developing NMSC and risk compared to individuals of the same age and gender were low in our sample. Own knowledge about NMSC was mostly perceived to be insufficient, and the majority of the sample would like to receive more information on NMSC. Our results emphasize a need to inform about the signs and risks of NMSC not only in the studied older age group but also in younger people. Full article

(This article belongs to the Special Issue Updates on Skin Cancer Prevention, Early Diagnosis and Treatment)

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13 pages, 1107 KiB

Open AccessEditor’s ChoiceArticle

Understanding Characteristics, Treatment Patterns, and Clinical Outcomes for Individuals with Advanced or Recurrent Endometrial Cancer in Alberta, Canada: A Retrospective, Population-Based Cohort Study

by Diana Martins, Dylan E. O’Sullivan, Devon J. Boyne, Winson Y. Cheung, Odette Allonby, Mara Habash, Darren R. Brenner, Justin Riemer and Jacob McGee

Curr. Oncol. 2023, 30(2), 2277-2289; https://doi.org/10.3390/curroncol30020176 - 14 Feb 2023

Cited by 6 | Viewed by 3858

Abstract

Endometrial cancer (EC) incidence has increased in recent decades. However, population-based outcomes data are limited. In this retrospective cohort study, we examined characteristics, treatment patterns, and clinical outcomes, including time to next treatment (TNNT) and overall survival (OS), among advanced/recurrent (A/R) EC patients [...] Read more.

Endometrial cancer (EC) incidence has increased in recent decades. However, population-based outcomes data are limited. In this retrospective cohort study, we examined characteristics, treatment patterns, and clinical outcomes, including time to next treatment (TNNT) and overall survival (OS), among advanced/recurrent (A/R) EC patients between 2010 and 2018 in Alberta, Canada. Kaplan–Meier statistics evaluated TTNT and OS, stratified by patient (A/R) and treatment. A total of 1053 patients were included: 620 (58.9%) advanced and 433 (41.1%) recurrent. A total of 713 (67.7%) patients received first-line therapy: 466 (75.2%) advanced and 247 (57.0%) recurrent. Platinum-based chemotherapy (PBCT) was the most common first-line regimen (overall: 78.6%; advanced: 96.1%; recurrent: 45.3%). The median TTNT and OS from first-line therapy were 19.9 months (95% confidence interval [CI]: 17.5–23.5) and 35.9 months (95% CI: 31.5–53.5), respectively. Following first-line PBCT, the median OS from second-line chemotherapy (N = 187) was 10.4 months (95% CI: 8.9–13.3) and higher for those rechallenged with PBCT (N = 72; 38.5%) versus no rechallenge (N = 115; 61.5%) (13.3 months [95% CI: 11.2–20.9] vs. 6.4 months [95% CI: 4.6–10.4; p < 0.001]). The findings highlight poor outcomes in A/R EC, particularly following first-line therapy, and that additional tolerable therapeutic options are needed to improve patient outcomes. Full article

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15 pages, 5792 KiB

Open AccessEditor’s ChoiceReview

The Landscape of Immunotherapy for Retroperitoneal Sarcoma

by Alicia A. Gingrich, Elise F. Nassif, Christina L. Roland and Emily Z. Keung

Curr. Oncol. 2023, 30(2), 2144-2158; https://doi.org/10.3390/curroncol30020165 - 9 Feb 2023

Cited by 6 | Viewed by 3530

Abstract

Significant multidisciplinary scientific effort has been undertaken to understand the heterogeneous family of neoplasms that comprise soft tissue sarcomas. Within this family of neoplasms, outcomes for retroperitoneal sarcomas (RPS) are currently limited given a lack of effective therapies. In this review, we focus [...] Read more.

Significant multidisciplinary scientific effort has been undertaken to understand the heterogeneous family of neoplasms that comprise soft tissue sarcomas. Within this family of neoplasms, outcomes for retroperitoneal sarcomas (RPS) are currently limited given a lack of effective therapies. In this review, we focus on immunotherapy and its relationship with the common RPS histologic subtypes. Although initial outcomes for RPS patients with immune checkpoint inhibition alone have been somewhat disappointing, subsequent analyses on histologies, the tumor microenvironment, sarcoma immune class, tumor infiltrating lymphocytes and genetic analysis for tumor mutational burden have yielded insight into the interplay between sarcomas and immunotherapy. Such approaches have all provided critical insight into the environment and characterization of these tumors, with targets for potential immunotherapy in future clinical trials. With this insight, molecularly tailored combination treatments for improving response rates and oncologic outcomes for RPS are promising. Full article

(This article belongs to the Special Issue New Frontiers in the Management of Retroperitoneal Soft Tissue Sarcoma)

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23 pages, 1894 KiB

Open AccessEditor’s ChoiceReview

Application of CRISPR/Cas9 Technology in Cancer Treatment: A Future Direction

by Ali A. Rabaan, Hajir AlSaihati, Rehab Bukhamsin, Muhammed A. Bakhrebah, Majed S. Nassar, Abdulmonem A. Alsaleh, Yousef N. Alhashem, Ammar Y. Bukhamseen, Khalil Al-Ruhimy, Mohammed Alotaibi, Roua A. Alsubki, Hejji E. Alahmed, Saleh Al-Abdulhadi, Fatemah A. Alhashem, Ahlam A. Alqatari, Ahmed Alsayyah, Ramadan Abdelmoez Farahat, Rwaa H. Abdulal, Ali H. Al-Ahmed, Mohd. Imran and Ranjan K. Mohapatra Show full author list Hide full author list

Curr. Oncol. 2023, 30(2), 1954-1976; https://doi.org/10.3390/curroncol30020152 - 6 Feb 2023

Cited by 36 | Viewed by 14296

Abstract

Gene editing, especially with clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9), has advanced gene function science. Gene editing’s rapid advancement has increased its medical/clinical value. Due to its great specificity and efficiency, CRISPR/Cas9 can accurately and swiftly screen the whole [...] Read more.

Gene editing, especially with clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9), has advanced gene function science. Gene editing’s rapid advancement has increased its medical/clinical value. Due to its great specificity and efficiency, CRISPR/Cas9 can accurately and swiftly screen the whole genome. This simplifies disease-specific gene therapy. To study tumor origins, development, and metastasis, CRISPR/Cas9 can change genomes. In recent years, tumor treatment research has increasingly employed this method. CRISPR/Cas9 can treat cancer by removing genes or correcting mutations. Numerous preliminary tumor treatment studies have been conducted in relevant fields. CRISPR/Cas9 may treat gene-level tumors. CRISPR/Cas9-based personalized and targeted medicines may shape tumor treatment. This review examines CRISPR/Cas9 for tumor therapy research, which will be helpful in providing references for future studies on the pathogenesis of malignancy and its treatment. Full article

(This article belongs to the Special Issue Successes, Challenges, and Ways Forward in the Field of Global Oncology)

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10 pages, 501 KiB

Open AccessEditor’s ChoiceSystematic Review

Temozolomide Chronotherapy in Glioma: A Systematic Review

by Jason L. Jia, Bader Alshamsan and Terry L. Ng

Curr. Oncol. 2023, 30(2), 1893-1902; https://doi.org/10.3390/curroncol30020147 - 4 Feb 2023

Cited by 27 | Viewed by 4671

Abstract

Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of [...] Read more.

Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review’s primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies—one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)—were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population. Full article

(This article belongs to the Special Issue Novel Therapeutic Strategies for Neuro-Oncology)

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11 pages, 754 KiB

Open AccessEditor’s ChoiceArticle

Combined Reporting of Surgical Quality and Cancer Control after Surgical Treatment for Penile Tumors with Inguinal Lymph Node Dissection: The Tetrafecta Achievement

by Aldo Brassetti, Umberto Anceschi, Gabriele Cozzi, Julian Chavarriaga, Pavel Gavrilov, Josep Maria Gaya Sopena, Alfredo Maria Bove, Francesco Prata, Mariaconsiglia Ferriero, Riccardo Mastroianni, Leonardo Misuraca, Gabriele Tuderti, Giulia Torregiani, Marco Covotta, Diego Camacho, Gennaro Musi, Rodolfo Varela, Alberto Breda, Ottavio De Cobelli and Giuseppe Simone

Curr. Oncol. 2023, 30(2), 1882-1892; https://doi.org/10.3390/curroncol30020146 - 3 Feb 2023

Cited by 4 | Viewed by 2472

Abstract

Background: To optimize results reporting after penile cancer (PC) surgery, we proposed a Tetrafecta and assessed its ability to predict overall survival (OS) probabilities. Methods: A purpose-built multicenter, multi-national database was queried for stage I–IIIB PC, requiring inguinal lymphadenectomy (ILND), from 2015 onwards. [...] Read more.

Background: To optimize results reporting after penile cancer (PC) surgery, we proposed a Tetrafecta and assessed its ability to predict overall survival (OS) probabilities. Methods: A purpose-built multicenter, multi-national database was queried for stage I–IIIB PC, requiring inguinal lymphadenectomy (ILND), from 2015 onwards. Kaplan–Meier (KM) method assessed differences in OS between patients achieving Tetrafecta or not. Univariable and multivariable regression analyses identified its predictors. Results: A total of 154 patients were included in the analysis. The 45 patients (29%) that achieved the Tetrafecta were younger (59 vs. 62 years; p = 0.01) and presented with fewer comorbidities (ASA score ≥ 3: 0% vs. 24%; p < 0.001). Although indicated, ILND was omitted in 8 cases (5%), while in 16, a modified template was properly used. Although median LNs yield was 17 (IQR: 11–27), 35% of the patients had <7 nodes retrieved from the groin. At Kaplan–Maier analysis, the Tetrafecta cohort displayed significantly higher OS probabilities (Log Rank = 0.01). Uni- and multivariable logistic regression analyses identified age as the only independent predictor of Tetrafecta achievement (OR: 0.97; 95%CI: 0.94–0.99; p = 0.04). Conclusions: Our Tetrafecta is the first combined outcome to comprehensively report results after PC surgery. It is widely applicable, based on standardized and reproducible variables and it predicts all-cause mortality. Full article

(This article belongs to the Special Issue Radical Surgery Advances in Oncology)

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13 pages, 640 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Pilomatrix Carcinoma: Report of Two Cases of the Head and Review of the Literature

by Ludovica Toffoli, Giulia Bazzacco, Claudio Conforti, Claudio Guarneri, Roberta Giuffrida, Enrico Zelin, Nicola di Meo and Iris Zalaudek

Curr. Oncol. 2023, 30(2), 1426-1438; https://doi.org/10.3390/curroncol30020109 - 19 Jan 2023

Cited by 10 | Viewed by 4129

Abstract

Background: Pilomatrix carcinoma (PC) is a rare skin tumor arising from hair follicle matrix cells. It is locally aggressive with a high rate of local recurrence after surgical excision. Few cases in the literature have been described and the management is not well [...] Read more.

Background: Pilomatrix carcinoma (PC) is a rare skin tumor arising from hair follicle matrix cells. It is locally aggressive with a high rate of local recurrence after surgical excision. Few cases in the literature have been described and the management is not well defined. Objectives: The aim of this study was to present two cases of PC located on the head and review the relevant literature about epidemiology, clinical and dermoscopic evaluation, characteristics of local and distant metastases, local recurrence rate and management of this rare skin tumor. Methods: We consulted databases from PubMed, Research Gate and Google Scholar, from January 2012 to November 2022. We reviewed the literature and reported two additional cases. Results: We selected 52 tumors in middle-aged to older patients located mostly on the head. Dermoscopy evaluation was rarely performed in the pre-operative diagnostic setting. The most definitive treatment was wide local excision, but local recurrences were common. In total, we observed 11 cases of recurrences and 9 patients with locoregional or distant metastases. Four patients received adjuvant radiotherapy, two patients needed chemotherapy and local cancer therapy and one patient received radiochemotherapy. Conclusion: Our reports and the review of the literature can provide a better awareness and management of this rare tumor. Full article

(This article belongs to the Section Dermato-Oncology)

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21 pages, 12907 KiB

Open AccessEditor’s ChoiceArticle

X or Y Cancer: An Extensive Analysis of Sex Differences in Lung Adenocarcinoma

by Raneem Yaseen Hammouz, Magdalena Orzechowska, Dorota Anusewicz and Andrzej K. Bednarek

Curr. Oncol. 2023, 30(2), 1395-1415; https://doi.org/10.3390/curroncol30020107 - 18 Jan 2023

Cited by 6 | Viewed by 3311

Abstract

Background: Cellular metabolism is a tightly controlled process during which cell growth and survival are maintained. Lung cancer is a disease with clear sex differences, where female patients have better survival rates than males. Evidence of sex differences is demonstrated in cancer risk, [...] Read more.

Background: Cellular metabolism is a tightly controlled process during which cell growth and survival are maintained. Lung cancer is a disease with clear sex differences, where female patients have better survival rates than males. Evidence of sex differences is demonstrated in cancer risk, prognosis and response to different therapies, yet a sex-specific approach to cancer studies is not widely considered. These different tumour characteristics attributed to sex that impact disease outcome, including constitutional genetic and somatic molecular differences, make it essential to assess viral and hormonal influences. Methods: In silico analysis of lung adenocarcinoma (LUAD) TCGA data, including K-means clustering algorithm, dimensional reduction with principal component analysis and differential expression analysis using EdgeR (p < 0.05), were used to explore some robust sex differences in LUAD that exist in core signalling pathways and metabolic processes between males and females. The correlation of differentially expressed genes (DEGs) expression with immune abundance in the LUAD cohort was analysed on TIMER2.0 and adjusted by tumour purity utilising Cox proportional hazard. Multiple factorial analysis heatmap visualisation was used to examine endogenous steroid hormonal effects on LUAD patients with different smoking status and age groups. Results: We found 161 DEGs showing key differences in regulation of immune system and cellular homeostasis, key elements of divergent cancer progression, between the two sexes. We also found male and female LUAD patients to favour different metabolic intermediates for energy production to support tumourigenesis. Additionally, high levels of Tregs accompanied by DEGs correlated with better LUAD prognosis, and circulating hormonal transcriptional targets affect proliferation and progression in males and females differently. Finally, we examined the role of oestrogen protection in men and pre-/postmenopausal women. Conclusions: Further studies should focus on sex-specific changes and investigate sex-specific gene regulatory networks of these DEGs. Several lifestyle factors, including tobacco smoking and diet, differ between males and females. These factors might affect metabolic pathways and can influence the activity of epigenetic regulators, resulting in significant global epigenetic changes. Full article

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18 pages, 4470 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Prognostic Significance of p53 and p63 in Diffuse Large B-Cell Lymphoma: A Single-Institution Experience

by Juan Carlos Alvarez Moreno, Hisham F. Bahmad, Abed Alhalim Aljamal, Ruben Delgado, Ali Salami, Carolina Guillot, Amilcar A. Castellano-Sánchez, Ana Maria Medina and Vathany Sriganeshan

Curr. Oncol. 2023, 30(2), 1314-1331; https://doi.org/10.3390/curroncol30020102 - 17 Jan 2023

Cited by 5 | Viewed by 2895

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. We evaluated the immunohistochemical (IHC) expression of p63 and p53 in DLBCL and their significance on overall survival (OS) and progression-free survival (PFS). We conducted a retrospective cohort study of 177 [...] Read more.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. We evaluated the immunohistochemical (IHC) expression of p63 and p53 in DLBCL and their significance on overall survival (OS) and progression-free survival (PFS). We conducted a retrospective cohort study of 177 patients with DLBCL who presented to Mount Sinai Medical Center of Florida (Miami Beach, Florida) between 2010 and 2020. IHC staining for p63 and p53 protein expression was performed. A significant correlation was found between p63 positivity and p53 expression, p53/p63 co-positivity, Ki-67 proliferation index, MYC expression, and MYC/BCL2 double expression. Regardless of the germinal center B-cell like (GCB) subgrouping, there was a trend among p53+ patients to have MYC/BCL2 double expression, positive MYC expression, and lower OS and PFS. A tendency of poor OS was seen in p53⁺ patients in the non-GCB, GCB, and double expressors subgroups and poor PFS in p53⁺ patients regardless of the subgrouping. In conclusion, our results suggest that p63 and p53 may represent potential additional prognostic biomarkers in DLBCL and may be included in the initial diagnostic work up of patients with DLBCL. Full article

(This article belongs to the Section Hematology)

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10 pages, 1408 KiB

Open AccessEditor’s ChoiceArticle

Purely Off-Clamp Laparoscopic Partial Nephrectomy Stands the Test of Time: 15 Years Functional and Oncologic Outcomes from a Single Center Experience

by Aldo Brassetti, Umberto Anceschi, Alfredo Maria Bove, Francesco Prata, Manuela Costantini, Mariaconsiglia Ferriero, Riccardo Mastroianni, Leonardo Misuraca, Gabriele Tuderti, Giulia Torregiani, Marco Covotta, Michele Gallucci and Giuseppe Simone

Curr. Oncol. 2023, 30(1), 1196-1205; https://doi.org/10.3390/curroncol30010092 - 15 Jan 2023

Cited by 8 | Viewed by 2388

Abstract

Background: Nephron-sparing surgery represents the gold standard treatment for organ-confined renal tumors. We present 15-years of outcomes after off-clamp laparoscopic partial nephrectomy (ocLPN). Methods: a retrospective analysis was performed on patients who underwent ocLPN between May 2001 and December 2005. Baseline demographic, clinical, [...] Read more.

Background: Nephron-sparing surgery represents the gold standard treatment for organ-confined renal tumors. We present 15-years of outcomes after off-clamp laparoscopic partial nephrectomy (ocLPN). Methods: a retrospective analysis was performed on patients who underwent ocLPN between May 2001 and December 2005. Baseline demographic, clinical, pathologic, surgical, functional and survival data were collected. The Kaplan–Meier method evaluated group-specific oncologic outcomes at 5, 10 and 15 years and the log rank test assessed differences between groups. The same analysis investigated the probabilities of developing a significant renal function impairment (sRFI) and achieving ROMeS. Cox analyses identified predictors of this latter tricomposite outcome. Results: We included 63 patients whose median tumor size was 3 cm (IQR:2–4). At 15 years, the chances of developing local recurrence, metachronous renal cancers or distant metastases were 2 ± 2%, 23 ± 6% and 17 ± 5%, respectively. Consequently, disease-free, cancer-specific and overall-survival probabilities were 68 ± 6%, 90 ± 4% and 72 ± 6%. MCRSS and UCISS well predicted oncologic outcomes. Overall, nine (14%) patients experienced an sRFI and 33 (52%) achieved ROMeS. Age (HR: 1.046; p = 0.033) and malignant histology (low-risk cancers HR: 3.233, p = 0.048) (intermediate/high risk cancers HR: 5.721, p = 0.023) were independent predictors of ROMeS non-achievement. Conclusions: At 15 years from ocLPN, most of patients will experience both excellent functional and oncologic outcomes. Full article

(This article belongs to the Special Issue Radical Surgery Advances in Oncology)

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15 pages, 878 KiB

Open AccessEditor’s ChoiceArticle

Machine Learning Approaches with Textural Features to Calculate Breast Density on Mammography

by Mario Sansone, Roberta Fusco, Francesca Grassi, Gianluca Gatta, Maria Paola Belfiore, Francesca Angelone, Carlo Ricciardi, Alfonso Maria Ponsiglione, Francesco Amato, Roberta Galdiero, Roberta Grassi, Vincenza Granata and Roberto Grassi

Curr. Oncol. 2023, 30(1), 839-853; https://doi.org/10.3390/curroncol30010064 - 7 Jan 2023

Cited by 21 | Viewed by 3734

Abstract

Background: breast cancer (BC) is the world’s most prevalent cancer in the female population, with 2.3 million new cases diagnosed worldwide in 2020. The great efforts made to set screening campaigns, early detection programs, and increasingly targeted treatments led to significant improvement in [...] Read more.

Background: breast cancer (BC) is the world’s most prevalent cancer in the female population, with 2.3 million new cases diagnosed worldwide in 2020. The great efforts made to set screening campaigns, early detection programs, and increasingly targeted treatments led to significant improvement in patients’ survival. The Full-Field Digital Mammograph (FFDM) is considered the gold standard method for the early diagnosis of BC. From several previous studies, it has emerged that breast density (BD) is a risk factor in the development of BC, affecting the periodicity of screening plans present today at an international level. Objective: in this study, the focus is the development of mammographic image processing techniques that allow the extraction of indicators derived from textural patterns of the mammary parenchyma indicative of BD risk factors. Methods: a total of 168 patients were enrolled in the internal training and test set while a total of 51 patients were enrolled to compose the external validation cohort. Different Machine Learning (ML) techniques have been employed to classify breasts based on the values of the tissue density. Textural features were extracted only from breast parenchyma with which to train classifiers, thanks to the aid of ML algorithms. Results: the accuracy of different tested classifiers varied between 74.15% and 93.55%. The best results were reached by a Support Vector Machine (accuracy of 93.55% and a percentage of true positives and negatives equal to TPP = 94.44% and TNP = 92.31%). The best accuracy was not influenced by the choice of the features selection approach. Considering the external validation cohort, the SVM, as the best classifier with the 7 features selected by a wrapper method, showed an accuracy of 0.95, a sensitivity of 0.96, and a specificity of 0.90. Conclusions: our preliminary results showed that the Radiomics analysis and ML approach allow us to objectively identify BD. Full article

(This article belongs to the Collection New Insights into Breast Cancer Diagnosis and Treatment)

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14 pages, 1490 KiB

Open AccessEditor’s ChoiceReview

Morbidity and Mortality after Surgery for Retroperitoneal Sarcoma

by Samantha M. Ruff, Valerie P. Grignol, Carlo M. Contreras, Raphael E. Pollock and Joal D. Beane

Curr. Oncol. 2023, 30(1), 492-505; https://doi.org/10.3390/curroncol30010039 - 29 Dec 2022

Cited by 13 | Viewed by 5475

Abstract

Retroperitoneal sarcoma (RPS) is a rare disease with over 100 histologic types and accounts for 10–15% of all soft tissue sarcomas. Due to the rarity of RPS, sarcoma centers in Europe and North America have created the Transatlantic RPS Working Group (TARPSWG) to [...] Read more.

Retroperitoneal sarcoma (RPS) is a rare disease with over 100 histologic types and accounts for 10–15% of all soft tissue sarcomas. Due to the rarity of RPS, sarcoma centers in Europe and North America have created the Transatlantic RPS Working Group (TARPSWG) to study this disease and establish best practices for its management. Current guidelines dictate complete resection of all macro and microscopic disease as the gold standard for patients with RPS. Complete extirpation often requires a multi-visceral resection. In addition, recent evidence suggests that en bloc compartmental resections are associated with reduced rates of local recurrence. However, this approach must be balanced by the potential for added morbidity. Strategies to mitigate postoperative complications include optimization of the patient through improved preoperative nutrition and pre-habilitation therapy, referral to a high-volume sarcoma center, and implementation of enhanced recovery protocols. This review will focus on the factors associated with perioperative complications following surgery for RPS and outline approaches to mitigate poor surgical outcomes in this patient population. Full article

(This article belongs to the Special Issue New Frontiers in the Management of Retroperitoneal Soft Tissue Sarcoma)

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10 pages, 1132 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Surgical Approaches and Use of Adjuvant Radiotherapy with Respect to Oncologic Outcomes in the Management of Clinically Early-Stage Cervical Carcinoma

by Laura Burgess, Wafa AlDuwaisan, Tinghua Zhang, Krystine Lupe, Michael Fung-Kee-Fung, Wylam Faught, Tien Le and Rajiv Samant

Curr. Oncol. 2022, 29(12), 9525-9534; https://doi.org/10.3390/curroncol29120748 - 5 Dec 2022

Viewed by 2718

Abstract

The standard of care for early-stage cervix cancer is radical hysterectomy with pelvic lymphadenectomy. Adjuvant radiotherapy (RT) or chemoradiotherapy may be administered to reduce the risk of recurrence in patients considered to be at elevated risk based on a combination of pathologic factors. [...] Read more.

The standard of care for early-stage cervix cancer is radical hysterectomy with pelvic lymphadenectomy. Adjuvant radiotherapy (RT) or chemoradiotherapy may be administered to reduce the risk of recurrence in patients considered to be at elevated risk based on a combination of pathologic factors. We performed a retrospective review to determine oncologic outcomes in patients treated for early-stage cervix cancer and to determine if surgical approach impacted oncologic outcomes or the decision to use adjuvant therapy. In total, 174 women underwent radical hysterectomy and pelvic lymphadenectomy over the 15-year period. Most of these women (146) had open surgery and 28 had minimally invasive surgery (MIS). In total, 81 had adjuvant pelvic RT; 76 in the open surgery group (52%) and 5 in the MIS group (18%). Five-year PFS and OS, respectively, were 84% and 91%. Five-year PFS was significantly lower in patients who had MIS vs. open surgery, without a difference in 5-year OS, suggesting MIS should be avoided. Five-year PFS was the same with RT or with its omission, despite those treated with RT having higher risk disease. We have demonstrated excellent outcomes in patients with early-stage cervix cancer after primary surgery and selective use of RT, with few recurrences and excellent survival. Full article

(This article belongs to the Section Gynecologic Oncology)

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8 pages, 250 KiB

Open AccessEditor’s ChoiceArticle

Acute Toxicity and Quality of Life in a Post-Prostatectomy Ablative Radiation Therapy (POPART) Multicentric Trial

by Raffaella Lucchini, Ciro Franzese, Suela Vukcaj, Giorgio Purrello, Denis Panizza, Valeria Faccenda, Stefano Andreoli, Gian Luca Poli, Davide Baldaccini, Lorenzo Lo Faro, Stefano Tomatis, Luigi Franco Cazzaniga, Marta Scorsetti and Stefano Arcangeli

Curr. Oncol. 2022, 29(12), 9349-9356; https://doi.org/10.3390/curroncol29120733 - 30 Nov 2022

Cited by 9 | Viewed by 4142

Abstract

Background: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). Methods: Patients with post-radical [...] Read more.

Background: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). Methods: Patients with post-radical prostatectomy PSA levels of ≥0.1–2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD2_1.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. Results: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55–82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18–1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0–0.48 ng/mL). Conclusions: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy. Full article

(This article belongs to the Collection New Insights into Prostate Cancer Diagnosis and Treatment)

17 pages, 1985 KiB

Open AccessEditor’s ChoiceArticle

Stratification of Length of Stay Prediction following Surgical Cytoreduction in Advanced High-Grade Serous Ovarian Cancer Patients Using Artificial Intelligence; the Leeds L-AI-OS Score

by Alexandros Laios, Daniel Lucas Dantas De Freitas, Gwendolyn Saalmink, Yong Sheng Tan, Racheal Johnson, Albina Zubayraeva, Sarika Munot, Richard Hutson, Amudha Thangavelu, Tim Broadhead, David Nugent, Evangelos Kalampokis, Kassio Michell Gomes de Lima, Georgios Theophilou and Diederick De Jong

Curr. Oncol. 2022, 29(12), 9088-9104; https://doi.org/10.3390/curroncol29120711 - 23 Nov 2022

Cited by 8 | Viewed by 2949

Abstract

(1) Background: Length of stay (LOS) has been suggested as a marker of the effectiveness of short-term care. Artificial Intelligence (AI) technologies could help monitor hospital stays. We developed an AI-based novel predictive LOS score for advanced-stage high-grade serous ovarian cancer (HGSOC) patients [...] Read more.

(1) Background: Length of stay (LOS) has been suggested as a marker of the effectiveness of short-term care. Artificial Intelligence (AI) technologies could help monitor hospital stays. We developed an AI-based novel predictive LOS score for advanced-stage high-grade serous ovarian cancer (HGSOC) patients following cytoreductive surgery and refined factors significantly affecting LOS. (2) Methods: Machine learning and deep learning methods using artificial neural networks (ANN) were used together with conventional logistic regression to predict continuous and binary LOS outcomes for HGSOC patients. The models were evaluated in a post-hoc internal validation set and a Graphical User Interface (GUI) was developed to demonstrate the clinical feasibility of sophisticated LOS predictions. (3) Results: For binary LOS predictions at differential time points, the accuracy ranged between 70–98%. Feature selection identified surgical complexity, pre-surgery albumin, blood loss, operative time, bowel resection with stoma formation, and severe postoperative complications (CD3–5) as independent LOS predictors. For the GUI numerical LOS score, the ANN model was a good estimator for the standard deviation of the LOS distribution by ± two days. (4) Conclusions: We demonstrated the development and application of both quantitative and qualitative AI models to predict LOS in advanced-stage EOC patients following their cytoreduction. Accurate identification of potentially modifiable factors delaying hospital discharge can further inform services performing root cause analysis of LOS. Full article

(This article belongs to the Section Gynecologic Oncology)

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20 pages, 1585 KiB

Open AccessEditor’s ChoiceSystematic Review

Chemo-Immunotherapy in First Line Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Systematic Review and Meta-Analysis

by Arani Sathiyapalan, Michela Febbraro, Gregory R. Pond and Peter M. Ellis

Curr. Oncol. 2022, 29(12), 9046-9065; https://doi.org/10.3390/curroncol29120709 - 22 Nov 2022

Cited by 18 | Viewed by 3976

Abstract

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with early metastatic potential. The standard-of-care treatment has not changed in years. Recent studies report improved progression-free survival (PFS) and overall survival (OS) with combined ICI and chemotherapy in ES-SCLC. We conducted a [...] Read more.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with early metastatic potential. The standard-of-care treatment has not changed in years. Recent studies report improved progression-free survival (PFS) and overall survival (OS) with combined ICI and chemotherapy in ES-SCLC. We conducted a systematic review and meta-analysis to assess the magnitude of survival benefits. We searched MEDLINE, EMBASE, and Cochrane between 1 January 2010 and 15 July 2022 and conference proceedings from 2018 to 2022, for randomised controlled trials, evaluating chemo-ICI compared with platinum-doublet chemotherapy in untreated ES-SCLC. Outcomes assessed were PFS, OS, objective response rate (ORR), duration of response (DoR), toxicity, and health-related quality of life (HRQoL). The search identified 8061 studies, with 8 (56 publications) included in the final analysis. PFS and OS were significantly improved for patients randomised to chemo-ICI (PFS hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.70–0.80) and (OS HR 0.79, 95% CI 0.73–0.85). Subgroup analysis demonstrated a differential effect between PD-1/PD-L1 and CTLA-4 inhibitors. There was no difference in ORR and DoR. All-grade adverse events (RR 1.06, 95% CI 1.00–1.12) were similar. The addition of ICI to chemotherapy in untreated ES-SCLC results in a 22% risk reduction in death, and a 25% risk reduction in disease progression with a minimal increase in toxicity. These improvements are modest but represent progress beyond the standard of care. Full article

(This article belongs to the Topic Advances in Anti-Cancer Drugs)

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27 pages, 9392 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Applying Deep Learning for Breast Cancer Detection in Radiology

by Ella Mahoro and Moulay A. Akhloufi

Curr. Oncol. 2022, 29(11), 8767-8793; https://doi.org/10.3390/curroncol29110690 - 16 Nov 2022

Cited by 38 | Viewed by 14442

Abstract

Recent advances in deep learning have enhanced medical imaging research. Breast cancer is the most prevalent cancer among women, and many applications have been developed to improve its early detection. The purpose of this review is to examine how various deep learning methods [...] Read more.

Recent advances in deep learning have enhanced medical imaging research. Breast cancer is the most prevalent cancer among women, and many applications have been developed to improve its early detection. The purpose of this review is to examine how various deep learning methods can be applied to breast cancer screening workflows. We summarize deep learning methods, data availability and different screening methods for breast cancer including mammography, thermography, ultrasound and magnetic resonance imaging. In this review, we will explore deep learning in diagnostic breast imaging and describe the literature review. As a conclusion, we discuss some of the limitations and opportunities of integrating artificial intelligence into breast cancer clinical practice. Full article

(This article belongs to the Collection New Insights into Breast Cancer Diagnosis and Treatment)

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14 pages, 4743 KiB

Open AccessEditor’s ChoiceReview

Magnetic Resonance-Guided Radiation Therapy for Head and Neck Cancers

by Danny Lavigne, Sweet Ping Ng, Brian O’Sullivan, Phuc Felix Nguyen-Tan, Edith Filion, Laurent Létourneau-Guillon, Clifton D. Fuller and Houda Bahig

Curr. Oncol. 2022, 29(11), 8302-8315; https://doi.org/10.3390/curroncol29110655 - 31 Oct 2022

Cited by 10 | Viewed by 3902

Abstract

Despite the significant evolution of radiation therapy (RT) techniques in recent years, many patients with head and neck cancer still experience significant toxicities during and after treatments. The increased soft tissue contrast and functional sequences of magnetic resonance imaging (MRI) are particularly attractive [...] Read more.

Despite the significant evolution of radiation therapy (RT) techniques in recent years, many patients with head and neck cancer still experience significant toxicities during and after treatments. The increased soft tissue contrast and functional sequences of magnetic resonance imaging (MRI) are particularly attractive in head and neck cancer and have led to the increasing development of magnetic resonance-guided RT (MRgRT). This approach refers to the inclusion of the additional information acquired from a diagnostic or planning MRI in radiation treatment planning, and now extends to online high-quality daily imaging generated by the recently developed MR-Linac. MRgRT holds numerous potentials, including enhanced baseline and planning evaluations, anatomical and functional treatment adaptation, potential for hypofractionation, and multiparametric assessment of response. This article offers a structured review of the current literature on these established and upcoming roles of MRI for patients with head and neck cancer undergoing RT. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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13 pages, 2017 KiB

Open AccessEditor’s ChoiceArticle

Efficacy and Feasibility of Proton Beam Therapy in Relapsed High-Risk Neuroblastoma-Experiences from the Prospective KiProReg Registry

by Danny Jazmati, Barbara Hero, Theresa M. Thole.-Kliesch, Julien Merta, Hedwig E. Deubzer, Christian Bäumer, Feline Heinzelmann, Stefanie Schulze Schleithoff, Friederike Koerber, Angelika Eggert, Rudolf Schwarz, Thorsten Simon and Beate Timmermann

Curr. Oncol. 2022, 29(11), 8222-8234; https://doi.org/10.3390/curroncol29110649 - 30 Oct 2022

Cited by 4 | Viewed by 3012

Abstract

Background: Despite an intensive multimodal treatment approach, approximately 50% of high-risk (HR) neuroblastoma (NB) patients experience progression. Despite the advances in targeted therapy, high-dose chemotherapy, and other systemic treatment options, radiation therapy (RT) to sites of relapsed disease can be an option to [...] Read more.

Background: Despite an intensive multimodal treatment approach, approximately 50% of high-risk (HR) neuroblastoma (NB) patients experience progression. Despite the advances in targeted therapy, high-dose chemotherapy, and other systemic treatment options, radiation therapy (RT) to sites of relapsed disease can be an option to reduce tumor burden and improve chance for disease control. Methods: Patients who received salvage irradiation with proton beam therapy (PBT) for local or metastatic relapse of HR NB within the prospective registry trials KiProReg and ProReg were eligible for this retrospective analysis. Data on patient characteristics, multimodality therapy, adverse events, and oncologic endpoints were evaluated. Adverse events were assessed before, during, and after PBT according to common terminology criteria for adverse events (CTCAE) V4.0. Results: Between September 2013 and September 2020, twenty (11 male; 9 female) consecutive patients experiencing local (N = 9) or distant recurrence (N = 25) were identified for this analysis. Distant recurrences included osteomedullary (N = 11) or CNS lesions (N = 14). Salvage therapy consisted of re-induction chemo- or chemo-immuno-therapy (N = 19), surgery (N = 6), high-dose chemotherapy and stem cell transplantation (N = 13), radiation (N = 20), and concurrent systemic therapy. Systemic therapy concurrent to RT was given to six patients and included temozolomide (N = 4), carboplatine (N = 1), or anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKI) (N = 1). A median dose of 36 Gy was applied to the 34 recurrent sites. Local RT was applied to 15 patients, while five patients, received craniospinal irradiation for CNS relapse. After a median follow-up (FU) of 20 months (4–66), the estimated rate for local control, distant metastatic free survival, and overall survival at 3 years was 68.0%, 37.9%, and 61.6%, respectively. During RT, ten patients (50%) presented with a higher-grade acute hematologic adverse event. Late higher-grade sequelae included transient myelitis with transverse section (N = 2) and secondary malignancy outside of the RT field (N = 1). Conclusion: Our study demonstrates the efficacy and safety of RT/PBT for recurrent HR NB in a multimodality second-line approach. To better define the role of RT for these patients, prospective studies would be desirable. Full article

(This article belongs to the Special Issue New Therapeutic and Management Strategies for Childhood Cancers)

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16 pages, 16332 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Evaluation of a Navigated 3D Ultrasound Integration for Brain Tumor Surgery: First Results of an Ongoing Prospective Study

by Danilo Aleo, Ziad Elshaer, Andreas Pfnür, Patrick J. Schuler, Marco Maria Fontanella, Christian Rainer Wirtz, Andrej Pala and Jan Coburger

Curr. Oncol. 2022, 29(9), 6594-6609; https://doi.org/10.3390/curroncol29090518 - 15 Sep 2022

Cited by 7 | Viewed by 2984

Abstract

The aim of the study was to assess the quality, accuracy and benefit of navigated 2D and 3D ultrasound for intra-axial tumor surgery in a prospective study. Patients intended for gross total resection were consecutively enrolled. Intraoperatively, a 2D and 3D iUS-based resection [...] Read more.

The aim of the study was to assess the quality, accuracy and benefit of navigated 2D and 3D ultrasound for intra-axial tumor surgery in a prospective study. Patients intended for gross total resection were consecutively enrolled. Intraoperatively, a 2D and 3D iUS-based resection was performed. During surgery, the image quality, clinical benefit and navigation accuracy were recorded based on a standardized protocol using Likert’s scales. A total of 16 consecutive patients were included. Mean ratings of image quality in 2D iUS were significantly higher than in 3D iUS (p < 0.001). There was no relevant decrease in rating during the surgery in 2D and 3D iUS (p > 0.46). The benefit was rated 2.2 in 2D iUS and 2.6 in 3D iUS (p = 0.08). The benefit remained stable in 2D, while there was a slight decrease in the benefit in 3D after complete tumor resection (p = 0.09). The accuracy was similar in both (mean 2.2 p = 0.88). Seven patients had a small tumor remnant in intraoperative MRT (mean 0.98 cm³) that was not appreciated with iUS. Crucially, 3D iUS allows for an accurate intraoperative update of imaging with slightly lower image quality than 2D iUS. Our preliminary data suggest that the benefit and accuracy of 2D and 3D iUS navigation do not undergo significant variations during tumor resection. Full article

(This article belongs to the Special Issue Recent Advancements in the Surgical Treatment of Brain Tumors)

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16 pages, 804 KiB

Open AccessEditor’s ChoiceReview

Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma

by Luisa M. Cardenas, Jasna E. Deluce, Shahrukh Khan, Omar Gulam, Saman Maleki Vareki, Ricardo Fernandes and Aly-Khan A. Lalani

Curr. Oncol. 2022, 29(8), 5426-5441; https://doi.org/10.3390/curroncol29080429 - 30 Jul 2022

Cited by 14 | Viewed by 6720

Abstract

While surgical resection has remained the mainstay of treatment in early-stage renal cell carcinoma (RCC), therapeutic options in the advanced setting have remarkably expanded over the last 20 years. Tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor (VEGF-TKIs) and anti-programmed cell [...] Read more.

While surgical resection has remained the mainstay of treatment in early-stage renal cell carcinoma (RCC), therapeutic options in the advanced setting have remarkably expanded over the last 20 years. Tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor (VEGF-TKIs) and anti-programmed cell death 1 (PD-1)/anti-programmed death-ligand 1 (PD-L1)-based immune checkpoint inhibitors (ICIs) have become globally accepted options in the upfront metastatic setting, with different ICI-based combination strategies improving overall survival compared to single-agent Sunitinib. Although some patients benefit from long-term responses, most eventually develop disease progression. Ongoing efforts to better understand the biology of RCC and the different mechanisms of acquired resistance have led to the identification of promising therapeutic targets. Belzutifan, a novel agent targeting the angiogenic pathway involving hypoxia-inducible factors (HIFs), has already been approved for the treatment of early-stage tumors associated with VHL disease and represents a very promising therapy in advanced RCC. Other putative targets include epigenetic regulation enzymes, as well as several metabolites such as adenosine, glutaminase and tryptophan, which are critical players in cancer cell metabolism and in the tumor microenvironment. Different methods of immune regulation are also being investigated, including CAR-T cell therapy and modulation of the gut microbiome, in addition to novel agents targeting the interleukin-2 (IL-2) pathway. This review aims to highlight the emergent novel therapies for RCC and their respective completed and ongoing clinical trials. Full article

(This article belongs to the Special Issue Beyond Immunotherapy in the Management of Genito-Urinary Malignancies)

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10 pages, 280 KiB

Open AccessEditor’s ChoiceArticle

Prospective Evaluation of Kidney Function in Long-Term Survivors of Pediatric CNS Tumors

by Natalia Stepien, Viktoria Handler, Johannes Gojo, Amedeo A. Azizi, Lisa Mayr, Chryssa Grylli, Daniela Schwarz, Monika Chocholous, Irene Slavc, Michael Boehm and Andreas Peyrl

Curr. Oncol. 2022, 29(8), 5306-5315; https://doi.org/10.3390/curroncol29080421 - 28 Jul 2022

Cited by 1 | Viewed by 2437

Abstract

Purpose: Numerous acute effects of chemotherapeutics on kidney function are well described. However, data on the long-term effects of chemotherapy in the growing population of childhood central nervous system (CNS) tumor survivors is limited. We aimed to evaluate the kidney function of a [...] Read more.

Purpose: Numerous acute effects of chemotherapeutics on kidney function are well described. However, data on the long-term effects of chemotherapy in the growing population of childhood central nervous system (CNS) tumor survivors is limited. We aimed to evaluate the kidney function of a cohort of long-term CNS tumor survivors treated with different standard chemotherapeutic regimens. Methods: Patients treated for a CNS tumor were prospectively evaluated up to 12 years after completion of their therapy. Examination of kidney function was performed during routine follow-up visits. Blood pressure and blood and urine parameters were analyzed for kidney function evaluation. Glomerular function was assessed by calculating the estimated glomerular filtration rate (eGFR), tubular functions were analyzed by measuring serum electrolytes, bicarbonate and phosphate reabsorption, and proteinuria was assessed by calculating the protein/creatinine ratio and phosphate reabsorption. Results: None of the 65 patients evaluated suffered from clinically relevant kidney impairment (eGFR < 90 mL/min/L, 73 m²). There was no association between chemotherapy dose and eGFR. Only two patients showed mild signs of tubulopathy and 11 patients were diagnosed with elevated blood pressure. Conclusion: With adequate supportive measures, such as sufficient hydration according to chemotherapy protocol guidelines, as well as avoidance or close monitoring of additional nephrotoxic medication, impaired kidney function is rare in CNS tumor survivors treated with standard chemotherapy. Nonetheless, long-term follow-up is essential for early detection of mild impairment of kidney function. Full article

(This article belongs to the Section Neuro-Oncology)

17 pages, 2167 KiB

Open AccessEditor’s ChoiceArticle

A 3-miRNA Signature Enables Risk Stratification in Glioblastoma Multiforme Patients with Different Clinical Outcomes

by Vivi Bafiti, Sotiris Ouzounis, Constantina Chalikiopoulou, Eftychia Grigorakou, Ioanna Maria Grypari, Gregory Gregoriou, Andreas Theofanopoulos, Vasilios Panagiotopoulos, Evangelia Prodromidi, Dionisis Cavouras, Vasiliki Zolota, Dimitrios Kardamakis and Theodora Katsila

Curr. Oncol. 2022, 29(6), 4315-4331; https://doi.org/10.3390/curroncol29060345 - 16 Jun 2022

Cited by 5 | Viewed by 3072

Abstract

Malignant gliomas constitute a complex disease phenotype that demands optimum decision-making as they are highly heterogeneous. Such inter-individual variability also renders optimum patient stratification extremely difficult. microRNA (hsa-miR-20a, hsa-miR-21, hsa-miR-21) expression levels were determined by RT-qPCR, upon FFPE tissue sample collection of glioblastoma [...] Read more.

Malignant gliomas constitute a complex disease phenotype that demands optimum decision-making as they are highly heterogeneous. Such inter-individual variability also renders optimum patient stratification extremely difficult. microRNA (hsa-miR-20a, hsa-miR-21, hsa-miR-21) expression levels were determined by RT-qPCR, upon FFPE tissue sample collection of glioblastoma multiforme patients (n = 37). In silico validation was then performed through discriminant analysis. Immunohistochemistry images from biopsy material were utilized by a hybrid deep learning system to further cross validate the distinctive capability of patient risk groups. Our standard-of-care treated patient cohort demonstrates no age- or sex- dependence. The expression values of the 3-miRNA signature between the low- (OS > 12 months) and high-risk (OS < 12 months) groups yield a p-value of <0.0001, enabling risk stratification. Risk stratification is validated by a. our random forest model that efficiently classifies (AUC = 97%) patients into two risk groups (low- vs. high-risk) by learning their 3-miRNA expression values, and b. our deep learning scheme, which recognizes those patterns that differentiate the images in question. Molecular-clinical correlations were drawn to classify low- (OS > 12 months) vs. high-risk (OS < 12 months) glioblastoma multiforme patients. Our 3-microRNA signature (hsa-miR-20a, hsa-miR-21, hsa-miR-10a) may further empower glioblastoma multiforme prognostic evaluation in clinical practice and enrich drug repurposing pipelines. Full article

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11 pages, 1304 KiB

Open AccessEditor’s ChoiceArticle

Trop-2 in Upper Tract Urothelial Carcinoma

by Eisuke Tomiyama, Kazutoshi Fujita, Kosuke Nakano, Ken Kuwahara, Takafumi Minami, Taigo Kato, Koji Hatano, Atsunari Kawashima, Motohide Uemura, Tetsuya Takao, Hiroaki Fushimi, Kotoe Katayama, Seiya Imoto, Kazuhiro Yoshimura, Ryoichi Imamura, Hirotsugu Uemura and Norio Nonomura

Curr. Oncol. 2022, 29(6), 3911-3921; https://doi.org/10.3390/curroncol29060312 - 30 May 2022

Cited by 22 | Viewed by 3838

Abstract

Trophoblast cell surface antigen 2 (Trop-2, encoded by TACSTD2) is the target protein of sacituzumab govitecan, a novel antibody-drug conjugate for locally advanced or metastatic urothelial carcinoma. However, the expression status of Trop-2 in upper tract urothelial carcinoma (UTUC) remains unclear. We [...] Read more.

Trophoblast cell surface antigen 2 (Trop-2, encoded by TACSTD2) is the target protein of sacituzumab govitecan, a novel antibody-drug conjugate for locally advanced or metastatic urothelial carcinoma. However, the expression status of Trop-2 in upper tract urothelial carcinoma (UTUC) remains unclear. We performed immunohistochemical analysis of 99 UTUC samples to evaluate the expression status of Trop-2 in patients with UTUC and analyze its association with clinical outcomes. Trop-2 was positive in 94 of the 99 UTUC samples, and high Trop-2 expression was associated with favorable progression-free survival (PFS) and cancer-specific survival (p = 0.0011, 0.0046). Multivariate analysis identified high Trop-2 expression as an independent predictor of favorable PFS (all cases, p = 0.045; high-risk group (pT3≤ or presence of lymphovascular invasion or lymph node metastasis), p = 0.014). Gene expression analysis using RNA sequencing data from 72 UTUC samples demonstrated the association between high TACSTD2 expression and favorable PFS (all cases, p = 0.069; high-risk group, p = 0.029). In conclusion, we demonstrated that Trop-2 is widely expressed in UTUC. Although high Trop-2 expression was a favorable prognostic factor in UTUC, its widespread expression suggests that sacituzumab govitecan may be effective for a wide range of UTUC. Full article

(This article belongs to the Section Genitourinary Oncology)

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11 pages, 1147 KiB

Open AccessEditor’s ChoiceArticle

Evolution of the Surgical Management of Lung Cancer Invading the Spine: A Single Center Experience

by Gabrielle Drevet, Théo Broussolle, Yanis Belaroussi, Lucie Duponchelle, Jean Michel Maury, Renaud Grima, Gualter Vaz, Clément Silvestre and François Tronc

Curr. Oncol. 2022, 29(5), 3061-3071; https://doi.org/10.3390/curroncol29050248 - 26 Apr 2022

Cited by 1 | Viewed by 2599

Abstract

For patients with locally advanced non-small cell lung cancer invading the spine, induction chemoradiotherapy combined with radical en bloc resection is the key to obtaining long-term survival. With time, our operative technique evolved to a two-step surgery as we experienced numerous perioperative complications [...] Read more.

For patients with locally advanced non-small cell lung cancer invading the spine, induction chemoradiotherapy combined with radical en bloc resection is the key to obtaining long-term survival. With time, our operative technique evolved to a two-step surgery as we experienced numerous perioperative complications during one step surgery. The aim of our study was to assess postoperative morbimortality and long-term survival of both techniques. We retrospectively reviewed all patients who underwent en bloc resection for lung cancer invading the spine between October 2012 and June 2020. Every patient underwent induction therapy. Sixteen patients were included: nine patients were operated on with one step surgery, seven patients were operated on with two step interventions. Twenty-five percent of patients had major perioperative complications and 56.2% of patients had major post-operative complications. Patients in the “one step” group tended to have more perioperative complications whereas patients in the “two step” group tended to have more post-operative complications. Overall 3-year survival was 40% in the one-step and 86% in the two-step surgery group. Although our practice has been improved by two-step interventions, post-operative morbidity remains significant. As long term survivals are encouraging, this type of treatment should still be proposed for highly selected patients, in specialized centers. Full article

(This article belongs to the Special Issue Treatments for Non-Small Cell Lung Cancer: The Multiple Options for Precision Medicine)

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17 pages, 695 KiB

Open AccessEditor’s ChoiceReview

Immune Checkpoint Inhibitors in Cancer Therapy

by Yavar Shiravand, Faezeh Khodadadi, Seyyed Mohammad Amin Kashani, Seyed Reza Hosseini-Fard, Shadi Hosseini, Habib Sadeghirad, Rahul Ladwa, Ken O’Byrne and Arutha Kulasinghe

Curr. Oncol. 2022, 29(5), 3044-3060; https://doi.org/10.3390/curroncol29050247 - 24 Apr 2022

Cited by 674 | Viewed by 38387

Abstract

The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field of cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these immune checkpoint proteins have been utilized successfully in patients with metastatic melanoma, renal cell carcinoma, head [...] Read more.

The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field of cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these immune checkpoint proteins have been utilized successfully in patients with metastatic melanoma, renal cell carcinoma, head and neck cancers and non-small lung cancer. The US FDA has successfully approved three different categories of immune checkpoint inhibitors (ICIs) such as PD-1 inhibitors (Nivolumab, Pembrolizumab, and Cemiplimab), PDL-1 inhibitors (Atezolimumab, Durvalumab and Avelumab), and CTLA-4 inhibitor (Ipilimumab). Unfortunately, not all patients respond favourably to these drugs, highlighting the role of biomarkers such as Tumour mutation burden (TMB), PDL-1 expression, microbiome, hypoxia, interferon-γ, and ECM in predicting responses to ICIs-based immunotherapy. The current study aims to review the literature and updates on ICIs in cancer therapy. Full article

(This article belongs to the Special Issue Immune Checkpoint Inhibitors in Cancer Therapy: State of the Art and Future Perspectives)

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18 pages, 1804 KiB

Open AccessEditor’s ChoiceReview

State of the Art in Combination Immuno/Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis

by Masoumeh Najafi, Amin Jahanbakhshi, Marzieh Gomar, Cinzia Iotti, Lucia Giaccherini, Omid Rezaie, Francesco Cavallieri, Letizia Deantonio, Lilia Bardoscia, Andrea Botti, Angela Sardaro, Salvatore Cozzi and Patrizia Ciammella

Curr. Oncol. 2022, 29(5), 2995-3012; https://doi.org/10.3390/curroncol29050244 - 22 Apr 2022

Cited by 19 | Viewed by 4481

Abstract

Objectives: Common origins for brain metastases (BMs) are melanoma, lung, breast, and renal cell cancers. BMs account for a large share of morbidity and mortality caused by these cancers. The advent of new immunotherapeutic treatments has made a revolution in the treatment of [...] Read more.

Objectives: Common origins for brain metastases (BMs) are melanoma, lung, breast, and renal cell cancers. BMs account for a large share of morbidity and mortality caused by these cancers. The advent of new immunotherapeutic treatments has made a revolution in the treatment of cancer patients and particularly, as a new concept, if it is combined with radiotherapy, may lead to considerably longer survival. This systematic review and meta-analysis aimed to evaluate the survival rate and toxicities of such a combination in brain metastases. Methods: To perform a systematic review of the literature until January 2021 using electronic databases such as PubMed, Cochrane Library, and Embase; the Newcastle–Ottawa Scale was used to evaluate the quality of cohort studies. For data extraction, two reviewers extracted the data blindly and independently. Hazard ratio with 95% confidence interval (CI), fixed-effect model, and inverse-variance method was calculated. The meta-analysis has been evaluated with the statistical software Stata/MP v.16 (The fastest version of Stata). Results: In the first step, 494 studies were selected to review the abstracts, in the second step, the full texts of 86 studies were reviewed. Finally, 28 studies were selected consisting of 1465 patients. The addition of IT to RT in the treatment of brain metastasis from melanoma and non-small-cell lung carcinoma was associated with a 39% reduction in mortality rate and has prolonged overall survival, with an acceptable toxicity profile. The addition of IT to RT compared with RT alone has a hazard ratio of 0.39(95% CI 0.34–0.44). Conclusions: A combination of immuno/radiotherapy (IR) for the treatment of patients with BMs from melanoma and non-small-cell lung carcinoma has prolonged overall survival and reduced mortality rate, with acceptable toxicity. In terms of timing, RT seems to have the best effect on the result when performed before or simultaneously with immunotherapy. Full article

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7 pages, 759 KiB

Open AccessEditor’s ChoiceArticle

Robot-Assisted Radical Prostatectomy for Potential Cancer Control in Patients with Metastatic Prostate Cancer

by Kimiaki Takagi, Makoto Kawase, Daiki Kato, Kota Kawase, Manabu Takai, Koji Iinuma, Keita Nakane, Noriyasu Hagiwara, Toru Yamada, Masayuki Tomioka and Takuya Koie

Curr. Oncol. 2022, 29(4), 2864-2870; https://doi.org/10.3390/curroncol29040233 - 18 Apr 2022

Cited by 6 | Viewed by 3201

Abstract

Recently, cytoreductive prostatectomy for metastatic prostate cancer (mPCa) has been associated with improved oncological outcomes. This study was aimed at evaluating whether robot-assisted radical prostatectomy (RARP) as a form of cytoreductive prostatectomy can improve oncological outcomes in patients with mPCa. We conducted a [...] Read more.

Recently, cytoreductive prostatectomy for metastatic prostate cancer (mPCa) has been associated with improved oncological outcomes. This study was aimed at evaluating whether robot-assisted radical prostatectomy (RARP) as a form of cytoreductive prostatectomy can improve oncological outcomes in patients with mPCa. We conducted a retrospective study of twelve patients with mPCa who had undergone neoadjuvant therapy followed by RARP. The endpoints were biochemical recurrence-free survival, treatment-free survival, and de novo metastasis-free survival. At the end of the follow-up period, none of the enrolled patients had died from PCa. The 1- and 2-year biochemical recurrence-free survival rates were 83.3% and 66.7%, respectively, and treatment-free survival rates were 75.0% and 56.3%, respectively. One patient developed de novo bone metastases 6.4 months postoperatively, and castration-resistant prostate cancer 8.9 months postoperatively. After RARP, the median duration of recovery of urinary continence was 5.2 months. One patient had severe incontinence (>2 pads/day) 24 months postoperatively. RARP may be a treatment option in patients with mPCa who have achieved a serum prostate-specific antigen level < 0.2 ng/mL, and present without new lesions on imaging. Full article

(This article belongs to the Special Issue Surgery for Prostate Cancer: Recent Advances and Future Directions)

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10 pages, 836 KiB

Open AccessEditor’s ChoiceArticle

Concordance between Preoperative mpMRI and Pathological Stage and Its Influence on Nerve-Sparing Surgery in Patients with High-Risk Prostate Cancer

by Clara Humke, Benedikt Hoeh, Felix Preisser, Mike Wenzel, Maria N. Welte, Lena Theissen, Boris Bodelle, Jens Koellermann, Thomas Steuber, Alexander Haese, Frederik Roos, Luis Alex Kluth, Andreas Becker, Felix K. H. Chun and Philipp Mandel

Curr. Oncol. 2022, 29(4), 2385-2394; https://doi.org/10.3390/curroncol29040193 - 28 Mar 2022

Cited by 7 | Viewed by 2450

Abstract

Background: We aimed to determine the concordance between the radiologic stage (rT), using multiparametric magnetic resonance imaging (mpMRI), and pathologic stage (pT) in patients with high-risk prostate cancer and its influence on nerve-sparing surgery compared to the use of the intraoperative frozen section [...] Read more.

Background: We aimed to determine the concordance between the radiologic stage (rT), using multiparametric magnetic resonance imaging (mpMRI), and pathologic stage (pT) in patients with high-risk prostate cancer and its influence on nerve-sparing surgery compared to the use of the intraoperative frozen section technique (IFST). Methods: The concordance between rT and pT and the rates of nerve-sparing surgery and positive surgical margin were assessed for patients with high-risk prostate cancer who underwent radical prostatectomy. Results: The concordance between the rT and pT stages was shown in 66.4% (n = 77) of patients with clinical high-risk prostate cancer. The detection of patients with extraprostatic disease (≥pT3) by preoperative mpMRI showed a sensitivity, negative predictive value and accuracy of 65.1%, 51.7% and 67.5%. In addition to the suspicion of extraprostatic disease in mpMRI (≥rT3), 84.5% (n = 56) of patients with ≥rT3 underwent primary nerve-sparing surgery with IFST, resulting in 94.7% (n = 54) of men with at least unilateral nerve-sparing surgery after secondary resection with a positive surgical margin rate related to an IFST of 1.8% (n = 1). Conclusion: Patients with rT3 should not be immediately excluded from nerve-sparing surgery, as by using IFST some of these patients can safely undergo nerve-sparing surgery. Full article

(This article belongs to the Special Issue Surgery for Prostate Cancer: Recent Advances and Future Directions)

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12 pages, 2124 KiB

Open AccessEditor’s ChoiceArticle

Comparison of Prognosis between Minimally Invasive and Abdominal Radical Hysterectomy for Patients with Early-Stage Cervical Cancer

by Tomohito Tanaka, Shoko Ueda, Shunsuke Miyamoto, Sousuke Hashida, Shinichi Terada, Hiromi Konishi, Yuhei Kogata, Kohei Taniguchi, Kazumasa Komura and Masahide Ohmichi

Curr. Oncol. 2022, 29(4), 2272-2283; https://doi.org/10.3390/curroncol29040185 - 24 Mar 2022

Cited by 5 | Viewed by 3205

Abstract

Minimally invasive surgery (MIS) is performed to treat cervical cancer patients; however, a recent study showed that MIS was associated with higher recurrence and death rate compared with abdominal radical hysterectomy (ARH). In the current study, the prognosis of patients with early-stage cervical [...] Read more.

Minimally invasive surgery (MIS) is performed to treat cervical cancer patients; however, a recent study showed that MIS was associated with higher recurrence and death rate compared with abdominal radical hysterectomy (ARH). In the current study, the prognosis of patients with early-stage cervical cancer who underwent MIS with vaginal closure or ARH was evaluated. One hundred and eighty-two patients underwent radical hysterectomy for cervical cancer with stage of IA2, IB1, and IIA1. MIS was performed by laparoscopy or a robot using the vaginal closure method. Disease-free survival (DFS) and overall survival (OS) were evaluated between the groups. Among the patients, 67 underwent MIS and 115 underwent ARH. The recurrence rate was 4.5% in MIS patients and 3.5% in ARH patients with a median follow-up (interquartile range) of 36 (18–60) and 78 (48–102) months, respectively. DFS and OS were not different between the groups (3y-DFS, 95.3% vs. 96.1%, p = 0.6; 3y-OS, 100% vs. 100%, p = 0.06). In early-stage cervical cancer patients, MIS with vaginal closure did not increase the risk for recurrence or death. Surgical techniques and procedures to avoid spillage of tumor cells could be important for a better prognosis. Full article

(This article belongs to the Special Issue New Frontiers in Treatment for Gynecologic Cancers)

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9 pages, 565 KiB

Open AccessEditor’s ChoiceArticle

Cutaneous Melanoma in Alpine Population: Incidence Trends and Clinicopathological Profile

by Alessandra Buja, Massimo Rugge, Giuseppe De Luca, Emanuela Bovo, Manuel Zorzi, Chiara De Toni, Claudia Cozzolino, Antonella Vecchiato, Paolo Del Fiore, Romina Spina, Sandro Cinquetti, Vincenzo Baldo, Carlo Riccardo Rossi and Simone Mocellin

Curr. Oncol. 2022, 29(3), 2165-2173; https://doi.org/10.3390/curroncol29030175 - 21 Mar 2022

Cited by 10 | Viewed by 3661

Abstract

Previous studies associated high-level exposure to ultraviolet radiation with a greater risk of cutaneous malignant melanoma (CMM). This study focuses on the changing incidence of CMM over time (from 1990 to 2017) in the Veneto region of Northeast Italy, and its Alpine area [...] Read more.

Previous studies associated high-level exposure to ultraviolet radiation with a greater risk of cutaneous malignant melanoma (CMM). This study focuses on the changing incidence of CMM over time (from 1990 to 2017) in the Veneto region of Northeast Italy, and its Alpine area (the province of Belluno). The clinicopathological profile of CMM by residence is also considered. A joinpoint regression analysis was performed to identify significant changes in the yearly incidence of CMM by sex and age. For each trend, the average annual percent change (AAPC) was also calculated. In the 2017 CMM cohort, the study includes a descriptive analysis of the disease’s categorical clinicopathological variables. In the population investigated, the incidence of CMM has increased significantly over the last 30 years. The AAPC in the incidence of CMM was significantly higher among Alpine residents aged 0–49 than for the rest of the region’s population (males: 6.9 versus 2.4; females 7.7 versus 2.7, respectively). Among the Alpine residents, the AAPC was 3.35 times greater for females aged 0–49 than for people aged 50+. The clinicopathological profile of CMM was significantly associated with the place of residence. Over three decades, the Veneto population has observed a significant increase in the incidence of CMM, and its AAPC. Both trends have been markedly more pronounced among Alpine residents, particularly younger females. While epidemiology and clinicopathological profiles support the role of UV radiation in CMM, the young age of this CMM-affected female population points to other possible host-related etiological factors. These findings also confirm the importance of primary and secondary prevention strategies. Full article

(This article belongs to the Special Issue Epidemiology and Risk Factors of Skin Cancer)

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15 pages, 262 KiB

Open AccessEditor’s ChoiceArticle

Brain Metastases among Cancer Patients Diagnosed from 2010–2017 in Canada: Incidence Proportion at Diagnosis and Estimated Lifetime Incidence

by Jiaqi L. Liu, Emily V. Walker, Yuba Raj Paudel, Faith G. Davis and Yan Yuan

Curr. Oncol. 2022, 29(3), 2091-2105; https://doi.org/10.3390/curroncol29030169 - 18 Mar 2022

Cited by 6 | Viewed by 4096

Abstract

The incidence of BM among Canadian cancer patients is unknown. We aimed to estimate IP of BM at the time of cancer diagnosis and during the lifetime of patients with selected primary cancers. Data on BM at diagnosis from 2010–2017 was obtained from [...] Read more.

The incidence of BM among Canadian cancer patients is unknown. We aimed to estimate IP of BM at the time of cancer diagnosis and during the lifetime of patients with selected primary cancers. Data on BM at diagnosis from 2010–2017 was obtained from the CCR. Site-specific IPs of BM were estimated from provincial registries containing ≥90% complete data on BM. The CCR IP estimates and the IP estimates from literature were applied to the total diagnosed primary cancers to estimate the number of concurrent BM and lifetime BM from 2010–2017 in Canada, respectively. The annual average number of patients with BM at diagnosis from all cancer sites was approximately 3227. The site-specific IPs of BM at diagnosis were: lung (9.42%; 95% CI: 9.16–9.68%), esophageal (1.58%; 95% CI: 1.15–2.02%), kidney/renal pelvis (1.33%; 95% CI: 1.12–1.54%), skin melanoma (0.73%; 95% CI: 0.61–0.84%), colorectal (0.22%; 95% CI: 0.18–0.26%), and breast (0.21%; 95% CI: 0.17–0.24%). Approximately 76,546 lifetime BM cases (or 5.70% of selected fifteen primary cancers sites) were estimated to have occurred from the 2010–2017 cancer patient cohort. These findings reflect results of population analyses in the US and Denmark. We recommend improved standardization of the collection of BM data within the CCR. Full article

(This article belongs to the Section Neuro-Oncology)

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27 pages, 7464 KiB

Open AccessEditor’s ChoiceReview

Current Advances in the Management of Adult Craniopharyngiomas

by Montserrat Lara-Velazquez, Yusuf Mehkri, Eric Panther, Jairo Hernandez, Dinesh Rao, Peter Fiester, Raafat Makary, Michael Rutenberg, Daryoush Tavanaiepour and Gazanfar Rahmathulla

Curr. Oncol. 2022, 29(3), 1645-1671; https://doi.org/10.3390/curroncol29030138 - 4 Mar 2022

Cited by 25 | Viewed by 8565

Abstract

Craniopharyngiomas (CPs) are slow growing, histologically benign intracranial tumors located in the sellar–suprasellar region. Although known to have low mortality, their location and relationship to the adjacent neural structures results in patients having significant neurologic, endocrine, and visual comorbidities. The invasive nature of [...] Read more.

Craniopharyngiomas (CPs) are slow growing, histologically benign intracranial tumors located in the sellar–suprasellar region. Although known to have low mortality, their location and relationship to the adjacent neural structures results in patients having significant neurologic, endocrine, and visual comorbidities. The invasive nature of this tumor makes complete resection a challenge and contributes to its recurrence. Additionally, these tumors are bimodally distributed, being treated with surgery, and are followed by other adjuncts, such as focused radiation therapy, e.g., Gamma knife. Advances in surgical techniques, imaging tools, and instrumentations have resulted in the evolution of surgery using endoscopic techniques, with residual components being treated by radiotherapy to target the residual tumor. Advances in molecular biology have elucidated the main pathways involved in tumor development and recurrence, but presently, no other treatments are offered to patients, besides surgery, radiation, and endocrine management, as the disease and tumor evolve. We review the contemporary management of these tumors, from the evolution of surgical treatments, utilizing standard open microscopic approaches to the more recent endoscopic surgery, and discuss the current recommendations for care of these patients. We discuss the developments in radiation therapy, such as radiosurgery, being used as treatment strategies for craniopharyngioma, highlighting their beneficial effects on tumor resections while decreasing the rates of adverse outcomes. We also outline the recent chemotherapy modalities, which help control tumor growth, and the immune landscape on craniopharyngiomas that allow the development of novel immunotherapies. Full article

(This article belongs to the Special Issue Recent Advancements in the Surgical Treatment of Brain Tumors)

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16 pages, 553 KiB

Open AccessEditor’s ChoiceReview

Immunotherapy in Gastric Cancer

by Anica Högner and Markus Moehler

Curr. Oncol. 2022, 29(3), 1559-1574; https://doi.org/10.3390/curroncol29030131 - 2 Mar 2022

Cited by 102 | Viewed by 14559

Abstract

Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal [...] Read more.

Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal junction cancer (GEJC) and esophageal cancer (EC), the combination of nivolumab and chemotherapy in first-line therapy improves overall survival (OS) in PD-L1 (programmed cell death protein 1)-positive patients with approval in Europe (PD-L1 CPS (combined positivity score) ≥ 5), USA and Taiwan (CHECKMATE-649) and pembrolizumab plus chemotherapy for GEJC and EC in Europe (CPS ≥ 10) and the USA (KEYNOTE-590). Furthermore, pembrolizumab plus trastuzumab and chemotherapy show clear benefits in OS and are approved as first-line treatment of Her2 (human epidermal growth factor receptor-2)-positive tumors in the USA (KEYNOTE-811). Nivolumab demonstrates superior OS regardless of PD-L1 expression in third-line therapy with approval in Japan (ATTRACTION-02) and pembrolizumab prolonged the duration of response in PD-L1 positive patients with approval in the USA in PD-L1 CPS ≥ 1 patients (KEYNOTE-059). This review reflects the rationale and current results of phase II and III clinical trials investigating various immune checkpoint inhibitors targeting PD-L1/1 and CTLA (anticytotoxic T-lymphocyte-associated antigen)-4 in combination with and without chemotherapy and Her2-targeted therapy in GC. Full article

(This article belongs to the Special Issue In Search of More Effective and Less Invasive Ways to Treat Esophagus and Stomach Cancer)

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18 pages, 2497 KiB

Open AccessEditor’s ChoiceArticle

Urothelial Bladder Carcinomas with High Tumor Mutation Burden Have a Better Prognosis and Targetable Molecular Defects beyond Immunotherapies

by Ioannis A. Voutsadakis

Curr. Oncol. 2022, 29(3), 1390-1407; https://doi.org/10.3390/curroncol29030117 - 24 Feb 2022

Cited by 23 | Viewed by 4463

Abstract

Background: Urothelial bladder carcinomas had traditionally been difficult to treat cancers, with high morbidity and mortality rates when invasive and metastatic. In recent years, immunotherapy with immune checkpoint inhibitors has improved outcomes in several cancers, including bladder carcinomas. Despite positive overall results, many [...] Read more.

Background: Urothelial bladder carcinomas had traditionally been difficult to treat cancers, with high morbidity and mortality rates when invasive and metastatic. In recent years, immunotherapy with immune checkpoint inhibitors has improved outcomes in several cancers, including bladder carcinomas. Despite positive overall results, many bladder cancer patients do not respond to immunotherapies. Validated predictive biomarkers of response would advance the selection of patients for these treatments. Tumor mutation burden (TMB) has been suggested as an immunotherapy biomarker and thus delineation of attributes of tumors with a high TMB is clinically relevant. Methods: Publicly available genomic and clinical data from the urothelial bladder carcinoma cohort of The Cancer Genome Atlas (TCGA) project are used to analyze characteristics and molecular alterations of the subset of cancers with an increased tumor mutation number compared with those with lower number of mutations. The cut-off for the high mutation burden in the analysis was set at 10 mutations per Megabase (MB). Results: In addition to their sensitivity to immune checkpoint inhibitors, urothelial carcinomas with high TMB possess several molecular defects that could be exploited for combinatorial treatments. Compared with bladder carcinomas with low TMB, carcinomas with high TMB display higher prevalence of mutations in tumor suppressor TP53, PIK3CA, in FAT4 cadherin and in genes encoding for several epigenetic modifier enzymes. The frequency of mutations in mismatch repair and DNA damage response genes is higher in cancers with high TMB. The group of urothelial carcinomas with high TMB has a better prognosis than the group with low TMB. This improved Overall Survival (OS) stems from improved survival of stage III cancers with high TMB compared with stage III cancers with low TMB, while stage II and stage IV cancers have similar OS, independently of their TMB. Conclusion: Differences of the landscape of high and low TMB urothelial cancers provides leads for further pathogenesis investigations and may prove useful for development of combination therapies including immunotherapies with targeted inhibitors. Full article

(This article belongs to the Special Issue Current Advances in Clinical Genomics and Treatment of Urothelial Carcinoma)

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9 pages, 1577 KiB

Open AccessEditor’s ChoiceArticle

Point of Care Molecular Testing: Community-Based Rapid Next-Generation Sequencing to Support Cancer Care

by Brandon S. Sheffield, Andrea Beharry, Joanne Diep, Kirstin Perdrizet, Marco A. J. Iafolla, William Raskin, Shaan Dudani, Mary Anne Brett, Blerta Starova, Brian Olsen and Parneet K. Cheema

Curr. Oncol. 2022, 29(3), 1326-1334; https://doi.org/10.3390/curroncol29030113 - 23 Feb 2022

Cited by 31 | Viewed by 7110

Abstract

Purpose: Biomarker data are critical to the delivery of precision cancer care. The average turnaround of next-generation sequencing (NGS) reports is over 2 weeks, and in-house availability is typically limited to academic centers. Lengthy turnaround times for biomarkers can adversely affect outcomes. [...] Read more.

Purpose: Biomarker data are critical to the delivery of precision cancer care. The average turnaround of next-generation sequencing (NGS) reports is over 2 weeks, and in-house availability is typically limited to academic centers. Lengthy turnaround times for biomarkers can adversely affect outcomes. Traditional workflows involve moving specimens through multiple facilities. This study evaluates the feasibility of rapid comprehensive NGS using the Genexus integrated sequencer and a novel streamlined workflow in a community setting. Methods: A retrospective chart review was performed to assess the early experience and performance characteristics of a novel approach to biomarker testing at a large community center. This approach to NGS included an automated workflow utilizing the Genexus integrated sequencer, validated for clinical use. NGS testing was further integrated within a routine immunohistochemistry (IHC) service, utilizing histotechnologists to perform technical aspects of NGS, with results reported directly by anatomic pathologists. Results: Between October 2020 and October 2021, 578 solid tumor samples underwent genomic profiling. Median turnaround time for biomarker results was 3 business days (IQR: 2–5). Four hundred eighty-one (83%) of the cases were resulted in fewer than 5 business days, and 66 (11%) of the cases were resulted simultaneously with diagnosis. Tumor types included lung cancer (310), melanoma (97), and colorectal carcinoma (68), among others. NGS testing detected key driver alterations at expected prevalence rates: lung EGFR (16%), ALK (3%), RET (1%), melanoma BRAF (43%), colorectal RAS/RAF (67%), among others. Conclusion: This is the first study demonstrating clinical implementation of rapid NGS. This supports the feasibility of automated comprehensive NGS performed and interpreted in parallel with diagnostic histopathology and immunohistochemistry. This novel approach to biomarker testing offers considerable advantages to clinical cancer care. Full article

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14 pages, 289 KiB

Open AccessEditor’s ChoiceReview

Minimally Invasive Surgery for Cervical Cancer in Light of the LACC Trial: What Have We Learned?

by Omar Touhami and Marie Plante

Curr. Oncol. 2022, 29(2), 1093-1106; https://doi.org/10.3390/curroncol29020093 - 14 Feb 2022

Cited by 26 | Viewed by 4843

Abstract

Cervical cancer is the most common gynecologic malignancy and the fourth most common cancer in women worldwide. Over the last two decades, minimally invasive surgery (MIS) emerged as the mainstay in the surgical management of cervical cancer, bringing advantages such as lower operative [...] Read more.

Cervical cancer is the most common gynecologic malignancy and the fourth most common cancer in women worldwide. Over the last two decades, minimally invasive surgery (MIS) emerged as the mainstay in the surgical management of cervical cancer, bringing advantages such as lower operative morbidity and shorter hospital stay compared to open surgery while maintaining comparable oncologic outcomes in numerous retrospective studies. However, in 2018, a prospective phase III randomized controlled trial, “Laparoscopic Approach to Carcinoma of the Cervix (LACC)”, unexpectedly reported that MIS was associated with a statistically significant poorer overall survival and disease-free survival compared to open surgery in patients with early-stage cervical cancer. Various hypotheses have been raised by the authors to try to explain these results, but the LACC trial was not powered to answer those questions. In this study, through an exhaustive literature review, we wish to explore some of the potential causes that may explain the poorer oncologic outcomes associated with MIS, including the type of MIS surgery, the size of the lesion, the impact of CO₂ pneumoperitoneum, prior conization, the use of uterine manipulator, the use of protective measures, and the effect of surgical expertise/learning curve. Full article

(This article belongs to the Special Issue New Frontiers in Treatment for Gynecologic Cancers)

11 pages, 3285 KiB

Open AccessEditor’s ChoiceSystematic Review

Delayed Effect of Dendritic Cells Vaccination on Survival in Glioblastoma: A Systematic Review and Meta-Analysis

by Salvatore Cozzi, Masoumeh Najafi, Marzieh Gomar, Patrizia Ciammella, Cinzia Iotti, Corrado Iaccarino, Massimo Dominici, Giacomo Pavesi, Chiara Chiavelli, Ali Kazemian and Amin Jahanbakhshi

Curr. Oncol. 2022, 29(2), 881-891; https://doi.org/10.3390/curroncol29020075 - 4 Feb 2022

Cited by 16 | Viewed by 4494

Abstract

Background: Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients’ long-term survival. This meta-analysis aims to assess the efficacy of DCV for newly diagnosed glioblastoma patients in clinical trials. Methods: The study databases, including [...] Read more.

Background: Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients’ long-term survival. This meta-analysis aims to assess the efficacy of DCV for newly diagnosed glioblastoma patients in clinical trials. Methods: The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: “glioblastoma multiforme”, “dendritic cell”, “vaccination”, “immunotherapy”, “immune system”, “immune response”, “chemotherapy”, “recurrence”, and “temozolomide”. Among the 157 screened, only 15 articles were eligible for the final analysis. Results: Regimens including DCV showed no effect on 6-month progression-free survival (PFS, HR = 1.385, 95% CI: 0.822–2.335, p = 0.673) or on 6-month overall survival (OS, HR = 1.408, 95% CI: 0.882–2.248, p = 0.754). In contrast, DCV led to significantly longer 1-year OS (HR = 1.936, 95% CI: 1.396–2.85, p = 0.001) and longer 2-year OS (HR = 3.670, 95% CI: 2.291–5.879, p = 0.001) versus control groups. Hence, introducing DCV could lead to increased 1 and 2-year survival of patients by 1.9 and 3.6 times, respectively. Conclusion: Antitumor regimens including DCV can effectively improve mid-term survival in patients suffering glioblastoma multiforme (GBM), but its impact emerges only after one year from vaccination. These data indicate the need for more time to achieve an anti-GBM immune response and suggest additional therapeutics, such as checkpoint inhibitors, to empower an earlier DCV action in patients affected by a very poor prognosis. Full article

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17 pages, 1371 KiB

Open AccessEditor’s ChoiceReview

Endometrial Cancer: Transitioning from Histology to Genomics

by Cristina Mitric and Marcus Q. Bernardini

Curr. Oncol. 2022, 29(2), 741-757; https://doi.org/10.3390/curroncol29020063 - 31 Jan 2022

Cited by 36 | Viewed by 12532

Abstract

Endometrial carcinoma (EC) is traditionally treated with surgery and adjuvant treatment depending on clinicopathological risk factors. The genomic analysis of EC in 2013 and subsequent studies using immunohistochemistry have led to the current EC molecular classification into: polymerase epsilon mutated (POLEmut), p53 abnormal [...] Read more.

Endometrial carcinoma (EC) is traditionally treated with surgery and adjuvant treatment depending on clinicopathological risk factors. The genomic analysis of EC in 2013 and subsequent studies using immunohistochemistry have led to the current EC molecular classification into: polymerase epsilon mutated (POLEmut), p53 abnormal (p53abn), mismatch repair deficient (MMRd), and no specific molecular profile (NSMP). The four groups have prognostic value and represent a promising tool for clinical decision-making regarding adjuvant treatment. Molecular classification was integrated into the recent European Society of Gynecologic Oncology (ESGO) management guidelines. POLEmut EC has favorable outcomes and retrospective studies found that omitting adjuvant treatment is safe in this group; two prospective clinical trials, PORTEC-4 and TAPER, are ongoing to assess this. p53 abn is associated with increased recurrence, decreased survival, and benefitted from chemotherapy in the PORTEC-3 subgroup molecular analysis. The clinical trials PORTEC-4a and CANSTAMP will prospectively assess this. MMRd and NSMP groups have intermediate prognosis and will likely continue to rely closely on clinicopathological features for adjuvant treatment decisions. In addition, the molecular classification has led to exploring novel treatments such as checkpoint inhibitors. Overall, the molecular perspective on EC and associated clinical trials will likely refine EC risk stratification to optimize care and avoid overtreatment. Full article

(This article belongs to the Special Issue New Frontiers in Treatment for Gynecologic Cancers)

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18 pages, 394 KiB

Open AccessEditor’s ChoiceReview

ROS-1 Fusions in Non-Small-Cell Lung Cancer: Evidence to Date

by Sébastien Gendarme, Olivier Bylicki, Christos Chouaid and Florian Guisier

Curr. Oncol. 2022, 29(2), 641-658; https://doi.org/10.3390/curroncol29020057 - 28 Jan 2022

Cited by 78 | Viewed by 10374

Abstract

The ROS-1 gene plays a major role in the oncogenesis of numerous tumors. ROS-1 rearrangement is found in 0.9–2.6% of non-small-cell lung cancers (NSCLCs), mostly lung adenocarcinomas, with a significantly higher rate of women, non-smokers, and a tendency to a younger age. It [...] Read more.

The ROS-1 gene plays a major role in the oncogenesis of numerous tumors. ROS-1 rearrangement is found in 0.9–2.6% of non-small-cell lung cancers (NSCLCs), mostly lung adenocarcinomas, with a significantly higher rate of women, non-smokers, and a tendency to a younger age. It has been demonstrated that ROS-1 is a true oncogenic driver, and tyrosine kinase inhibitors (TKIs) targeting ROS-1 can block tumor growth and provide clinical benefit for the patient. Since 2016, crizotinib has been the first-line reference therapy, with two-thirds of the patients’ tumors responding and progression-free survival lasting ~20 months. More recently developed are ROS-1-targeting TKIs that are active against resistance mechanisms appearing under crizotinib and have better brain penetration. This review summarizes current knowledge on ROS-1 rearrangement in NSCLCs, including the mechanisms responsible for ROS-1 oncogenicity, epidemiology of ROS-1-positive tumors, methods for detecting rearrangement, phenotypic, histological, and molecular characteristics, and their therapeutic management. Much of this work is devoted to resistance mechanisms and the development of promising new molecules. Full article

(This article belongs to the Special Issue Treatments for Non-Small Cell Lung Cancer: The Multiple Options for Precision Medicine)

18 pages, 4372 KiB

Open AccessEditor’s ChoiceArticle

Circulating Exosomal microRNAs as Predictive Biomarkers of Neoadjuvant Chemotherapy Response in Breast Cancer

by Valentina K. Todorova, Stephanie D. Byrum, Allen J. Gies, Cade Haynie, Hunter Smith, Nathan S. Reyna and Issam Makhoul

Curr. Oncol. 2022, 29(2), 613-630; https://doi.org/10.3390/curroncol29020055 - 28 Jan 2022

Cited by 28 | Viewed by 6314

Abstract

Background: Neoadjuvant chemotherapy (NACT) is an increasingly used approach for treatment of breast cancer. The pathological complete response (pCR) is considered a good predictor of disease-specific survival. This study investigated whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with [...] Read more.

Background: Neoadjuvant chemotherapy (NACT) is an increasingly used approach for treatment of breast cancer. The pathological complete response (pCR) is considered a good predictor of disease-specific survival. This study investigated whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with NACT. Method: Plasma samples of 20 breast cancer patients treated with NACT were collected prior to and after the first cycle. RNA sequencing was used to determine microRNA profiling. The Cancer Genome Atlas (TCGA) was used to explore the expression patterns and survivability of the candidate miRNAs, and their potential targets based on the expression levels and copy number variation (CNV) data. Results: Three miRNAs before that NACT (miR-30b, miR-328 and miR-423) predicted pCR in all of the analyzed samples. Upregulation of miR-127 correlated with pCR in triple-negative breast cancer (TNBC). After the first NACT dose, pCR was predicted by exo-miR-141, while miR-34a, exo-miR182, and exo-miR-183 predicted non-pCR. A significant correlation between the candidate miRNAs and the overall survival, subtype, and metastasis in breast cancer, suggesting their potential role as predictive biomarkers of pCR. Conclusions: If the miRNAs identified in this study are validated in a large cohort of patients, they might serve as predictive non-invasive liquid biopsy biomarkers for monitoring pCR to NACT in breast cancer. Full article

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13 pages, 739 KiB

Open AccessEditor’s ChoiceReview

The Psychosocial Impact of COVID-19 on Older Adults with Cancer: A Rapid Review

by Ridhi Verma, Heather M. Kilgour and Kristen R. Haase

Curr. Oncol. 2022, 29(2), 589-601; https://doi.org/10.3390/curroncol29020053 - 28 Jan 2022

Cited by 16 | Viewed by 4119

Abstract

Background: Older adults with cancer are amongst the most vulnerable population to be negatively impacted by COVID-19 due to their likelihood of comorbidities and compromised immune status. Considering the longevity of the pandemic, understanding the subjective perceptions and psychosocial concerns of this population [...] Read more.

Background: Older adults with cancer are amongst the most vulnerable population to be negatively impacted by COVID-19 due to their likelihood of comorbidities and compromised immune status. Considering the longevity of the pandemic, understanding the subjective perceptions and psychosocial concerns of this population may help ameliorate the psychological aftermath. In this review, we systematically analyze the literature surrounding the psychosocial impact and coping strategies among older adults with cancer within the context of COVID-19. Methods: We conducted a rapid review of literature following PRISMA guidelines between January 2020 to August 2021 using (1) MEDLINE, (2) Embase, (3) CINAHL, and (4) PsychINFO and keyword searches for “cancer” and “COVID-19” focused on adults 65 years or older. Results: Of the 6597 articles screened, 10 met the inclusion criteria. Based on the included articles, the psychosocial impact of COVID-19 was reported under four domains, (1) impact of COVID-19 on quality of life (QoL), (2) concerns related to COVID-19, (3) coping with the impact of COVID-19, and (4) recommendations for future care. Results pertaining to perceived quality of life were inconsistent across the included articles. The most common concerns related to: contracting COVID-19, survivorship transitions, and feelings of isolation. Coping strategies reported by older adults included: spiritual care, lived experience, acceptance, and positive reinterpretation. Conclusions: We found many psychosocial impacts of the pandemic on older adults with cancer. The findings from this review can inform interventions related to shared decision-making and tailored patient care in the future. Full article

(This article belongs to the Special Issue Improving Care for Older Adults with Cancer)

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6 pages, 828 KiB

Open AccessEditor’s ChoiceArticle

Efficacy of Capecitabine and Temozolomide in Small Bowel (Midgut) Neuroendocrine Tumors

by Taymeyah Al-Toubah, Brian Morse and Jonathan Strosberg

Curr. Oncol. 2022, 29(2), 510-515; https://doi.org/10.3390/curroncol29020046 - 26 Jan 2022

Cited by 10 | Viewed by 3382

Abstract

The capecitabine/temozolomide regimen has significant activity in pancreatic NETs; however, data are limited in NETs of the small bowel (midgut). A retrospective study of all patients with metastatic midgut NETs seen at Moffitt Cancer Center between January 2008 and June 2019 treated with [...] Read more.

The capecitabine/temozolomide regimen has significant activity in pancreatic NETs; however, data are limited in NETs of the small bowel (midgut). A retrospective study of all patients with metastatic midgut NETs seen at Moffitt Cancer Center between January 2008 and June 2019 treated with CAPTEM was conducted. 32 patients with proven or suspected well-differentiated primary small bowel NETs (excluding duodenum) were identified. 6 patients were found to have a radiographic response (19%), 5 of whom had high-grade disease. Only one patient among 23 with low/intermediate-grade disease responded (4%), whereas the response rate for patients with high-grade disease was 56%. Among patients with low/intermediate-grade disease, 44% discontinued due to poor tolerability. The CAPTEM regimen appears to have an activity in patients with high-grade small bowel NETs and is largely inactive in patients with low/intermediate-grade tumors. Full article

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13 pages, 660 KiB

Open AccessEditor’s ChoiceSystematic Review

A Portrait of SARS-CoV-2 Infection in Patients Undergoing Hematopoietic Cell Transplantation: A Systematic Review of the Literature

by Adrian J. M. Bailey, Aidan M. Kirkham, Madeline Monaghan, Risa Shorr, C. Arianne Buchan, Christopher Bredeson and David S. Allan

Curr. Oncol. 2022, 29(1), 337-349; https://doi.org/10.3390/curroncol29010030 - 13 Jan 2022

Cited by 15 | Viewed by 3895

Abstract

The management of COVID-19 in hematopoietic cell transplant (HCT) recipients represents a special challenge given the variable states of immune dysregulation and altered vaccine efficacy in this population. A systematic search (Ovid Medline and Embase on 1 June 2021) was needed to better [...] Read more.

The management of COVID-19 in hematopoietic cell transplant (HCT) recipients represents a special challenge given the variable states of immune dysregulation and altered vaccine efficacy in this population. A systematic search (Ovid Medline and Embase on 1 June 2021) was needed to better understand the presenting features, prognostic factors, and treatment options. Of 897 records, 29 studies were identified in our search. Most studies reporting on adults and pediatric recipients described signs and symptoms that were typical of COVID-19. Overall, the mortality rates were high, with 21% of adults and 6% of pediatric HCT recipients succumbing to COVID-19. The factors reported to be associated with increased mortality included age (HR = 1.21, 95% CI 1.03–1.43, p = 0.02), ICU admission (HR = 4.42, 95% CI 2.25–8.65, p < 0.001 and HR = 2.26, 95% CI 1.22–4.20, p = 0.01 for allogeneic and autologous HCT recipients), and low platelet count (OR = 21.37, 95% CI 1.71–267.11, p = 0.01). Performance status was associated with decreased mortality (HR = 0.83, 95% CI 0.74–0.93, p = 0.001). A broad range of treatments was described, although no controlled studies were identified. The risk of bias, using the Newcastle–Ottawa scale, was low. Patients undergoing HCT are at a high risk of severe morbidity and mortality associated with COVID-19. Controlled studies investigating potential treatments are required to determine the efficacy and safety in this population. Full article

(This article belongs to the Section Cell Therapy)

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12 pages, 1467 KiB

Open AccessEditor’s ChoiceSystematic Review

Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

by Ilaria Attili, Antonio Passaro, Pasquale Pisapia, Umberto Malapelle and Filippo de Marinis

Curr. Oncol. 2022, 29(1), 255-266; https://doi.org/10.3390/curroncol29010024 - 9 Jan 2022

Cited by 49 | Viewed by 10166

Abstract

Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high [...] Read more.

Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4–26% of total EGFR mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding de novoEGFR exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40–80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20–70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound EGFR mutations, taking into account different sensitivity profile of accompanying EGFR mutations for selecting the most adequate EGFR TKI for individual patients. Full article

(This article belongs to the Section Thoracic Oncology)

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17 pages, 1492 KiB

Open AccessEditor’s ChoiceArticle

Health and Budget Impact of Liquid-Biopsy-Based Comprehensive Genomic Profile (CGP) Testing in Tissue-Limited Advanced Non-Small Cell Lung Cancer (aNSCLC) Patients

by Yuti P. Patel, Donald Husereau, Natasha B. Leighl, Barbara Melosky and Julian Nam

Curr. Oncol. 2021, 28(6), 5278-5294; https://doi.org/10.3390/curroncol28060441 - 11 Dec 2021

Cited by 13 | Viewed by 4399

Abstract

BACKGROUND AND OBJECTIVES: Molecular genetic testing using tissue biopsies can be challenging for patients due to unfavorable tumor sites, the invasive nature of a tissue biopsy, and the added time of booking a repeat biopsy (re-biopsy). Centers in Canada have found insufficient tissue [...] Read more.

BACKGROUND AND OBJECTIVES: Molecular genetic testing using tissue biopsies can be challenging for patients due to unfavorable tumor sites, the invasive nature of a tissue biopsy, and the added time of booking a repeat biopsy (re-biopsy). Centers in Canada have found insufficient tissue rates to be approximately 10%, and even among successful biopsies, insufficient DNA in tissue samples is approximately 16%, triggering the lengthy process of re-biopsies. Using aNSCLC as an example, this study sought to characterize the health and budget impact of alternative liquid-biopsy(LBx)-based comprehensive genomic profile (CGP) testing in tissue-limited patients (TL-LBx-CGP) from a Canadian publicly funded healthcare perspective. MATERIAL AND METHODS: An economic model was developed to estimate the incremental cost and life-years gained as a population associated with adopting TL-LBx-CGP. The eligible patient population was modeled using a top-down epidemiological approach based on the published literature and expert clinician input. Treatment allocation was modeled based on biomarker prevalence in the published literature, and the availability of funded therapies. Costs included molecular testing, as well as drug, administrative, and supportive costs, and relevant health data included median overall survival and median progression-free survival data. RESULTS: Incorporation of TL-LBx-CGP demonstrated an overall impact of $14.7 million with 168 life-years gained to the Canadian publicly funded healthcare system in the 3-year time horizon. Full article

(This article belongs to the Section Health Economics)

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14 pages, 1297 KiB

Open AccessFeature PaperEditor’s ChoiceReview

A Review of Canadian Cancer-Related Clinical Practice Guidelines and Resources during the COVID-19 Pandemic

by Eliya Farah, Rami Ali, Parker Tope, Mariam El-Zein, Eduardo L. Franco and McGill Task Force on COVID-19 and Cancer

Curr. Oncol. 2021, 28(2), 1020-1033; https://doi.org/10.3390/curroncol28020100 - 25 Feb 2021

Cited by 16 | Viewed by 5867

Abstract

(1) Background: Preventive measures taken in response to the coronavirus disease 2019 (COVID-19) pandemic have adversely affected an entire range of cancer-related medical activities. The reallocation of medical resources, staff, and ambulatory services, as well as critical shortages in pharmaceutical and medical supplies [...] Read more.

(1) Background: Preventive measures taken in response to the coronavirus disease 2019 (COVID-19) pandemic have adversely affected an entire range of cancer-related medical activities. The reallocation of medical resources, staff, and ambulatory services, as well as critical shortages in pharmaceutical and medical supplies have compelled healthcare professionals to prioritize patients with cancer to treatment and screening services based on a set of classification criteria in cancer-related guidelines. Cancer patients themselves have been affected on multiple levels, and addressing their concerns poses another challenge to the oncology community. (2) Methods: We conducted a Canada-wide search of cancer-related clinical practice guidelines on the management and prioritization of individuals into treatment and screening services. We also outlined the resources provided by Canadian cancer charities and patient advocacy groups to provide cancer patients, or potential cancer patients, with useful information and valuable support resources. (3) Results: The identified provincial guidelines emphasized cancer care (i.e., treatment) more than cancer control (i.e., screening). For cancer-related resources, a clear significance was placed on knowledge & awareness and supportive resources, mainly relating to mental health. (4) Conclusion: We provided a guidance document outlining cancer-related guidelines and resources that are available to healthcare providers and patients across Canada during the COVID-19 pandemic. Full article

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12 pages, 543 KiB

Open AccessEditor’s ChoiceArticle

A Randomized Controlled Trial Comparing Alloderm-RTU with DermACELL in Immediate Subpectoral Implant-Based Breast Reconstruction

by Angel Arnaout, Jing Zhang, Simon Frank, Moein Momtazi, Erin Cordeiro, Amanda Roberts, Ammara Ghumman, Dean Fergusson, Carol Stober, Gregory Pond, Ahwon Jeong, Lisa Vandermeer, Brian Hutton, Mark Clemons and on behalf of the REaCT Investigators

Curr. Oncol. 2021, 28(1), 184-195; https://doi.org/10.3390/curroncol28010020 - 25 Dec 2020

Cited by 15 | Viewed by 3778

Abstract

Background: The effectiveness of different acellular dermal matrices (ADM) used for implant-based reconstruction immediately following mastectomy is an important clinical question. A prospective randomized clinical trial was performed to evaluate the superiority of DermACELL over Alloderm-RTU in reducing drain duration. Methods: Patients undergoing [...] Read more.

Background: The effectiveness of different acellular dermal matrices (ADM) used for implant-based reconstruction immediately following mastectomy is an important clinical question. A prospective randomized clinical trial was performed to evaluate the superiority of DermACELL over Alloderm-RTU in reducing drain duration. Methods: Patients undergoing mastectomy with subpectoral immediate and permanent implant-based breast reconstruction were randomized to Alloderm-RTU or DermACELL. The primary outcome was seroma formation, measured by the duration of postoperative drain placement. Secondary outcomes included: post drain removal seroma aspiration, infection, redbreast syndrome, wound dehiscence, loss of the implant, and unplanned return to the operating room. Results: 62 patients were randomized for 81 mastectomies (41 Alloderm-RTU, 40 DermACELL). Baseline characteristics were similar. There was no statistically significant difference in mean drain duration (p = 0.16), with a trend towards longer duration in the Alloderm-RTU group (1.6 days; 95%CI, 0.7 to 3.9). The overall rate of minor and major complications were statistically similar between the two groups; although patients with Alloderm-RTU had 3 times as many infections requiring antibiotics (7.9% vs. 2.5%) with a risk difference of 5.4 (95%CI −4.5 to 15.2), and twice as many unplanned returns to the operating room (15.8% vs. 7.5%) with a risk difference of 8.3 (95% CI −5.9 to 22.5) as DermACELL. Conclusion: This is the first prospective randomized clinical trial comparing the two most commonly used human-derived ADMs. There was no statistically significant difference in drain duration, minor, or major complications between DermACELL over Alloderm-RTU in immediate subpectoral permanent implant-based breast reconstruction post-mastectomy. Full article

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