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Curr. Oncol., Volume 30, Issue 6 (June 2023) – 50 articles

Cover Story (view full-size image): The approval of CDK4/6 inhibitors has dramatically improved care for the treatment of HR+/HER2– advanced breast cancer, but navigating the rapidly expanding evidence base is challenging. In this review, we provide best-practice recommendations for the first-line treatment of HR+/HER2– advanced breast cancer in Canada based on the relevant literature, clinical guidelines, and our own clinical experience. Ribociclib + aromatase inhibitor is our preferred first-line treatment for de novo advanced disease or relapse ≥12 months after the completion of adjuvant endocrine therapy, and ribociclib or abemaciclib + fulvestrant is our preferred first-line treatment for patients experiencing early relapse. Considerations for special populations are also explored. View this paper
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14 pages, 1803 KiB  
Article
Characteristics of Phase IV Clinical Trials in Oncology: An Analysis Using the ClinicalTrials.gov Registry Data
by Brandon Michael Henry, Giuseppe Lippi, Ameen Nasser and Patryk Ostrowski
Curr. Oncol. 2023, 30(6), 5932-5945; https://doi.org/10.3390/curroncol30060443 - 20 Jun 2023
Viewed by 2270
Abstract
The present study analyzed the characteristics of phase IV clinical trials in oncology using data from the ClinicalTrials.gov registry. The included trials were conducted between January 2013 and December 2022 and were examined for key characteristics, including outcome measures, interventions, sample sizes, and [...] Read more.
The present study analyzed the characteristics of phase IV clinical trials in oncology using data from the ClinicalTrials.gov registry. The included trials were conducted between January 2013 and December 2022 and were examined for key characteristics, including outcome measures, interventions, sample sizes, and study design, different cancer types, and geographic regions. The analysis included 368 phase IV oncology studies. An amount of 50% of these studies examined both safety and efficacy, while 43.5% only reported efficacy outcome measures, and 6.5% only described safety outcome measures. Only 16.9% of studies were powered to detect adverse events with a frequency of 1 in 100. Targeted therapies accounted for the majority of included studies (53.5%), with breast (32.91%) and hematological cancers (25.82%) being the most frequently investigated malignancies. Most phase IV oncology studies lacked sufficient power to detect rare adverse events due to their small sample sizes and instead focused on effectiveness. To ensure that there is no gap in drug safety data collection and detection of rare adverse events due to limited phase IV clinical trials, there is a significant need for additional education and participation by both health care providers and patients in spontaneous reporting processes. Full article
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26 pages, 3686 KiB  
Review
Leptomeningeal Metastasis: A Review of the Pathophysiology, Diagnostic Methodology, and Therapeutic Landscape
by Andrew Nguyen, Alexander Nguyen, Oluwaferanmi T. Dada, Persis D. Desai, Jacob C. Ricci, Nikhil B. Godbole, Kevin Pierre and Brandon Lucke-Wold
Curr. Oncol. 2023, 30(6), 5906-5931; https://doi.org/10.3390/curroncol30060442 - 19 Jun 2023
Cited by 9 | Viewed by 6982
Abstract
The present review aimed to establish an understanding of the pathophysiology of leptomeningeal disease as it relates to late-stage development among different cancer types. For our purposes, the focused metastatic malignancies include breast cancer, lung cancer, melanoma, primary central nervous system tumors, and [...] Read more.
The present review aimed to establish an understanding of the pathophysiology of leptomeningeal disease as it relates to late-stage development among different cancer types. For our purposes, the focused metastatic malignancies include breast cancer, lung cancer, melanoma, primary central nervous system tumors, and hematologic cancers (lymphoma, leukemia, and multiple myeloma). Of note, our discussion was limited to cancer-specific leptomeningeal metastases secondary to the aforementioned primary cancers. LMD mechanisms secondary to non-cancerous pathologies, such as infection or inflammation of the leptomeningeal layer, were excluded from our scope of review. Furthermore, we intended to characterize general leptomeningeal disease, including the specific anatomical infiltration process/area, CSF dissemination, manifesting clinical symptoms in patients afflicted with the disease, detection mechanisms, imaging modalities, and treatment therapies (both preclinical and clinical). Of these parameters, leptomeningeal disease across different primary cancers shares several features. Pathophysiology regarding the development of CNS involvement within the mentioned cancer subtypes is similar in nature and progression of disease. Consequently, detection of leptomeningeal disease, regardless of cancer type, employs several of the same techniques. Cerebrospinal fluid analysis in combination with varied imaging (CT, MRI, and PET-CT) has been noted in the current literature as the gold standard in the diagnosis of leptomeningeal metastasis. Treatment options for the disease are both varied and currently in development, given the rarity of these cases. Our review details the differences in leptomeningeal disease as they pertain through the lens of several different cancer subtypes in an effort to highlight the current state of targeted therapy, the potential shortcomings in treatment, and the direction of preclinical and clinical treatments in the future. As there is a lack of comprehensive reviews that seek to characterize leptomeningeal metastasis from various solid and hematologic cancers altogether, the authors intended to highlight not only the overlapping mechanisms but also the distinct patterning of disease detection and progression as a means to uniquely treat each metastasis type. The scarcity of LMD cases poses a barrier to more robust evaluations of this pathology. However, as treatments for primary cancers have improved over time, so has the incidence of LMD. The increase in diagnosed cases only represents a small fraction of LMD-afflicted patients. More often than not, LMD is determined upon autopsy. The motivation behind this review stems from the increased capacity to study LMD in spite of scarcity or poor patient prognosis. In vitro analysis of leptomeningeal cancer cells has allowed researchers to approach this disease at the level of cancer subtypes and markers. We ultimately hope to facilitate the clinical translation of LMD research through our discourse. Full article
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8 pages, 1320 KiB  
Brief Report
Robotic Lobectomy without Complete Fissure for Non-Small Cell Lung Cancer: Technical Aspects and Perioperative Outcomes of the Tunnel Technique
by Filippo Tommaso Gallina, Daniele Forcella, Enrico Melis and Francesco Facciolo
Curr. Oncol. 2023, 30(6), 5898-5905; https://doi.org/10.3390/curroncol30060441 - 19 Jun 2023
Viewed by 1240
Abstract
Even though the use of the “fissure-last” technique in mini-invasive lobectomy with the fissureless condition is well accepted, in terms of perioperative outcomes, controversies still surround the hilar lymph node dissection. In this article, we reported a description of the robotic “tunnel technique” [...] Read more.
Even though the use of the “fissure-last” technique in mini-invasive lobectomy with the fissureless condition is well accepted, in terms of perioperative outcomes, controversies still surround the hilar lymph node dissection. In this article, we reported a description of the robotic “tunnel technique” approach in the right upper lobectomy in the absence of a defined fissure. We then compared the short terms outcomes of 30 consecutive cases treated using this technique, with 30 patients treated using the “fissure last” VATS approach in the same institution, before the start of the robotic surgery program. Full article
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22 pages, 779 KiB  
Review
Neurologic Complications of Cancer Immunotherapy
by Aseel N. Alsalem, Leslie A. Scarffe, Hannah R. Briemberg, Ashley E. Aaroe and Rebecca A. Harrison
Curr. Oncol. 2023, 30(6), 5876-5897; https://doi.org/10.3390/curroncol30060440 - 19 Jun 2023
Cited by 2 | Viewed by 2436
Abstract
Immunotherapy has revolutionized cancer treatment over the past decade. As it is increasingly introduced into routine clinical practice, immune-related complications have become more frequent. Accurate diagnosis and treatment are essential, with the goal of reduced patient morbidity. This review aims to discuss the [...] Read more.
Immunotherapy has revolutionized cancer treatment over the past decade. As it is increasingly introduced into routine clinical practice, immune-related complications have become more frequent. Accurate diagnosis and treatment are essential, with the goal of reduced patient morbidity. This review aims to discuss the various clinical manifestations, diagnosis, treatments, and prognosis of neurologic complications associated with the use of immune checkpoint inhibitors, adoptive T-cell therapies, and T-cell redirecting therapies. We also outline a suggested clinical approach related to the clinical use of these agents. Full article
(This article belongs to the Special Issue Current and Future Research in Immunotherapy for Brain Tumors)
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13 pages, 1379 KiB  
Review
Current Landscape of Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma
by Samantha M. Ruff, Ashish Manne, Jordan M. Cloyd, Mary Dillhoff, Aslam Ejaz and Timothy M. Pawlik
Curr. Oncol. 2023, 30(6), 5863-5875; https://doi.org/10.3390/curroncol30060439 - 18 Jun 2023
Cited by 7 | Viewed by 3065
Abstract
The liver maintains a balance between immune tolerance and activation in its role as a filtration system. Chronic inflammation disrupts this immune microenvironment, thereby allowing for the rise and progression of cancer. Hepatocellular carcinoma (HCC) is a liver tumor generally diagnosed in the [...] Read more.
The liver maintains a balance between immune tolerance and activation in its role as a filtration system. Chronic inflammation disrupts this immune microenvironment, thereby allowing for the rise and progression of cancer. Hepatocellular carcinoma (HCC) is a liver tumor generally diagnosed in the setting of chronic liver disease. When diagnosed early, the primary treatment is surgical resection, liver transplantation, or liver directed therapies. Unfortunately, patients with HCC often present at an advanced stage or with poor liver function, thereby limiting options. To further complicate matters, most systemic therapies are relatively limited and ineffective among patients with advanced disease. Recently, the IMbrave150 trial demonstrated that the combination of atezolizumab and bevacizumab was associated with better survival compared to sorafenib among patients with advanced HCC. As such, atezolizumab and bevacizumab is now recommended first-line therapy for these patients. Tumor cells work to create an immunotolerant environment by preventing the activation of stimulatory immunoreceptors and upregulating expression of proteins that bind inhibitory immunoreceptors. ICIs work to block these interactions and bolster the anti-tumor function of the immune system. We herein provide an overview of the use of ICIs in the treatment of HCC. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma: Epidemiology, Pathogenesis and Treatment)
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14 pages, 2144 KiB  
Article
Lymph Node Staging in Perihilar Cholangiocarcinoma: The Key to the Big Picture
by Nina A. Rogacka, Tamas Benkö, Fuat H. Saner, Eugen Malamutmann, Moritz Kaths, Juergen W. Treckmann and Dieter Paul Hoyer
Curr. Oncol. 2023, 30(6), 5849-5862; https://doi.org/10.3390/curroncol30060438 - 17 Jun 2023
Viewed by 1688
Abstract
Klatskin tumors have a bad prognosis despite aggressive therapy. The role and extent of lymph node dissection during surgery is a matter of discussion. This retrospective study analyzes our current experience of surgical treatments in the last decade. Patients and Methods: A retrospective [...] Read more.
Klatskin tumors have a bad prognosis despite aggressive therapy. The role and extent of lymph node dissection during surgery is a matter of discussion. This retrospective study analyzes our current experience of surgical treatments in the last decade. Patients and Methods: A retrospective single-center analysis of patients (n = 317) who underwent surgical treatment for Klatskin tumors. Univariable and multivariable logistic regression and Cox proportional analysis were performed. The primary endpoint was to investigate the role of lymph node metastasis for patient survival after complete tumor resection. The secondary endpoint was the prediction of lymph node status and long-term survival from preoperatively available parameters. Results: In patients with negative resection margins, a negative lymph node status was the prognosis-determining factor with a 1-, 3-, and 5-year survival rate of 87.7%, 37%, and 26.4% compared with 69.5%, 13.9%, and 9.3% for lymph-node-positive patients, respectively. Multivariable logistic regression for complete resection and negative lymph node status demonstrated only Bismuth type 4 (p = 0.01) and tumor grading (p = 0.002) as independent predictors. In multivariate Cox regression analysis, independent predictors of survival after surgery were the preoperative bilirubin level (p = 0.03), intraoperative transfusion (p = 0.002), and tumor grading (G) (p = 0.001). Conclusion: Lymph node dissection is of utmost importance for adequate staging in patients undergoing surgery for perihilar cholangiocarcinoma. In spite of extensive surgery, long-term survival is clearly associated with the aggressiveness of the disease. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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14 pages, 330 KiB  
Review
The Stigma Surrounding Opioid Use as a Barrier to Cancer-Pain Management: An Overview of Experiences with Fear, Shame, and Poorly Controlled Pain in the Context of Advanced Cancer
by Hannah Harsanyi, Colleen Cuthbert and Fiona Schulte
Curr. Oncol. 2023, 30(6), 5835-5848; https://doi.org/10.3390/curroncol30060437 - 17 Jun 2023
Cited by 2 | Viewed by 2184
Abstract
Cancer-related pain affects a majority of patients with advanced cancer and is often undertreated. The treatment of this pain is largely reliant on the use of opioids, which are essential medicines for symptom management and the maintenance of quality of life (QoL) for [...] Read more.
Cancer-related pain affects a majority of patients with advanced cancer and is often undertreated. The treatment of this pain is largely reliant on the use of opioids, which are essential medicines for symptom management and the maintenance of quality of life (QoL) for patients with advanced cancer. While there are cancer-specific guidelines for the treatment of pain, widespread publication and policy changes in response to the opioid epidemic have drastically impacted perceptions of opioid use. This overview therefore aims to investigate how manifestations of opioid stigma impact pain management in cancer settings, with an emphasis on the experiences of patients with advanced cancer. Opioid use has been widely stigmatized in multiple domains, including public, healthcare, and patient populations. Physician hesitancy in prescribing and pharmacist vigilance in dispensing were identified as barriers to optimal pain management, and may contribute to stigma in the context of advanced cancer. Evidence in the literature suggests that opioid stigma may result in patient deviations from prescription instructions, which generally leads to pain undertreatment. Patients reflected on experiencing shame and fear surrounding their prescription opioid use and feeling uncomfortable communicating with their healthcare providers on these topics. Our findings indicate that future work is required to educate patients and providers in order to de-stigmatize opioid use. Through alleviating stigma, patients may be better able to make decisions regarding their pain management which lead to freedom from cancer-related pain and improved QoL. Full article
(This article belongs to the Section Psychosocial Oncology)
7 pages, 790 KiB  
Communication
Integrated Analysis of the RASH Study with the Use of the “Burden of Therapy” (BOTh®TM) Methodology—A Novel Tool for Assessing Adverse Events in Metastatic Pancreatic Cancer
by Klara Dorman, Stefan Boeck, Robert J. Snijder, Jens T. Siveke, Michael Schenk, Julia Mayerle, Karel Caca, Jens Freiberg-Richter, Ludwig Fischer von Weikersthal, Frank Kullmann, Anke Reinacher-Schick, Martin Fuchs, Stephan Kanzler, Volker Kunzmann, Thomas J. Ettrich, Danmei Zhang, Swantje Held, Ayad Abdul-Ahad, Michael von Bergwelt-Baildon, Volker Heinemann and Michael Haasadd Show full author list remove Hide full author list
Curr. Oncol. 2023, 30(6), 5828-5834; https://doi.org/10.3390/curroncol30060436 - 17 Jun 2023
Viewed by 1313
Abstract
This analysis of the RASH trial (NCT01729481) aimed at gaining a better understanding of the “Burden of Therapy” (BOTh®TM) in pancreatic ductal adenocarcinoma (PDAC). In the RASH study, 150 patients with newly diagnosed metastatic PDAC were treated with gemcitabine plus erlotinib [...] Read more.
This analysis of the RASH trial (NCT01729481) aimed at gaining a better understanding of the “Burden of Therapy” (BOTh®TM) in pancreatic ductal adenocarcinoma (PDAC). In the RASH study, 150 patients with newly diagnosed metastatic PDAC were treated with gemcitabine plus erlotinib (gem/erlotinib) for four weeks. Patients who developed a skin rash during this four-week run-in phase continued with the gem/erlotinib treatment, while rash-negative patients were switched to FOLFIRINOX. The study demonstrated a 1-year survival rate of rash-positive patients who received gem/erlotinib as first-line treatment that was comparable to previous reports of patients receiving FOLFIRINOX. To understand whether these comparable survival rates may be accompanied by better tolerability of the gem/erlotinib treatment compared to FOLFIRINOX, the BOTh®TM methodology was used to continuously quantify and depict the burden of therapy generated by treatment emergent events (TEAEs). Sensory neuropathy was significantly more common in the FOLFIRINOX arm, and prevalence as well as severity increased over time. In both arms, the BOTh®TM associated with diarrhea decreased over the course of treatment. The BOTh®TM caused by neutropenia was comparable in both arms but decreased in the FOLFIRINOX arm over time, possibly due to chemotherapy dose reductions. Overall, gem/erlotinib was associated with a slightly higher overall BOTh®TM, but the difference was not statistically significant (p = 0.6735). In summary, the BOTh®TM analysis facilitates the evaluation of TEAEs. In patients fit for intense chemotherapeutic regimens, FOLFIRINOX is associated with a lower BOTh®TM than gem/erlotinib. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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12 pages, 2867 KiB  
Case Report
Fast Track Management of Primary Thyroid Lymphoma in the Very Elderly Patient
by Pierre Yves Marcy, Frederic Bauduer, Juliette Thariat, Olivier Gisserot, Edouard Ghanassia, Bruno Chetaille, Laurys Boudin and Jean Baptiste Morvan
Curr. Oncol. 2023, 30(6), 5816-5827; https://doi.org/10.3390/curroncol30060435 - 15 Jun 2023
Cited by 3 | Viewed by 1850
Abstract
A rapid growing cervical mass mobile while swallowing is the most common clinical presentation of severe thyroid malignancy. A 91-year-old female patient with a history of Hashimoto thyroiditis presented with clinical compressive neck symptoms. The patient had gastric Maltoma diagnosed that was surgically [...] Read more.
A rapid growing cervical mass mobile while swallowing is the most common clinical presentation of severe thyroid malignancy. A 91-year-old female patient with a history of Hashimoto thyroiditis presented with clinical compressive neck symptoms. The patient had gastric Maltoma diagnosed that was surgically resected thirty years ago. A straightforward process was needed to reach full histological diagnosis and initiate prompt therapy. Ultrasound (US) showed a 67 mm hypoechoic left thyroid mass with reticulated pattern without signs of locoregional invasion. Percutaneous trans isthmic US-guided 18G core needle biopsy (CNB) disclosed diffuse large B cell lymphoma of the thyroid gland. FDG PET revealed two distinct thyroid and gastric foci (both SUVmax 39.1). Therapy was initiated rapidly to decrease clinical symptoms in this aggressive stage III primitive malignant thyroid lymphoma. The prognostic nomogram was calculated by using a seven-item scale, which disclosed a one-year overall survival rate of 52%. The patient underwent three R-CVP chemotherapy courses, then refused further treatment and died within five months. Real-time US-guided CNB approach led to rapid patient’s management that was tailored to patient’s characteristics. Transformation of Maltoma into diffuse large B cell lymphoma (DLBCL) into two body areas is deemed to be extremely rare. Full article
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9 pages, 231 KiB  
Article
Data Dissemination of the Role of Neoadjuvant Radiation in Retroperitoneal Sarcoma: A CTOS and CSSO Survey
by Sarah Corn, Carolyn Nessim, Christina L. Roland, Alessandro Gronchi, Carolyn Freeman and Sinziana Dumitra
Curr. Oncol. 2023, 30(6), 5807-5815; https://doi.org/10.3390/curroncol30060434 - 14 Jun 2023
Viewed by 1548
Abstract
Consensus guidelines call for complete resection of retroperitoneal sarcoma with consideration of neoadjuvant radiation for curative-intent treatment. The 15-month delay from the initial presentation of an abstract to the final publication of the STRASS trial results assessing the impact of neoadjuvant radiation led [...] Read more.
Consensus guidelines call for complete resection of retroperitoneal sarcoma with consideration of neoadjuvant radiation for curative-intent treatment. The 15-month delay from the initial presentation of an abstract to the final publication of the STRASS trial results assessing the impact of neoadjuvant radiation led to a dilemma of how patients should be managed in the interim. This study aims to (1) understand perspectives regarding neoadjuvant radiation for RPS during this period; and (2) assess the process of integrating data into practice. A survey was distributed to international organizations including all specialties treating RPS. Eighty clinicians responded, including surgical (60.5%), radiation (21.0%) and medical oncologists (18.5%). Low kappa correlation coefficients on a series of clinical scenarios querying individual recommendations before and after initial presentation as an abstract indicate considerable change. Over 62% of respondents identified a practice change; however, most also noted discomfort in adopting changes without a manuscript available. Of the 45 respondents indicating discomfort with practice changes without a full manuscript, 28 (62%) indicated that their practice changed in response to the abstract. There was substantial variability in recommendations for neoadjuvant radiation between the presentation of the abstract and the publication of trial results. The difference in the proportion of clinicians describing comfort with changing practice based on the presentation of the abstract versus those that had done so shows that indications for proper integration of data into practice are not clear. Endeavors to resolve this ambiguity and expedite availability of practice-changing data are warranted. Full article
12 pages, 544 KiB  
Review
Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS?
by Ezra Hahn, Danielle Rodin, Rinku Sutradhar, Sharon Nofech-Mozes, Sabina Trebinjac, Lawrence Frank Paszat and Eileen Rakovitch
Curr. Oncol. 2023, 30(6), 5795-5806; https://doi.org/10.3390/curroncol30060433 - 13 Jun 2023
Cited by 3 | Viewed by 1767
Abstract
Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce [...] Read more.
Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce the risk of local recurrence (LR), including invasive LR, which carries a subsequent risk of breast cancer mortality. However, reliable and accurate individual risk prediction remains elusive and RT continues to be standardly recommended for most women with DCIS. Three molecular biomarkers have been studied to better estimate LR risk after BCS—Oncotype DX DCIS score, DCISionRT Decision Score and its associated Residual Risk subtypes, and Oncotype 21-gene Recurrence Score. All these molecular biomarkers represent important efforts towards improving predicted risk of LR after BCS. To prove clinical utility, these biomarkers require careful predictive modeling with calibration and external validation, and evidence of benefit to patients; on this front, further research is needed. Most trials do not incorporate molecular biomarkers in evaluating de-escalation of therapy for DCIS; however, one—the Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk DCIS (ELISA) trial—incorporates the Oncotype DX DCIS score in defining a low-risk population and is an important next step in this line of research. Full article
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26 pages, 732 KiB  
Review
Immunotherapy in Prostate Cancer: State of Art and New Therapeutic Perspectives
by Felicia Maria Maselli, Francesco Giuliani, Carmelo Laface, Martina Perrone, Assunta Melaccio, Pierluigi De Santis, Anna Natalizia Santoro, Chiara Guarini, Maria Laura Iaia and Palma Fedele
Curr. Oncol. 2023, 30(6), 5769-5794; https://doi.org/10.3390/curroncol30060432 - 13 Jun 2023
Cited by 2 | Viewed by 2592
Abstract
Prostate cancer (PC) is the most common type of tumor in men. In the early stage of the disease, it is sensitive to androgen deprivation therapy. In patients with metastatic castration-sensitive prostate cancer (mHSPC), chemotherapy and second-generation androgen receptor therapy have led to [...] Read more.
Prostate cancer (PC) is the most common type of tumor in men. In the early stage of the disease, it is sensitive to androgen deprivation therapy. In patients with metastatic castration-sensitive prostate cancer (mHSPC), chemotherapy and second-generation androgen receptor therapy have led to increased survival. However, despite advances in the management of mHSPC, castration resistance is unavoidable and many patients develop metastatic castration-resistant disease (mCRPC). In the past few decades, immunotherapy has dramatically changed the oncology landscape and has increased the survival rate of many types of cancer. However, immunotherapy in prostate cancer has not yet given the revolutionary results it has in other types of tumors. Research into new treatments is very important for patients with mCRPC because of its poor prognosis. In this review, we focus on the reasons for the apparent intrinsic resistance of prostate cancer to immunotherapy, the possibilities for overcoming this resistance, and the clinical evidence and new therapeutic perspectives regarding immunotherapy in prostate cancer with a look toward the future. Full article
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31 pages, 1898 KiB  
Guidelines
2023 Canadian Colposcopy Guideline: A Risk-Based Approach to Management and Surveillance of Cervical Dysplasia
by Karla Willows, Amanda Selk, Marie-Hélène Auclair, Brent Jim, Naana Jumah, Jill Nation, Lily Proctor, Melissa Iazzi and James Bentley
Curr. Oncol. 2023, 30(6), 5738-5768; https://doi.org/10.3390/curroncol30060431 - 13 Jun 2023
Cited by 4 | Viewed by 9524
Abstract
This guideline provides evidence-based guidance on the risk-based management of cervical dysplasia in the colposcopy setting in the context of primary HPV-based screening and HPV testing in colposcopy. Colposcopy management of special populations is also discussed. The guideline was developed by a working [...] Read more.
This guideline provides evidence-based guidance on the risk-based management of cervical dysplasia in the colposcopy setting in the context of primary HPV-based screening and HPV testing in colposcopy. Colposcopy management of special populations is also discussed. The guideline was developed by a working group in collaboration with the Gynecologic Oncology Society of Canada (GOC), Society of Colposcopists of Canada (SCC) and the Canadian Partnership Against Cancer (CPAC). The literature informing these guidelines was obtained through a systematic review of the relevant literature via a multi-step search process led by information specialists. The literature was reviewed up to June 2021 with manual searches of relevant national guidelines and more recent publications. Quality of the evidence and strength of recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The intended users of this guideline include gynecologists, colposcopists, screening programs and healthcare facilities. Implementation of the recommendations is intended to promote equitable and standardized care for all people undergoing colposcopy in Canada. The risk-based approach aims to improve personalized care and reduce over-/under-treatment in colposcopy. Full article
(This article belongs to the Section Gynecologic Oncology)
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11 pages, 2027 KiB  
Systematic Review
Systematic Review of Calcineurin Inhibitors and Incidence of Skin Malignancies after Kidney Transplantation in Adult Patients: A Study of 309,551 Cases
by Aleksandra Kulbat, Karolina Richter, Tomasz Stefura, Marta Kołodziej-Rzepa, Michał Kisielewski, Tomasz Wojewoda and Wojciech M. Wysocki
Curr. Oncol. 2023, 30(6), 5727-5737; https://doi.org/10.3390/curroncol30060430 - 13 Jun 2023
Cited by 2 | Viewed by 1972
Abstract
The purpose of this systematic review and meta-analysis was to compare the risk of non-melanoma skin cancer (NMSC) and melanoma development in renal transplant recipients who receive calcineurin inhibitors to that of patients treated with other immunosuppressive agents, and investigate the possible association [...] Read more.
The purpose of this systematic review and meta-analysis was to compare the risk of non-melanoma skin cancer (NMSC) and melanoma development in renal transplant recipients who receive calcineurin inhibitors to that of patients treated with other immunosuppressive agents, and investigate the possible association between the type of maintenance immunosuppression and the incidence of NSMC and melanoma in this group of patients. The authors searched databases such as PubMed, Scopus, and Web of Science for articles that would help establish the influence of calcineurin inhibitors on skin cancer development. The inclusion criteria for the study consisted of randomized clinical trials, cohort studies, and case-control studies that compared patients who received kidney transplants and were treated with a calcineurin inhibitor (CNI), such as cyclosporine A (CsA) or tacrolimus (Tac), to those who received alternative immunosuppressants and did not receive a CNI. Seven articles were analyzed overall. The results revealed a correlation between CNI treatment in renal transplant recipients and increased total skin cancer risk (OR 1.28; 95% CI: 0.10–16.28; p < 0.01), melanoma risk (OR 1.09; 95% CI: 0.25–4.74; p < 0.01), and NMSC risk (OR 1.16; 95% CI: 0.41–3.26; p < 0.01). In conclusion, the calcineurin inhibitors used after kidney transplantation are associated with a higher risk of skin cancer—both non-melanoma and melanoma—when compared with other immunosuppressive therapies. This finding suggests that careful monitoring for skin lesions in post-transplant patients must be conducted. However, the decision on the kind of immunotherapy used should always be considered on an individual basis for each renal transplant recipient. Full article
(This article belongs to the Special Issue Epidemiology and Risk Factors of Skin Cancer)
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8 pages, 441 KiB  
Article
The Role of Financial Difficulties as a Mediator between Physical Symptoms and Depression in Advanced Cancer Patients
by Eun Mi Lee, Paula Jiménez-Fonseca, Raquel Hernández, Patricia Cruz-Castellanos, Ana Fernández-Montes, Jacobo Rogado, Mireia Gil-Raga, Mónica Antoñanzas, Helena López-Ceballos and Caterina Calderon
Curr. Oncol. 2023, 30(6), 5719-5726; https://doi.org/10.3390/curroncol30060429 - 12 Jun 2023
Viewed by 1275
Abstract
Financial difficulties experienced by cancer patients negatively impact the mental health of the patients. The objective of this study was to examine the mediating role of financial difficulties between physical symptoms and depression in patients with advanced cancer. A prospective, cross-sectional design was [...] Read more.
Financial difficulties experienced by cancer patients negatively impact the mental health of the patients. The objective of this study was to examine the mediating role of financial difficulties between physical symptoms and depression in patients with advanced cancer. A prospective, cross-sectional design was adopted in the study. The data were collected from 861 participants with advanced cancer in 15 different tertiary hospitals in Spain. The participants’ socio-demographic characteristics were collected using a standardized self-report form. Hierarchical linear regression models were used to explore the mediating role of financial difficulties. In the results, 24% of patients reported a high level of financial difficulties. Physical symptoms were positively associated with financial difficulties and depression (β = 0.46 and β = 0.43, respectively), and financial difficulties was positively associated with depression (β = 0.26). Additionally, financial difficulties played a role in explaining the relationship between physical symptoms and depression, showing a standardized regression coefficient of 0.43 which decreased to 0.39 after the financial difficulties were controlled. Healthcare professionals should consider the importance of providing financial resources and emotional support to help patients and their families cope with the financial burden associated with cancer treatment and its symptoms. Full article
(This article belongs to the Special Issue Financial Toxicity of Cancer Treatment and Care)
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15 pages, 601 KiB  
Review
Translational Models in Glioma Immunotherapy Research
by Alexander L. Ren, Janet Y. Wu, Si Yeon Lee and Michael Lim
Curr. Oncol. 2023, 30(6), 5704-5718; https://doi.org/10.3390/curroncol30060428 - 11 Jun 2023
Viewed by 2331
Abstract
Immunotherapy is a promising therapeutic domain for the treatment of gliomas. However, clinical trials of various immunotherapeutic modalities have not yielded significant improvements in patient survival. Preclinical models for glioma research should faithfully represent clinically observed features regarding glioma behavior, mutational load, tumor [...] Read more.
Immunotherapy is a promising therapeutic domain for the treatment of gliomas. However, clinical trials of various immunotherapeutic modalities have not yielded significant improvements in patient survival. Preclinical models for glioma research should faithfully represent clinically observed features regarding glioma behavior, mutational load, tumor interactions with stromal cells, and immunosuppressive mechanisms. In this review, we dive into the common preclinical models used in glioma immunology, discuss their advantages and disadvantages, and highlight examples of their utilization in translational research. Full article
(This article belongs to the Special Issue Current and Future Research in Immunotherapy for Brain Tumors)
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14 pages, 850 KiB  
Article
Comparative Effectiveness of Chemotherapy Alone Versus Radiotherapy-Based Regimens in Locally Advanced Pancreatic Cancer: A Real-World Multicenter Analysis (PAULA-1)
by Alessandra Arcelli, Giuseppe Tarantino, Francesco Cellini, Milly Buwenge, Gabriella Macchia, Federica Bertini, Alessandra Guido, Francesco Deodato, Savino Cilla, Valerio Scotti, Maria Elena Rosetto, Igor Djan, Salvatore Parisi, Gian Carlo Mattiucci, Michele Fiore, Pierluigi Bonomo, Liliana Belgioia, Rita Marina Niespolo, Pietro Gabriele, Mariacristina Di Marco, Nicola Simoni, Johnny Ma, Lidia Strigari, Renzo Mazzarotto and Alessio Giuseppe Morgantiadd Show full author list remove Hide full author list
Curr. Oncol. 2023, 30(6), 5690-5703; https://doi.org/10.3390/curroncol30060427 - 10 Jun 2023
Viewed by 1636
Abstract
Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a [...] Read more.
Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a real-world setting in terms of overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). LAPC patients from a multicentric retrospective database were included (2005–2018). Survival curves were calculated using the Kaplan–Meier method. Multivariable Cox analysis was performed to identify predictors of LC, OS, and DMFS. Of the 419 patients included, 71.1% were treated with CRT, 15.5% with CHT, and 13.4% with SBRT. Multivariable analysis showed higher LC rates for CRT (HR: 0.56, 95%CI 0.34–0.92, p = 0.022) or SBRT (HR: 0.27, 95%CI 0.13–0.54, p < 0.001), compared to CHT. CRT (HR: 0.44, 95%CI 0.28–0.70, p < 0.001) and SBRT (HR: 0.40, 95%CI 0.22–0.74, p = 0.003) were predictors of prolonged OS with respect to CHT. No significant differences were recorded in terms of DMFS. In selected patients, the addition of radiotherapy to CHT is still an option to be considered. In patients referred for radiotherapy, CRT can be replaced by SBRT considering its duration, higher LC rate, and OS rate, which are at least comparable to that of CRT. Full article
(This article belongs to the Special Issue New Frontiers in Treatment of Pancreatic Cancer)
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10 pages, 694 KiB  
Article
Associations of Clinical and Dosimetric Parameters with Urinary Toxicities after Prostate Brachytherapy: A Long-Term Single-Institution Experience
by Masaya Ito, Chiyoko Makita, Takayuki Mori, Hirota Takano, Tomoyasu Kumano, Masayuki Matsuo, Koji Iinuma, Makoto Kawase, Keita Nakane, Masahiro Nakano and Takuya Koie
Curr. Oncol. 2023, 30(6), 5680-5689; https://doi.org/10.3390/curroncol30060426 - 9 Jun 2023
Viewed by 1389
Abstract
To examine the association of clinical, treatment, and dose parameters with late urinary toxicity after low-dose-rate brachytherapy (LDR-BT) for prostate cancer, we retrospectively studied patients with prostate cancer who underwent LDR-BT from January 2007 through December 2016. Urinary toxicity was assessed using the [...] Read more.
To examine the association of clinical, treatment, and dose parameters with late urinary toxicity after low-dose-rate brachytherapy (LDR-BT) for prostate cancer, we retrospectively studied patients with prostate cancer who underwent LDR-BT from January 2007 through December 2016. Urinary toxicity was assessed using the International Prostate Symptom Score (IPSS) and Overactive Bladder (OAB) Symptom Score (OABSS). Severe and moderate lower urinary tract symptoms (LUTS) were defined as IPSS ≥ 20 and ≥ 8, respectively; OAB was defined as a nocturnal frequency of ≥ 2 and a total OABSS of ≥ 3. In total, 203 patients (median age: 66 years) were included, with a mean follow-up of 8.4 years after treatment. The IPSS and OABSS worsened after 3 months of treatment; these scores improved to pretreatment levels after 18–36 months in most patients. Patients with a higher baseline IPSS and OABSS had a higher frequency of moderate and severe LUTS and OAB at 24 and 60 months, respectively. LUTS and OAB at 24 and 60 months were not correlated with the dosimetric factors of LDR-BT. Although the rate of long-term urinary toxicities assessed using IPSS and OABSS was low, the baseline scores were related to long-term function. Refining patient selection may further reduce long-term urinary toxicity. Full article
(This article belongs to the Special Issue Radiotherapy for Genitourinary Cancer)
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28 pages, 823 KiB  
Guidelines
Canadian Guideline on the Management of a Positive Human Papillomavirus Test and Guidance for Specific Populations
by Tiffany Zigras, Marie-Hélène Mayrand, Celine Bouchard, Shannon Salvador, Lua Eiriksson, Chelsea Almadin, Sarah Kean, Erin Dean, Unjali Malhotra, Nicole Todd, Daniel Fontaine and James Bentley
Curr. Oncol. 2023, 30(6), 5652-5679; https://doi.org/10.3390/curroncol30060425 - 9 Jun 2023
Cited by 3 | Viewed by 5949
Abstract
The purpose of this paper is to provide evidence-based guidance on the management of a positive human papilloma virus (HPV) test and to provide guidance around screening and HPV testing for specific patient populations. The guideline was developed by a working group in [...] Read more.
The purpose of this paper is to provide evidence-based guidance on the management of a positive human papilloma virus (HPV) test and to provide guidance around screening and HPV testing for specific patient populations. The guideline was developed by a working group in collaboration with the Gynecologic Oncology Society of Canada (GOC), Society of Colposcopists of Canada (SCC), and the Canadian Partnership Against Cancer. The literature informing these guidelines was obtained through a systematic review of relevant literature by a multi-step search process led by an information specialist. The literature was reviewed up to July 2021 with manual searches of relevant national guidelines and more recent publications. The quality of the evidence and strength of recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The intended users of this guideline include primary care providers, gynecologists, colposcopists, screening programs, and healthcare facilities. The implementation of the recommendations will ensure an optimum implementation of HPV testing with a focus on the management of positive results. Recommendations for appropriate care for underserved and marginalized groups are made. Full article
(This article belongs to the Section Gynecologic Oncology)
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21 pages, 2749 KiB  
Article
Investigation of the Incidence and Geographic Distribution of Bone and Soft Tissue Sarcomas in Canada: A National Population-Based Study
by Badria Alkazemi, Feras M. Ghazawi, François Lagacé, Vladimir Nechaev, Andrei Zubarev and Ivan V. Litvinov
Curr. Oncol. 2023, 30(6), 5631-5651; https://doi.org/10.3390/curroncol30060424 - 9 Jun 2023
Cited by 1 | Viewed by 1663
Abstract
Sarcomas are a heterogeneous group of mesenchymal malignancies with various genetic and environmental risk factors. This study analyzed the epidemiology of sarcomas to gain insight into the incidence and mortality rates of these cancers in Canada, as well as to elucidate their potential [...] Read more.
Sarcomas are a heterogeneous group of mesenchymal malignancies with various genetic and environmental risk factors. This study analyzed the epidemiology of sarcomas to gain insight into the incidence and mortality rates of these cancers in Canada, as well as to elucidate their potential environmental risk factors. Data for this study were obtained from le Registre Québécois du Cancer (LRQC) and from the Canadian Cancer Registry (CCR) for the period from 1992 to 2010. Mortality data were obtained from the Canadian Vital Statistics (CVS) database for the period from 1992 to 2010 using the International Classification of Diseases for Oncology, ICD-O-3, ICD-9, or ICD-10 codes, for all subtypes of sarcomas. We found that the overall sarcoma incidence in Canada decreased during the study period. However, there were select subtypes with increasing incidence. Peripherally located sarcomas were found to have lower mortality rates compared to axially located sarcomas, as expected. Clustering of Kaposi sarcoma cases in self-identified LGBTQ+ communities and in postal codes with a higher proportion of African-Canadian and Hispanic populations was observed. Forward Sortation Area (FSA) postal codes with a lower socioeconomic status also had higher Kaposi sarcoma incidence rates. Full article
(This article belongs to the Special Issue What’s New in Musculoskeletal Oncology?)
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16 pages, 1847 KiB  
Article
The Effects of Second Primary Malignancies and Frailty on Overall Survival and Mortality in Geriatric Turkish Patients with Multiple Myeloma
by Yildiz Ipek, Nevra Karademir, Onur Yilmazer and Guven Yilmaz
Curr. Oncol. 2023, 30(6), 5615-5630; https://doi.org/10.3390/curroncol30060423 - 9 Jun 2023
Viewed by 1432
Abstract
The study aims to investigate second primary malignancy (SPM) development and frailty in Turkish geriatric patients with multiple myeloma (MM) and to assess the relationship between overall survival (OS) and various characteristics including SPM and frailty. Seventy-two patients diagnosed with and treated for [...] Read more.
The study aims to investigate second primary malignancy (SPM) development and frailty in Turkish geriatric patients with multiple myeloma (MM) and to assess the relationship between overall survival (OS) and various characteristics including SPM and frailty. Seventy-two patients diagnosed with and treated for MM were enrolled in the study. Frailty was determined by the IMWG Frailty Score. Fifty-three participants (73.6%) were found to have clinically-relevant frailty. Seven patients (9.7%) had SPM. Median follow-up was 36.5 (22–48.5) months, and 17 patients died during the follow-up period. Overall (OS) was 49.40 (45.01–53.80) months. Shorter OS was found in patients with SPM (35.29 (19.66–50.91) months) compared to those without (51.05 (46.7–55.4) months) (Kaplan–Meier; p = 0.018). The multivariate cox proportional hazards model revealed that patients with SPM had 4.420-fold higher risk of death than those without (HR: 4.420, 95% CI: 1.371–14.246, p = 0.013). Higher ALT levels were also independently associated with mortality (p = 0.038). The prevalence of SPM and frailty was high in elderly patients with MM in our study. The development of SPM independently reduces survival in MM; however, frailty was not found to be independently associated with survival. Our results suggest the importance of individualized approaches in the management of patients with MM, particularly with regard to SPM development. Full article
(This article belongs to the Section Hematology)
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22 pages, 956 KiB  
Article
Young Adults’ Lived Experiences with Cancer-Related Cognitive Impairment: An Exploratory Qualitative Study
by Sitara Sharma and Jennifer Brunet
Curr. Oncol. 2023, 30(6), 5593-5614; https://doi.org/10.3390/curroncol30060422 - 9 Jun 2023
Cited by 2 | Viewed by 2162
Abstract
Cancer-related cognitive impairment (CRCI; e.g., disrupted memory, executive functioning, and information processing) affects many young adults, causing significant distress, reducing quality of life (QoL), and thwarting their ability to engage in professional, recreational, and social experiences. The purpose of this exploratory qualitative study [...] Read more.
Cancer-related cognitive impairment (CRCI; e.g., disrupted memory, executive functioning, and information processing) affects many young adults, causing significant distress, reducing quality of life (QoL), and thwarting their ability to engage in professional, recreational, and social experiences. The purpose of this exploratory qualitative study was to investigate young adults’ lived experiences with CRCI, and any strategies (including physical activity) they use to self-manage this burdensome side effect. Sixteen young adults (Mage = 30.8 ± 6.0 years; 87.5% female; Myears since diagnosis = 3.2 ± 3) who reported clinically meaningful CRCI whilst completing an online survey were interviewed virtually. Four themes comprising 13 sub-themes were identified through an inductive thematic analysis: (1) descriptions and interpretations of the CRCI phenomenon, (2) effects of CRCI on day-to-day and QoL, (3) cognitive–behavioural self-management strategies, and (4) recommendations for improving care. Findings suggest CRCI is detrimental to young adults’ QoL and must be addressed more systematically in practice. Results also illuminate the promise of PA in coping with CRCI, but research is needed to confirm this association, test how and why this may occur, and determine optimal PA prescriptions for young adults to self-manage their CRCI. Full article
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19 pages, 698 KiB  
Review
The Role of mTOR Inhibitors after Liver Transplantation for Hepatocellular Carcinoma
by Letizia Todeschini, Luca Cristin, Alessandro Martinino, Amelia Mattia, Salvatore Agnes and Francesco Giovinazzo
Curr. Oncol. 2023, 30(6), 5574-5592; https://doi.org/10.3390/curroncol30060421 - 9 Jun 2023
Cited by 4 | Viewed by 2252
Abstract
Liver transplantation is a treatment option for nonresectable patients with early-stage HCC, with more significant advantages when Milan criteria are fulfilled. An immunosuppressive regimen is required to reduce the risk of graft rejection after transplantation, and CNIs represent the drugs of choice in [...] Read more.
Liver transplantation is a treatment option for nonresectable patients with early-stage HCC, with more significant advantages when Milan criteria are fulfilled. An immunosuppressive regimen is required to reduce the risk of graft rejection after transplantation, and CNIs represent the drugs of choice in this setting. However, their inhibitory effect on T-cell activity accounts for a higher risk of tumour regrowth. mTOR inhibitors (mTORi) have been introduced as an alternative immunosuppressive approach to conventional CNI-based regimens to address both immunosuppression and cancer control. The PI3K-AKT-mTOR signalling pathway regulates protein translation, cell growth, and metabolism, and the pathway is frequently deregulated in human tumours. Several studies have suggested the role of mTORi in reducing HCC progression after LT, accounting for a lower recurrence rate. Furthermore, mTOR immunosuppression controls the renal damage associated with CNI exposure. Conversion to mTOR inhibitors is associated with stabilizing and recovering renal dysfunction, suggesting an essential renoprotective effect. Limitations in this therapeutic approach are related to their negative impact on lipid and glucose metabolism as well as on proteinuria development and wound healing. This review aims to summarize the roles of mTORi in managing patients with HCC undergoing LT. Strategies to overcome common adverse effects are also proposed. Full article
(This article belongs to the Topic Targeting Signaling Networks for Cancer Therapy)
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14 pages, 1020 KiB  
Article
Factors Associated with Long-Term Prostate Cancer Survival after Palliative Radiotherapy to a Bone Metastasis and Contemporary Palliative Systemic Therapy: A Retrospective, Population-Based Study
by Bindu Venugopal, Shaheer Shahhat, James Beck, Nikesh Hanumanthappa, Aldrich D. Ong, Arbind Dubey, Rashmi Koul, Bashir Bashir, Amitava Chowdhury, Gokulan Sivananthan and Julian Oliver Kim
Curr. Oncol. 2023, 30(6), 5560-5573; https://doi.org/10.3390/curroncol30060420 - 9 Jun 2023
Viewed by 1609
Abstract
Background: Radiation therapy (RT) is an established palliative treatment for bone metastases; however, little is known about post-radiation survival and factors which impact it. The aim of this study was to assess a population-based sample of metastatic prostate cancer patients receiving palliative radiation [...] Read more.
Background: Radiation therapy (RT) is an established palliative treatment for bone metastases; however, little is known about post-radiation survival and factors which impact it. The aim of this study was to assess a population-based sample of metastatic prostate cancer patients receiving palliative radiation therapy to bone metastases and contemporary palliative systemic therapy and identify factors that impact long-term survival. Materials/methods: This retrospective, population-based, cohort study assessed all prostate cancer patients receiving palliative RT for bone metastases at a Canadian provincial Cancer program during a contemporary time period. Baseline patient, disease, and treatment characteristics were extracted from the provincial medical physics databases and the electronic medical record. Post-RT Survival intervals were defined as the time interval from the first fraction of palliative RT to death from any cause or date of the last known follow-up. The median survival of the cohort was used to dichotomize the cohort into short- and long-term survivors following RT. Univariable and multivariable hazard regression analyses were performed to identify variables associated with post-RT survival. Results: From 1 January 2018 until 31 December 2019, 545 palliative RT courses for bone metastases were delivered to n = 274 metastatic prostate cancer patients with a median age of 76 yrs (Interquartile range (IQR) 39–83) and a median follow-up of 10.6 months (range 0.2 to 47.9). The median survival of the cohort was 10.6 months (IQR 3.5–25 months). The ECOG performance status of the whole cohort was ≤2 in n = 200 (73%) and 3–4 in n = 67 (24.5%). The most commonly treated sites of bone metastasis were the pelvis and lower extremities n = 130 (47.4%), skull and spine n = 114 (41.6%), and chest and upper extremities n = 30 (10.9%). Most patients had CHAARTED high volume disease n = 239 (87.2%). On multivariable hazard regression analysis, an ECOG performance status of 3–4 (p = 0.02), CHAARTED high volume disease burden (p = 0.023), and non-receipt of systemic therapy (p = 0.006) were significantly associated with worse post-RT survival. Conclusion: Amongst metastatic prostate cancer patients treated with palliative radiotherapy to bone metastases and modern palliative systemic therapies, ECOG performance status, CHAARTED metastatic disease burden, and type of first-line palliative systemic therapy were significantly associated with post-RT survival durations. Full article
(This article belongs to the Special Issue Radiotherapy for Prostate Cancer)
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14 pages, 3677 KiB  
Article
Prediction of Disease Progression to Upfront Pembrolizumab Monotherapy in Advanced Non-Small-Cell Lung Cancer with High PD-L1 Expression Using Baseline CT Disease Quantification and Smoking Pack Years
by Ali Silver, Cheryl Ho, Qian Ye, Jianjun Zhang, Ian Janzen, Jessica Li, Montgomery Martin, Lang Wu, Ying Wang, Stephen Lam, Calum MacAulay, Barbara Melosky and Ren Yuan
Curr. Oncol. 2023, 30(6), 5546-5559; https://doi.org/10.3390/curroncol30060419 - 8 Jun 2023
Cited by 1 | Viewed by 1867
Abstract
Health Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and [...] Read more.
Health Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and clinical factors can help identify those patients who may progress. In 138 eligible patients from our institution, we retrospectively collected their baseline variables, including baseline CT findings (primary lung tumor size and metastatic site), smoking pack years, performance status, tumor pathology, and demographics. The treatment response was assessed via RECIST 1.1 using the baseline and first follow-up CT. Associations between the baseline variables and progressive disease (PD) were tested by logistic regression analyses. The results showed 46/138 patients had PD. The baseline CT “number of involved organs” by metastasis and smoking pack years were independently associated with PD (p < 0.05), and the ROC analysis showed a good performance of the model that integrated these variables in predicting PD (AUC: 0.79). This pilot study suggests that the combination of baseline CT disease and smoking PY can identify who may progress on pembrolizumab monotherapy and can potentially facilitate decision-making for the optimal first-line treatment in the high PD-L1 cohort. Full article
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17 pages, 745 KiB  
Article
Estimating the Associated Burden of Illness and Healthcare Utilization of Newly Diagnosed Patients Aged ≥65 with Mantle Cell Lymphoma (MCL) in Ontario, Canada
by Peter Anglin, Julia Elia-Pacitti, Maria Eberg, Sergey Muratov, Atif Kukaswadia, Arushi Sharma and Emmanuel M. Ewara
Curr. Oncol. 2023, 30(6), 5529-5545; https://doi.org/10.3390/curroncol30060418 - 8 Jun 2023
Cited by 1 | Viewed by 1548
Abstract
Background: With the emergence of therapies for mantle cell lymphoma (MCL), understanding the treatment patterns and burden of illness among older patients with MCL in Canada is essential to inform decision making. Methods: A retrospective study using administrative data matched individuals aged ≥65 [...] Read more.
Background: With the emergence of therapies for mantle cell lymphoma (MCL), understanding the treatment patterns and burden of illness among older patients with MCL in Canada is essential to inform decision making. Methods: A retrospective study using administrative data matched individuals aged ≥65 who were newly diagnosed with MCL between 1 January 2013 and 31 December 2016 with general population controls. Cases were followed for up to 3 years in order to assess healthcare resource utilization (HCRU), healthcare costs, time to next treatment or death (TTNTD), and overall survival (OS); all were stratified according to first-line treatment. Results: This study matched 159 MCL patients to 636 controls. Direct healthcare costs were highest among MCL patients in the first year following diagnosis (Y1: CAD 77,555 ± 40,789), decreased subsequently (Y2: CAD 40,093 ± 28,720; Y3: CAD 36,059 ± 36,303), and were consistently higher than the costs for controls. The 3-year OS after MCL diagnosis was 68.6%, with patients receiving bendamustine + rituximab (BR) experiencing a significantly higher OS compared to patients treated with other regimens (72.4% vs. 55.6%, p = 0.041). Approximately 40.9% of MCL patients initiated a second-line therapy or died within 3 years. Conclusion: Newly diagnosed MCL presents a substantial burden to the healthcare system, with almost half of all patients progressing to a second-line therapy or death within 3 years. Full article
(This article belongs to the Section Health Economics)
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14 pages, 5878 KiB  
Article
Role of Immune Microenvironment in Pancreatic Ductal Adenocarcinoma: Could It Be Considered a Predictor of Prognosis?
by Ottavia De Simoni, Luca Dal Santo, Marco Scarpa, Giada Munari, Ylenia Camilla Spolverato, Antonio Scapinello, Sara Lonardi, Caterina Soldà, Francesca Bergamo, Alberto Fantin, Romeo Bardini, Pierluigi Pilati, Matteo Fassan and Mario Gruppo
Curr. Oncol. 2023, 30(6), 5515-5528; https://doi.org/10.3390/curroncol30060417 - 8 Jun 2023
Cited by 1 | Viewed by 1760
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumor microenvironment (TME). The aim of this study is to determine the potential significant TME immune markers of long-term survival. Methods: We retrospectively included patients with a diagnosis of resectable PDAC having [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumor microenvironment (TME). The aim of this study is to determine the potential significant TME immune markers of long-term survival. Methods: We retrospectively included patients with a diagnosis of resectable PDAC having undergone upfront surgery. Immunohistochemical (IHC) staining using tissue microarray for PD-L1, CD3, CD4, CD8, FOXP3, CD20, iNOS and CD163 was performed in order to characterize the TME. The primary endpoint was long-term survival, defined as the Overall Survival > 24 months from surgery. Results: A total of 38 consecutive patients were included, and 14 (36%) of them were long-term survivors. Long-term survivors showed a higher density of CD8+ lymphocytes intra- and peri-acinar (p = 0.08), and a higher CD8/FOXP3 intra- and peri-tumoral ratio (p = 0.05). A low density of intra- and peri-tumoral FOXP3 infiltration is a good predictor of long-term survival (p = 0.04). A significant association of the low density of intra- and peri-tumoral tumor-associated macrophages (TAMs) iNOS+ with long-term survival was detected (p = 0.04). Conclusions: Despite the retrospective nature and small sample size, our study showed that the high infiltration of CD8+ lymphocytes and low infiltration of FOXP3+ and TAMs iNOS+ are predictors of good prognosis. A preoperative assessment of these potential immune markers could be useful and determinant in the staging process and in PDAC management. Full article
(This article belongs to the Topic Advances in Tumor Microenvironment)
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18 pages, 1962 KiB  
Review
High-LET-Radiation-Induced Persistent DNA Damage Response Signaling and Gastrointestinal Cancer Development
by Kamendra Kumar, Santosh Kumar, Kamal Datta, Albert J. Fornace, Jr. and Shubhankar Suman
Curr. Oncol. 2023, 30(6), 5497-5514; https://doi.org/10.3390/curroncol30060416 - 7 Jun 2023
Cited by 4 | Viewed by 2419
Abstract
Ionizing radiation (IR) dose, dose rate, and linear energy transfer (LET) determine cellular DNA damage quality and quantity. High-LET heavy ions are prevalent in the deep space environment and can deposit a much greater fraction of total energy in a shorter distance within [...] Read more.
Ionizing radiation (IR) dose, dose rate, and linear energy transfer (LET) determine cellular DNA damage quality and quantity. High-LET heavy ions are prevalent in the deep space environment and can deposit a much greater fraction of total energy in a shorter distance within a cell, causing extensive DNA damage relative to the same dose of low-LET photon radiation. Based on the DNA damage tolerance of a cell, cellular responses are initiated for recovery, cell death, senescence, or proliferation, which are determined through a concerted action of signaling networks classified as DNA damage response (DDR) signaling. The IR-induced DDR initiates cell cycle arrest to repair damaged DNA. When DNA damage is beyond the cellular repair capacity, the DDR for cell death is initiated. An alternative DDR-associated anti-proliferative pathway is the onset of cellular senescence with persistent cell cycle arrest, which is primarily a defense mechanism against oncogenesis. Ongoing DNA damage accumulation below the cell death threshold but above the senescence threshold, along with persistent SASP signaling after chronic exposure to space radiation, pose an increased risk of tumorigenesis in the proliferative gastrointestinal (GI) epithelium, where a subset of IR-induced senescent cells can acquire a senescence-associated secretory phenotype (SASP) and potentially drive oncogenic signaling in nearby bystander cells. Moreover, DDR alterations could result in both somatic gene mutations as well as activation of the pro-inflammatory, pro-oncogenic SASP signaling known to accelerate adenoma-to-carcinoma progression during radiation-induced GI cancer development. In this review, we describe the complex interplay between persistent DNA damage, DDR, cellular senescence, and SASP-associated pro-inflammatory oncogenic signaling in the context of GI carcinogenesis. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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12 pages, 503 KiB  
Review
Safety of CDK4/6 Inhibitors Combined with Radiotherapy in Patients with Metastatic Breast Cancer: A Review of the Literature
by Rejane Franco, Jeffrey Q. Cao, Michael Yassa and Tarek Hijal
Curr. Oncol. 2023, 30(6), 5485-5496; https://doi.org/10.3390/curroncol30060415 - 6 Jun 2023
Cited by 1 | Viewed by 2093
Abstract
Recent evidence suggests that cyclin-dependent kinase 4/6 (CDK4/6) inhibitors significantly improve progression-free survival and overall survival among metastatic breast cancer patients. However, given the effects on cell cycle arrest, there is potential for CDK4/6 inhibitors and radiotherapy (RT) to work synergistically, enhancing the [...] Read more.
Recent evidence suggests that cyclin-dependent kinase 4/6 (CDK4/6) inhibitors significantly improve progression-free survival and overall survival among metastatic breast cancer patients. However, given the effects on cell cycle arrest, there is potential for CDK4/6 inhibitors and radiotherapy (RT) to work synergistically, enhancing the effect and toxicities of RT. A comprehensive review of the literature on the combination of RT and CDK4/6 inhibitors was performed with 19 eligible studies included in the final analysis. A total of 373 patients who received radiotherapy combined with CDK4/6 inhibitors were evaluated across 9 retrospective studies, 4 case reports, 3 case series, and 3 letters to the editor. The CDK4/6 inhibitor used, RT target, and RT technique were assessed in terms of toxicities. This literature review demonstrates generally limited toxicities with the combination of CDK4/6 inhibitors and palliative radiotherapy to metastatic breast cancer patients. The current evidence is nonetheless limited, and further results of ongoing prospective clinical trials will help clarify whether these treatments can be safely combined. Full article
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15 pages, 1180 KiB  
Article
Are Extensive Open Lung Resections for Elderly Patients with Lung Cancer Justified?
by Nikolaos Panagopoulos, Konstantinos Grapatsas, Vasileios Leivaditis, Michail Galanis and Dimitrios Dougenis
Curr. Oncol. 2023, 30(6), 5470-5484; https://doi.org/10.3390/curroncol30060414 - 5 Jun 2023
Cited by 1 | Viewed by 1594
Abstract
Background: Older patients with malignancies are more comorbid than younger ones and are usually undertreated only because of their age. The aim of this study is to investigate the safety of open anatomical lung resections for lung cancer in elderly patients. Methods: We [...] Read more.
Background: Older patients with malignancies are more comorbid than younger ones and are usually undertreated only because of their age. The aim of this study is to investigate the safety of open anatomical lung resections for lung cancer in elderly patients. Methods: We retrospectively analyzed all patients who underwent lung resection for lung cancer in our institution and categorized them into two groups: the elderly group (≥70 years old) and the control (<70). Results: In total, 135 patients were included in the elderly group and 375 in the control. Elderly patients were more frequently diagnosed with squamous cell carcinoma (59.3% vs. 51.5%, p = 0.037), higher differentiated tumors (12.6% vs. 6.4%, p = 0.014), and at an earlier stage (stage I: 55.6% for elderly vs. 36.6%, p = 0.002). Elderly patients were more vulnerable to postoperative pneumonia (3.7% vs. 0.8%, p = 0.034), lung atelectasis (7.4% vs. 2.9%, p = 0.040), and pleural empyema (3.2% vs. 0%, p = 0.042), however, with no increased 30-day-mortality (5.2% for elderly vs. 2.7%, p = 0.168). Survival was comparable in both groups (43.4 vs. 45.3 months, p = 0.579). Conclusions: Elderly patients should not be excluded from open major lung resections as the survival benefit is not reduced in selected patients. Full article
(This article belongs to the Special Issue Advancements in Thoracic Surgical Oncology)
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