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Curr. Oncol., Volume 28, Issue 5 (October 2021) – 29 articles

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Article
Radiation-Induced Emesis (RIE) in Extended-Field Radiotherapy for Gynecological Malignancies: Dosimetric and Non-Dosimetric Factors
Curr. Oncol. 2021, 28(5), 3602-3609; https://doi.org/10.3390/curroncol28050308 - 17 Sep 2021
Viewed by 192
Abstract
Radiation-induced emesis (RIE) is usually noted during abdominal-pelvic radiotherapy. In gynecological malignancies, it is usually noted in para-aortic but not whole-pelvic irradiation. Irradiated small bowel (SB) may be associated with RIE. The significance of SB dosimetry remains unclear. Dosimetric and non-dosimetric factors were [...] Read more.
Radiation-induced emesis (RIE) is usually noted during abdominal-pelvic radiotherapy. In gynecological malignancies, it is usually noted in para-aortic but not whole-pelvic irradiation. Irradiated small bowel (SB) may be associated with RIE. The significance of SB dosimetry remains unclear. Dosimetric and non-dosimetric factors were evaluated and correlated with RIE in 45 patients with gynecological malignancies undergoing extended-field radiotherapy (EFRT) (median 45 Gy) from 2006 to 2021. Early-onset RIE (within 72 h after the first fraction of EFRT) was noted in 10 of 12 RIE patients. RIE was significantly associated with the SB mean dose. The RIE rates were 58.3% and 15.2% (p = 0.007) in patients with a low (<63%) and high (≥63%) SB mean dose. Logistic regression revealed that the SB mean dose remained the independent factor of overall RIE (p = 0.049) and early-onset RIE (p = 0.014). Therefore, constraint of the SB mean dose limited to less than 63% of the prescribed dose is suggested to decrease RIE. Full article
(This article belongs to the Section Gynecologic Oncology)
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Article
Detection of Cervical Cancer Cells in Whole Slide Images Using Deformable and Global Context Aware Faster RCNN-FPN
Curr. Oncol. 2021, 28(5), 3585-3601; https://doi.org/10.3390/curroncol28050307 - 16 Sep 2021
Viewed by 195
Abstract
Cervical cancer is a worldwide public health problem with a high rate of illness and mortality among women. In this study, we proposed a novel framework based on Faster RCNN-FPN architecture for the detection of abnormal cervical cells in cytology images from a [...] Read more.
Cervical cancer is a worldwide public health problem with a high rate of illness and mortality among women. In this study, we proposed a novel framework based on Faster RCNN-FPN architecture for the detection of abnormal cervical cells in cytology images from a cancer screening test. We extended the Faster RCNN-FPN model by infusing deformable convolution layers into the feature pyramid network (FPN) to improve scalability. Furthermore, we introduced a global contextual aware module alongside the Region Proposal Network (RPN) to enhance the spatial correlation between the background and the foreground. Extensive experimentations with the proposed deformable and global context aware (DGCA) RCNN were carried out using the cervical image dataset of “Digital Human Body” Vision Challenge from the Alibaba Cloud TianChi Company. Performance evaluation based on the mean average precision (mAP) and receiver operating characteristic (ROC) curve has demonstrated considerable advantages of the proposed framework. Particularly, when combined with tagging of the negative image samples using traditional computer-vision techniques, 6–9% increase in mAP has been achieved. The proposed DGCA-RCNN model has potential to become a clinically useful AI tool for automated detection of cervical cancer cells in whole slide images of Pap smear. Full article
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Article
Cytochrome 4Z1 Expression Is Correlated with Poor Prognosis in Patients with Cervical Cancer
Curr. Oncol. 2021, 28(5), 3573-3584; https://doi.org/10.3390/curroncol28050306 - 16 Sep 2021
Viewed by 661
Abstract
Background: cervical cancer is one of the most common malignancies in women worldwide and its management remains challenging and complex. As Cytochrome4Z1 (CYP4Z1) is overexpressed in many tumours, its expression in cervical cancer is unknown. Therefore, the present study aimed to evaluate CYP4Z1 [...] Read more.
Background: cervical cancer is one of the most common malignancies in women worldwide and its management remains challenging and complex. As Cytochrome4Z1 (CYP4Z1) is overexpressed in many tumours, its expression in cervical cancer is unknown. Therefore, the present study aimed to evaluate CYP4Z1 expression in cervical cancers. Methods: CYP4Z1 expression was immunohistochemically assessed in 100 cases of cervical cancers along with ten normal cervix tissues, and the enzyme’s relationship to several clinicopathological features and survival was explored. Results: CYP4Z1 was strongly expressed in 55% of cervical cancer patients. Normal cervix samples were negative for CYP4Z1 expression. Importantly, this expression was significantly found in patients with the late stage of the disease, lymph node metastasis, and high tumour invasion (p < 0.05). Interestingly, CYP4Z1 expression was significantly correlated with shorter survival times of cervical cancer patients. Univariate analysis showed that CYP4Z1 expression, tumour stage, lymph node metastasis, and tumour invasion were significantly correlated with patient survival (p < 0.05). The multivariate analysis revealed that only CYP4Z1 expression and tumour stage were significantly correlated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is associated with cervical cancer patients’ survival and may serve as an independent predictor of poor prognosis in cervical cancer patients. Full article
(This article belongs to the Section Gynecologic Oncology)
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Article
Comprehensive Proteomic Analysis of Colon Cancer Tissue Revealed the Reason for the Worse Prognosis of Right-Sided Colon Cancer and Mucinous Colon Cancer at the Protein Level
Curr. Oncol. 2021, 28(5), 3554-3572; https://doi.org/10.3390/curroncol28050305 - 15 Sep 2021
Viewed by 277
Abstract
To clarify the molecular mechanisms underlying the poor prognosis of right-sided and mucinous colon cancer at the proteomic level. A tandem mass tag-proteomics approach was used to identify differentially expressed proteins (DEPs) in colon carcinoma tissues from different locations and with different histological [...] Read more.
To clarify the molecular mechanisms underlying the poor prognosis of right-sided and mucinous colon cancer at the proteomic level. A tandem mass tag-proteomics approach was used to identify differentially expressed proteins (DEPs) in colon carcinoma tissues from different locations and with different histological types to reveal the underlying mechanisms of these differences at the protein level. In additional, the DEPs were analyzed using bioinformatics methods. The proteomics profiles among colon cancers with different tumor locations and histological types were dramatically distinguished. In terms of tumor locations, the right-sided carcinoma specific DEPs may promote the tumor progression via activating inflammation, metastasis associated pathways. When referring to histological types, the mucinous colon cancers perhaps increased the invasion and metastasis through distinct mechanisms in different tumor locations. For mucinous cancer located in right-sided colon, the mucinous specific DEPs were mainly associated with ECM-related remodeling and the IL-17 signal pathway. For mucinous cancer located in left-sided colon, the mucinous specific DEPs showed a strong relationship with ACE2/Ang-(1–7)/MasR axis. The proteomics profiles of colon cancers showed distinct differences related to locations and histological types. These results suggested a distinct mechanism underlying the diverse subtypes of colon cancers. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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Graphical abstract

Guidelines
Management of Pyrexia Associated with the Combination of Dabrafenib and Trametinib: Canadian Consensus Statements
Curr. Oncol. 2021, 28(5), 3537-3553; https://doi.org/10.3390/curroncol28050304 - 14 Sep 2021
Viewed by 308
Abstract
The combination of dabrafenib and trametinib is a well-established treatment for BRAF-mutated melanoma. However, the effectiveness of this approach may be hindered by the development of treatment-related pyrexia syndrome, which occurs in at least 50% of treated patients. Without appropriate intervention, pyrexia syndrome [...] Read more.
The combination of dabrafenib and trametinib is a well-established treatment for BRAF-mutated melanoma. However, the effectiveness of this approach may be hindered by the development of treatment-related pyrexia syndrome, which occurs in at least 50% of treated patients. Without appropriate intervention, pyrexia syndrome has the potential to worsen and can result in hypotension secondary to dehydration and associated organ-related complications. Furthermore, premature treatment discontinuation may result in a reduction in progression-free and overall survival. Despite existing guidance, there is still a wide variety of therapeutic approaches suggested in the literature for both the definition and management of dabrafenib and trametinib-related pyrexia. This is reflected in the practice variation of its prevention and treatment within and between Canadian cancer centres. A Canadian working group was formed and consensus statements were constructed based on evidence and finalised through a two-round modified Delphi approach. The statements led to the development of a pyrexia treatment algorithm that can easily be applied in routine practice. The Canadian working group consensus statements serve to provide practical guidance for the management of dabrafenib and trametinib-related pyrexia, hopefully leading to reduced discontinuation rates, and ultimately improve patients’ quality of life and cancer-related outcomes. Full article
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Article
Retrospective Cohort Study of Caveolin-1 Expression as Prognostic Factor in Unresectable Locally Advanced or Metastatic Pancreatic Cancer Patients
Curr. Oncol. 2021, 28(5), 3525-3536; https://doi.org/10.3390/curroncol28050303 - 09 Sep 2021
Viewed by 358
Abstract
Caveolin-1 (Cav-1) plays a key role in various neoplastic diseases and is upregulated in different cancers, including pancreatic ductal adenocarcinoma (PDAC). Furthermore, Cav-1 is critical for the uptake of albumin as well as nab-paclitaxel in PDAC cells. Here, we investigated the prognostic impact [...] Read more.
Caveolin-1 (Cav-1) plays a key role in various neoplastic diseases and is upregulated in different cancers, including pancreatic ductal adenocarcinoma (PDAC). Furthermore, Cav-1 is critical for the uptake of albumin as well as nab-paclitaxel in PDAC cells. Here, we investigated the prognostic impact of Cav-1 expression in a cohort of 39 metastatic PDAC patients treated with different first-line chemotherapy regimens. We also assessed the predictive value of Cav-1 in patients treated with gemcitabine and nab-paclitaxel. Cav-1 expression was evaluated by immunohistochemistry staining in neoplastic and stromal cells, using metastatic sites or primary tumor tissue specimens. Higher levels of Cav-1 expression were associated with significantly worse overall survival (OS) and progression-free survival (PFS). No differences in OS were found between patients treated with gemcitabine + nab-paclitaxel vs. other chemotherapy options. Multivariate analysis for OS and PFS confirmed the independent prognostic role of Cav-1 expression. Our study evidenced a negative prognostic role of Cav-1 in patients affected by metastatic/locally advanced unresectable PDAC. Moreover, Cav-1 expression seems not to predict different response rates to different types of first-line treatment. Future prospective trials will be necessary to confirm the prognostic role of Cav-1 and explore Cav-1 specific inhibitors as a therapeutic option for advanced PDAC patients. Full article
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Article
Prospective Monitoring of Circulating Epithelial Tumor Cells (CETC) Reveals Changes in Gene Expression during Adjuvant Radiotherapy of Breast Cancer Patients
Curr. Oncol. 2021, 28(5), 3507-3524; https://doi.org/10.3390/curroncol28050302 - 08 Sep 2021
Viewed by 515
Abstract
Circulating epithelial tumor cells (CETC) are considered to be responsible for the formation of metastases. Therefore, their importance as prognostic and/or predictive markers in breast cancer is being intensively investigated. Here, the reliability of single cell expression analyses in isolated and collected CETC [...] Read more.
Circulating epithelial tumor cells (CETC) are considered to be responsible for the formation of metastases. Therefore, their importance as prognostic and/or predictive markers in breast cancer is being intensively investigated. Here, the reliability of single cell expression analyses in isolated and collected CETC from whole blood samples of patients with early-stage breast cancer before and after radiotherapy (RT) using the maintrac® method was investigated. Single-cell expression analyses were performed with qRT-PCR on a panel of selected genes: GAPDH, EpCAM, NANOG, Bcl-2, TLR 4, COX-2, PIK3CA, Her-2/neu, Vimentin, c-Met, Ki-67. In all patients, viable CETC were detected prior to and at the end of radiotherapy. In 7 of the 9 (77.8%) subjects examined, the CETC number at the end of the radiotherapy series was higher than before. The majority of genes analyzed showed increased expression after completion of radiotherapy compared to baseline. Procedures and methods used in this pilot study proved to be feasible. The method is suitable for further investigation of the underlying molecular biological mechanisms occurring in cells surviving radiotherapy and possibly the development of radiation resistance. Full article
(This article belongs to the Special Issue Translational Research in Breast Cancer Patients)
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Systematic Review
Virtual Care in Patients with Cancer: A Systematic Review
Curr. Oncol. 2021, 28(5), 3488-3506; https://doi.org/10.3390/curroncol28050301 - 08 Sep 2021
Viewed by 348
Abstract
Virtual care in cancer care existed in a limited fashion globally before the COVID-19 pandemic, mostly driven by geographic constraints. The pandemic has required dramatic shifts in health care delivery, including cancer care. We conducted a systematic review of comparative studies evaluating virtual [...] Read more.
Virtual care in cancer care existed in a limited fashion globally before the COVID-19 pandemic, mostly driven by geographic constraints. The pandemic has required dramatic shifts in health care delivery, including cancer care. We conducted a systematic review of comparative studies evaluating virtual versus in-person care in patients with cancer. Embase, APA PsycInfo, Ovid MEDLINE, and the Cochrane Library were searched for literature from January 2015 to 6 August 2020. We adhered to PRISMA guidelines and used the modified GRADE approach to evaluate the data. We included 34 full-text publications of 10 randomized controlled trials, 13 non-randomized comparative studies, and 5 ongoing randomized controlled trials. Evidence was divided into studies that provide psychosocial or genetic counselling and those that provide or assess medical and supportive care. The limited data in this review support that in the general field of psychological counselling, virtual or remote counselling can be equivalent to in-person counselling. In the area of genetic counselling, telephone counselling was more convenient and noninferior to usual care for all outcomes (knowledge, decision conflict, cancer distress, perceived stress, genetic counseling satisfaction). There are few data for clinical outcomes and supportive care. Future research should assess the role of virtual care in these areas. Protocol registration: PROSPERO CRD42020202871. Full article
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Article
Long-Term Results of Postoperative Hypofractionated Accelerated Breast and Lymph Node Radiotherapy (HypoAR) with Hypofractionated Boost
Curr. Oncol. 2021, 28(5), 3474-3487; https://doi.org/10.3390/curroncol28050300 - 07 Sep 2021
Viewed by 372
Abstract
We report long-term results (median follow-up 12 years) of hypofractionated accelerated radiotherapy (HypoAR) in patients treated with breast-conserving surgery. In total, 367 women were treated with HypoAR. Axillary and supraclavicular area (ASA) were treated in patients with involved nodes. In total, 290 patients [...] Read more.
We report long-term results (median follow-up 12 years) of hypofractionated accelerated radiotherapy (HypoAR) in patients treated with breast-conserving surgery. In total, 367 women were treated with HypoAR. Axillary and supraclavicular area (ASA) were treated in patients with involved nodes. In total, 290 patients (scheme A) received 3.5 Gy/day ×10 fractions (breast/ASA) followed by two 4 Gy fractions with electrons to the affected breast quadrant within 16 days. In total, 77 patients (Scheme B) received 2.7 Gy/day for 16 consecutive fractions (breast/ASA) within 22 days, while concurrently, the affected breast quadrant received an electron booster dose of 0.8 Gy for the first 13 fractions. Amifostine was offered to 252/367 patients. Early radiation toxicity was minimal. Regarding late toxicities, symptomatic breast edema was noted in 2.2%, asymptomatic breast fibrosis in 1.9%, and arm lymphedema in 3.7% of patients. Amifostine reduced early radiation dermatitis (p = 0.001). In total, 2.2% of patients developed contralateral breast and 1.6% other carcinomas. Locoregional recurrence (LR) occurred in 3.1% of patients (0% for in situ carcinomas). Positive margins after surgery, extracapsular node invasion, and HER2-enriched/triple-negative tumors were linked with significantly worse LR-free survival. The involvement of more than three nodes and luminal type other than A were independent prognostic variables of metastasis and death events. HypoAR delivering a biological dose of 50–52 Gy to the breast/ASA is a safe and effective therapy for patients treated with conservative surgery. The risk of carcinogenesis is low. Positive surgical margins, extracapsular node invasion, and HER2-enriched/triple-negative phenotypes appear as a cluster of features linked with a higher risk for locoregional relapse. Full article
(This article belongs to the Section Gynecologic Oncology)
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Article
Distal Fibula Reconstruction in Primary Malignant Tumours
Curr. Oncol. 2021, 28(5), 3463-3473; https://doi.org/10.3390/curroncol28050299 - 07 Sep 2021
Viewed by 273
Abstract
(1) Background: Restoration of ankle biomechanics after distal fibula (DF) resection in bone sarcomas can be performed with different techniques. We report the functional and oncological outcomes of a case series; (2) Methods: Ten patients (5 females and 5 males) with a mean [...] Read more.
(1) Background: Restoration of ankle biomechanics after distal fibula (DF) resection in bone sarcomas can be performed with different techniques. We report the functional and oncological outcomes of a case series; (2) Methods: Ten patients (5 females and 5 males) with a mean age of 27 years (range 10–71) were retrospectively evaluated. Following the resection, different techniques were used to reconstruct the ankle: tibiotalar arthrodesis, residual lateral malleolus fixed to the tibia, non-vascularized or rotational vascularized fibula transposition and intercalary allograft. All complications were recorded, and the functional outcomes were evaluated; (3) Results: The mean follow-up time was 54 months (range, 13–116). Six patients were free of disease while four patients died of disease. All patients had a stable ankle and bone union, which was achieved after a mean of 9.4 months (range 3–20). The mean MSTS Score was 26.7 (range 21–30). Chronic ankle pain and peroneal external nerve palsy were observed. Patients underwent additional surgeries for deep infection and for equinus ankle deformity. No local recurrence was observed. Metastasis occurred in four patients after a mean of 14.7 months (range 2–34); (4) Conclusions: After DF resection, the restoration of ankle biomechanics gives acceptable functional results, but a larger series of patients with long-time follow-up are required to confirm the durability of the reconstruction. Full article
(This article belongs to the Section Bone and Soft Tissue Oncology)
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Article
Contrast-Enhanced Spectral Mammography Assessment of Patients Treated with Neoadjuvant Chemotherapy for Breast Cancer
Curr. Oncol. 2021, 28(5), 3448-3462; https://doi.org/10.3390/curroncol28050298 - 06 Sep 2021
Viewed by 370
Abstract
Background: Evaluating the tumor response to neoadjuvant chemotherapy is key to planning further therapy of breast cancer. Our study aimed to evaluate the effectiveness of low-energy and subtraction contrast-enhanced spectral mammography (CESM) images in the detection of complete response (CR) for neoadjuvant chemotherapy [...] Read more.
Background: Evaluating the tumor response to neoadjuvant chemotherapy is key to planning further therapy of breast cancer. Our study aimed to evaluate the effectiveness of low-energy and subtraction contrast-enhanced spectral mammography (CESM) images in the detection of complete response (CR) for neoadjuvant chemotherapy (NAC) in breast cancer. Methods: A total of 63 female patients were qualified for our retrospective analysis. Low-energy and subtraction CESM images just before the beginning of NAC and as a follow-up examination 2 weeks before the end of chemotherapy were compared with one another and assessed for compliance with the postoperative histopathological examination (HP). The response to preoperative chemotherapy was evaluated based on the RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). Results: Low-energy images tend to overestimate residual lesions (6.28 mm) and subtraction images tend to underestimate them (2.75 mm). The sensitivity of low-energy images in forecasting CR amounted to 33.33%, while the specificity was 92.86%. In the case of subtraction CESM, the sensitivity amounted to 85.71% and the specificity to 71.42%. Conclusions: CESM is characterized by high sensitivity in the assessment of CR after NAC. The use of only morphological assessment is insufficient. CESM correlates well with the size of residual lesions on histopathological examination but tends to underestimate the dimensions. Full article
(This article belongs to the Special Issue Breast Cancer Imaging and Therapy)
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Review
New Insights into the Biology and Diagnosis of Splenic Marginal Zone Lymphomas
Curr. Oncol. 2021, 28(5), 3430-3447; https://doi.org/10.3390/curroncol28050297 - 06 Sep 2021
Viewed by 299
Abstract
Splenic marginal zone lymphoma (SMZL) is a small B-cell lymphoma, which has been recognized as a distinct pathological entity since the WHO 2008 classification. It classically presents an indolent evolution, but a third of patients progress rapidly and require aggressive treatments, such as [...] Read more.
Splenic marginal zone lymphoma (SMZL) is a small B-cell lymphoma, which has been recognized as a distinct pathological entity since the WHO 2008 classification. It classically presents an indolent evolution, but a third of patients progress rapidly and require aggressive treatments, such as immuno-chemotherapy or splenectomy, with all associated side effects. In recent years, advances in the comprehension of SMZL physiopathology have multiplied, thanks to the arrival of new devices in the panel of available molecular biology techniques, allowing the discovery of new molecular findings. In the era of targeted therapies, an update of current knowledge is needed to guide future researches, such as those on epigenetic modifications or the microenvironment of these lymphomas. Full article
(This article belongs to the Special Issue B Cell Lymphoma in the Spleen)
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Article
Radiotherapy or Surgery? Comparative, Qualitative Assessment of Online Patient Education Materials on Prostate Cancer
Curr. Oncol. 2021, 28(5), 3420-3429; https://doi.org/10.3390/curroncol28050296 - 06 Sep 2021
Viewed by 360
Abstract
As multiple different treatment options are available for prostate cancer (PCa) and YouTube is commonly used as a source for medical information, we performed a systematic and comparative assessment of available videos guiding patients on their choice for the optimal treatment. An independent [...] Read more.
As multiple different treatment options are available for prostate cancer (PCa) and YouTube is commonly used as a source for medical information, we performed a systematic and comparative assessment of available videos guiding patients on their choice for the optimal treatment. An independent search for surgical therapy or radiotherapy of PCa on YouTube was performed and the 40 most viewed videos of both groups were analyzed. The validated DISCERN questionnaire and PEMAT were utilized to evaluate their quality and misinformation. The median overall quality of the videos was found to be low for surgery videos, while radiotherapy videos results reached a moderate quality. The median PEMAT understandability score was 60% (range 0–100%) for radiotherapy and 75% (range 40–100) for surgery videos. The radiotherapy videos contained less misinformation and were judged to be of higher quality. Summarized, the majority of the provided videos offer insufficient quality of content and are potentially subject to commercial bias without reports on possible conflict of interest. Thus, most of available videos on YouTube informing PCa patients about possible treatment methods are not suited for a balanced patient education or as a basis for the patient’s decision. Full article
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Article
Risk-Stratified Pathways for Cancer Survivorship Care: Insights from a Deliberative Multi-Stakeholder Consultation
Curr. Oncol. 2021, 28(5), 3408-3419; https://doi.org/10.3390/curroncol28050295 - 05 Sep 2021
Viewed by 479
Abstract
Risk-stratified pathways of survivorship care seek to optimize coordination between cancer specialists and primary care physicians based on the whole person needs of the individual. While the principle is supported by leading cancer institutions, translating knowledge to practice confronts a lack of clarity [...] Read more.
Risk-stratified pathways of survivorship care seek to optimize coordination between cancer specialists and primary care physicians based on the whole person needs of the individual. While the principle is supported by leading cancer institutions, translating knowledge to practice confronts a lack of clarity about the meaning of risk stratification, uncertainties around the expectations the model holds for different actors, and health system structures that impede communication and coordination across the care continuum. These barriers must be better understood and addressed to pave the way for future implementation. Recognizing that an innovation is more likely to be adopted when user experience is incorporated into the planning process, a deliberative consultation was held as a preliminary step to developing a pilot project of risk-stratified pathways for patients transitioning from specialized oncology teams to primary care providers. This article presents findings from the deliberative consultation that sought to understand the perspectives of cancer specialists, primary care physicians, oncology nurses, allied professionals, cancer survivors and researchers regarding the following questions: what does a risk stratified model of cancer survivorship care mean to care providers and users? What are the prerequisites for translating risk stratification into practice? What challenges are involved in establishing these prerequisites? The multi-stakeholder consultation provides empirical data to guide actions that support the development of risk-stratified pathways to coordinate survivorship care. Full article
Case Report
Spontaneous Regression of Metastatic Renal Cell Carcinoma after SARS-CoV-2 Infection: A Report of Two Cases
Curr. Oncol. 2021, 28(5), 3403-3407; https://doi.org/10.3390/curroncol28050294 - 03 Sep 2021
Viewed by 384
Abstract
Spontaneous regression of metastatic renal cell carcinoma (mRCC) is a rare event, often associated with an activation of innate immunity by various triggers. SARS-CoV-2 infection induces a strong inflammatory response in some patients and a cytokine storm is one of the main causes [...] Read more.
Spontaneous regression of metastatic renal cell carcinoma (mRCC) is a rare event, often associated with an activation of innate immunity by various triggers. SARS-CoV-2 infection induces a strong inflammatory response in some patients and a cytokine storm is one of the main causes of severe morbidity and mortality associated with the virus. Here, we describe two cases of patients with histologically and radiologically proven mRCC whose treatment was delayed due to COVID-19 and who experienced spontaneous tumour regression following the infection. Both patients reported here had predominantly pulmonary and mediastinal involvement and underwent nephrectomy. The interval between the diagnosis of COVID-19 and the detection of tumour regression was 3 and 4 months, respectively. Although approved vaccines and other measures are clearly the best way to prevent COVID-19-associated morbidity and mortality in cancer patients, we hypothesize that innate immunity activation by the infection can contribute to tumour regression in special circumstances. Full article
(This article belongs to the Section Genitourinary Oncology)
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Review
Ampullary Carcinoma: An Overview of a Rare Entity and Discussion of Current and Future Therapeutic Challenges
Curr. Oncol. 2021, 28(5), 3393-3402; https://doi.org/10.3390/curroncol28050293 - 01 Sep 2021
Viewed by 351
Abstract
Ampullary carcinomas (ACs) represent a rare entity, accounting for approximately 0.2% of all gastrointestinal solid tumors and 20% of all periampullary cancers (PACs). Unfortunately, few data are available regarding the optimal therapeutic strategy for ACs due to their rarity, and physicians frequently encounter [...] Read more.
Ampullary carcinomas (ACs) represent a rare entity, accounting for approximately 0.2% of all gastrointestinal solid tumors and 20% of all periampullary cancers (PACs). Unfortunately, few data are available regarding the optimal therapeutic strategy for ACs due to their rarity, and physicians frequently encounter significant difficulties in the management of these malignancies. In this review, we will provide an overview of current evidence on AC, especially focusing on biological features, histological characteristics, and available data guiding present and future therapeutic strategies for these rare, and still barely known, tumors. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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Case Report
Complex Differential Diagnosis between Primary Breast Cancer and Breast Metastasis from EGFR-Mutated Lung Adenocarcinoma: Case Report and Literature Review
Curr. Oncol. 2021, 28(5), 3384-3392; https://doi.org/10.3390/curroncol28050292 - 31 Aug 2021
Viewed by 357
Abstract
We present a case of a woman with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma who received gefitinib for 2 years and obtained a partial response. The patient then developed liver metastasis and a breast lesion, displaying high estrogen receptor (ER) expression and [...] Read more.
We present a case of a woman with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma who received gefitinib for 2 years and obtained a partial response. The patient then developed liver metastasis and a breast lesion, displaying high estrogen receptor (ER) expression and harboring the same EGFR mutation. From the radiological studies, it was not possible to make a differential diagnosis between primary breast cancer and breast metastasis from lung cancer. After the removal of the breast nodule, thanks to the clinical history, radiology, and above all, molecular and immunohistochemical investigations, a diagnosis of breast metastasis from lung adenocarcinoma was made. This case emphasizes the importance of a comprehensive clinical, pathological, and molecular analysis in the differential diagnosis between primary breast cancer and metastases from extramammary tumor to guide adequate treatment decision making. Full article
(This article belongs to the Section Thoracic Oncology)
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Article
Brazilian Validation of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group (QLG) Computerised Adaptive Tests (CAT) Core
Curr. Oncol. 2021, 28(5), 3373-3383; https://doi.org/10.3390/curroncol28050291 - 31 Aug 2021
Viewed by 377
Abstract
Background: This study aimed to validate the Brazilian version of EORTC CAT Core and compare the Brazilian results with those from the original European EORTC CAT Core validation study. Methods: After validated translation, 168 cancer patients from Brazil receiving radiation therapy with or [...] Read more.
Background: This study aimed to validate the Brazilian version of EORTC CAT Core and compare the Brazilian results with those from the original European EORTC CAT Core validation study. Methods: After validated translation, 168 cancer patients from Brazil receiving radiation therapy with or without chemotherapy was assessed. Translated EORTC CAT Core and all QLQ-C30 items were administered to patients using CHES (Computer-Based Health Evaluation System) before (T0) and after (T1) treatment initiation. The association between QLQ-C30 and CAT scores and ceiling/floor effects were estimated. Based on estimates of relative validity (cross-sectional, known-group differences and changes over time), relative sample-size requirements for CAT compared to QLQ-C30 were estimated. Results: Correlation coefficients between CAT and QLQ-C30 domains ranged from 0.63 to 0.93; except for dyspnoea, all coefficients were >0.82 (corresponding figures were 0.81–0.93 in the European study). On average across domains, floor/ceiling was reduced by 10% using CAT (9% in the European study) corresponding to a relative reduction of 32% (37% in the European study). Analyses of known-group validity and responsiveness indicated that, on average across domains, the sample-size requirements may be reduced by 17% using CAT rather than QLQ-C30, without loss of power (28% in the European study). The Brazilian sample had less symptom/quality of life impairment than the European sample, which likely explains the lower sample-size reduction using CAT when comparing with the European sample. Conclusions: The results in the Brazilian cohort were generally similar to those from the European sample and confirm the validity and usefulness of the EORTC CAT Core. Full article
Review
Current Overview of Treatment for Metastatic Bone Disease
Curr. Oncol. 2021, 28(5), 3347-3372; https://doi.org/10.3390/curroncol28050290 - 29 Aug 2021
Viewed by 424
Abstract
The number of patients with bone metastasis increases as medical management and surgery improve the overall survival of patients with cancer. Bone metastasis can cause skeletal complications, including bone pain, pathological fractures, spinal cord or nerve root compression, and hypercalcemia. Before initiation of [...] Read more.
The number of patients with bone metastasis increases as medical management and surgery improve the overall survival of patients with cancer. Bone metastasis can cause skeletal complications, including bone pain, pathological fractures, spinal cord or nerve root compression, and hypercalcemia. Before initiation of treatment for bone metastasis, it is important to exclude primary bone malignancy, which would require a completely different therapeutic approach. It is essential to select surgical methods considering the patient’s prognosis, quality of life, postoperative function, and risk of postoperative complications. Therefore, bone metastasis treatment requires a multidisciplinary team approach, including radiologists, oncologists, and orthopedic surgeons. Recently, many novel palliative treatment options have emerged for bone metastases, such as stereotactic body radiation therapy, radiopharmaceuticals, vertebroplasty, minimally invasive spine stabilization with percutaneous pedicle screws, acetabuloplasty, embolization, thermal ablation techniques, electrochemotherapy, and high-intensity focused ultrasound. These techniques are beneficial for patients who may not benefit from surgery or radiotherapy. Full article
(This article belongs to the Special Issue Treatment of Bone Metastasis)
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Review
Androgen Deprivation Therapy, Hypogonadism and Cardiovascular Toxicity in Men with Advanced Prostate Cancer
Curr. Oncol. 2021, 28(5), 3331-3346; https://doi.org/10.3390/curroncol28050289 - 28 Aug 2021
Viewed by 395
Abstract
Androgen deprivation therapy (ADT) is successfully used in patients with advanced prostatic cancer, but there are many concerns about its systemic side effects, especially due to advanced age and frequent comorbidities in most patients. In patients treated with ADT there are metabolic changes [...] Read more.
Androgen deprivation therapy (ADT) is successfully used in patients with advanced prostatic cancer, but there are many concerns about its systemic side effects, especially due to advanced age and frequent comorbidities in most patients. In patients treated with ADT there are metabolic changes involving the glycaemic control and lipid metabolism, increased thrombotic risk, an increased risk of myocardial infarction, severe arrhythmia and sudden cardiac death. Still, these adverse effects can be also due to the subsequent hypogonadism. Men with heart failure or coronary artery disease have a lower level of serum testosterone than normal men of the same age, and hypogonadism is related to higher cardiovascular mortality. Many clinical studies compared the cardiovascular effects of hypogonadism post orchiectomy or radiotherapy with those of ADT but their results are controversial. However, current data suggest that more intensive treatment of cardiovascular risk factors and closer cardiological follow-up of older patients under ADT might be beneficial. Our paper is a narrative review of the literature data in this field. Full article
(This article belongs to the Section Genitourinary Oncology)
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Article
COVID-19 Pandemic-Adapted Radiotherapy Guidelines: Are They Really Followed?
Curr. Oncol. 2021, 28(5), 3323-3330; https://doi.org/10.3390/curroncol28050288 - 27 Aug 2021
Viewed by 310
Abstract
Background: In our department, we provided guidelines to the radiation oncologists (ROs) regarding the omission, delay, or shortening of radiotherapy (RT). The purpose was to reduce the patients’ exposure to the hospital environment and to minimize the departmental overcrowding. The aim was to [...] Read more.
Background: In our department, we provided guidelines to the radiation oncologists (ROs) regarding the omission, delay, or shortening of radiotherapy (RT). The purpose was to reduce the patients’ exposure to the hospital environment and to minimize the departmental overcrowding. The aim was to evaluate the ROs’ compliance to these guidelines. Methods: ROs were asked to fill out a data collection form during patients’ first visits in May and June 2020. The collected data included the ROs’ age and gender, patient age and residence, RT purpose, treated tumor, the dose and fractionation that would have been prescribed, and RT changes. The chi-square test and binomial logistic regression were used to analyze the correlation between the treatment prescription and the collected parameters. Results: One hundred and twenty-six out of 205 prescribed treatments were included in this analysis. Treatment was modified in 61.1% of cases. More specifically, the treatment was omitted, delayed, or shortened in 7.9, 15.9, and 37.3% of patients, respectively. The number of delivered fractions was reduced by 27.9%. A statistically significant correlation (p = 0.028) between younger patients’ age and lower treatment modifications rate was recorded. Conclusion: Our analysis showed a reasonably high compliance of ROs to the pandemic-adapted guidelines. The adopted strategy was effective in reducing the number of admissions to our department. Full article
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Article
Mismatch Repair Protein Expression and Microsatellite Instability in Cutaneous Squamous Cell Carcinoma
Curr. Oncol. 2021, 28(5), 3316-3322; https://doi.org/10.3390/curroncol28050287 - 27 Aug 2021
Viewed by 389
Abstract
There exist relatively sparse and conflicting data on high-level microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) in cutaneous malignancies. We aimed to determine the expression profiles of MMR proteins (MSH2, MSH6, MLH1, and PMS2) in different progression stages of cutaneous squamous cell [...] Read more.
There exist relatively sparse and conflicting data on high-level microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) in cutaneous malignancies. We aimed to determine the expression profiles of MMR proteins (MSH2, MSH6, MLH1, and PMS2) in different progression stages of cutaneous squamous cell carcinoma (cSCC, 102 patients in total) by immunohistochemistry, and search for MSI-H in patients with low-level MMR or dMMR using multiplex-PCR. Low-level MMR protein expression was observed in five patients: One patient with primary cSCC < 2 mm thickness and low-level MLH1, three patients with primary cSCC > 6 mm (including one with low-level MSH2, as well as MSH6 expression, and two with low-level PMS2), and one patient with a cSCC metastasis showing low-level MSH2 as well as MSH6. Intergroup protein expression analysis revealed that MLH1 and MSH2 expression in actinic keratosis was significantly decreased when compared to Bowen’s disease, cSCC < 2 mm, cSCC > 6 mm, and cSCC metastasis. In cases with low-level MMR, we performed MSI-H tests revealing three cases with MSI-H and one with low-level MSI-L. We found low-level MMR expression in a small subset of patients with invasive or metastatic cSCC. Hence, loss of MMR expression may be associated with tumour progression in a small subgroup of patients with non-melanoma skin cancer. Full article
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Article
Quality of End-of-Life Care for People with Advanced Non-Small Cell Lung Cancer in Ontario: A Population-Based Study
Curr. Oncol. 2021, 28(5), 3297-3315; https://doi.org/10.3390/curroncol28050286 - 26 Aug 2021
Viewed by 372
Abstract
Ensuring high quality end of life (EOL) care is necessary for people with advanced non-small-cell lung cancer (NSCLC), given its high incidence, mortality and symptom burden. Aggressive EOL care can adversely affect the quality of life of NSCLC patients without providing meaningful oncologic [...] Read more.
Ensuring high quality end of life (EOL) care is necessary for people with advanced non-small-cell lung cancer (NSCLC), given its high incidence, mortality and symptom burden. Aggressive EOL care can adversely affect the quality of life of NSCLC patients without providing meaningful oncologic benefit. Objectives: (1) To describe EOL health services quality indicators and timing of palliative care consultation provided to patients dying of NSCLC. (2) To examine associations between aggressive and supportive care and patient, disease and treatment characteristics. Methods: This retrospective population-based cohort study describes those who died of NSCLC in Ontario, Canada from 2009–2017. Socio-demographic, patient, disease and treatment characteristics as well as EOL health service quality and use of palliative care consultation were investigated. Multivariable logistic regression models examined factors associated with receiving aggressive or supportive care. Results: Aggressive care quality indicators were present in 50.3% and supportive care indicators in 60.3% of the cohort (N = 37,203). Aggressive care indicators decreased between 2009 and 2017 (57.4% to 45.3%) and increased for supportive care (54.2% to 67.5%). Benchmarks were not met by 2017 in 3 of 4 cases. Male sex and greater comorbidity were associated with more aggressive EOL care and less supportive care. Older age was negatively associated and rurality positively associated with aggressive care. No palliative care consultation occurred in 56.0%. Conclusions: While improvements in the use of supportive rather than aggressive care were noted, established Canadian benchmarks were not met. Moreover, there is variation in EOL quality between groups and use of earlier palliative care must improve. Full article
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Article
Peripheral Blood Lymphocyte Percentage May Predict Chemotolerance and Survival in Patients with Advanced Pancreatic Cancer. Association between Adaptive Immunity and Nutritional State
Curr. Oncol. 2021, 28(5), 3280-3296; https://doi.org/10.3390/curroncol28050285 - 26 Aug 2021
Viewed by 455
Abstract
Pancreatic Carcinoma (PC) cells have the ability to induce patient immunosuppression and to escape immunosurveillance. Low circulating lymphocytes are associated with an advanced stage of PC and reduced survival. Blood lymphocytes expressed as a percentage of Total White Blood Cells (L% TWBC) could [...] Read more.
Pancreatic Carcinoma (PC) cells have the ability to induce patient immunosuppression and to escape immunosurveillance. Low circulating lymphocytes are associated with an advanced stage of PC and reduced survival. Blood lymphocytes expressed as a percentage of Total White Blood Cells (L% TWBC) could predict chemotolerance (n° of tolerated cycles), survival time and Body Weight (BW) more effectively than lymphocytes expressed as an absolute value (LAB > 1500 n°/mm3) or lymphocytes >22%, which is the lowest limit of normal values in our laboratory. Forty-one patients with advanced PC, treated with chemotherapy, were selected for this observational retrospective study. Patients were evaluated at baseline (pre-chemotherapy), and at 6, 12 and 18 months, respectively, after diagnosis of PC. The study found L ≥ 29.7% to be a better predictor of survival (COX model, using age, sex, BW, serum creatinine, bilirubin and lymphocytes as covariates), chemotolerance (r = +0.50, p = 0.001) and BW (r = +0.35, p = 0.027) than LAB > 1500 or L > 22%. BW did not significantly correlate with chemotolerance or survival. The preliminary results of this study suggest that L ≥ 29.7% is more effective than LAB > 1500 or L > 22% at predicting chemotolerance, survival time and nutritional status. A possible impact of nutritional status on chemotherapy and survival seems to be lymphocyte-mediated given the association between BW and L%. This study may serve as the basis for future research to explore whether nutritional interventions can improve lymphopenia, and if so, how this may be possible. Full article
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Article
Reflex ROS1 IHC Screening with FISH Confirmation for Advanced Non-Small Cell Lung Cancer—A Cost-Efficient Strategy in a Public Healthcare System
Curr. Oncol. 2021, 28(5), 3268-3279; https://doi.org/10.3390/curroncol28050284 - 25 Aug 2021
Viewed by 503
Abstract
ROS1 rearrangements are identified in 1–2% of lung adenocarcinoma cases, and reflex testing is guideline-recommended. We developed a decision model for population-based ROS1 testing from a Canadian public healthcare perspective to determine the strategy that optimized detection of true-positive (TP) cases while minimizing [...] Read more.
ROS1 rearrangements are identified in 1–2% of lung adenocarcinoma cases, and reflex testing is guideline-recommended. We developed a decision model for population-based ROS1 testing from a Canadian public healthcare perspective to determine the strategy that optimized detection of true-positive (TP) cases while minimizing costs and turnaround time (TAT). Eight diagnostic strategies were compared, including reflex single gene testing via immunohistochemistry (IHC) screening, fluorescence in-situ hybridization (FISH), next-generation sequencing (NGS), and biomarker-informed (EGFR/ALK/KRAS wildtype) testing initiated by pathologists and clinician-initiated strategies. Reflex IHC screening with FISH confirmation of positive cases yielded the best results for TAT, TP detection rate, and cost. IHC screening saved CAD 1,000,000 versus reflex FISH testing. NGS was the costliest reflex strategy. Biomarker-informed testing was cost-efficient but delayed TAT. Clinician-initiated testing was the least costly but resulted in long TAT and missed TP cases, highlighting the importance of reflex testing. Thus, reflex IHC screening for ROS1 with FISH confirmation provides a cost-efficient strategy with short TAT and maximizes the number of TP cases detected. Full article
(This article belongs to the Section Thoracic Oncology)
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Article
Safety of Immune Checkpoint Inhibitors in Elderly Patients: An Observational Study
Curr. Oncol. 2021, 28(5), 3259-3267; https://doi.org/10.3390/curroncol28050283 - 25 Aug 2021
Viewed by 361
Abstract
Background: Immunotherapy has completely changed the treatment of solid tumors. Although immune checkpoint inhibitors (ICIs) seem to be an appealing alternative to chemotherapy, especially in elderly patients, due to a more tolerable toxicity profile, they can lead to a peculiar variety of immune-related [...] Read more.
Background: Immunotherapy has completely changed the treatment of solid tumors. Although immune checkpoint inhibitors (ICIs) seem to be an appealing alternative to chemotherapy, especially in elderly patients, due to a more tolerable toxicity profile, they can lead to a peculiar variety of immune-related adverse events (irAEs). However, data on tolerability and outcome of ICIs in the elderly are lacking due to poor accrual in clinical trials of these patients. Methods: We performed a retro-prospective analysis on patients treated with single agent anti-PD-L1/PD-1 at the Clinical Oncology Unit, Careggi University Hospital, from March 2016 to March 2020. Data on the treatment responses, type and severity of irAEs, as well as the corticosteroids (CCS) dosage used for irAEs and the discontinuation rate, were described per each patient, according to two different age-based cohorts of patients (< or ≥70 years). Results: We reported a lower incidence of all-grade toxicity in elderly compared to younger patients (64.9% vs. 44.9%, p = 0.018). The two age-cohorts showed a different profile of irAEs. Endocrine irAEs were significantly higher in younger patients (39.7% vs. 21.7%, p = 0.002), while dermatologic toxicities were more common in the older group (35.0% vs. 11.3%, p = 0.047). Use of CCS and treatment discontinuation rate do not differ significantly between the two age groups. Conclusion: Our findings suggest that treatment with ICIs in elderly populations is safe and feasible. Patients over 70 years are more prone to develop skin irAEs, while younger patients are more subject to experience endocrine toxicities. Full article
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Article
18F-DCFPyL (PSMA) PET in the Management of Men with Biochemical Failure after Primary Therapy: Initial Clinical Experience of an Academic Cancer Center
Curr. Oncol. 2021, 28(5), 3251-3258; https://doi.org/10.3390/curroncol28050282 - 25 Aug 2021
Viewed by 275
Abstract
Purpose: To describe the initial experience of an academic center using 18F-DCFPyL PET in managing men with recurrent prostate cancer. Materials & Methods: This prospective, single-arm IRB-approved study included men with biochemical failure after primary therapy for prostate cancer and negative/equivocal CT [...] Read more.
Purpose: To describe the initial experience of an academic center using 18F-DCFPyL PET in managing men with recurrent prostate cancer. Materials & Methods: This prospective, single-arm IRB-approved study included men with biochemical failure after primary therapy for prostate cancer and negative/equivocal CT and bone scintigraphy who were candidates for salvage therapy, as determined by a multidisciplinary panel of experts. 18F-DCFPyL PET was assessed for the presence and extent of recurrence: local, oligometastatic (≤4), or extensive. Post-PET management and clinical outcome, including PSA response, was documented. For patients who received PET-directed ablative therapies, response was categorized as “complete” if PSA became undetectable or “favorable” if PSA decreased ≥50%. Results: Forty-seven men with biochemical failure after radical prostatectomy (n = 29), primary radiotherapy (n = 15) or focal tumor ablation (n = 3) were included. PET was positive in (43/47) 91.5%, including local recurrence in (9/47) 19.2%; oligometastatic disease in (16/47) 34%; and extensive metastatic disease in (18/47) 38.3%. PET-directed focal ablative therapies without systemic therapy were given to (13/29) 44.8% of patients without extensive metastases on PET with a mean PSA response of 69% (median, 74.5%; range: 35–100). Favorable biochemical response was observed in (10/13) 76.9% of patients with limited recurrence on PET, and in 23.1% (3/13), there was complete response. Conclusion: 18F-DCFPyL PET was positive in >90% of patients with biochemical failure. For those with limited recurrence, PSMA PET-directed local ablative therapies resulted in favorable outcome in more than 3 in 4 patients, and in nearly a quarter of them, there was complete biochemical response. Full article
(This article belongs to the Section Medical Oncology)
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Brief Report
Sensorineural Hearing Loss as the Prominent Symptom in Meningeal Carcinomatosis
Curr. Oncol. 2021, 28(5), 3240-3250; https://doi.org/10.3390/curroncol28050281 - 25 Aug 2021
Viewed by 380
Abstract
Sensorineural hearing loss (SNHL) has been reported rarely in patients with meningeal carcinomatosis (MC). We summarized the clinical data of eight MC patients with SNHL and 35 patients reported from publications. In the eight patients with SNHL, the medium onset age was 48 [...] Read more.
Sensorineural hearing loss (SNHL) has been reported rarely in patients with meningeal carcinomatosis (MC). We summarized the clinical data of eight MC patients with SNHL and 35 patients reported from publications. In the eight patients with SNHL, the medium onset age was 48 (range from 37 to 66) years and six (75%) were male. Seven (87.5%) suffered from headaches as the initial symptom, and they experienced SNHL during the first two months after the occurrence of headaches (0.5 to 2 months, average 1.5 months). The audiogram configuration was flat in three patients (37.5%) and showed total deafness in five patients (62.5%). The damage of cranial nerves VI (abducens) was observed in six patients (75%), and four patients (50%) had cranial nerves VII (facial) injury during the disease course. The percentage of damage of cranial nerves was higher than the patients without SNHL (VIth, 75.0% vs. 13.3%, p = 0.002 and VIIth 50.0% vs. 6.7%, p = 0.012). Four (50%) patients suffered from lung adenocarcinoma as primary tumor, two (25%) experienced stomach adenocarcinoma, one had colon cancer, and one patient was unknown. The symptom of SNHL improved after individualized therapy in four patients (focal radiotherapy and chemotherapy for three patients and whole brain radiotherapy for one patient), but all passed away from 2 to 11 months after diagnosis. Total deafness and flat hearing loss in audiogram were the common types of SNHL resulting from MC. MC patients with SNHL were more likely to suffer from the damage of other cranial nerves, especially to cranial nerves VI and VII. Treatment might improve SNHL, but not improve the case fatality rate. Full article
Case Report
Multitumor Case Series of Germline BRCA1, BRCA2 and CHEK2-Mutated Patients Responding Favorably on Immune Checkpoint Inhibitors
Curr. Oncol. 2021, 28(5), 3227-3239; https://doi.org/10.3390/curroncol28050280 - 24 Aug 2021
Viewed by 358
Abstract
In recent years, immune checkpoint inhibitors (ICPI) have become widely used for multiple solid malignancies. Reliable predictive biomarkers for selection of patients who would benefit most are lacking. Several tumor types with somatic or germline alterations in genes involved in the DNA damage [...] Read more.
In recent years, immune checkpoint inhibitors (ICPI) have become widely used for multiple solid malignancies. Reliable predictive biomarkers for selection of patients who would benefit most are lacking. Several tumor types with somatic or germline alterations in genes involved in the DNA damage response (DDR) pathway harbor a higher tumor mutational burden, possibly associated with an increased tumoral neoantigen load. These neoantigens are thought to lead to stronger immune activation and enhanced response to ICPIs. We present a series of seven patients with different malignancies with germline disease-associated variants in DDR genes (BRCA1, BRCA2, CHEK2) responding favorably to ICPIs. Full article
(This article belongs to the Special Issue Next Gen Sequencing: Clinical Molecular Genetics Findings)
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