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With the expansion of communication in the globalised world, translation has gained importance all over the world. Books, articles, magazines have been translated for over years. A new field in translation is song translation. The aim of the study is to analyze translation strategies that are applied in the translation process of songs in Walt Disney's Animated Musical Movies; namely "Hercules" (1997) and "Frozen" (2013) into Turkish within the framework of Skopos Theory. From each movie, 2 songs were selected. The names of the songs are The Gospel Truth 1 and Zero to Hero from "Hercules", Love is an Open Door and For the First Time Forever from "Frozen". The study focuses on the translation strategies based on Peter Low's strategies (2005); translation, adaptation and replacement. It is a descriptive qualitative research. The result of the study showed that there were 80 verses in "Hercules" and 86 verses in "Frozen". In addition, from the three translation strategies proposed by Peter Low (2005), the most frequently used translation strategy is "Replacement" in "Hercules", while it is "Translation" in "Frozen".

The article investigates the effect of ferulic acid and chitosan on cell suspension cultures of Decalepis hamiltonii Wight & Arn. The study analyzes and quantifies vanillin using liquid chromatography-mass spectrometry following ferulic acid and chitosan treatments. It observes the biomass of suspension cultures and accumulation of vanillin, callus development on murashige and skoog (MS) medium containing Picloram and benzylaminopurine (BAP), and cell suspension cultures created on MS medium.

A triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst and ipsilateral ejaculatory duct obstruction has been called Zinner syndrome since its first description in 1914 by Zinner. It is a very rare congenital abnormality of the male genitourinary tract due to abnormal embryologic development of the Wolffian ducts. There have been several case reports from different parts of the world about the clinical and imaging findings of these anomaly. In this case report, we present the first case report of Zinner syndrome in a 28-year-old male Ethiopian patient.

Importance: Between 5% and 10% of breast cancer cases are associated with an inherited germline pathogenic or likely pathogenic variant (GPV) in a breast cancer susceptibility gene (BCSG), which could alter local and systemic therapy recommendations. Traditional genetic testing criteria misses a proportion of these cases., Objective: To evaluate the prevalence and clinicopathological associations of GPVs in 2 groups of BCSGs among an ethnically diverse cohort of women with newly diagnosed breast cancer., Design, Setting, and Participants: This cross-sectional study, conducted at 3 Montreal hospitals between September 2019 and April 2022, offered universal genetic counseling and testing to all women with a first diagnosis of invasive breast cancer. Women were offered an obligatory primary panel of BRCA1, BRCA2, and PALB2 (B1B2P2) and an optional secondary panel of 14 additional BCSGs. Eligible participants were women 18 years of age or older who received a diagnosis of a first primary invasive breast cancer not more than 6 months before the time of referral to the study. Data were analyzed from November 2023 to June 2024., Results: Of 1017 referred patients, 805 were eligible and offered genetic counseling and testing, and 729 of those 805 (90.6%) consented to be tested. The median age at breast cancer diagnosis was 53 years (range, 23-91 years), and 65.4% were White and of European ancestry. Fifty-four GPVs were identified in 53 patients (7.3%), including 39 patients (5.3%) with B1B2P2 and 15 patients (2.1%) with 6 of the 14 secondary panel BCSGs (ATM, BARD1, BRIP1, CHEK2, RAD51D, and STK11). On multivariable analysis, clinical factors independently associated with B1B2P2-positive status included being younger than 40 years of age at diagnosis (odds ratio [OR], 6.83; 95% CI, 2.22-20.90), triple-negative breast cancer (OR, 3.19; 95% CI, 1.20-8.43), high grade disease (OR, 1.68; 95% CI, 1.05-2.70), and family history of ovarian cancer (OR, 9.75; 95% CI, 2.65-35.85). Of 39 B1B2P2-positive patients, 13 (33.3%) were eligible for poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors., Conclusions and Relevance: In this cross-sectional universal genetic testing study of women with newly diagnosed invasive breast cancer, the prevalence of GPVs was 7.3%, with 5.3% of patients testing positive for B1B2P2. Among B1B2P2-women women, one-third were eligible for PARP inhibitors.

Introduction: SCLC has traditionally been considered to arise from toxic exposure factors, such as smoking. Recent evidence has revealed that germline mutations may also affect the development of SCLC; however, these alterations remain understudied. We sought to identify novel germline mutations in SCLC including germline copy number variations (CNVs) in our cohort of patients., Methods: We designed a custom hybrid-capture gene panel to evaluate germline alterations in 192 cancer-predisposition and frequently mutated genes in SCLC. We applied this panel to germline analysis of a treatment-naive cohort of 67 patients with SCLC at our institution. Subsequently, we annotated the variants using the American College of Medical Genetics criteria and further classified variants of uncertain significance using a set of in silico tools, including DeepMind AlphaMissense, MutationTaster, SIFT, and Polyphen2., Results: We identified American College of Medical Genetics pathogenic or likely pathogenic alterations in seven of 67 patients. Five (71%) were novel alterations ( BCORL1 , FANCC , ATR , and BBC3 ) and a novel CNV ( SLFN11 ) with two (29%) previously described mutations ( CHEK1 and BRIP1 ). We also identified 191 variants of uncertain significance in 60 of 67 patients, of which, depending on the in silico tool, 5% to 14% were predicted to be pathogenic. Patients with SCLC with the seven pathogenic alterations were observed to have a numerically longer overall survival (hazard ratio = 0.50) and progression-free survival (hazard ratio = 0.45) though not statistically significant compared with the remaining cohort., Conclusions: Our study identifies novel germline alterations, including a CNV, and provides additional evidence that germline factors could be important contributing factors to the development of SCLC., Competing Interests: Dr. Bratman is an inventor on patents related to cell-free DNA mutation and methylation analysis technologies that have been licensed to Roche and AdelaBio, respectively, and is co-founder of, has ownership in, and serves in a leadership role at AdelaBio. Dr. Liu reports receiving grants and personal fees from AstraZeneca and Takeda; grants from Boehringer Ingelheim; and personal fees from Hoffman-La Roche, Merck, Bristol-Myers Squibb, and Pfizer outside of the submitted work. Dr. Lok reports receiving grants from 10.13039/100004319Pfizer and grants, personal fees, and nonfinancial support from 10.13039/100004325AstraZeneca outside the submitted work. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Objectives: Immune checkpoint inhibitors (ICIs) are indicated for metastatic urothelial cancer (mUC), but predictive and prognostic factors are lacking. We investigated clinical variables associated with ICI outcomes., Methods: We performed a multicentre retrospective cohort study of 135 patients who received ICI for mUC, 2016-2021, at three Canadian centres. Clinical characteristics, body mass index (BMI), metastatic sites, neutrophil-to-lymphocyte ratio (NLR), response and survival were abstracted from chart review., Results: We identified 135 patients and 62% had received ICI as a second-line or later treatment for mUC. A BMI ≥25 was significantly correlated to a higher overall response rate (ORR) (45.4% vs 16.3%, p value=0.020). Patients with BMI ≥30 experienced longer median overall survival (OS) of 24.8 vs 14.4 for 25≤BMI<30 and 8.5 months for BMI <25 (p value=0.012). The ORR was lower in the presence of bone metastases (16% vs 41%, p value=0.006) and liver metastases (16% vs 39%, p value=0.013). Metastatic lymph nodes were correlated with higher ORR (40% vs 20%, p value=0.032). The median OS for bone metastases was 7.3 versus 18 months (p value <0.001). Patients with liver metastases had a median OS of 8.6 versus 15 months (p value=0.006). No difference for lymph nodes metastases (13.5 vs 12.7 months, p value=0.175) was found. NLR ≥4 had worse OS (8.2 vs 17.7 months, p value=0.0001). In multivariate analysis, BMI ≥30, bone metastases, NLR ≥4, performance status ≥2 and line of ICI ≥2 were independent factors for OS., Conclusions: Our data identified BMI and bone metastases as novel clinical biomarkers that were independently associated with ICI outcomes in mUC. External and prospective validation are warranted., Competing Interests: Competing interests: Nicholas Meti—Honoraria: Takeda, Novartis. Consulting: Takeda, Seagen, AstraZeneca, Pfizer. Srikala S Sridhar—Consulting: Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, BMS, Eisai, EMD Serono, Gilead, Ipsen, Janssen, Merck, Pfizer, Seagen; Research funding (Institution): Janssen, Seagen, EMD Serono. Rossanna C Pezo—Honoraria: Pfizer, Novartis, BMS, Merck, Sanofi, Gilead, AstraZeneca; Research funding (Institution): Merck, Novartis, Pfizer, Taiho, Jazz Pharmaceuticals, ZymeWorks, AstraZeneca. Cristiano Ferrario—Honoraria: Pfizer, Bayer, Novartis, Roche, Bayer, Knight therapeutics, AstraZeneca, Merck, Astellas Pharma; Consulting—Merck, Novartis, AstraZeneca, Roche; Research funding (Institution): Merck, Novartis, Pfizer, Lilly, ZymeWorks, AstraZeneca, Janssen Oncology, Bayer, Astellas Pharma, Roche, Sanofi, Seattle Genetics, Semonix Pharmaceuticals, Bicycle Therapeutics, Immunomedics. Susanna Cheng—Consulting: AstraZeneca, Merck. April A N Rose—Consulting: EMD Serono, Advanced accelerator applications/Novartis; Research funding (Personal): Canadian Institutes of Health Research CIHR, Canadian Cancer Society, Conquer Cancer Foundation, Jewish General Hospital Foundation, TransMedTech Institute, Canada Foundation of Innovation; Research Funding (Institution): AstraZeneca, Merck, Pfizer, Seattle Genetics; Employment: Family member Merck. Soumaya Labidi, Mengqi Li, Sonia V Del Rincon, Reeta Barua, Jamila Riromar, Di Maria Jiang, Nazanin Fallah-Rad, Adrian G Sacher: no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The role for radiotherapy or surgery in the upfront management of brain metastases (BrM) in epidermal growth factor receptor mutant ( EGFR m) or anaplastic lymphoma kinase translocation positive ( ALK +) non-small cell lung cancer (NSCLC) is uncertain because of a lack of prospective evidence supporting tyrosine kinase inhibitor (TKI) monotherapy. Further understanding of practice heterogeneity is necessary to guide collaborative efforts in establishing guideline recommendations., Methods: We conducted an international survey among medical (MO), clinical (CO), and radiation oncologists (RO), as well as neurosurgeons (NS), of treatment recommendations for asymptomatic BrM (in non-eloquent regions) EGFRm or ALK+ NSCLC patients according to specific clinical scenarios. We grouped and compared treatment recommendations according to specialty. Responses were summarized using counts and percentages and analyzed using the Fisher exact test., Results: A total of 449 surveys were included in the final analysis: 48 CO, 85 MO, 60 NS, and 256 RO. MO and CO were significantly more likely than RO and NS to recommend first-line TKI monotherapy, regardless of the number and/or size of asymptomatic BrM (in non-eloquent regions). Radiotherapy in addition to TKI as first-line management was preferred by all specialties for patients with ≥4 BrM. NS recommended surgical resection more often than other specialties for BrM measuring >2 cm., Conclusions: Recommendations for the management of BrM from EGFRm or ALK+ NSCLC vary significantly according to oncology sub-specialties. Development of multidisciplinary guidelines and further research on establishing optimal treatment strategies is warranted., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-697/coif). NM serves on the advisory boards of Pfizer, Novartis, and Seagen. NM reports honoraria from Takeda Oncology and Astra Zeneca. FYM reports consulting fees from Elekta, and honoraria from Astra Zeneca and IASLC; grants and contracts from CTAQ Queen’s University. JCHY reports participation in advisory board with Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Ono Pharmaceuticals, Pfizer, Roche/Genentech, Takeda, Yuhan Pharmaceuticals, JNJ, Puma Technology, Gilead, and GSK; grant support with Astra Zeneca. JHL reports participation in advisory boards with Novartis, Takeda, Eli Lilly, and Astra Zeneca; consulting fees from Pfizer, and payments or honoraria from Bayer, Pfizer, Daiichi-Sankyo, Novartis and Boehringer Ingelheim. NP reports research support from Pfizer, Bayer, and Roche; Honoraria from Boehringer Ingelheim, Pfizer, Roche, Takeda, Pieere-Faber; Advisory board participation from Boehringer Ingelheim, MSD, Astra Zeneca, Merck, Bristol Meyers Squibb, Pfizer, Roche, Takeda, AllVascular, Beigene, Novartis. PK reports financial compensation from Medexus Pharmaceuticals Canada. MD reports consulting fees from Roche, Astra Zeneca, Takeda, Eisai, and Merck; honoraria from Roche and Astra Zeneca. NBL reports research support from Amgen, Array, Astra Zeneca, Bayer, Eli Lilly, EMD Serono, Pfizer, Roche, Guardant Health, Takeda; Honoraria from Amgen, Astra Zeneca, BMS, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and Takeda. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Outcomes for breast cancer patients with residual disease (RD) after neoadjuvant chemotherapy (NACT) and HER2-targeted therapy may be better than anticipated leading to a smaller absolute benefit of adjuvant trastuzumab emtansine (T-DM1). Therefore, accurate estimates of 3-year disease-free survival (DFS) can aid in treatment planning., Methods: We reviewed randomized trials of NACT and HER2-targeted therapy in breast cancer (excluding T-DM1) and calculated mean 3-year DFS weighted by study sample size. Meta-regression comprising linear regression weighted by sample size (mixed-effects) was performed to explore associations between 3-year DFS and year of accrual and trial-level patient, disease, and treatment factors. Data were reported quantitatively irrespective of statistical significance., Results: Eleven studies (N = 3581) were included in the primary analysis. The mean 3-year DFS for patients with RD was 79.7% (95% CI 77.4-80.9). This was higher for trials completing accrual after 2010 [83% (95% CI 79.3-86.3)] and for those receiving dual HER2 targeted therapy [83.4% (95% CI 79.2-87.7]. Better outcomes for ER positivity, later accrual and dual Her-2 targeted therapy were confirmed in meta-regression. Negative quantitative significance was observed for larger clinical tumor size and nodal involvement., Conclusions: The 3-year DFS for patients with RD has improved over time possibly due to dual HER2 targeted therapy. This will reduce the absolute benefit of adjuvant T-DM1 in this group of patients., Competing Interests: Conflict of Interest Statement E. Amir: Honoraria from Sandoz, Novartis, and Exact Sciences outside the submitted work. All remaining authors have declared no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Small-cell lung cancer (SCLC) methylome is understudied. Here, we comprehensively profile SCLC using cell-free methylated DNA immunoprecipitation followed by sequencing (cfMeDIP-seq). Cell-free DNA (cfDNA) from plasma of 74 patients with SCLC pre-treatment and from 20 non-cancer participants, genomic DNA (gDNA) from peripheral blood leukocytes from the same 74 patients, and 7 accompanying circulating tumor cell-derived xenografts (CDXs) underwent cfMeDIP-seq. Peripheral blood leukocyte methylation (PRIME) subtraction to improve tumor specificity. SCLC cfDNA methylation is distinct from non-cancer but correlates with CDX tumor methylation. PRIME and k-means consensus identified two methylome clusters with prognostic associations that related to axon guidance, neuroactive ligand-receptor interaction, pluripotency of stem cells, and differentially methylated at long noncoding RNA and other repeats features. We comprehensively profiled the SCLC methylome in a large patient cohort and identified methylome clusters with prognostic associations. Our work demonstrates the potential of liquid biopsies in examining SCLC biology encoded in the methylome., Competing Interests: S.S. reports grants from AstraZeneca, BMS, Janssen, Von Tobel foundation, Fill the Gap, and has served on all institutional advisory board for BMS, AstraZeneca, MSD. N.M. reports personal fees from Takeda Oncology, Pfizer, and Novartis, outside of the submitted work. M.-S.T. reports research grant from Bayer and AstraZeneca, outside the submitted work, and personal fees from AstraZeneca, Amgen, BMS, Daiichi-Sankyo and Lilly, outside the submitted work. D. de Carvalho received research funds from Pfizer and is co-founder and shareholder of Adela Inc. S.V.B. is inventor on patents related to cell-free DNA mutation and methylation analysis technologies that have been licensed to Roche and Adela, respectively, and is co-founder of, has ownership in, and serves in a leadership role at Adela. G.L. reports grants and personal fees from AstraZeneca and Takeda; grants from Boehringer Ingelheim; and personal fees from Hoffman La Roche, Merck, Bristol Myers Squibb, and Pfizer outside the submitted work. B.H.L. reports grants from Pfizer; and grants, personal fees, and non-financial support from AstraZeneca outside the submitted work., (© 2022 The Author(s).)

Virtual cancer care (i.e., teleoncology) was rapidly adopted during the COVID-19 pandemic to meet the needs of patients with cancer. However, there is a paucity of guidance for clinicians regarding virtual cancer care. We sought to develop consensus-based statements to guide the optimal provision of virtual care for clinicians caring for patients with cancer, using a modified Delphi consensus process with a 29-member panel consisting of an interprofessional group of clinicians caring for patients with cancer and patient representatives. The consensus process consisted of two rounds and one synchronous final consensus meeting. At the end of the modified Delphi process, 62 of 62 statements achieved consensus. Fifty-seven statements reached consensus in the first round of the process. Concerns regarding the ability to convey difficult news virtually and maintaining similar standards as in-person care without disproportionate strain on clinicians and patients were addressed in the consensus process. We achieved interprofessional consensus on virtual cancer care practices. Further research examining the impact of virtual cancer care on person-centred and clinical outcomes are needed to inform practices during the COVID-19 pandemic and beyond.

Purpose: Current guidelines recommend somatic genomic sequencing for patients with advanced pancreatic cancer to identify targetable alterations amenable to targeted therapy. The benefit of somatic genomic sequencing in pancreatic cancer remains unclear. This study aims to assess the evidence supporting genomic sequencing to inform treatment selection for patients with advanced pancreatic cancer., Methods: A systematic review identified prospective studies of exocrine pancreatic cancer patients published before August 2020 which conducted genomic sequencing to inform treatment selection. Outcomes of interest included the proportion of patients with targetable alterations, the proportion that received targeted treatments, and the impact of targeted treatments on overall survival. Meta-analysis for proportions and hazard ratios was performed using Dersimonian and Laird random effect models., Results: 19 studies (representing 2048 pancreatic cancer patients) were included. Sequencing methodologies, definitions of targetable alterations, and approaches treatment selection varied across studies and were incompletely reported. 590 of 1382 sequenced patients harboured a targetable alteration (random effects meta-analysis estimate of the proportion 0.46, 95% confidence interval 0.32-0.61). The proportion of patients with targetable alterations was highly heterogenous between studies (I 2 93%, P < 0.001). 91 of 1390 patients received a matched therapy based on their targetable alterations (random effects meta-analysis estimate of the proportion 0.12, 95% CI 0.06-0.23). One observational study reported an overall survival benefit of matched therapy., Conclusions: Genomic sequencing frequently identifies targetable alterations in pancreatic cancers. Further research is required to standardize the definitions of targetable alterations, the approach to treatment matching, and quantify the benefit of targeted therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The addition of platinum agents to anthracycline and taxane-based chemotherapy in early-stage triple negative breast cancer (TNBC) patients improves pathological complete response (pCR). Long-term outcomes, such as disease-free survival (DFS) and overall survival (OS), have not been well-established., Methods: A systematic literature review identified studies using platinum-based treatment in TNBC patients in the neoadjuvant or adjuvant setting with reportable long-term outcomes. Hazard ratios (HR) from collected data were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on treatment setting and study design., Results: Fourteen studies comprising 3518 patients met the inclusion criteria. Median follow up was 56.2 months. All studies reported DFS and 9 studies (64%) reported OS. DFS was significantly better in platinum-based treatment (HR 0.71, 95% confidence interval (CI) 0.56-0.89; p = 0.03). However, OS was no different (HR 0.98, 95% CI 0.75-1.27; p = 0.87). There was a non-significant difference between platinum exposure in the adjuvant compared to neoadjuvant setting for both DFS (HR 0.75 vs 0.62, p = 0.43) and for OS (HR 0.90 vs 1.10, p = 0.58). The addition of platinum was associated with more thrombocytopenia and all-grade neuropathy and non-significant increases in neutropenia and grade 3-4 neuropathy., Conclusions: Platinum-based treatment improves DFS but not OS. The reporting of toxicity was suboptimal, but in general adding platinum increased toxicity. The discordant effect of platinum-based treatment on DFS and OS suggest the potential development of platinum resistance and worse outcomes after recurrence. Platinum-based chemotherapy cannot be recommended in unselected patients with early TNBC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

During the COVID-19 pandemic, most cancer centers shifted from in-person to virtual cancer care to curb community spread and ensure care continuity. This qualitative descriptive study aimed to understand cancer patient-perceived risks related to COVID-19 and cancer treatment, as well as the patient-perceived and experienced value of virtual care. From June to August 2020, focus groups were conducted with patients under active management or observation for a diagnosed malignancy in Toronto, Canada. A thematic analysis of six focus groups found that most participants worried more about treatment delays than they did about COVID-19 infection. Despite some concern about COVID-19 exposure in the hospital, care delays contributed to increased anxiety among participants who already subscribed to strict safety measures in their everyday lives. Most participants accepted virtual care for some appointment types; however, preference for in-person care was found to sustain the humanistic and therapeutic aspects of cancer care that many participants valued. Nuances in the appropriateness and adequacy of virtual cancer care still need exploration. Preserving the humanistic aspects of care is of paramount importance., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: There are limited data regarding the quality of patient-reported outcome (PRO) data in immune checkpoint inhibitor (ICI) clinical trial publications., Methods: A systematic search of citations from various databases was conducted to identify prospective clinical trials involving ICI in advanced tumors from 2003 to 2020. A 30-point score was adapted from the CONSORT PRO extension statement to assess adherence to CONSORT PRO reporting. Linear regression was used to identify factors associated with quality reporting., Results: After the review of 8058 articles, 33 trials were included with ICIs as either monotherapy (91%) or part of a combination regimen (9%). The median score was 23.5 points (range 15-29). In the majority of cases (82%), PROs were reported in a separate publication from the original study. Most of the trials were conducted in the metastatic setting and predominantly in melanoma, lung, and renal cell carcinoma (RCC) (73%). Univariate analysis revealed that trials with greater than 250 patients were associated with a higher score. The score was more likely to be lower in disease sites other than melanoma, lung, and RCC and was higher in the KEYNOTE than in the CHECKMATE trial series. There was no significant correlation between the score and whether a trial met its primary end-point or if the trial improved or worsened the quality of life. In the multivariate analysis, the number of patients enrolled to the trial, disease site, and trial series remained significant., Conclusions: The quality of reporting of PROs in ICI phase II and III clinical trials is heterogeneous across various cancer sites. As PRO data are increasingly used to counsel patients and complement clinical decision making, innovative and collaborative efforts are required to improve the reporting of these essential data., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Claudin-2 promotes breast cancer liver metastasis by enabling seeding and early cancer cell survival. We now demonstrate that Claudin-2 is functionally required for colorectal cancer liver metastasis and that Claudin-2 expression in primary colorectal cancers is associated with poor overall and liver metastasis-free survival. We have examined the role of Claudin-2, and other claudin family members, as potential prognostic biomarkers of the desmoplastic and replacement histopathological growth pattern associated with colorectal cancer liver metastases. Immunohistochemical analysis revealed higher Claudin-2 levels in replacement type metastases when compared to those with desmoplastic features. In contrast, Claudin-8 was highly expressed in desmoplastic colorectal cancer liver metastases. Similar observations were made following immunohistochemical staining of patient-derived xenografts (PDXs) that we have established, which faithfully retain the histopathology of desmoplastic or replacement type colorectal cancer liver metastases. We provide evidence that Claudin-2 status in patient-derived extracellular vesicles may serve as a relevant prognostic biomarker to predict whether colorectal cancer patients have developed replacement type liver metastases. Such a biomarker will be a valuable tool in designing optimal treatment strategies to better manage patients with colorectal cancer liver metastases.

Breast cancer is currently the second most common cause of cancer-related death in women. Presently, the clinical benchmark in cancer diagnosis is tissue biopsy examination. However, the manual process of histopathological analysis is laborious, time-consuming, and limited by the quality of the specimen and the experience of the pathologist. This study's objective was to determine if deep convolutional neural networks can be trained, with transfer learning, on a set of histopathological images independent of breast tissue to segment tumor nuclei of the breast. Various deep convolutional neural networks were evaluated for the study, including U-Net, Mask R-CNN, and a novel network (GB U-Net). The networks were trained on a set of Hematoxylin and Eosin (H&E)-stained images of eight diverse types of tissues. GB U-Net demonstrated superior performance in segmenting sites of invasive diseases (AJI = 0.53, mAP = 0.39 & AJI = 0.54, mAP = 0.38), validated on two hold-out datasets exclusively containing breast tissue images of approximately 7,582 annotated cells. The results of the networks, trained on images independent of breast tissue, demonstrated that tumor nuclei of the breast could be accurately segmented.

Breast cancer screening has been shown to significantly reduce mortality in women. The increased utilization of screening examinations has led to growing demands for rapid and accurate diagnostic reporting. In modern breast imaging centers, full-field digital mammography (FFDM) has replaced traditional analog mammography, and this has opened new opportunities for developing computational frameworks to automate detection and diagnosis. Artificial intelligence (AI), and its subdomain of deep learning, is showing promising results and improvements on diagnostic accuracy, compared to previous computer-based methods, known as computer-aided detection and diagnosis.In this commentary, we review the current status of computational radiology, with a focus on deep neural networks used in breast cancer screening and diagnosis. Recent studies are developing a new generation of computer-aided detection and diagnosis systems, as well as leveraging AI-driven tools to efficiently interpret digital mammograms, and breast tomosynthesis imaging. The use of AI in computational radiology necessitates transparency and rigorous testing. However, the overall impact of AI to radiology workflows will potentially yield more efficient and standardized processes as well as improve the level of care to patients with high diagnostic accuracy.

Patients with cancer are more vulnerable to severe COVID-19. As a result, routine SARS-CoV-2 testing of asymptomatic patients with cancer is recommended prior to treatment. However, there is limited evidence of its clinical usefulness. The objective of this study is to evaluate the value of routine testing of asymptomatic patients with cancer. Asymptomatic patients with cancer attending Odette Cancer Centre (Toronto, ON, Canada) were tested for SARS-CoV-2 prior to and during treatment cycles. Results were compared to positivity rates of SARS-CoV-2 locally and provincially. All 890 asymptomatic patients tested negative. Positivity rates in the province were 1.5%, in hospital were 1.0%, and among OCC's symptomatic cancer patients were 0% over the study period. Given our findings and the low SARS-CoV-2 community positivity rates, we recommend a dynamic testing model of asymptomatic patients that triggers testing during increasing community positivity rates of SARS-CoV-2.

Purpose: Neoadjuvant chemotherapy (NAC) is used to treat locally advanced breast cancer (LABC) and high-risk early breast cancer (BC). Pathological complete response (pCR) has prognostic value depending on BC subtype. Rates of pCR, however, can be variable. Predictive modeling is desirable to help identify patients early who may have suboptimal NAC response. Here, we test and compare the predictive performances of machine learning (ML) prediction models to a standard statistical model, using clinical and pathological data., Methods: Clinical and pathological variables were collected in 431 patients, including tumor size, patient demographics, histological characteristics, molecular status, and staging information. A standard multivariable logistic regression (MLR) was developed and compared with five ML models: k-nearest neighbor classifier, random forest (RF) classifier, naive Bayes algorithm, support vector machine, and multilayer perceptron model. Model performances were measured using a receiver operating characteristic (ROC) analysis and statistically compared., Results: MLR predictors of NAC response included: estrogen receptor (ER) status, human epidermal growth factor-2 (HER2) status, tumor size, and Nottingham grade. The strongest MLR predictors of pCR included HER2+ versus HER2- BC (odds ratio [OR], 0.13; 95% CI, 0.07 to 0.23; P < .001) and Nottingham grade G3 versus G1-2 (G1-2: OR, 0.36; 95% CI, 0.20 to 0.65; P < .001). The area under the curve (AUC) for the MLR was AUC = 0.64. Among the various ML models, an RF classifier performed best, with an AUC = 0.88, sensitivity of 70.7%, and specificity of 84.6%, and included the following variables: menopausal status, ER status, HER2 status, Nottingham grade, tumor size, nodal status, and presence of inflammatory BC., Conclusion: Modeling performances varied between standard versus ML classification methods. RF ML classifiers demonstrated the best predictive performance among all models.

Background: Anti-cancer drugs are approved typically on the basis of efficacy and safety as evaluated in phase III randomized trials (RCTs). Health-related quality of life (HRQoL) is a direct measure of patient benefit, but is under-reported. Here we explore associations with reporting of HRQoL data in phase III RCTs in common solid tumors., Methods: We searched ClinicalTrials.gov to identify phase III RCTs evaluating new drugs in adults with advanced cancers that completed accrual between January 2005 and October 2016. Data on HRQoL, safety, and tolerability comprising treatment-related death, treatment discontinuation and commonly reported grade 3 or 4 adverse events (AEs) were extracted. Associations between these measures and reporting of HRQoL data were explored using logistic regression., Results: Of 377 phase III RCTs identified initially, 143 studies were analysed and comprised 55% positive trials and 90% industry sponsored trials. HRQoL was listed as an endpoint in 59% trials; and of these, only 65% reported HRQoL data. There were higher odds of reporting HRQoL data for positive trials (OR 2.05, P = .04) and trials published in journals with higher impact factor (OR 1.35, P = .01). Reporting of HRQoL was not associated with treatment-related death (OR 1.25, P = .40) or treatment discontinuation (OR 1.12, P = .61), but was positively associated with dyspnea and dermatological adverse events., Conclusions: HRQoL is reported in only two-thirds of RCTs that describe collecting such data. Reporting of HRQoL is associated with positive trial outcome and higher journal impact factor, but not associated with overall safety and tolerability of anti-cancer drugs., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: Marie Hudson reports receiving a grant from Bristol-Myers Squibb, outside the submitted work. Khashayar Esfahani reports receiving speaker’s fees from Bristol-Myers Squibb, outside the submitted work. Wilson Miller reports receiving grants from Bristol-Myers Squibb, Merck, Roche, Novartis, AstraZeneca, Amgen, Bayer, MedImmune and GlaxoSmithKline, outside the submitted work, as well as personal fees from Bristol-Myers Squibb, Merck, Roche, Novartis, Amgen and GlaxoSmithKline. No other competing interests were declared.

Hodgkin Lymphoma (HL) is a unique disease entity both in its pathology and the young patient population that it primarily affects. Although cure rates are high, survivorship can be linked with significant recent long-term morbidity associated with both chemotherapy and radiotherapy. The most significant advances have been with the use of the anti-CD30-drug conjugated antibody brentuximab vedotin (BV) and inhibitors of program death 1 (PD-1). HL is genetically wired to up-regulate program death ligand 1 (PD-L1) in >95% of cases, creating a state of so-called &ldquo;T cell exhaustion&rdquo;, which can be reversed with immune checkpoint-inhibitor blockade. The overall and complete response rates to PD-1 inhibitors in patients with relapsed or refractory HL are 70% and 20%, respectively, with a long median duration of response of ~16 months. In fact, PD-1 inhibitors can benefit a wide spectrum of relapsed HL patients, including some who have &ldquo;progressive disease&rdquo; by strict response criteria. We review the biology of HL, with a focus on the immune micro-environment and mechanisms of immune evasion. We also provide the rationale supporting the use of PD-1 inhibitors in HL and highlight some of the challenges of monitoring disease response in patients treated with this immunotherapy.

Motivated behaviors and many psychopathologies typically involve changes in dopamine release from the projections of the ventral tegmental area (VTA) and/or the substantia nigra pars compacta (SNc). The morphogen Sonic Hedgehog (Shh) specifies fates of midbrain dopamine neurons, but VTA-specific effects of Shh signaling are also being uncovered. In this study, we assessed the role of the Shh receptor Cdon in the development of VTA and SNc dopamine neurons. We find that Cdon is expressed in the proliferating progenitor zone of the embryonic ventral midbrain and that the number of proliferating cells in this region is increased in mouse Cdon(-/-) embryos. Consistent with a role of Shh in the regulation of neuronal proliferation in this region, we find that the number of tyrosine hydroxylase (TH)-positive neurons is increased in the VTA of Cdon(-/-) mice at birth and that this effect endures into adulthood. In contrast, the number of TH-positive neurons in the SNc is not altered in Cdon(-/-) mice at either age. Moreover, adult Cdon(-/-) mice have a greater number of medial prefrontal cortex (mPFC) dopamine presynaptic sites, and increased baseline concentrations of dopamine and dopamine metabolites selectively in this region. Finally, consistent with increased dopamine function in the mPFC, we find that adult Cdon(-/-) mice fail to exhibit behavioral plasticity upon repeated amphetamine treatment. Based on these data, we suggest that Cdon plays an important role encoding the diversity of dopamine neurons in the midbrain, influencing both the development of the mesocortical dopamine pathway and behavioral outputs that involve this neural circuitry.

Background: Transcatheter interventions are currently undertaken using "generic" fluoroscopic viewing angles. However, the position and orientation of heart structures may vary across patients and disease-specific remodeling processes., Objective: This study uses multislice computed tomography to determine optimal fluoroscopic viewing angles of the aortic and mitral annuli, the left atrial appendage and the atrial septum. We explored differences between patients with severe aortic stenosis (AS) and severe mitral regurgitation (MR)., Methods and Results: The multislice computed tomographies of 28 patients with severe aortic stenosis (AS) and 32 patients with severe functional mitral regurgitation (MR) were analyzed. For each patient, we evaluated the optimal fluoroscopic viewing angles of the aortic and mitral annuli (en face, maximal and minimal diameters, aortic root with right, left and non coronary sinus in center), left atrial appendage orifice (en face, maximal and minimal diameters), and atrial septum (fossa ovalis) en face. The TAVR implantation view with right coronary sinus in center was LAO 9 - CRA 0 in the AS group and LAO 6 - CAU 5 in the MR group (p = NS). AS and MR patients differed significantly with respect to the fluoroscopic angulation of the aortic annulus en face (8.3°), the aortic annulus maximal (17.7°) and minimal (18.5°) diameters, the mitral annulus aorto-mural diameter (11.3°), and the left atrial appendage orifice en face (11.1°) (all p-values<0.05)., Conclusion: Optimal fluoroscopic viewing angles of left-sided structures vary considerably between patients. Multislice computed tomography is a valuable tool to determine the most procedurally relevant angulations, with the potential to optimize procedural safety, efficacy and duration., (Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)