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Objective: Hot flashes are one of the major symptoms of climacteric syndrome. Despite the high prevalence of these symptoms, few questionnaires assessing the impact of hot flashes on quality of life have been validated. The aim of this study was to validate a French version of the Hot Flash Related Daily Interference Scale (HFRDIS) in a sample of French women., Methods: In this prospective study, data were obtained from two groups of women aged between 40 and 60 years from both women without breast cancer and women under hormone therapy for breast cancer between March 2021 and February 2022. Translation was made by an official English-French translator using the forward-backward method., Results: One hundred and sixty-seven women completed the HFRDIS questionnaire. The scree plots confirmed unidimensional structure. Cronbach's α coefficient was 0.92 [0.90-0.94] similar to the original version. The intra-class correlation coefficients of each item ranged between 0.58 and 0.71 Concordance of the scores of each item with those obtained during the validation of the original version of the HFRDIS was confirmed., Conclusion: The validation results show that the French version of the HFRDIS questionnaire is a valid tool to evaluate the impact of hot flashes on the daily life activities of patients.

Abstract: A 73-year-old woman was referred for 68 Ga-DOTATOC PET/CT staging of a grade 2 pancreatic neuroendocrine tumor, which showed the primary pancreatic tumor, liver metastases, one left pleural metastasis, and high uptake in a mass of the right triceps brachii muscle. Two years before, she underwent 18 F-FDG PET/CT and 111 In-pentetreotide scan, respectively, with low and high uptake of each radiotracer in the triceps mass. Histopathological analysis revealed a solitary fibrous tumor. Immunohistochemistry showed no staining for SSTR-2 and SSTR-5, suggesting tumor overexpression of another somatostatin receptor. This case highlighted a potential pitfall on 68 Ga-DOTATOC PET/CT., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Muscle-invasive bladder cancer (BLCA) is an aggressive disease. Consensus BLCA transcriptomic subtypes have been proposed, with two major Luminal and Basal subgroups, presenting distinct molecular and clinical characteristics. However, how these distinct subtypes are regulated remains unclear. We hypothesized that epigenetic activation of distinct super-enhancers could drive the transcriptional programs of BLCA subtypes. Through integrated RNA-sequencing and epigenomic profiling of histone marks in primary tumours, cancer cell lines, and normal human urothelia, we established the first integrated epigenetic map of BLCA and demonstrated the link between subtype and epigenetic control. We identified the repertoire of activated super-enhancers and highlighted Basal, Luminal and Normal-associated SEs. We revealed super-enhancer-regulated networks of candidate master transcription factors for Luminal and Basal subgroups including FOXA1 and ZBED2, respectively. FOXA1 CRISPR-Cas9 mutation triggered a shift from Luminal to Basal phenotype, confirming its role in Luminal identity regulation and induced ZBED2 overexpression. In parallel, we showed that both FOXA1 and ZBED2 play concordant roles in preventing inflammatory response in cancer cells through STAT2 inhibition. Our study furthers the understanding of epigenetic regulation of muscle-invasive BLCA and identifies a co-regulated network of super-enhancers and associated transcription factors providing potential targets for the treatment of this aggressive disease., (© 2023. The Author(s).)

Introduction: Currently, bladder cancer detection is based on cytology and cystoscopy. White light cystoscopy (WLC) is an invasive procedure and may under-detect flat lesions. Blue light cystoscopy (BLC) and narrow band imaging (NBI) cystoscopy are new modalities that could improve the detection of non-muscle invasive bladder cancer (NMIBC) and its recurrence or progression to muscle invasive bladder cancer. We present a systematic review on BLC and NBI cystoscopy for bladder cancer diagnosis and NMIBC follow-up., Material and Methods: All available systematic reviews and meta-analyses on cystoscopy published in PubMed® between May 2010 and March 2021 were identified and reviewed. The main endpoints were clinical performance for bladder cancer diagnosis and for recurrence or progression detection during NMIBC follow-up, and additional value compared with cytology and/or WLC., Results: Most of the meta-analyses and systematic reviews published suggest a better sensitivity of BLC and NBI cystoscopy compared to WLC, particularly for the detection of flat lesions (CIS). NBI- and BLC-guided TURBT could decrease the recurrence rates. However, their clinical utility to reduce progression rate and increase survival is still unclear., Conclusions: BLC and NBI cystoscopy are efficient techniques for bladder cancer diagnosis and NMIBC follow-up. However, their clinical benefit remains to be confirmed., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Metastasis is the major cause of cancer death, and the development of therapy resistance is common. The tumor microenvironment can confer chemotherapy resistance (chemoresistance), but little is known about how specific host cells influence therapy outcome. We show that chemotherapy induces neutrophil recruitment and neutrophil extracellular trap (NET) formation, which reduces therapy response in mouse models of breast cancer lung metastasis. We reveal that chemotherapy-treated cancer cells secrete IL-1β, which in turn triggers NET formation. Two NET-associated proteins are required to induce chemoresistance: integrin-αvβ1, which traps latent TGF-β, and matrix metalloproteinase 9, which cleaves and activates the trapped latent TGF-β. TGF-β activation causes cancer cells to undergo epithelial-to-mesenchymal transition and correlates with chemoresistance. Our work demonstrates that NETs regulate the activities of neighboring cells by trapping and activating cytokines and suggests that chemoresistance in the metastatic setting can be reduced or prevented by targeting the IL-1β-NET-TGF-β axis., Competing Interests: Declaration of interests M.E. is a member of the research advisory board for brensocatib for Insmed, Inc., a member of the scientific advisory board for Vividion Therapeutics, Inc., and a consultant for Protalix, Inc., and holds shares in Agios Pharmaceuticals, Inc. J.A., C.G., and A.M. have a patent related to this work (EP22306004)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Craniopharyngioma (CP) in adults is a rare benign tumor associated with many morbidities, with limited contemporary studies to define treatment, and follow-up guidelines., Methods: A single-center retrospective study was conducted on patients aged ≥ 18 years from 2006-2018 with CP and who were treated with proton therapy (PT). Late toxicity was defined as a minimum of 18 months from diagnosis. Overall survival (OS), local recurrence-free survival (LRFS), and toxicity were characterized using Kaplan-Meier and Cox regression analyses., Results: Ninety-one patients met the criteria, with a median age of 37 years (range 18-82 years). PT was conducted after tumor resection in 88 patients (97%), in 64 patients (70.3%) as an adjuvant strategy and in 27 (29.7%) after recurrent disease. Three patients received exclusive PT. A median MRI follow-up of 39 months revealed 35.2% complete response, 49.5% partial response, and 9.9% stable disease. Five patients developed local recurrence (LR). The pattern of failure study showed that these five LR were within the GTV volume. The 5-year LRFS was 92.0% [CI 95% 84.90-99.60]. All the patients were alive at the end of the follow-up. Patients requiring treatment adaptation during PT tend to have a higher risk of LR (P = .084). Endocrinopathy was the most frequent grade ≥ 2 late toxicity. Among patients who were symptom-free before the start of treatment, none developed hearing toxicity but four (9.8%) developed visual disorders and 10 (11.3%) symptomatic memory impairment. Patients with large tumors had a higher risk of developing symptomatic memory impairment (P = .029)., Conclusion: Adults with CP treated with PT have favorable survival outcomes, with acceptable late toxicity. Prospective quality-of-life and neurocognitive studies are needed to define late adverse effects better., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Collecting duct carcinoma (also known as Bellini tumour) and renal medullary carcinoma are two extremely rare and aggressive renal cancers. They are both less responsive to conventional treatments used in clear cell renal carcinoma. There are very few studies evaluating their optimal management and currently, at the metastatic stage, polychemotherapy based on platinum salts remains the most widely used. The emergence of new treatments such as anti-angiogenic TKIs, immunotherapy or treatments targeting specific genetic abnormalities, opens up a new field of possibilities in the management of these cancers. The evaluation of the response to these treatments is therefore essential. In this article, we will review the status of their management and the various studies that have evaluated recent treatments in these two cancers., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Data on the role of the microbiota in cancer have accumulated in recent years, with particular interest in intratumoral bacteria. Previous results have shown that the composition of intratumoral microbiome is different depending on the type of primary tumour and that bacteria from the primary tumour could migrate to metastatic sites., Methods: Seventy-nine patients with breast, lung, or colorectal cancer and available biopsy samples from lymph node, lung, or liver site, treated in the SHIVA01 trial were analysed. We performed bacterial 16S rRNA gene sequencing on these samples to characterise the intratumoral microbiome. We assessed the association between microbiome composition, clinicopathological characteristics, and outcomes., Results: Microbial richness (Chao1 index), evenness (Shannon index) and beta-diversity (Bray Curtis distance) were associated with biopsy site (p = 0.0001, p = 0.03 and p < 0.0001, respectively) but not with primary tumour type (p = 0.52, p = 0.54 and p = 0.82, respectively). Furthermore, microbial richness was inversely associated with tumour-infiltrating lymphocytes (TILs, p = 0.02), and PD-L1 expression on immune cells (p = 0.03), or assessed by Tumor Proportion Score (TPS, p = 0.02) or Combined Positive Score (CPS, p = 0.04). Beta-diversity was also associated with these parameters (p < 0.05). Patients with lower intratumoral microbiome richness had shorter overall survival (p = 0.03) and progression-free survival (p = 0.02) in multivariate analysis., Conclusion: Biopsy site, rather than primary tumour type, was strongly associated with microbiome diversity. Immune histopathological parameters such as PD-L1 expression and TILs were significantly associated with alpha and beta-diversity supporting the cancer-microbiome-immune axis hypothesis., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: In the KEYNOTE-826 study, the addition of the anti-PD-1 monoclonal antibody pembrolizumab to chemotherapy with or without bevacizumab improved overall survival and progression-free survival (primary endpoints) versus placebo plus chemotherapy with or without bevacizumab, with manageable toxicity, in patients with persistent, recurrent, or metastatic cervical cancer. In this Article, we report patient-reported outcomes (PROs) from KEYNOTE-826., Methods: KEYNOTE-826 is a multicentre, randomised, phase 3 trial in 151 cancer treatment centres in 19 countries. Eligible patients were aged 18 years or older with persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemotherapy (previous radiosensitising chemotherapy was allowed) and not amenable to curative treatment and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) centrally by means of an interactive voice response system in a double-blind manner to receive either pembrolizumab 200 mg or placebo every 3 weeks intravenously for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m 2 plus cisplatin 50 mg/m 2 or carboplatin area under the curve 5 mg/mL per min, intravenously) with or without bevacizumab 15 mg/kg every 3 weeks intravenously. Randomisation (block size of 4) was stratified by metastatic disease at diagnosis, planned bevacizumab use, and PD-L1 combined positive score. Patients, investigators, and other study personnel involved in study treatment administration or clinical evaluation of patients were unaware of treatment group assignments. PRO instruments were the EORTC Quality-of-Life-Core 30 (QLQ-C30), the EORTC cervical cancer module (QLQ-CX24), and the EuroQol-5 dimension-5 level (EQ-5D-5L) visual analogue scale, each collected before treatment at cycles 1-14 and every other cycle thereafter. Primary endpoints were overall survival and progression-free survival per RECIST version 1.1 by investigator review. Change from baseline in QLQ-C30 global health status (GHS)-quality of life (QoL) was a prespecified secondary endpoint and was assessed in the PRO full analysis population (all patients who received at least one dose of study treatment and completed at least one post-baseline PRO assessment). Other PRO analyses were protocol-specified exploratory endpoints. The study is registered with ClinicalTrials.gov, NCT03635567, and is ongoing., Findings: Between Nov 20, 2018, and Jan 31, 2020, of 883 patients screened, 617 were randomly assigned (pembrolizumab group, n=308; placebo group, n=309). 587 (95%) of 617 patients received at least one dose of study treatment and completed at least one post-baseline PRO assessment and were therefore included in the PRO analyses (pembrolizumab group, n=290; placebo group, n=297). Median follow-up was 22·0 months (IQR 19·1-24·4). At week 30, QLQ-C30 completion was 199 (69%) of 290 patients in the pembrolizumab group and 168 (57%) of 297 patients in the placebo group; compliance was 199 (94%) of 211 and 168 (90%) of 186, respectively. The least squares mean change in QLQ-C30 GHS-QoL score from baseline to week 30 was -0·3 points (95% CI -3·1 to 2·6) in the pembrolizumab group and -1·3 points (-4·2 to 1·7) in the placebo group, with a between-group difference in least squares mean change of 1·0 point (95% CI -2·7 to 4·7). Median time to true deterioration in GHS-QoL was not reached (NR; 95% CI 13·4 months-NR) in the pembrolizumab group and 12·9 months (6·6-NR) in the placebo group (hazard ratio 0·84 [95% CI 0·65-1·09]). 122 (42%) of 290 patients in the pembrolizumab group versus 85 (29%) of 297 in the placebo group had improved GHS-QoL at any time during the study (p=0·0003)., Interpretation: Addition of pembrolizumab to chemotherapy with or without bevacizumab did not negatively affect health-related quality of life. Along with the efficacy and safety results already reported from KEYNOTE-826, these data support the benefit of pembrolizumab and the value of immunotherapy in patients with recurrent, persistent, or metastatic cervical cancer., Funding: Merck Sharp & Dohme., Competing Interests: Declaration of interests All authors' institutions received research funding from Merck Sharp & Dohme, a subsidiary of Merck (Rahway, NJ, USA), for the conduct of this study. BJM was a consultant to or received honoraria from AbbVie, Agenus, Akeso Biopharma, Aravive, AstraZeneca, Clovis Oncology, Eisai, Elevar Therapeutics, EMD Serono, Genentech, Genmab–Seattle Genetics, GlaxoSmithKline, GOG Foundation, Gradalis, ImmunoGen, Incyte Corporation, Iovance Biotherapeutics, Janssen Biotech, Karyopharm Therapeutics, Merck, Mersana Therapeutics, Myriad Genetic Laboratories, Novocure, Pfizer, Pfizer International, Puma Biotechnology, Regeneron Pharmaceuticals, Sorrento Therapeutics, Takeda Development Center Americas, US Oncology, and VBL Therapeutics. KST received research grant to institution, and consultant–speaker's bureau fees from Merck. CD was on an endpoint review committee for Merck. KH was a scientific advisory board member and received honoraria, contracted research and study funding to their institution from Merck Sharp & Dohme. RS-F received speaker honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Sanofi, Roche, Medison, and Neopharm; a research grant to their institution from Merck Sharp & Dohme, and was an advisory board member for Merck Sharp and Dohme, VBL Therapeutics, and Clovis Oncology. PS received research support from Merck and participated in advisory boards for BMS, AstraZeneca, Janssen, and Novartis. MG received speaker's bureau–advisory board fees from Amgen, and received advisory board fees (institutional) from from AstraZeneca, Bristol Myers Squibb, Gilead Sciences, Merck, Novartis, Pfizer, and Takeda Oncology, and travel fees from F Hoffmann-La Roche. VS was a consultant or advisory board member for GlaxoSmithKline and Merck. VC received a grant to institution from AstraZeneca, Bayer, Bayer Healthcare, Bristol Myers Squibb, Merck, Seagen; consultant–advisory board fees from Bristol Myers Squibb, Ipsen Biopharmaceuticals, Merck, Pfizer Canada, and Seagen; and consultant fees from AstraZeneca Canada and Pfizer Canada. CT, KL, AMN, and MJM are employees of Merck Sharp & Dohme and own stock in Merck. NC reports fees for advisory board membership from AstraZeneca, Clovis Oncology, Eisai, GlaxoSmithKline, Immunogen, Mersana, Merck Sharp & Dohme–Merck, Nuvation Bio, Onxerna, Pfizer, PharmaMar, Pieris, Roche; fees as an invited speaker for AstraZeneca, Novartis, Clovis Oncology, GlaxoSmithKline, and Merck–Merck Sharp & Dohme; institutional research grants from AstraZeneca, PharmaMar, and Roche; and non-remunerated activities as member of the ESMO Guidelines Steering Committee and chairs for of the Scientific Committee of Alleanza contro il tumore ovarico. DL was a consultant for Amgen, AstraZeneca, Clovis Oncology, GlaxoSmithKline, Gynecological Cancer InterGroup, Merck Sharp and Dohme, Pharma Mar; received a research grant to institution from AstraZeneca, Clovis Oncology, F Hoffmann-La Roche, Genmab, GlaxoSmithKline, ImmunoGen, Incyte Corporation, Merck, Merck Sharp and Dohme, PharmaMar; and was a data and safety monitoring board member for Novartis. MVC, EY, MOHdM, and AA declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The aggressive basal/squamous (Ba/Sq) bladder cancer (BLCA) subtype is often diagnosed at the muscle-invasive stage and can progress to the sarcomatoid variant. Identification of molecular changes occurring during progression from non-muscle-invasive BLCA (NMIBC) to Ba/Sq muscle-invasive BLCA (MIBC) is thus challenging in human disease. We used the N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) mouse model of Ba/Sq MIBC to study longitudinally the molecular changes leading to the Ba/Sq phenotype and to the sarcomatoid variant using IHC and microdissection followed by RNA-seq at all stages of progression. A shift to the Ba/Sq phenotype started in early progression stages. Pathway analysis of gene clusters with coordinated expression changes revealed Shh signaling loss and a shift from fatty acid metabolism to glycolysis. An upregulated cluster, appearing early in carcinogenesis, showed relevance to human disease, identifying NMIBC patients at risk of progression. Similar to the human counterpart, sarcomatoid BBN tumors displayed a Ba/Sq phenotype and epithelial-mesenchymal transition (EMT) features. An EGFR/FGFR1 signaling switch occurred with sarcomatoid dedifferentiation and correlated with EMT. BLCA cell lines with high EMT were the most sensitive to FGFR1 knockout and resistant to EGFR knockout. Taken together, these findings provide insights into the underlying biology of Ba/Sq BLCA progression and sarcomatoid dedifferentiation with potential clinical implications. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

ESR1 mutation ( ESR1 m) is a frequent cause of acquired resistance to aromatase inhibitor (AI) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which is a first-line therapy for hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that in a phase II study significantly improved progression-free survival (PFS) over fulvestrant (also a SERD) in ER+/HER2- ABC. SERENA-6 (NCT04964934) is a randomized, double-blind, phase III study evaluating the efficacy and safety of switching from an AI to camizestrant, while maintaining the same CDK4/6i, upon detection of ESR1 m in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/HER2- ABC. The aim is to treat ESR1 m clones and extend the duration of control of ER-driven tumor growth, delaying the need for chemotherapy. The primary end point is PFS; secondary end points include chemotherapy-free survival, time to second progression event (PFS2), overall survival, patient-reported outcomes and safety.

Introduction: The objective of this study was to determine whether computed tomography (CT) could be a useful tool for nonsolid lung nodule (NSN) treatment planning, surgery or stereotactic body radiation therapy (SBRT), by assessing the macroscopic and microscopic extension of these nodules., Methods: The study prospectively included 23 patients undergoing anatomic resection at the Foch Hospital in 2020/2021 for NSN with a ground-glass component of more than 50%. Firstly, for each patient, both the macroscopic dimensions of the NSN were assessed on CT and during pathologic analysis. Secondly, the microscopic extension was assessed during pathologic examination. Wilcoxon sign rank tests were used to compare these dimensions. Spearman correlation test and Bland-Altman analysis were used to evaluate the agreement between radiological and pathologic measurements., Results: On CT, the median largest diameter and volume of NSN were 21 mm and 3780 cc, while on pathologic analysis, they were 15 mm and 1800 cc, respectively. Therefore, the largest diameter and volume of the NSN were significantly higher on CT than on pathological analysis. For microscopic extension, the median largest diameter and volume of NSN were 17 mm and 2040 cc, respectively. No significant difference was observed between the macroscopic size and the microscopic extension assessed during pathologic analysis. Moreover, correlation analysis and Bland-Altman plots showed that radiological and pathologic measurements could provide equivalent precision., Conclusion: Our study showed that CT did not underestimate the macroscopic size and microscopic extension of NSN and confirmed that CT can be used for NSN treatment planning., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Bisphenol A is an endocrine disruptor used in the composition of food containers. It was partially banned in France in 2015 and classified as a "very high-risk substance" in 2017. Bisphenol A's carcinogenic effects have been demonstrated in animal testing. Bisphenol A acts through estrogen-dependent and estrogen-independent pathways. It induces epigenetic changes and impacts the microenvironment of the mammary gland. However, the role of bisphenol A exposure in the development of breast cancer in humans remains controversial. This study documents the current thinking on bisphenol A with an analysis of the mechanisms and a meta-analysis., Materials and Methods: A literature review and a statistical analysis of linear regression type, with the creation of a Forest plot, were used to perform the meta-analysis of 9 studies including 10,695 patients., Results: Nine case-control studies, published between 1990 and 2021, investigating the association between breast cancer and mean urinary, blood or tissue bisphenol A levels were selected. The meta-analysis did not find a significant association between bisphenol A exposure and the development of breast cancer with an OR=(1 IC95% [0.92-1.08])., Discussion: This meta-analysis does not show a link between breast cancer and bisphenol A exposure. Nevertheless, the analysis of a pathogenic link between bisphenol A and breast cancer requires additional cohort studies to conclude because of methods of available studies., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objective: To compare the prevalence of contraception in breast cancer (BC) patients at risk of unintentional pregnancy (i.e. not currently pregnant or trying to get pregnant) and matched controls., Study Design: The FEERIC study (Fertility, Pregnancy, Contraception after BC in France) is a prospective, multicenter case-control study, including localized BC patients aged 18-43 years, matched for age and parity to cancer-free volunteer controls in a 1:2 ratio. Data were collected through online questionnaires completed on the Seintinelles research platform., Results: In a population of 1278 women at risk of unintentional pregnancy, the prevalence of contraception at study inclusion did not differ significantly between cases (340/431, 78.9%) and controls (666/847, 78.6%, p = 0.97). Contrarily, the contraceptive methods used were significantly different, with a higher proportion of copper IUD use in BC survivors (59.5% versus 25.0% in controls p < 0.001). For patients at risk of unintentional pregnancy, receiving information about chemotherapy-induced ovary damage at BC diagnosis (OR = 2.47 95%CI [ 1.39-4.37] and anti-HER2 treatment (OR = 2.46, 95% CI [ 1.14-6.16]) were significantly associated with the use of a contraception in multivariate analysis., Conclusion: In this large French study, BC survivors had a prevalence of contraception use similar to that for matched controls, though almost one in five women at risk of unintentional pregnancy did not use contraception. Dedicated consultations at cancer care centers could further improve access to information and contraception counseling., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Bladder cancer detection and follow-up is based on cystoscopy and/or cytology, but it remains imperfect and invasive. Current research focuses on diagnostic biomarkers that could improve bladder cancer detection and follow-up by discriminating patients at risk of aggressive cancer who need confirmatory TURBT (Transurethral Resection of Bladder Tumour) from patients at no risk of aggressive cancer who could be spared from useless explorations., Objective: To perform a systematic review of data on the clinical validity and clinical utility of eleven urinary biomarkers (VisioCyt ® , Xpert ® Bladder, BTA stat ® , BTA TRAK™, NMP22 BC ® , NMP22 ® BladderChek ® Test, ImmunoCyt™/uCyt1+™, UroVysion Bladder Cancer Kit ® , Cxbladder, ADXBLADDER, Urodiag ® ) for bladder cancer diagnosis and for non-muscle invasive bladder cancer (NMIBC) follow-up., Methods: All available studies on the 11 biomarkers published between May 2010 and March 2021 and present in MEDLINE ® were reviewed. The main endpoints were clinical performance for bladder cancer detection, recurrence or progression during NMIBC monitoring, and additional value compared to cytology and/or cystoscopy., Results: Most studies on urinary biomarkers had a prospective design and high level of evidence. However, their results should be interpreted with caution given the heterogeneity among studies. Most of the biomarkers under study displayed higher detection sensitivity compared with cytology, but lower specificity. Some biomarkers may have clinical utility for NMIBC surveillance in patients with negative or equivocal cystoscopy or negative or atypical urinary cytology findings, and also for recurrence prediction., Conclusion: Urinary biomarkers might have a complementary place in bladder cancer diagnosis and NMIBC surveillance. However, their clinical benefit remains to be confirmed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate whether radiomics from [18F]-FDG PET and/or MRI before re-irradiation (reRT) of recurrent head and neck cancer (HNC) could predict the occurrence and the location "in-field" or "outside" of a second locoregional recurrence (LR)., Methods: Among the 55 patients re-irradiated at curative intend for HNC from 2012 to 2019, 48 had an MRI and/or PET before the start of the reRT. Thirty-nine radiomic features (RF) were extracted from the re-irradiated GTV (rGTV) using LIFEx software. Student t tests and Spearman correlation coefficient were used to select the RF that best separate patients who recurred from those who did not, and "in-field" from "outside" recurrences. Principal component analysis involving these features only was used to create a prediction model. Leave-one-out cross-validation was performed to evaluate the models., Results: After a median follow-up of 17 months, 40/55 patients had developed a second LR, including 18 "in-field" and 22 "outside" recurrences. From pre-reRT MRI, a model based on three RF (GLSZM&#95;SZHGLE, GLSZM&#95;LGLZE, and skewness) predicted whether patients would recur with a balanced accuracy (BA) of 83.5%. Another model from pre-reRT MRI based on three other RF (GLSZM&#95; LZHGE, NGLDM&#95;Busyness, and GLZLM&#95;SZE) predicted whether patients would recur "in-field" or "outside" with a BA of 78.5%. From pre-reRT PET, a model based on four RF (Kurtosis, SUVbwmin, GLCM&#95;Correlation, and GLCM&#95;Contrast) predicted the LR location with a BA of 84.5%., Conclusion: RF characterizing tumor heterogeneity extracted from pre-reRT PET and MRI predicted whether patients would recur, and whether they would recur "in-field" or "outside"., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: In France, dispensation is defined by the validation of a prescription associated with a pharmaceutical analysis, preparation of medication and provision of information necessary for proper use. There are very few data available in the literature that describe prescription analysis modality in radiopharmacy. The aim was to secure a place for paediatric prescription analysis in radiopharmacy by designing a flow chart validated by experts., Methods: Experts from different disciplines and health setups (ie, public, private) were selected to represent the various paediatric patient care processes. A review of the literature on pharmaceutical analysis and paediatric prescription in radiopharmacy was conducted. A Delphi approach comprising two rounds (Google Form survey) was used to validate the flow chart. Answers were graded according to a nine-point Likert scale for agreement. Open-ended questions allowed experts to comment on the propositions. A consensus between experts was reached if more than 70% of the experts agreed on an item and fewer than 30% disagreed., Results: Sixty-five experts were solicited: two oncopaediatricians, three nuclear medicine physicians, 46 radiopharmacists, three residents in radiopharmacy, one hospital pharmacist, five medical physicists, one pharmacy technician, two X-ray technicians and two patients who are pharmacists. The first round survey included a draft of the flow chart: 31 experts answered (48%). All professional disciplines were represented except pharmacy technician. The second round survey was sent with a new flow chart that had been improved by the experts' comments. After 3 weeks, 18 answers were obtained (28%). After the first round, consensus was obtained for each item. Experts gave a total of 97 comments. The second flow chart had three steps: regulatory aspects, patient data, and radiopharmaceutical data, and it was accompanied by descriptive text explaining the field of application., Conclusion: The resulting flow chart will secure the pharmaceutical analysis step for this special patient population., Competing Interests: Competing interests: The authors declare that they have no competing interests in this study. The authors declare that they did not receive funding for this study., (© European Association of Hospital Pharmacists 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The diagnosis, histomolecular classes of breast cancers (luminal A, luminal B, HER2-enriched, and basal-like), and accurate prediction of prognosis are commonly determined using morphological and phenotypical analyses in clinical practice worldwide. Therapeutic strategies are mostly based on the disease stage and molecular subclasses of breast cancer. Targeted therapies, such as anti-HER2s, poly-ADP ribose polymerase inhibitors or, to a lesser extent, phosphatidylinositol 3 kinase inhibitors, have substantially improved breast cancer patient prognosis over the past decades. Human epidermal growth factor receptor 2 (HER2) overexpression is widely determined based on immunohistochemistry, while next-generation sequencing (NGS) is currently employed to assess the presence of molecular alterations, including breast cancer gene 1 (BRCA1) and 2 or phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations, which are targets of these new approved therapies. In addition, next-generation sequencing (NGS) can aid the pathologist in challenging situations, such as a diagnostic workup for a metastatic carcinoma in lymph nodes of unknown origin, differential diagnosis of spindle cell tumourtumor in the breast between metaplastic carcinoma, malignant PT and sarcoma, o, as well as determining relatedness between primary breast cancers and recurrences. NGS offers a powerful tool that enables the pathologist to combine morphological analyses together with molecular alterations in challenging diagnostic situations., (© 2022 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Introduction: The COVID-19 pandemic had a profound impact on health-care systems and reduced access to care. This study assays the mid-term effects of the COVID-19 pandemic on breast cancer management over a 2-year-period in a single French Comprehensive Cancer Center., Methods: We performed, in a French comprehensive cancer center, an observational study including all patients with newly diagnosed breast cancer between 2019 and 2021. We collected the number of first consultations for breast cancer, the number of breast and axillary surgeries, pTNM and ypTNM cancer staging, the therapeutic sequence (surgery or neoadjuvant chemotherapy as a primary treatment), patients' age and their place of residence., Results: In total, 14,772 patients had a first consultation for breast cancer. Among these 9058 breast and axillary surgeries were performed, 1798 patients had neoadjuvant chemotherapy as a primary treatment. During the first COVID-19 lockdown ( March17, 2020-May 10, 2020), we observed a reduction in the number of first consultations for breast cancer and breast cancer surgeries giving respectively a 42.3% and 27% rate of change. Subsequently, we observed a resumption of consultations and surgeries with a slight increase in early 2021 compared to 2019. In addition, we did not find any difference in terms of therapeutic sequence, pTNM and ypTNM stages, age at diagnosis or place of residence between the reference year 2019 and the years 2020 and 2021., Conclusion: Our study shows a decrease in activity during the first lockdown of 2020, then a resumption of activity. These reassuring results only concern patients with breast cancer, and are specific to our institution, whose oncology activity was preserved during the COVID-19 pandemic., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Female thyroid cancer survivors are more likely to have a higher risk of breast cancer compared to the general population, and the underlying causes are yet to be understood. The potential role of I-131 treatment on this association remains controversial., Methods: We pooled individual data of women who were treated for differentiated thyroid cancer from 1934 to 2005 in France, Italy and Sweden. Standardized incidence ratios (SIRs) for breast cancer were estimated by comparison with age, sex and calendar-year expected values of the general population in each country. We estimated breast cancer risk in relation to I-131 treatment using time-dependent Poisson models., Results: Of 8475 women (mean age at diagnosis: 45 years, range 2-90 years), 335 were diagnosed with breast cancer [SIR = 1.52, 95% confidence interval (CI): 1.36-1.69] during a median follow-up time of 12.7 years since diagnosis. Overall, breast cancer risk did not differ between women treated or not with I-131 (relative risk=1.07, 95% CI 0.84-1.35). However, breast cancer risk increased with increasing cumulative I-131 activity, without significant departure from linearity (excess relative risk per 100 mCi=17%, 95% CI: 2% to 38%). The higher risk associated with a cumulative I-131 activity of ≥100 mCi and ≥400 mCi was translated into 4 (95% CI -4 to 13) and 42 (95% CI -8 to 93) excess breast cancer cases per 10,000 person-years, respectively., Conclusions: An elevated risk was observed for the highest cumulative administered activity (>=400 mCi), and a significant dose-dependent association was observed among thyroid cancer survivors who were treated with I-131. However, overall, I-131 treatment might only explain partly the increase in breast cancer risk among female thyroid cancer survivors., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Despite an increasing number of therapeutic indications, there are no specific recommendations regarding the management of PARP inhibitors other than what is specified in the SmPC of each substance. A Delphi French consensus was conducted to establish practical guidelines to meet the needs identified by healthcare professionals and patients., Method: Following the Delphi method, statements to optimize PARP inhibitor management were drafted by a multidisciplinary Steering Committee made up of 17 experts. These statements were submitted to the independent and anonymous vote of clinicians involved in treating patients on PARP inhibitors., Results: This article presents 52 statements on the following topics: initiation and treatment; management of adverse events (hematological effects, gastrointestinal effects, renal effects, pulmonary effects, cutaneous effects, hypertension, insomnia, fatigue, dizziness); special populations and situations; communication with the patient; adherence. Forty-nine statements obtained voter consensus after 3 voting rounds. A hematologist and a nephrologist supplemented this task by drafting an expert opinion on the risk of occurrence of secondary leukemia and nephrological toxicity., Conclusions: This paper is the first Delphi consensus on the practical management of PARP inhibitors. The pragmatic recommendations resulting from this paper should make it possible to manage the side effects of PARP inhibitors better and thus prevent early treatment discontinuation and improve patient adherence by preserving quality of life., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Importance: Evidence suggests that patients with human epidermal growth factor receptor 2-positive (ERBB2+ [formerly HER2+]) metastatic breast cancer (MBC) have different clinical characteristics and outcomes according to their hormone receptor (HR) status. The place of endocrine therapy (ET) for patients with HR+/ERBB2+ is still not clearly defined in this setting., Objective: To evaluate the association of HR status and first-line inclusion of ET with outcomes among patients with ERBB2+ MBC., Design, Setting, and Participants: This cohort study was an analysis of clinical data from the French clinical Epidemiological Strategy and Medical Economics (ESME) cohort, including patients with MBC who started treatment between 2008 and 2017. The last date of follow-up was June 18, 2020. Data were analyzed from May 2021 to May 2022., Exposures: Patients were treated with first-line ERBB2-targeted therapy and either chemotherapy (CT) with or without ET or ET alone. For the study of the association of maintenance ET with outcomes, we included patients treated with first-line ERBB2-targeted therapy with CT and with or without maintenance ET., Main Outcomes and Measures: Median overall survival (OS) and median first-line progression-free survival (PFS) were reported using the Kaplan-Meier method. Cox proportional hazards models and a propensity score were constructed to report and adjust for prognostic factors. Multivariable analysis included age at MBC, time to MBC, number of metastatic sites, type of metastases, and Eastern Cooperative Oncology Group performance status., Results: Among 4145 women with ERBB2+ MBC, 2696 patients had HR+ (median [IQR] age, 58.0 [47.0-67.0] years) and 1449 patients had HR- (56.0 [47.0-64.0] years) tumors. The median OS for patients with HR+ vs HR- tumors was 55.9 months (95% CI, 53.7-59.4 months) vs 42.0 months (95% CI, 38.8-45.2 months), confirmed in multivariable analysis (hazard ratio, 1.40; 95% CI, 1.26-1.56; P < .001). The median PFS for patients with HR+ vs HR- tumors was 12.2 months (95% CI, 11.5-12.9 months) vs 9.8 months (95% CI, 9.2-11.0 months; P = .01), and the HR was 1.15 (95% CI, 1.06-1.26; P < .001). In multivariable analysis, no significant difference was found in OS or PFS for 1520 patients treated with ERBB2-targeted therapy with CT and with or without ET vs 203 patients receiving ERBB2-targeted therapy with ET, regardless of type of ERBB2-targeted therapy (trastuzumab or trastuzumab with pertuzumab). This result was confirmed by matching patients using a propensity score. Using the time-dependent ET variable among patients with ERBB2-targeted therapy with CT, those with maintenance ET had significantly better PFS (hazard ratio, 0.70; 95% CI, 0.60-0.82; P < .001) and OS (hazard ratio, 0.47; 95% CI, 0.39-0.57; P < .001)., Conclusions and Relevance: These results suggest that ET-containing first-line regimens may be associated with benefits among a subgroup of patients with HR+/ERBB2+ MBC.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported the results of a randomized phase II study in patients with newly diagnosed primary CNS lymphoma (age 18-60 years). Patients were treated with high-dose methotrexate-based induction chemotherapy followed by whole-brain radiotherapy (WBRT) or high-dose chemotherapy (thiotepa-busulfan-cyclophosphamide) with autologous stem-cell transplantation (ASCT). The median follow-up was 33 months. In this report, we provide long-term data (median follow-up, 8 years) regarding the outcomes and toxicities. Fifty-three and 44 patients received induction chemotherapy followed by WBRT or ASCT, respectively. Their 8-year event-free survival from random assignment was 67% and 39% in the ASCT and WBRT arms, respectively ( P = .03), with a significantly lower risk of relapse after ASCT (hazard ratio, 0.13; P < .001). One third of patients who relapsed after WBRT were alive after salvage treatment. Five and four patients died of ASCT and WBRT-related toxicities, respectively. The 8-year overall survival was 69% and 65% in the ASCT and WBRT arms, respectively (not significant). Balance (52% v 10%, P ≤ 0.001) and neurocognition (64% v 13%, P < .001) significantly deteriorated after WBRT compared with ASCT during the follow-up. This study shows that 40 Gy WBRT should be avoided in first-line treatment because of its neurotoxicity and suboptimal efficacy in reducing relapses while ASCT appears to be highly efficient in preventing relapses.

To optimise management of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection identifying high-risk patients and maintaining treatment dose intensity is an important issue in patients with aggressive lymphomas. In the present study, we report on the presentation, management, and outcome of an international series of 91 patients with primary central nervous system lymphoma and SARS-CoV-2 infection. SARS-CoV-2 was diagnosed before/during first-line treatment in 64 patients, during follow-up in 21, and during salvage therapy in six. Among the 64 patients infected before/during first-line chemotherapy, 38 (59%) developed pneumonia and 26 (41%) did not clear the virus. Prolonged exposure to steroids before viral infection and/or treatment with high-dose cytarabine favoured pneumonia development and virus persistence and were associated with poorer survival; 81% of patients who did not clear virus died early from coronavirus disease 2019 (COVID-19). Vaccination was associated with lower pneumonia incidence and in-hospital mortality. Chemotherapy was initiated/resumed in 43 (67%) patients, more commonly among patients who did not develop pneumonia, cleared the virus, or did not receive steroids during infection. Chemotherapy resumption in patients with viral persistence should be indicated cautiously as it was associated with a poorer survival (6-month, 70% and 87%, p = 0.07). None of the 21 patients infected during follow-up died from COVID-19, requiring similar measures as infected subjects in the general population., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: To analyze outcomes of patients treated with curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for recurrent head and neck squamous cell carcinoma (HNSCC)., Materials: Among the 55 patients reirradiated for head and neck cancer from 30/08/2012 to 08/04/2019, 23 had HNSCC and received IMRT (52.2%) or PT (47.8%) at a median maximum dose to the CTV of 66 Gy., Results: After a median follow-up of 41.3 months, 18 patients developed a locoregional recurrence (LR), of which eight (44.4%) occurred within the previously reirradiated volume. Two-year locoregional failure-free survival and overall survival were 18.3%[95%CI:7.1%-47.1%] and 42.5%[95%CI:26.2%-69.1%], respectively. Disease-free survival was significantly longer in the PT group (p = 0.031). Main late grade ≥2 toxicities were dysphagia and trismus., Conclusion: Curative reRT in HNSCC is possible for selected cases, but the LR rate in the irradiated field and the risk of toxicity grade ≥2 remain high., (© 2022 Wiley Periodicals LLC.)

Skin damage is the most common and most important toxicity during and after radiation therapy (RT). Its assessment and understanding of the factors influencing its occurrence, is a major issue in the management of patients irradiated for an early breast cancer. CANTO is a prospective clinical cohort study of 10 150 patients with stage I-III BC treated from 2012 to 2017 in 26 cancer centres. In our study, we used CANTO-RT, a subcohort of CANTO, including 3480 patients who received RT. We are focus on specific skin toxicities: erythema, fibrosis, telangiectasia and cutaneous pigmentation. The prevalence of toxicities of interest varied over time, so at baseline for early toxicity Month (M) 0-3-6, 41.1% of patients had erythema while 24.8% of patients had fibrosis. At M12 and M36, the prevalence of erythema decreased, respectively, while fibrosis remains stable. The prevalence of telangiectasia increases from 1% to 7.1% from M0-3-6 to M36. After adjustments, we showed an association between the occurrence of skin erythema and obesity; the type of surgery; the presence of axillary dissection; the use of taxane-based CT and the 3D vs IMRT irradiation technique. Regarding fibrosis, an association is found, at M0-3-6, with age at diagnosis, obesity, tobacco and the use of boost. Only obesity and the type of surgery received by the patient remained statistically significant at M12 and M36. In our study we identified several risk factors for acute and late skin reactions. The use of a boost was mainly related to the occurrence of fibrosis while the use of IMRT-type technique decreased the occurrence of skin erythema., (© 2022 UICC.)

Cancer progression is driven in part by genomic alterations 1 . The genomic characterization of cancers has shown interpatient heterogeneity regarding driver alterations 2 , leading to the concept that generation of genomic profiling in patients with cancer could allow the selection of effective therapies 3,4 . Although DNA sequencing has been implemented in practice, it remains unclear how to use its results. A total of 1,462 patients with HER2-non-overexpressing metastatic breast cancer were enroled to receive genomic profiling in the SAFIR02-BREAST trial. Two hundred and thirty-eight of these patients were randomized in two trials (nos. NCT02299999 and NCT03386162) comparing the efficacy of maintenance treatment 5 with a targeted therapy matched to genomic alteration. Targeted therapies matched to genomics improves progression-free survival when genomic alterations are classified as level I/II according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) 6 (adjusted hazards ratio (HR): 0.41, 90% confidence interval (CI): 0.27-0.61, P < 0.001), but not when alterations are unselected using ESCAT (adjusted HR: 0.77, 95% CI: 0.56-1.06, P = 0.109). No improvement in progression-free survival was observed in the targeted therapies arm (unadjusted HR: 1.15, 95% CI: 0.76-1.75) for patients presenting with ESCAT alteration beyond level I/II. Patients with germline BRCA1/2 mutations (n = 49) derived high benefit from olaparib (gBRCA1: HR = 0.36, 90% CI: 0.14-0.89; gBRCA2: HR = 0.37, 90% CI: 0.17-0.78). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with metastatic breast cancer., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Higher consumption of coffee and tea has been associated with improved health outcomes in the general population and improved breast cancer (BC) prognosis. This study investigated patterns of coffee and tea consumption and association with patient-reported outcomes (PROs) and clinical outcomes among survivors of BC., Methods: The authors included survivors of stage I-III BC enrolled in the CANTO cohort (NCT01993498) that provided post-treatment assessment of coffee and tea consumption from years 1 to 4 after diagnosis. Group-based trajectory modeling clustered patients according to daily consumption of coffee and tea. Multivariable mixed models and Cox models examined associations between consumption, PROs and clinical outcomes., Results: Among 3788 patients, the authors identified four stable patterns of consumption: "Low" (25.8%), "Moderate" (37.6%), "High" (25.3%), and "Very high" (11.3%), corresponding to <1, 2, 3, and ≥ 4 cups of coffee and/or tea per day. Patients in the "Very high" group (vs. "Low"), were more likely to be younger, smokers, with higher monthly income and education. PROs and survival outcomes were similar across the four groups., Conclusions: Over one in three survivors of BC reported high or very high consumption of coffee and/or tea. The authors found no association between higher consumption of coffee and/or tea, worse PROs and clinical outcomes., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: The IONESCO (IFCT-1601) trial assessed the feasibility of neoadjuvant durvalumab, for early-stage resectable non-small-cell lung cancer (NSCLC)., Methods: In a multicenter, single-arm, phase II trial, patients with IB (≥4 cm)-IIIA, non-N2, resectable NSCLC received three doses of durvalumab (750 mg every 2 weeks) and underwent surgery between 2 and 14 days after the last infusion. The primary endpoint was the complete surgical resection rate. Secondary endpoints included tumor response rate, major histopathological response (MPR: ≤10% remaining viable tumor cells), disease-free survival (DFS), overall survival (OS), durvalumab-related safety, and 90-day postoperative mortality (NCT03030131)., Results: Forty-six patients were eligible (median age 60.9 years); 67% were male, 98% were smokers, and 41% had squamous cell carcinoma. Regarding tumor response, 9% had a partial response, 78% had stable disease, and 13% had progressive disease. Among the operated patients (n=43), 41 achieved complete resection (89%, 95% CI 80.1% to 98.1%)), and eight achieved MPR (19%). The 12-month median OS and DFS rates were 89% (95% CI 75.8% to 95.3%) and 78% (95% CI 63.4% to 87.7%), respectively (n=46). The median follow-up was 28.4 months (12.8-41.1). All patients in whom MPR was achieved were disease-free at 12 months compared to only 11% of those with &gt;10% residual tumor cells (p=0.04). No durvalumab-related serious or grade 3-5 events were reported. The unexpected 90-day postoperative mortality of four patients led to premature study termination. None of these four deaths was considered secondary to direct durvalumab-related toxicity., Conclusions: Neoadjuvant durvalumab given as monotherapy was associated with an 89% complete resection rate and an MPR of 19%. Despite an unexpectedly high rate of postoperative deaths, which prevented us from completing the trial, we were able to show a significant association between MPR and DFS., Competing Interests: Competing interests: Marie Wislez, reports grants from Astra-Zeneca, honoraria for speaker’s bureau from Roche, Bristol Myers Squibb and Boehringer Ingelheim, participation on a Data Safety Monitoring Board or Advisory Board from Astra-Zeneca, Merck Sharp and Dohme and Novartis, non-financial interests from Astra-Zeneca, Bristol Myers Squibb, Merck Sharp and Dohme, Novartis, Lilly Merck KgA, Merus, GlaxoSmithKline and Amgen, outside the submitted work. Julien Mazières reports honoraria for lectures from Bristol Myers Squibb, Roche Genentech, Astra-Zeneca and Merck Sharp and Dohme, outside the submitted work. Gérard Zalcman reports grants from Roche and Bristol Myers Squibb, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra-Zeneca and Bristol Myers Squibb, support for attending meetings and/or travel from Astra-Zeneca, Abbvie, Bristol Myers Squibb and Pfizer, participation on a Data Safety Monitoring Board or Advisory Board from Astra-Zeneca, Inventiva, Da Volterra and Bristol Myers Squibb, outside the submitted work. Olivier Molinier reports participation on a Data Safety Monitoring Board or Advisory Board from Astra-Zeneca, outside the submitted work. Virginie Westeel reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra-Zeneca, Bristol Myers Squibb, Merck Sharp and Dohme and Roche, Support for attending meetings and/or travel from Astra-Zeneca, Bristol Myers Squibb, Merck Sharp and Dohme, Pfizer and Roche, Participation on a Data Safety Monitoring Board or Advisory Board from Astra-Zeneca, Bristol Myers Squibb, Merck Sharp and Dohme, Takeda and Roche, outside the submitted work. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The prognosis of poorly differentiated thyroid carcinomas (PDTC) defined by the Turin criteria is variable. The aim of this study on 51 PDTC patients was to determine clinical, histological and molecular prognostic factors associated with recurrence in patients with localized disease at initial treatment and with overall survival in patients with distant metastases. Of 40 patients for whom next-generation sequencing (NGS) by ThyroSeq v3 was able to be performed on historical samples, we identified high-risk molecular signature (TERT, TP53 mutations) in 24 (60%) cases, intermediate risk signature in 9 (22.5%) cases and low-risk signature in 7 (17.5%) cases. Potentially actionable mutations were identified in 10% of cases. After a median follow-up of 57.5 months, recurrence occurred in 11 (39%) of the 28 patients with localized disease. The American Thyroid Association (ATA) high risk of relapse, high mitotic count, high molecular risk signature and CD163 expression were associated with recurrence (P = 0.009, 0.01, 0.049, 0.03 respectively). After a median follow-up of 49.5 months, thyroid cancer-related death occurred in 53% of the patients with distant metastases. There was no significant prognostic factor associated with death in univariate analysis. However, none of the patients with intermediate ATA risk of recurrence and none of the patients with low-risk molecular signature died from the disease. In addition, high molecular-risk signature was associated with the presence of synchronous or metachronous distant metastasis (P = 0.007) and with poor overall survival (P = 0.01). In conclusion, ATA risk of relapse and high mitotic count was associated with higher rate of recurrence in localized PDTC. High molecular-risk signature was associated with the presence of distant metastasis and poor overall survival. Further studies are needed to determine if molecular testing adds to ATA risk stratification or response to therapy in predicting outcomes.

Purpose: We aimed to characterize long-term quality of life (QOL) trajectories among patients with breast cancer treated with adjuvant chemotherapy and to identify related patterns of health behaviors., Methods: Female stage I-III breast cancer patients receiving chemotherapy in CANTO (CANcer TOxicity; ClinicalTrials.gov identifier: NCT01993498) were included. Trajectories of QOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 Summary Score) and associations with trajectory group membership were identified by iterative estimations of group-based trajectory models and multivariable multinomial logistic regression, respectively., Results: Four trajectory groups were identified (N = 4,131): excellent (51.7%), very good (31.7%), deteriorating (10.0%), and poor (6.6%) QOL. The deteriorating trajectory group reported fairly good baseline QOL (mean [95% CI], 78.3/100 [76.2 to 80.5]), which significantly worsened at year-1 (58.1/100 [56.4 to 59.9]) and never recovered to pretreatment values through year-4 (61.1/100 [59.0 to 63.3]) postdiagnosis. Healthy behaviors were associated with better performing trajectory groups. Obesity (adjusted odds ratio [aOR] v lean, 1.51 [95% CI, 1.28 to 1.79]; P < .0001) and current smoking (aOR v never, 1.52 [95% CI, 1.27 to 1.82]; P < .0001) at diagnosis were associated with membership to the deteriorating group, which was also characterized by a higher prevalence of patients with excess body weight and insufficient physical activity through year-4 and by frequent exposure to tobacco smoking during chemotherapy. Additional factors associated with membership to the deteriorating group included younger age (aOR, 1-year decrement 1.01 [95% CI, 1.01 to 1.02]; P = .043), comorbidities (aOR v no, 1.22 [95% CI, 1.06 to 1.40]; P = .005), lower income (aOR v wealthier households, 1.21 [95% CI, 1.07 to 1.37]; P = .002), and endocrine therapy (aOR v no, 1.14 [95% CI, 1.01 to 1.30]; P = .047)., Conclusion: This latent-class analysis identified some patients with upfront poor QOL and a high-risk cluster with severe, persistent postchemotherapy QOL deterioration. Screening relevant patient-level characteristics may inform tailored interventions to mitigate the detrimental impact of chemotherapy and preserve QOL, including early addressal of behavioral concerns and provision of healthy lifestyle support programs.

Centrosome amplification, the presence of more than two centrosomes in a cell is a common feature of most human cancer cell lines. However, little is known about centrosome numbers in human cancers and whether amplification or other numerical aberrations are frequently present. To address this question, we have analyzed a large cohort of primary human epithelial ovarian cancers (EOCs) from 100 patients. We found that rigorous quantitation of centrosome number in tumor samples was extremely challenging due to tumor heterogeneity and extensive tissue disorganization. Interestingly, even if centrosome clusters could be identified, the incidence of centrosome amplification was not comparable to what has been described in cultured cancer cells. Surprisingly, centrosome loss events where a few or many nuclei were not associated with centrosomes were clearly noticed and overall more frequent than centrosome amplification. Our findings highlight the difficulty of characterizing centrosome numbers in human tumors, while revealing a novel paradigm of centrosome number defects in EOCs., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Importance: As life span has increased among patients with cancer, survivorship has become an important component of breast cancer care. Among survivorship concerns, adequate contraceptive counseling is needed for premenopausal patients who are not seeking to become pregnant., Objective: To examine contraceptive use and chosen methods and to assess factors associated with contraceptive use over time in patients with early breast cancer., Design, Setting, and Participants: The Cancer Toxicity (CANTO) study was a multicenter nationwide prospective cohort study that enrolled women diagnosed with stage I to stage III breast cancer in France between March 2012 and December 2017. This analysis included 2900 premenopausal women who were 50 years of age or younger at diagnosis. Data were analyzed from July 2020 to July 2022., Exposures: Contraceptive use and method at diagnosis, shortly after the end of primary treatment (year 1), and during follow-up (year 2)., Main Outcomes and Measures: Contraceptive use and methods were longitudinally evaluated at diagnosis, year 1, and year 2 after breast cancer diagnosis. Multivariable logistic regression models were used to assess the associations of clinical, socioeconomic, treatment, adverse effect, and patient-reported outcome variables with contraceptive use after diagnosis., Results: A total of 2900 patients (mean [SD] age, 43.1 [5.6] years) were included in the analysis; 2050 of 2894 women (70.8%) received chemotherapy, and 2305 of 2880 women (80.0%) received endocrine therapy. After diagnosis, 1182 of 2625 patients (45.0%) at year 1 and 1553 of 2363 patients (65.7%) at year 2 reported consulting with a gynecologist in the previous year. At diagnosis, 1487 of 2744 patients (54.2%) reported contraceptive use, with most patients (921 of 1470 women [62.7%]) using hormonal methods. The use of contraception significantly decreased after diagnosis (911 of 2342 patients [38.9%] at year 1 and 808 of 1961 patients [41.2%] at year 2; P < .001 for trend), when most patients (848 of 900 women [94.2%] at year 1 and 767 of 805 women [95.3%] at year 2) reported use of nonhormonal methods; these methods were primarily reversible mechanical approaches (copper intrauterine devices: 656 of 848 patients [77.4%] at year 1 and 577 of 767 patients [75.2%] at year 2; male condoms: 115 of 848 patients [13.6%] at year 1 and 110 of 767 patients [14.3%] at year 2). In the multivariable model, factors significantly associated with contraceptive use at year 1 included using contraception at diagnosis (adjusted odds ratio [aOR], 4.02; 95% CI, 3.15-5.14), being younger (aOR, 1.09; 95% CI, 1.07-1.13 per decreasing year), having better sexual function (aOR, 1.13; 95% CI, 1.07-1.19 per 10-point increment), having children (aOR, 4.21; 95% CI, 1.80-9.86), reporting the presence of leukorrhea (aOR, 1.32; 95% CI, 1.03-1.70), receiving tamoxifen treatment alone (aOR, 1.39; 95% CI, 1.01-1.92), and consulting with a gynecologist in the previous year (aOR, 1.29; 95% CI, 1.02-1.63). Similar factors were associated with contraceptive use at year 2, with the addition of partnered status (aOR, 1.61; 95% CI, 1.07-2.44)., Conclusions and Relevance: Findings from this study support the importance of raising awareness and improving targeted contraceptive counseling for premenopausal women with early breast cancer.

Background: Regular physical activity is associated with improved symptom control in patients with breast cancer but its association with chemotherapy completion or response is unclear., Methods: Using a prospective design, 1075 breast cancer patients receiving neoadjuvant chemotherapy between March 2012 and February 2017 were studied. Physical activity was assessed using the Global Physical Activity Questionnaire [GPAQ-16], quantified in standardised MET-h/wk. Chemotherapy completion was defined as the proportion of patients completing planned treatment course, requiring dose reduction, or requiring dose delay. Response was evaluated by pathologic complete response (pCR). Associations between physical activity and primary outcomes were assessed using multivariable logistic regression models., Results: There was no differences between any chemotherapy completion outcome on the basis of physical activity classification. The percent of patients not completing planned treatment was 5.7% for ≦0.33 MET-h/wk, compared with 6.8% for 0.34-16.65 MET-h/wk, and 4.6% for ≥16.6 MET-h/wk (p = 0.52). No significant relationships were observed between physical activity dose classification and pCR for the overall cohort or upon stratification by clinical subtype., Conclusion: Future studies are required to further investigate the relationship between pre-treatment levels of physical activity and function on treatment completion and response in breast and other cancer populations., Clinical Trial Registration: NCT01993498., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The benefit of chemotherapy for older patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC) is a key area of debate. Gene expression profiling (GEP) may identify patients deriving benefit, but their predictive role has not been established for older adults. We summarise evidence on efficacy, safety, and quality-of-life impacts of chemotherapy and on GEP use and impact in older HR-positive, HER2-negative EBC patients., Methods: We conducted a literature search of PubMed and Embase on publications describing prospective studies evaluating chemotherapy in older adults with HR-positive, HER2-negative EBC and on publications describing retrospective and prospective studies evaluating GEP in older adults., Results: Eight publications on chemotherapy use, including 2,035 older patients with EBC were selected. Only one trial evaluated chemotherapy survival benefits in older adults, showing no benefit. Of four studies comparing different regimens, only one showed the superiority of taxanes versus anthracyclines alone. Those investigating alternative regimens did not show improvements over standard regimens despite significant limitations. Five publications on GEP, including 445,323 older patients, were included and investigated Oncotype DX. Limited evidence shows that GEP aids treatment decisions in this population. GEP was offered less frequently to older versus younger patients. Higher Recurrence Score was prognostic for distant recurrence, but chemotherapy did not improve prognosis., Conclusions: In older patients with HR-positive, HER2-negative, chemotherapy survival benefits EBC are unclear and GEP is less used. Although its prognostic role is well established, its predictive role remains unknown., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: NMLB has received advisory fees from Pfizer and Sanofi, speaker fees from Pfizer, Sanofi, Roche and AbbVie and travel grants from Pfizer, Lilly and Genomic Health. AR has received advisory board and speaker fees from Roche, AZ, Seagen, Novartis, Pfizer, MSD and Lilly. MB has received speaker fees from Lilly, and travel grants from Pfizer. LB has received advisory board and speaker fees from AstraZeneca, Daiichi-Sankyo, Celgene, Eisai, Genomic Health, Ipsen, Lilly, Novartis, Pfizer, Pierre Fabre, Puma Biotechnology, Roche, Takeda. HW's institution received financial compensation on his behalf for advisory boards and lecture fees from Immutep Pty, MSD, AstraZeneca Ireland, Daiichi, AbbVie, Lilly, PSI CRO AG, KCE, EISAI, AstraZeneca, Roche, Congres care, Pfizer, ARIEZ, Sirtex, TRM Oncology, ORION Corporation, Novartis, Biocartes and Puma Biotech. HW's institution received an unrestricted research grant on his behalf from Roche and he received travel support from Pfizer and Roche. EB has received travel supports from AstraZeneca, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, honoraria or consultation fees from BMS, Eli Lilly, G1 Therapeutics, Pfizer, Sandoz and Seagen. KLC has received advisory fees from Genomic Health and consulting fees from Roche. SML is supported by the NCI Cancer Center Support Grant (P30CA008748). The remaining authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: At the start of 2021, oncologists lacked the necessary scientific knowledge to adapt their clinical practices optimally when faced with cancer patients refusing or reluctant to be vaccinated against COVID-19, despite the marked vulnerability of these patients to severe, and even fatal forms of this new viral infectious disease. Oncologists at Foch Hospital were confronted with this phenomenon, which was observed worldwide, in both the general population and the population of cancer patients., Methods: Between April and November 2021, the Ethics and Oncology Departments of Foch Hospital decided to investigate this subject, through an empirical and interdisciplinary study in bioethics. Our scientific objective was to try to identify and resolve the principal bio-ethical issues, with a view to improving clinical practices in oncology during future major pandemics of this kind, from a highly specific bio-ethical standpoint (= quality of life/survival). We used a mainly qualitative methodological approach based on questionnaires and interviews., Results: In April 2021, 29 cancer patients refused or were reluctant to be vaccinated (5.6%; 29/522). Seventeen of these patients said that making vaccination mandatory would have helped them to accept vaccination. In October 2021, only 10 cancer patients continued to maintain their refusal (1.9%; 10/522). One of the main reasons for the decrease in refusals was probably the introduction of the "pass sanitaire" (health pass) in July 2021, which rendered vaccination indispensable for many activities. However, even this was not sufficient to convince these 10 cancer patients., Conclusion: We identified a key bio-ethical issue, which we then tried to resolve: vaccination policy. We characterized a major tension between "the recommendation of anti-COVID-19 vaccination" (a new clinical practice) and "free will" (a moral value), and the duty to "protect each other" (a moral standard). Mandatory vaccination, at least in France, could resolve this tension, with positive effects on quality of life (i.e. happiness), or survival, in cancer patients initially refusing or reluctant to be vaccinated, but only if collective and individual scales are clearly distinguished., (© 2022. The Author(s).)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Muscle-invasive bladder cancer (MIBC) and upper urinary tract urothelial carcinoma (UTUC) are molecularly heterogeneous. Despite chemotherapies, immunotherapies, or anti-fibroblast growth factor receptor (FGFR) treatments, these tumors are still of a poor outcome. Our objective was to develop a bank of patient-derived xenografts (PDXs) recapitulating the molecular heterogeneity of MIBC and UTUC, to facilitate the preclinical identification of therapies., Methods: Fresh tumors were obtained from patients and subcutaneously engrafted into immune-compromised mice. Patient tumors and matched PDXs were compared regarding histopathology, transcriptomic (microarrays), and genomic profiles [targeted Next-Generation Sequencing (NGS)]. Several PDXs were treated with chemotherapy (cisplatin/gemcitabine) or targeted therapies [FGFR and epidermal growth factor (EGFR) inhibitors]., Results: A total of 31 PDXs were established from 1 non-MIBC, 25 MIBC, and 5 upper urinary tract tumors, including 28 urothelial (UC) and 3 squamous cell carcinomas (SCCs). Integrated genomic and transcriptomic profiling identified the PDXs of three different consensus molecular subtypes [basal/squamous (Ba/Sq), luminal papillary, and luminal unstable] and included FGFR3 -mutated PDXs. High histological and genomic concordance was found between matched patient tumor/PDX. Discordance in molecular subtypes, such as a Ba/Sq patient tumor giving rise to a luminal papillary PDX, was observed (n=5) at molecular and histological levels. Ten models were treated with cisplatin-based chemotherapy, and we did not observe any association between subtypes and the response. Of the three Ba/Sq models treated with anti-EGFR therapy, two models were sensitive, and one model, of the sarcomatoid variant, was resistant. The treatment of three FGFR3-mutant PDXs with combined FGFR/EGFR inhibitors was more efficient than anti-FGFR3 treatment alone., Conclusions: We developed preclinical PDX models that recapitulate the molecular heterogeneity of MIBCs and UTUC, including actionable mutations, which will represent an essential tool in therapy development. The pharmacological characterization of the PDXs suggested that the upper urinary tract and MIBCs, not only UC but also SCC, with similar molecular characteristics could benefit from the same treatments including anti-FGFR for FGFR3-mutated tumors and anti-EGFR for basal ones and showed a benefit for combined FGFR/EGFR inhibition in FGFR3-mutant PDXs, compared to FGFR inhibition alone., Competing Interests: Author’s CB, ML, YM and PL were employed by Urosphere and author FD was employed by Inovarion, Institut Curie, Strasbourg University and Urosphere have a collaboration contract for the transcriptomic, genomic, and pharmacological characterization of the PDX. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lang, Béraud, Cabel, Fontugne, Lassalle, Krucker, Dufour, Groeneveld, Dixon, Meng, Kamoun, Chapeaublanc, De Reynies, Gamé, Rischmann, Bieche, Masliah-Planchon, Beaurepere, Allory, Lindner, Misseri, Radvanyi, Lluel, Bernard-Pierrot and Massfelder.)

Despite unprecedented amount of information now available in medical records, health data remain underexploited due to their heterogeneity and complexity. Simple charts and hypothesis-driven statistics can no longer apprehend the content of information-rich clinical data. There is, therefore, a clear need for powerful interactive visualization tools enabling medical practitioners to perceive the patterns and insights gained by state-of-the-art machine learning algorithms. Here, we report an interactive graphical interface for use as the front end of a machine learning causal inference server (MIIC), to facilitate the visualization and comprehension by clinicians of relationships between clinically relevant variables. The widespread use of such tools, facilitating the interactive exploration of datasets, is crucial both for data visualization and for the generation of research hypotheses. We demonstrate the utility of the MIIC interactive interface, by exploring the clinical network of a large cohort of breast cancer patients treated with neoadjuvant chemotherapy (NAC). This example highlights, in particular, the direct and indirect links between post-NAC clinical responses and patient survival. The MIIC interactive graphical interface has the potential to help clinicians identify actionable nodes and edges in clinical networks, thereby ultimately improving the patient care pathway., (© 2022. The Author(s).)

Background and Purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group., Materials and Methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two., Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines., Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

We aimed to predict the presence of vaccine-induced hypermetabolic lymph nodes (v-HLNs) on 18 F-FDG PET/CT after coronavirus disease 2019 (COVID-19) vaccination and determine their association with lymphocyte counts. Methods: In this retrospective single-center study, we included consecutive patients who underwent 18 F-FDG PET/CT imaging after messenger RNA- or viral vector-based COVID-19 vaccination between early March and late April 2021. Demographics, clinical parameters, and absolute lymphocyte count (ALC) were collected, and their association with the presence of v-HLNs in the draining territory was studied by logistic regression. Results: In total, 260 patients were eligible, including 209 (80%) women and 145 (56%) with breast cancer. The median age was 50 y (range, 23-96 y). The messenger RNA vaccine had been given to 233 (90%). Ninety (35%) patients had v-HLNs, with a median SUV max of 3.7 (range, 2.0-26.3), and 74 (44%) displayed lymphopenia, with a median ALC of 1.4 × 10 9 /L (range, 0.3-18.3 × 10 9 /L). An age of no more than 50 y (odds ratio [OR], 2.2; 95% CI, 1.0-4.5), the absence of lymphopenia (OR, 2.2; 95% CI, 1.1-4.3), and less than a 30-d interval from the last vaccine injection to the 18 F-FDG PET/CT (OR, 2.6; 95% CI, 1.3-5.6) were independent factors for v-HLNs on multivariate analysis. In breast cancer patients, the absence of lymphopenia was the only independent factor significantly associated with v-HLNs (OR, 2.9; 95% CI, 1.2-7.4). Conclusion: Patients with a normal ALC after COVID-19 vaccination were more likely to have v-HLNs on 18 F-FDG PET/CT, both of which might be associated with a stronger immune response to vaccination., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

A prevalence of around 26% of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has been previously reported. HPV induced oncogenesis mainly involving E6 and E7 viral oncoproteins. In some cases, HPV viral DNA has been detected to integrate with the host genome and possibly contributes to carcinogenesis by affecting the gene expression. We retrospectively assessed HPV integration sites and signatures in 80 HPV positive patients with HNSCC, by using a double capture-HPV method followed by next-generation Sequencing. We detected HPV16 in 90% of the analyzed cohort and confirmed five previously described mechanistic signatures of HPV integration [episomal (EPI), integrated in a truncated form revealing two HPV-chromosomal junctions colinear (2J-COL) or nonlinear (2J-NL), multiple hybrid junctions clustering in a single chromosomal region (MJ-CL) or scattered over different chromosomal regions (MJ-SC) of the human genome]. Our results suggested that HPV remained episomal in 38.8% of the cases or was integrated/mixed in the remaining 61.2% of patients with HNSCC. We showed a lack of association of HPV genomic signatures to tumour and patient characteristics, as well as patient survival. Similar to other HPV associated cancers, low HPV copy number was associated with worse prognosis. We identified 267 HPV-human junctions scattered on most chromosomes. Remarkably, we observed four recurrent integration regions: PDL1/PDL2/PLGRKT (8.2%), MYC/PVT1 (6.1%), MACROD2 (4.1%) and KLF5/KLF12 regions (4.1%). We detected the overexpression of PDL1 and MYC upon integration by gene expression analysis. In conclusion, we identified recurrent targeting of several cancer genes such as PDL1 and MYC upon HPV integration, suggesting a role of altered gene expression by HPV integration during HNSCC carcinogenesis., (© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Purpose: The optimal salvage pelvic treatment for nodal recurrences in prostate cancer is not yet clearly defined. We aimed to compare outcomes of salvage involved-field radiation therapy (s-IFRT) and salvage extended-field radiation therapy (s-EFRT) for positron emission tomography/computed tomography-positive nodal-recurrent prostate cancer and to analyze patterns of progressions after salvage nodal radiation therapy., Methods and Materials: Patients with 18 F-fluorocholine or 68 Ga prostate-specific membrane antigen ligand positron emission tomography/computed tomography-positive nodal-recurrent prostate cancer and treated with s-IFRT or s-EFRT were retrospectively selected. Time to biochemical failure, time to palliative androgen deprivation therapy (ADT), and distant metastasis-free survival were analyzed., Results: Between 2009 and 2019, 86 patients were treated with salvage nodal radiation therapy: 38 with s-IFRT and 48 with s-EFRT. After a median follow-up of 41.9 months (5.4-122.1 months), 47 patients presented a further relapse: 31 after s-IFRT and 16 after s-EFRT, with only 1 in-field relapse. The median time to palliative ADT was 24.8 months (95% confidence interval [CI], 13.3-93.5 months) in the s-IFRT group and not yet reached (95% CI, 40.3 months to not yet reached) in the s-EFRT group ( P  = .010). The 3-year biochemical failure-free rate was 70.2% (95% CI, 51.5%-82.9%) with s-IFRT and 73.9% (95% CI, 55.4%-85.7%) with s-EFRT ( P  = .657). The 3-year distant metastasis-free survival was 74.1% (95% CI, 56.0%-85.7%) with s-IFRT and 82.0% (95% CI, 63.0%-91.8%) with s-EFRT ( P  = .338)., Conclusions: s-EFRT and s-IFRT for positron emission tomography-positive nodal-recurrent prostate cancer provide excellent local control. Time to palliative ADT was longer following s-EFRT than following s-IFRT., (© 2022 The Author(s).)

Background: The optimal treatment duration of ICIs for patients with advanced NSCLC remains uncertain. In phase 3 clinical trials, treatment continued for 2 years or until disease progression with similar long-term survival rates. Real-life data are missing., Patients and Methods: This academic multicentric retrospective study aims at analyzing the characteristics of patients who discontinued treatment after at least 18 months of ICI monotherapy, in the setting of controlled disease., Results: Of the 1127 patients treated with immunotherapy in the given period in six centers, 107 patients had their tumor controlled after at least 18 months of treatment and 54 (50%) of them had discontinued ICI. The median duration of treatment was 26 months. Treatment was stopped due to prescriber choice or toxicity in 46% and 22% of cases, respectively. After a median follow-up of 21 months from ICI discontinuation (95% CI 15.0-26.1 months), 18 (33%) patients experienced tumor progression after a median time of 10.0 months (range 2-33). From discontinuation, 12-month overall survival (OS) and progression-free survival (PFS) were 90% (95% CI 77.7-95.7) and 71% (95% CI 56.8-81.5), respectively; 24-month OS and PFS were 84% (95% CI 68.7-92.2) and 63% (95% CI 46.1-76.2), respectively. Duration of disease control after ICI discontinuation was correlated with tumor response at treatment discontinuation: PFS rate at 12 months was 76% after complete response (CR n = 11) or partial response (PR n = 37) and 22% after only stable disease (SD n = 6) as best response, p-value = 0.0002. PFS rate at 12 months was 80% for CR and/or complete metabolic response with 18F-FDG PET/CT (CMR) and 65% for others. Fourteen patients out of the 18 relapse patients received a subsequent treatment: seven with ICI rechallenge (best response 14% PR and 86% SD) and five with localized therapy with 60% CR., Conclusions: This real-life study provides new insight into long-term outcomes of patients with advanced NSCLC treated with ICI for at least 18 months before treatment discontinuation in the absence of PD. Tumor response and CMR with FDG PET just before therapy discontinuation may be a predictive factor of prolonged disease control upon discontinuation. These results call for caution in discontinuing treatment in patients with stable disease as the best response., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Gene fusions provide access to new therapeutic opportunities for patients treated for a colorectal cancer (CRC). However, they do not excess 1% of patients. A better identification of patients in whom gene fusions are highly prevalent is a major issue in a therapeutic and medico-economics perspective. This study assesses the rates of gene fusions in CRC patients with MSI/RAS-BRAF WT in our routine practice detected with a commercially available NGS-based fusion panel. Among the 130 MSI CRC tumors, 43 (33%) were KRAS-NRAS-BRAF WT . A gene fusion was detected in 7 (25.9%) of the 27 MSI/RAS-BRAF WT samples, which had RNA suitable for analysis after quality control. These fusions involved mainly NTRK1/3 (n = 5), as well as ALK (n = 1) and BRAF (n = 1). In the present study, we confirm that patients with MSI/RAS-BRAF WT CRCs represent a subpopulation in which targetable gene fusions are overrepresented. Our results support the use of a two-step algorithm for molecular screening, in which metastatic CRC patients would have routine MSI and RAS/BRAF testing, and then only those with MSI/RAS-BRAFWT would be screened with dedicated NGS RNA panel for gene fusions., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Fatigue is recognized as one of the most burdensome and long-lasting adverse effects of cancer and cancer treatment. We aimed to characterize long-term fatigue trajectories among breast cancer survivors., Methods: We performed a detailed longitudinal analysis of fatigue using a large ongoing national prospective clinical study (CANcer TOxicity, ClinicalTrials.gov identifier: NCT01993498) of patients with stage I-III breast cancer treated from 2012 to 2015. Fatigue was assessed at diagnosis and year 1, 2, and 4 postdiagnosis. Baseline clinical, sociodemographic, behavioral, tumor-related, and treatment-related characteristics were available. Trajectories of fatigue and risk factors of trajectory-group membership were identified by iterative estimates of group-based trajectory models., Results: Three trajectory groups were identified for severe global fatigue (n = 4,173). Twenty-one percent of patients were in the high -risk group, having risk estimates of severe global fatigue of 94.8% (95% CI, 86.6 to 100.0) at diagnosis and 64.6% (95% CI, 59.2 to 70.1) at year 4; 19% of patients clustered in the deteriorating group with risk estimates of severe global fatigue of 13.8% (95% CI, 6.7 to 20.9) at diagnosis and 64.5% (95% CI, 57.3 to 71.8) at year 4; 60% were in the low -risk group with risk estimates of 3.6% (95% CI, 2.5 to 4.7) at diagnosis and 9.6% (95% CI, 7.5 to 11.7) at year 4. The distinct dimensions of fatigue clustered in different trajectory groups than those identified by severe global fatigue, being differentially affected by sociodemographic, clinical, and treatment-related factors., Conclusion: Our findings highlight the multidimensional nature of cancer-related fatigue and the complexity of its risk factors. This study helps to identify patients with increased risk of severe fatigue and to inform personalized interventions to ameliorate this problem., Competing Interests: Ines Vaz-LuisHonoraria: AstraZeneca (Inst), Amgen (Inst), Pfizer (Inst) Barbara PistilliConsulting or Advisory Role: Puma Biotechnology, Pierre Fabre, Novartis, Myriad Genetics, AstraZeneca, Daiichi Sankyo/UCB JapanResearch Funding: Pfizer (Inst), Puma Biotechnology (Inst), Merus (Inst), Daiichi-Sankyo (Inst)Travel, Accommodations, Expenses: Pfizer, AstraZeneca, MSD Oncology, Novartis, Pierre Fabre Paul H. CottuHonoraria: Pfizer, Novartis (Inst), Roche, NanoString Technologies (Inst), LillyConsulting or Advisory Role: Pfizer, LillyResearch Funding: Pfizer (Inst)Travel, Accommodations, Expenses: Roche, Pfizer Florence LereboursConsulting or Advisory Role: AstraZeneca, Eisai, Lilly, Pierre Fabre, Roche, PfizerTravel, Accommodations, Expenses: Lilly, Novartis, Pfizer, Roche, Pierre Fabre Sarah DauchyHonoraria: Servier, Novartis, MSD Oncology, BMS, NutriciaTravel, Accommodations, Expenses: Servier Suzette DelalogeConsulting or Advisory Role: AstraZeneca (Inst), Sanofi (Inst), Besins Healthcare (Inst), Rappta Therapeutics (Inst)Research Funding: AstraZeneca (Inst), Pfizer (Inst), Roche/Genentech (Inst), Puma Biotechnology (Inst), Lilly (Inst), Novartis (Inst), Sanofi (Inst), Exact Sciences (Inst), Bristol Myers Squibb (Inst)Travel, Accommodations, Expenses: Pfizer, AstraZeneca, Novartis (Inst) Nancy U. LinConsulting or Advisory Role: Seattle Genetics, Puma Biotechnology, Daiichi Sankyo, Denali Therapeutics, AstraZeneca, Prelude Therapeutics, Voyager Therapeutics, Affinia Therapeutics, PfizerResearch Funding: Genentech (Inst), Pfizer (Inst), Seattle Genetics (Inst), Merck (Inst), Zion (Inst)Patents, Royalties, Other Intellectual Property: Royalties for chapter in Up-to-Date regarding management of breast cancer brain metastases, Royalties, Jones & Bartlett Patricia A. GanzLeadership: Intrinsic LifeSciencesStock and Other Ownership Interests: Xenon Pharma, Intrinsic LifeSciences, Silarus Therapeutics, Teva, Novartis, Merck, Johnson & Johnson, Pfizer, GlaxoSmithKline, Abbott LaboratoriesConsulting or Advisory Role: InformedDNA, Vifor Pharma, Ambys Medicines, Global Blood Therapeutics, GlaxoSmithKline, Ionis Pharmaceuticals, Akebia Therapeutics, Protagonist Therapeutics, Regeneron, Sierra Oncology, Rockwell Medical Technologies Inc, Astellas Pharma, Gossamer Bio, American Regent, Disc Medicine, Blue Note Therapeutics, GrailResearch Funding: Blue Note Therapeutics (Inst)Patents, Royalties, Other Intellectual Property: Related to iron metabolism and the anemia of chronic disease, Up-to-Date royalties for section editor on survivorshipTravel, Accommodations, Expenses: Intrinsic LifeSciences Ann H. PartridgePatents, Royalties, Other Intellectual Property: I receive small royalty payments for coauthoring the breast cancer survivorship section of UpToDateOpen Payments Link: https://openpaymentsdata.cms.gov/physician/835197 Fabrice AndréStock and Other Ownership Interests: PegacsyResearch Funding: AstraZeneca (Inst), Novartis (Inst), Pfizer (Inst), Lilly (Inst), Roche (Inst), Daiichi (Inst)Travel, Accommodations, Expenses: Novartis, Roche, GlaxoSmithKline, AstraZeneca Stefan MichielsConsulting or Advisory Role: IDDI, Sensorion, Biophytis, Servier, Yuhan, Amaris Consulting, RocheNo other potential conflicts of interest were reported.

Patients with high-risk, nonmuscle-invasive bladder cancer (NMIBC) frequently relapse after standard intravesical bacillus Calmette-Guérin (BCG) therapy and may have a dismal outcome. The mechanisms of resistance to such immunotherapy remain poorly understood. Here, using cancer cell lines, freshly resected human bladder tumors, and samples from cohorts of patients with bladder cancer before and after BCG therapy, we demonstrate 2 distinct patterns of immune subversion upon BCG relapse. In the first pattern, intracellular BCG infection of cancer cells induced a posttranscriptional downregulation of HLA-I membrane expression via inhibition of autophagy flux. Patients with HLA-I-deficient cancer cells following BCG therapy had a myeloid immunosuppressive tumor microenvironment (TME) with epithelial-mesenchymal transition (EMT) characteristics and dismal outcomes. Conversely, patients with HLA-I-proficient cancer cells after BCG therapy presented with CD8+ T cell tumor infiltrates, upregulation of inflammatory cytokines, and immune checkpoint-inhibitory molecules. The latter patients had a very favorable outcome. We surmise that HLA-I expression in bladder cancers at relapse following BCG does not result from immunoediting but rather from an immune subversion process directly induced by BCG on cancer cells, which predicts a dismal prognosis. HLA-I scoring of cancer cells by IHC staining can be easily implemented by pathologists in routine practice to stratify future treatment strategies for patients with urothelial cancer.