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Background: Combination of chemotherapy and immunotherapy is the current standard of care for advanced endometrial cancer. However, survival outcome remains poor, highlighting the urgent need for new treatments and reliable tools to identify patients who will benefit from them. Patient-Derived Tumor Organoids (PDTO) are three-dimensional structures established from patient tumors, and are closely mimicking the features of the tumor of origin. Moreover, more and more evidences show that PTDOs hold promises as predictive tools for the response to treatment of patients., Method: The PENDOR study is a monocentric observational study designed to assess the feasibility of generating and testing PDTOs derived from endometrial cancer for evaluating treatment sensitivity. PDTOS will be established from surgical specimens not required for anatomopathological diagnosis. Tumor cells will be dissociated, embedded in extracellular matrix, and cultured in a medium supplemented with growth factors and signaling pathways inhibitors. Molecular and histological analyses will be conducted to validate the resemblance of PDTO to the original tumor. Response of PDTO to conventional chemotherapy and PARP inhibitors will be evaluated and compared to clinical response and to the results of an academic HRD test Genomic Instability Scar (GIScar), respectively, to assess their predictive value., Discussion: This pilot study aims to validate the feasibility to develop PDTOs from endometrial cancer from patients who will undergo surgical resection. We aim to provide a proof of concept regarding the predictive value of these models for their potential application into routine clinical practice as part of precision medicine. This approach could therefore facilitate the identification of patients who could benefit from PARP inhibitors., Trial Registration: This clinical trial (N°ID-RCB: 2024-A01206-41) has been validated by local research ethic committee on July 16th 2024 and registered at ClinicalTrials.gov with the identifier NCT06603506 on September 6th 2024, version 1., Competing Interests: Declarations. Ethics approval and consent to participate: This study has received ethical approval from the « West II » ethical commitee (IDRCB: 2024-A01206-41) on July 16th, 2024. This committee is independent and not related with any affiliation of the authors. Any subsequent will of modification of the protocol would be submitted for approval from the committee. The clinical trial has been registered registered at ClinicalTrials.gov with the identifier NCT06603506 on September 19th, 2024. The study will be explained to the patients by the surgeons or the medical oncologists and an informed consent form will be obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: Immune Checkpoints Inhibitors (ICI) have changed the therapeutic landscape of metastatic renal cell carcinoma first-line treatment with complete response (CR) at metastatic sites observed in 10 to 15% of cases. Delayed nephrectomy could be discussed for patients having a clinical benefit from immunotherapy-based treatment. However, it is unclear whether prior immunotherapy exposure adversely influences the complexity of surgery. The aim of this study was to assess oncological outcomes of differed nephrectomy after immunotherapy, and to identify predictive factors associated with surgical complexity., Methods: This is a multicenter retrospective study from a national cohort of 102 patients treated between March 2015 and March 2023 by differed nephrectomy after complete response (CR) or major partial response (mPR defined as > 80% according to RECIST criteria) on metastatic sites following immunotherapy-based combination treatment. Tumor downsizing was assessed by calculating the percentage reduction from the largest measured tumor diameter, comparing before and after immunotherapy., Results: A total of 102 patients (median age 63.3 years) were included. ICI was administered as first-line in 84.3% of cases, with an ICI-ICI (74.5%) or ICI-TKI combination (25.5%), and with a median duration of treatment of 10 [1-57] months. The majority of procedures are radical nephrectomies (n = 85, 83.3%) with an open approach performed in 52.9% of cases (n = 54). Median operative time was 180 [90-563] minutes and median blood loss was 300 cc [0-4000] cc. Surgeons experienced difficulties due to adhesions and inflammatory reactions at the kidney and the surrounding tissue in 65.7% of cases (n = 67), more frequently in case of partial nephrectomy compared to radical surgery (85% vs. 61%, p = 0.04). In 15 cases (14.7%), the surgical approach changed during the procedure due to these intraoperative difficulties (including 10 patients with open conversion and 3 partial nephrectomies finally converted to radical). We highlighted a relationship between primary renal tumor downsizing and intraoperative complexity. Tumor downsizing > 10% is more likely to induce surgical difficulties (76.1% vs. 45.7%, p = 0.002), but without any impact on postoperative complications rate. Pathology reports show a complete response in 13.7% (n = 14), a pT1-pT2 stage in 29.4% (n = 30) and a pT3-pT4 stage in 56.9% (n = 58), a median ISUP grade 3 and a clear cell carcinoma histology in 95.1% (n = 97). After a median follow-up of 29.6 months, 48% of patients were free from progression and without systemic treatment. Patients with a complete response at the metastatic sites had a better prognosis in terms of recurrence-free survival (82.1% vs. 37.9% at 3 years, p = 0.001)., Conclusion: Delayed nephrectomy after immunotherapy could be a challenging surgical procedure but offers encouraging oncological outcomes., Competing Interests: Declarations. Research involving human participants and/or animals: N/A. Informed consent: N/A. Financial interests: None. Non-financial interests: None. Conflicts of interest: The authors have no conflicts of interest to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Currently three antibody-drug-conjugates (ADC) are approved by the European Medicines Agency (EMA) for treatment of breast cancer (BC) patient: trastuzumab-emtansine, trastuzumab-deruxtecan and sacituzumab-govitecan. ADC are composed of a monoclonal antibody (mAb) targeting a specific antigen, a cytotoxic payload and a linker. Pharmacokinetics (PK) and pharmacodynamics (PD) distinguish ADC from conventional chemotherapy and must be understood by clinicians., Areas Covered: Our review delineates the PK/PD profiles of ADC approved for the treatment of BC with insight for future development. This is an expert opinion literature review based on the EMA's Assessment Reports, enriched by a comprehensive literature search performed on Medline in August 2023., Expert Opinion: All three ADC distributions are described by a two-compartment structure: tissue and serum. Payload concentration peak is immediate but remains at low concentration. The distribution varied for all ADC only with body weight. mAb will be metabolised firstly by the saturable complex formation of ADC/Tumour-Receptor and secondly by binding of FcgRs in immune cells. They are all excreted in the bile and faeces with minimal urine elimination. Dose adjustments, apart from weight, are not recommended. Novel ADC are composed of cleavable linkers with various targets/payloads with the same PK/PD properties, but novel structures of ADC are in development.

Introduction: The Coronavirus (COVID-19) pandemic and its associated health restrictions have harmed the population psychologically. We aimed to compare the post-traumatic stress disorder (PTSD) symptoms and Quality of Life (QoL) in older French patients with cancer to the younger ones., Materials and Methods: This longitudinal multicenter study named COVIPACT began in April 2020 during the first French lockdown and has included 579 outpatients receiving treatment for a solid or hematological malignancy. Data were collected every three months, namely at the first release period (M3), at the second lockdown (M6), at the second release period (M9), and finally at the last curfew period (M12) in France. Standardized validated self-questionnaires were used to assess PTSD symptoms (using the Event Scale-Revised self-questionnaire), insomnia (through the Insomnia Severity Index questionnaire), QoL (using the Functional Assessment of Cancer Therapy - General questionnaire), and cognitive complaints (through the Functional Assessment of Cancer Therapy - Cognition questionnaire). Student (or Wilcoxon) tests and Chi-squared tests were used for continuous or discrete variables, respectively. We conducted linear mixed model to study the change during follow-up., Results: Out of 579 included patients, 157 (27%) were ≥ 70 years old at baseline, of whom 104 participated in the longitudinal study. At baseline, older patients reported fewer PTSD symptoms (17% versus 23%, p = .06), insomnia (17% versus 27%, p = .02), and cognitive complaint (3% versus 16%, p < .01) than younger patients. QoL at baseline was similar between age subgroups. We observed no significant difference in the trajectory of PTSD symptoms, insomnia, or emotional well-being between both groups during the follow-up. Cognitive complaints were lower at baseline in older patients but steadily increased during the follow-up and reached the same level as younger patients at one year., Discussion: One in five older patients reported PTSD symptoms, evolving similarly to younger patients during the first year of the COVID-19 pandemic. While cognitive complaints tend to recover in a bell-shaped curve at one year in younger patients, the trend is increasing in older ones. Screening for PTSD symptoms and late cognitive impairment should be given special attention in older patients., Trial Registration: Clinicaltrials.gov identifier: NCT04366154., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest with this work., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Triple negative breast cancers (TNBC) account for approximately 15% of all breast cancers and are associated with a shorter median survival mainly due to locally advanced tumor and high risk of metastasis. The current neoadjuvant treatment for TNBC consists of a regimen of immune checkpoint blocker and chemotherapy (chemo-ICB). Despite the frequent use of this combination for TNBC treatment, moderate results are observed and its clinical benefit in TNBC remains difficult to predict. Patient-derived tumor organoids (PDTO) are 3D in vitro cellular structures obtained from patient's tumor samples. More and more evidence suggest that these models could predict the response of the tumor from which they are derived. PDTO may thus be used as a tool to predict chemo-ICB efficacy in TNBC patients., Method: The TRIPLEX study is a single-center observational study conducted to investigate the feasibility of generating PDTO from TNBC and to evaluate their ability to predict clinical response. PDTO will be obtained after the dissociation of biopsies and embedding into extra cellular matrix. PDTO will be cultured in a medium supplemented with growth factors and signal pathway inhibitors. Molecular and histological analyses will be performed on established PDTO lines to validate their phenotypic proximity with the original tumor. Response of PDTO to chemo-ICB will be assessed using co-cultures with autologous immune cells collected from patient blood samples. PDTO response will finally be compared with the response of the patient to evaluate the predictive potential of the model., Discussion: This study will allow to assess the feasibility of using PDTO as predictive tools for the evaluation of the response of TNBC patients to treatments. In the event that PDTO could faithfully predict patient response in clinically relevant time frames, a prospective clinical trial could be designed to use PDTO to guide clinical decision. This study will also permit the establishment of a living biobank of TNBC PDTO usable for future innovative strategies evaluation., Trial Registration: The clinical trial (version 1.2) has been validated by local research ethic committee on December 30 th 2021 and registered at ClinicalTrials.gov with the identifier NCT05404321 on June 3 rd 2022, version 1.2., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: COVID-19 outbreak rapidly spread since early 2020 leading to the implementation of nationwide lockdowns. To cope with this sudden change, management guidelines were quickly published to adapt oncological care, with potential impact on cancer outcomes., Methods: We conducted a retrospective comparative cohort study to assess the impact of the COVID-19 outbreak in 2020 on cancer outcomes in metastatic patients. Two cohorts of metastatic patients receiving intravenous (iv) therapy in a French oncological day care hospital were assessed: a 2020 cohort during the first French lockdown, and a 2018 historical cohort before the COVID-19 pandemic. We performed a propensity score analysis to match patients from the two cohorts. After one-year follow-up, we compared progression-free survival (PFS) and overall survival (OS) between cohorts. Adaptations of medical oncological treatments in 2020 were also analysed., Results: The 376 patients of the 2020 cohort were matched with 376 of the 2018 cohort. No SARS-CoV-2 infection was observed in the 2020 cohort. The adjusted PFS was significantly shorter in 2020 compared to 2018 (HR = 1.23; 95% CI: 1.03-1.46), as well as among patients without treatment adaptation compared to matched patients of the 2018 cohort (HR = 1.33; 95% CI: 1.10-1.61). We did not observe any significant difference of PFS among the group with treatment adaptations. OS was not significantly different., Conclusion: Metastatic cancer patients treated during the first lockdown had a higher risk of disease progression 1 year after COVID-19 outbreak. However, oncological treatment adaptations or SARS-CoV-2 infections do not explain these results. A longer follow-up is needed to observe the impact on OS., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Identifying prognostic factors and evaluating the impact of adjuvant chemotherapy in patients with sex cord stromal tumors (SCST) is crucial. In this study, we aimed to address these challenges., Methods: We conducted a retrospective analysis of data from 13 centers of the French Rare malignant gynecological tumors (TMRG) network. We enrolled 469 adult patients with malignant SCST who received upfront surgery since 2011 to July 2015., Results: 75% were diagnosed with adult Granulosa cell tumors, and 23% had another subtype. With a median follow-up of 6.4 years, 154 patients (33%) developed a first recurrence, 82 (17%) two recurrences, and 49 (10%) three recurrences. Adjuvant chemotherapy was administered in 14.7% of patients at initial diagnosis. In relapse, perioperative chemotherapy was administered in 58.5%, 28.2%, and 23.8% of patients, respectively, in the first, second, and third relapse. In the first-line therapy, age under 70 years, FIGO stage, and complete surgery were associated with longer progression-free survival (PFS). Chemotherapy had no impact on PFS in early-stage disease (FIGO I-II). The PFS was similar using BEP or other chemotherapy regimens (HR 0.88 [0.43; 1.81]) in the first-line therapy. In case of recurrence, PFS was statistically prolonged by complete surgery, but perioperative chemotherapy use did not impact PFS., Conclusion: Chemotherapy use did not impact survival in the first-line or relapse setting in SCST. Only surgery and its quality demonstrated benefit for PFS in ovarian SCST in any lines of treatment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Patients with cancer may be particularly vulnerable to psychological consequences of the COVID-19 pandemic. We studied the prevalence and evolution of posttraumatic stress symptoms (PTSS) in patients with cancer during the pandemic waves, and we investigated factors associated with high symptoms., Methods: COVIPACT is a 1-year longitudinal prospective study of French patients with solid/hematologic malignancies receiving treatment during the first nationwide lockdown. PTSS were measured every 3 months from April 2020 using the Impact of Event Scale-Revised. Patients also completed questionnaires on their quality of life, cognitive complaints, insomnia, and COVID-19 lockdown experience., Results: Longitudinal analyses involved 386 patients with at least one PTSS assessment after baseline (median age, 63 years; 76% female). Among them, 21.5% had moderate/severe PTSS during the first lockdown. The rate of patients reporting PTSS decreased at lockdown release (13.6%), increased again at second lockdown (23.2%), and slightly declined from the second release period (22.7%) to the third lockdown (17.5%). Patients were grouped into 3 trajectories of evolution. Most patients had stable low symptoms throughout the period, 6% had high baseline symptoms slowly decreasing over time, and 17.6% had moderate symptoms worsening during the second lockdown. Female sex, feeling socially isolated, worrying about COVID-19 infection, and using psychotropic drugs were associated with PTSS. PTSS were associated with impaired quality of life, sleep, and cognition., Conclusions: Approximately one-fourth of patients with cancer experienced high and persistent PTSS over the first year of the COVID-19 pandemic and may benefit from psychological support., Clinicaltrials: gov identifier: NCT04366154.

Background: Immune checkpoint inhibitor-based combination therapy (ICI-based combination) is a new standard of care for metastatic clear cell renal cell carcinoma (mRCC) in the frontline setting. Patients with poor performance status (PS) (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-based combination therapy in this group of patients is still unknown., Methods: We performed a multicentre retrospective study of PS ≥2 mRCC patients who received frontline ICI-based combination, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (AP). Patients' characteristics, clinical outcomes, and toxicity were collected. We analysed overall response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS) and grade ≥3 adverse events (G ≥ 3AEs). The association between the predictive biomarker IPI (immune prognostic index) and ORR/PFS/OS was also evaluated., Results: We identified 70 mRCC patients with PS ≥2 treated with ICI-based combination across 14 institutions between October 2017 and December 2021, including 45 and 25 patients were treated with NI and AP, respectively. Median age at diagnosis was 63 years, 51 (73%) were male, only 17 (24%) had prior nephrectomy, 50 (71%) had synchronous metastatic disease at diagnosis, and 16 (23%) had brain metastases. Sixty-one (87%) and 9 (13%) patients had ECOG (Eastern Cooperative Oncology Group) PS 2 and 3, respectively, and 25 (36%) and 45 (64%) patients were intermediate and poor International Metastatic RCC Database Consortium (IMDC) risk, respectively. Among all, 91% were clear cell RCC, 7 patients had sarcomatoid features. At the time of the analysis (median follow-up 11.1 months), 41% patients were dead. Median PFS and mOS in the entire cohort were 5.4 months and 16.0 months, respectively; ORR was 31%. No significant differences in ORR, PFS, OS, or G ≥3AEs were seen between NI and AP. The intermediate and poor IPI groups were significantly associated with reduced ORR and shorter PFS., Conclusion: We report the first cohort of PS ≥2 mRCC patients treated with frontline ICI-based combination therapy. The survival outcomes in our cohort were inferior to that reported in pivotal trials. No significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. Prospective real-world studies are needed to confirm these results., Competing Interests: Conflict of interest statement LCA: BMS Belgium Travel, Accommodation and Expenses. EC: Consulting or Advisory Role – BMS; Ipsen; Sanofi; GSK; Eisai; Merck; Janssen; Pfizer; Travel, Accommodations, Expenses – BMS Brazil; Pfizer; IPSEN. BE: Honoraria – Bristol-Myers Squibb; EUSA Pharma; Ipsen; Novartis; Oncorena; Pfizer; Roche/Genentech Consulting or Advisory Role – AVEO; Bristol-Myers Squibb; EUSA Pharma; Ipsen; Novartis; Pfizer; Roche/Genentech Research Funding – BMS France (Inst) Travel, Accommodations, Expenses – Bristol-Myers Squibb; Ipsen; MSD; Pfizer; Roche/Genentech. LA: Consulting fees compensated to the institution for Pfizer, Novartis, Bristol Myer Squibb, Ipsen, Roche, MSD, AstraZeneca, Merck, Amgen, Astellas, Exelixis, Corvus Pharmaceuticals, Peloton Therapeutics, outside the submitted work. RM: Honoraria for advisory role and speaker: BMS, MSD, Pfizer, Ipsen, AstraZeneca, Roche, Janssen, Astellas, Tecnofarma. AF: Honoraria: BMS, Ipsen, MSD, Pfizer. Travel, Accommodations, Expenses – BMS; Ipsen; MSD; Pfizer. Rest of authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Cyclin dependent kinase inhibitors (CdK4/6i) changed the course of hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (mBC). To date, no factors have been shown to predict response to CdK4/6i. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory response, is an independent prognostic factor for survival in cancers. We conducted this study to evaluate the impact of NLR on survival in mBC patients treated with first line CdK4/6i., Methods: All mBC patients treated with first line CdK4/6i between November 2015 and December 2019 were retrospectively included. The biomarker threshold was defined using ROC curves. We analyzed progression free survival (PFS), overall survival (OS), 12-month PFS and response rate according to NLR in univariable and multivariable analysis., Results: A total of 126 patients treated with palbociclib (n=101), ribociclib (n=18) or abemaciclib (n=7) were included, with a median follow-up of 33 months [range: 2.9-57]. Median age was 65 years [29-86], 40% patients had good performance status (ECOG-PS 0). Most patients (71%) were included at the metastatic relapse stage and 29% had only bone metastases. Median PFS and median OS were 27 and 51 months, respectively. High NLR (≥ 2.53) was significantly associated with worse PFS (Hazard Ratio (HR)=0.50, CI 95% = [0.32-0.79]) and worse OS (HR=0.45, [CI 95% : 0.23-0.87]). In multivariable analysis, NLR and ECOG PS were independently factors associated with PFS (p=0.016 and p=0.001, respectively)., Conclusion: High NLR was associated with worse PFS and OS in HR+ HER2- mBC patients treated with first line CdK4/6i. NLR is a reliable and inexpensive prognostic marker, easily accessible in routine clinical practice, which could help optimize the therapeutic strategy. These results need to be confirmed in larger prospective studies., 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., (Copyright © 2023 Rottier, Emile, Johnson, Levy, Allouache, Hrab, Segura, Morel, Villemin, Dubot-Poitelon, Boismoreau, Cherifi, Lequesne and Da Silva.)

Purpose: The aim of this study was to analyse the impact of adjuvant trastuzumab on fatigue, emotional status, and quality of personal and work life of patients treated for localised breast cancer., Methods: In a prospective setting, we recruited age-matched localised breast cancer patients, treated by adjuvant chemotherapy with (group 1) or without IV trastuzumab (group 2), between September 2011 and May 2014. Patients completed questionnaires on quality of life (FACT-G, FACT-B), fatigue (FACIT-F, ICQ), anxiety-depression (HADS), and work life (dedicated self-questionnaire) at inclusion then at 3, 6, 9, and 15 months., Results: We included 35 patients in each group. No significant difference was found between the two groups concerning return to work, fatigue, and quality of life scores at each phase of the study. In total, 39 patients (72.2%) reported having returned to work at T15, with no significant difference between the two groups (p = 0.53). Significantly higher scores for'helplessness' outcomes were observed in group 1, 9, and 15 months (6.138 and 5.731; p = 0.047 and 0.048, respectively). Patients in group 1 reported higher score of anxiety-depression than group 2 at 3 months (p = 0.027) then no significant difference was observed at the other times of the study., Conclusion: Trastuzumab does not appear to affect fatigue and return to work in patients with localised breast cancer. The emotional well-being could be affected in patients treated by trastuzumab, with a more pronounced 'helplessness' feeling which could be more related to the additional follow-up imposed by the prescription of trastuzumab., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Identifying new modifiable prognostic markers is important for ovarian cancer (OC). Low parasympathic activity is associated with inflammation, oxidative stress and sympathetic nervous system activation. Previous studies reported that low vagal nerve activity, measured by low heart rate variability (HRV), may predict poor cancer prognosis. We aimed to examine the prognostic value of HRV in OC., Methods: This bicentric retrospective study included patients diagnosed with serous OC FIGO stage ≥IIB, between January 2015 and August 2019, with electrocardiograms (ECG) available around diagnosis. HRV was measured from ECG using the time domain parameter of standard deviation of all normal-to-normal heartbeat intervals (SDNN). Optimal SDNN cut-off was determined using the Youden index criteria of time-dependent ROC curves. We used multivariate cox proportional hazard models to investigate the association between HRV and overall survival (OS), while adjusting for well-known OC prognostic factors., Results: The 202 patients included were 65.7 years-old on average, 93% had stage FIGO IIIC/IV, 56% had complete surgical resection. Median OS was 38.6 months [95%CI:34.4-47.4]. The median SDNN was 11.1ms, with an optimal cut-off of 10ms to predict OS. OS was shorter for patients with low HRV compared to high HRV (26.4 vs 45.1 months; p<0.001). In multivariate analysis, HRV remained an independent prognostic factor with a two-fold higher risk of death among patients with low SDNN compared to those with high SDNN (HR=2.03, 95%CI=1.35-3.06, p<0.001)., Conclusion: Low HRV, was associated with worse OS in OC patients, supporting previous studies on the prognostic role of HRV in cancer. If replicated in prospective studies, vagal nerve activity may be a new therapeutic target in OC., Competing Interests: FJ reports participating in advisory boards with AstraZeneca, GSK, Clovis, MSD and seagen, reports consulting fees from GSK, and support for attending meetings from GSK, Astrazeneca and MSD. YG was a chair in psycho-oncology during 2017-2019 from the French National Cancer Institute. 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 Cherifi, Lefevre Arbogast, Font, Abdeddaim, Becourt, Penel, Coquan, Lequesne, Gidron and Joly.)

Background: HER2 expression has a prognostic and predictive impact in early-stage breast cancer (BC). HER2 positive BC (immunohistochemistry (IHC) score 3 + or 2 + with in situ hybridization (ISH) amplification) are treated with HER2 targeted therapies. The concept of HER2-low BC (IHC score 1 + or 2 + without ISH amplification) is drawing attention as anti-HER2 treatment has recently shown efficacy in this subgroup. We aimed to explore the response to neoadjuvant chemotherapy (NAC) in HER2-low early BC according to the HER2 score (1 + or 2 + without amplification)., Methods: We conducted a retrospective study in two French comprehensive cancer centers. All patients with HER2-low BC treated with NAC from January 2014 to December 2020 were included. The primary objective was to analyze the pathological complete response (pCR) rate to NAC using the Sataloff or RCB system, according to the HER2 score. Secondary objectives were to assess disease free survival (DFS), overall survival (OS) and to explore the immune environment through the Neutrophil-to-Lymphocyte Ratio (NLR), according to HER2 expression. Univariate and multivariate analyses were performed., Results: We included 237 tumors for 229 patients. Of these, 160 (67.5%) tumors were HER2 1 + , 77 (32.5%) were HER2 2 + , and 152 (64.1%) were hormone receptor (HR) positive. The median age was 53.9 years. No differences in tumor characteristics were observed between HER2 1 + and HER2 2 + subgroups. pCR was achieved in 38 tumors (17%), without any difference between HER2 1 + and HER2 2 + subgroups (p = 0.77). DFS and OS were significantly different between HER2 1 + and HER2 2 + patients (HR = 0.41,CI95%[0.17;0.97] p = 0.037 and HR = 0.31,CI95%[0.09;1.02] p = 0.042, respectively). HER2 status was still associated with DFS and OS after adjustment for age, HR status and NLR, with better outcomes in favor of HER2 score 2 + (HR = 0.35 [0.15-0.84] and HR = 0.24 [0.07-0.81], respectively). NLR was not associated with worse DFS or OS., Conclusion: In HER2-low early BC, no differences in pCR were observed between HER2 1 + and HER2 2 + tumors, however patients with HER2 2 + tumors had a better DFS and OS than those with HER2 1 + . Further investigations are needed to describe the intrinsic differences in the spectrum of HER2-low BC., (© 2022. The Author(s).)

Objective: To assess the impact of a global pretherapeutic comprehensive supportive care assessment performed in an outpatient supportive care clinic (OSCC) and early supportive care interventions on oncological treatment choice in patients with chemoradiation (CRT) indication for head and neck cancer (HNC)., Methods: In this monocentric prospective observational study, we included all patients considered for CRT (exclusive or post-operative) for HNC from February 2019 to March 2020. The following frailty indicators were assessed: comorbidities (Charlson index), nutritional status, altered functional ability (ADL and IADL), social precarity (EPICES score), cognitive impairment (MoCA score), addictive habits and pain., Results: OSCC led to a change in treatment for 13.7% of patients, mainly de-escalations. Ninety-three percent of patients had at least one altered domain, including 50% with three or more altered domains. Cognitive function was the most frequently altered domain (66.7%). Altered functional ability was significantly associated with treatment de-escalation after OSCC. Treatment interruptions were significantly associated with treatment de-escalation and social precarity. De-escalation was also associated with a significantly poorer PFS (median of 23.2 mos. vs 8.8 mos., HR = 2.18 95%IC[1.02-4.63] p = 0.037)) and a non-significant trend towards worse OS (median 23.3mos. vs not reached (HR = 2.16 95%CI[0.88-5.31] p = 0.0836)., Conclusion: We strongly encourage the creation of OSCC for patients treated with chemoradiation for HNC. This practice, through an exhaustive assessment, favours therapeutic adaptation, personalized follow-up and optimization of supportive care., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Paraneoplastic neurological syndrome (PNS) is uncommon and not well known. PNS can reveal cancer, but its role in seminomas has not been described explicitly. We report the case of a 36-year-old man with unremarkable medical history and no comorbidities who was diagnosed with a retroperitoneal metastatic seminoma. The patient's general condition deteriorated, and he developed progressive neurological palsy without other clinical anomalies. Electromyography revealed demyelinating, non-lengthy neuropathy. Guillain-Barré syndrome was initially suspected. However, a positron emission tomography scan revealed a retroperitoneal mass, and blood markers revealed increased human chorionic gonadotropin. The patient was diagnosed with PNS, and a computed tomography-guided biopsy revealed a metastatic seminoma without a primary tumor. No circulating neural antibodies were detected. Human polyvalent immunoglobulin was simultaneously administered with chemotherapy. After three cycles of a cisplatin-etoposide-bleomycin, a complete biological and metabolic response rate was observed, and his neurological symptoms rapidly improved. Four years later, the patient responded completely, without any neurological complaints. Paraneoplastic demyelinating inflammatory neuropathy can lead to advanced seminoma diagnosis. Prompt management of seminomas with cisplatin-based regimens provides the best chance of cure for both advanced seminoma and paraneoplastic syndrome., (© 2022 S. Karger AG, Basel.)

Cyclin-dependent-kinase 4-6 inhibitors (CDK4/6i) have improved the management of hormone receptor (HR) + /human epidermal growth factor receptor (HER)2 - metastatic breast cancer (mBC). Currently, there are no valid prognostic factors for response to CDK4/6i. Baseline lymphopenia is reported as a prognostic factor in several types of cancer. The present retrospective study aimed to evaluate the effect of baseline absolute lymphocyte count (ALC) on response to palbociclib. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints were overall survival (OS), best response and safety. A total of 114 patients treated for mBC between 2016 and 2019 were included. Median baseline ALC was 1.4 g/l (range, 0.2-4.3 g/l). A total of 65 (57%) and 49 (43%) patients had baseline ALC values of <1.5 and ≥1.5 g/l, respectively. Patients with baseline lymphopenia exhibited significantly shorter PFS (6 vs. 10 months; P=0.004) and OS (20 vs. 33 months; P=0.02). ALC <1.5 g/l independently predicted worse survival, as indicated by multivariate analysis (P=0.04; hazard ratio, 1.76; 95% confidence interval, 1.02-3.02). Patients with baseline ALC <1.5 g/l had significantly less partial response (14 vs. 22%; P=0.016) and more disease progression (46 vs. 20%; P=0.016) than those with ALC ≥1.5 g/l. ALC is a strong and easy-to-use dosage with prognostic factor for patients with HR + /HER2 - mBC treated with palbociclib and endocrine therapy. Lymphopenia may also be a predictive factor of early progression. These data need to be verified in a larger prospective study., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021, Spandidos Publications.)

Electronic structures and thermoelectric (TE) properties of KBiBa and KBiSr half-Heusler compounds are investigated by using the combined framework of first-principles and semi-classical Boltzmann transport theory. Elastic and phonon properties calculations reveal that these compounds are mechanically and dynamically stable. Band structures calculations, using the Tran and Blaha modified Becke-Johnson potential including spin-orbit coupling, show that KBiBa and KBiSr compounds are semiconductors with an indirect bandgap of 0.88 and 0.95 eV respectively. Performing calculations on lattice thermal conductivity, deformation potential, effective mass of charge carriers and their relaxation times allow us to deduce the dependence of the figure of merit ZT on doping concentration and temperature. At 1200 K, KBiBa and KBiSr compounds exhibit a ZT peak value of 2.68 and 1.56 at optimized n -doping values of 2.2 × 10 19 and 1.7 × 10 19  cm -3 , respectively. Considering high ZT values, KBiBa and KBiSr are considered to be ideal TE candidates at high temperature., (© 2021 IOP Publishing Ltd.)

Introduction: Swallowing difficulties in patients with advanced head and neck cancer (HNC) represent an obstacle to adequate antiemetic prophylaxis before chemotherapy. We aim to assess chemotherapy-induced nausea and vomiting (CINV) risk in HNC patients in our center, with a specific focus among patients who could not receive appropriate NK1 receptor antagonist (NK1-RA) prophylaxis., Materials and Methods: Prospective observational monocentric study. CINV were evaluated with the MASCC Antiemesis Tool self-questionnaire (MAT) for all patients treated by platinum-based chemotherapy for advanced HNC (January-April 2019), thereafter, only for patients without NK1-RA prophylaxis due to swallowing difficulties were included (May-October 2019)., Results: Sixty-one patients were included (82% male, 49.2% reccurent/metastatic disease), 18 did not received NK1-RA prophylaxis due to swallowing difficulties. Among 52 patients included from January to April 2019, 17.3% reported swallowing difficulties. The chemotherapy regimen was highly and moderately emetic for 40 (65.6%) and 21 patients (34.4%), respectively. CINV was associated with both cisplatin-based chemotherapy (OR 10.66, 95% CI [2.17-52.08]) and exclusive chemotherapy (OR 7.76, 95% CI [1.79-33.78]). Patients who did not receive anti-NK1 prophylaxis had no more CINV than patients with adequate CINV prophylaxis., Discussion: CINV remains frequent in patients treated by platinum-based chemotherapy for HNC. Oral NK1-RA prophylaxis can be unavailable because of swallowing difficulties, without an increased risk of CINV., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Adenoid Cystic Carcinoma is a rare tumor of the head and neck sphere. The purpose of this review is a state of the art of systemic treatments (chemotherapies, targeted therapies, immunotherapies) for locally recurrent or metastatic disease., Material and Methods: Our inclusion criteria included head and neck adult patient, metastatic or locally advanced, treated by a systemic therapy, and with at least 10 or more patients., Results: Forty articles have been selected in this review. The objective response rate under chemotherapy was predominantly<10% (0-70%) with objective responses in monotherapy with cisplatin, mitoxantrone, vinorelbine and eribuline, and with cisplatin-vinorelbine combination. EGFR inhibitors provided 40% objective responses only in combination. Inhibitors of VEGF and histone deacetylase have allowed disease stabilization in progressive patients, with about 10% of objective response. Inhibitors of c-KIT monotherapy yield objective response rates of<5%. Direct inhibitors of the PI3K/AKT/mTOR pathway display 0% objective response rate., Conclusion: The best objective response rates were obtained with cisplatin-vinorelbine combination. Many targetable molecular abnormalities have been identified and studies have shown prolonged stabilization with EGFR, VEGF and HDAC inhibitors. Multi-disciplinary collaborative consultation (MCC) meetings such as French network of experts in rare head and neck tumors (REFCOR) or Molecular MCC should be proposed and may allow referral to centers proposing specific therapeutic trials., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objective: To determine the incidence, demographic data, risk factors, indications, outcome and complications of emergency peripartum hysterectomy (EPH) performed in two major tertiary care hospitals in Dubai, and to compare the results with the literature., Materials and Methods: The records of all women who underwent EPH from January 2000 to December 2015 in two major tertiary care hospitals in Dubai were accessed and reviewed. Maternal characteristics, hysterectomy indications, outcomes, and postoperative complications were recorded using descriptive statistics to describe the cohort., Results: There were 79 EPH out of 168.293 deliveries, a rate of 0.47/1000 deliveries. The most common indications for hysterectomy were abnormal placentation (previa and/or accreta) and uterine atony. The majority of hysterectomies were subtotal (70%). The complications were dominated by massive transfusion, urinary tract injuries, one case of maternal death, and one case of neonatal death., Conclusion: The main indication for EPH was abnormal placentation in scarred uterus and uterine atony. The major method of prevention of EPH is to assess women's risks and to reduce the number of cesarean section deliveries, by limiting the rate of primary cesareans. This is challenging in the United Arab Emirates (UAE) where the culture is for high gravidity and high parity. Recommendations to act to reduce primary and repeated cesareans should be included on the national agenda in UAE., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.