PD-L1 expression and its prognostic value in metastatic papillary renal cell carcinoma: Results from a GETUG multicenter retrospective cohort.

INTRODUCTION: Papillary renal cell carcinoma (pRCC) is a rare and aggressive cancer with no specifically established therapeutic strategy in the metastatic setting. Combinations of tyrosine kinase and immune checkpoint inhibitors (ICI) are a promising option. We aimed to study the immune landscape of metastatic pRCC, and its interactions with angiogenesis pathways, to search for potential therapeutic targets. METHODS: The expression of immune markers (PD-L1, PD-1, PD-L2, LAG-3) and angiogenic pathways (CAIX, c-MET), was analyzed by immunohistochemistry on 68 metastatic pRCC retrieved from a retrospective multicenter GETUG cohort. Our primary endpoint was to estimate the prevalence of PD-L1 expression and its prognostic impact in metastatic pRCC. Secondary endpoints included the evaluation of other immune markers (PD-1, PD-L2, and LAG-3) and their association with PD-L1. We also assessed angiogenic markers and their association with PD-L1. RESULTS: Overall, 27.9 % of tumors were PD-L1 positive. PD-L2 was more frequently expressed (45.6 %), PD-1 and LAG-3 were positive in 17.6 % and 19.1 % respectively. None of these markers was correlated with PD-L1 expression. 66 % (45/68) expressed at least one immune marker, and 43 % (29/68) were "double-positive", as they expressed both immune and angiogenic markers. OS was significantly shorter for patients with PD-L1 positive pRCC. A multivariate analysis confirmed a significant association between PD-L1 expression and shorter overall survival (HR = 4.0, p = 0.01). CONCLUSION: These results reinforce clinical data on the expected benefit of ICI in metastatic pRCC treatment, as PD-L1 expression is a factor of poor prognosis in this multicenter cohort.

Why do second-cycle medical students choose oncology? A literature overview.

INTRODUCTION: Given the current global cancer epidemic across the world, the need for healthcare professionals in this field is crucial. Little is known about the factors that drive medical students toward oncology. METHOD: We conducted a systematic review of the literature (from 1980 to the present), using several search equations and selecting original articles written in English based on qualitative or quantitative surveys, to understand what motivates medical students to choose oncology. RESULTS: We identified only seven articles that reported quantitative surveys; no qualitative surveys were found. These seven surveys are composed of closed-ended questions and are pragmatic questionnaires based on field knowledge, but without an underlying theory. These studies most often interrogate students already oriented towards oncology. The following five concepts associated with the choice of oncology had the highest recurrence among these seven surveys, which had been conducted in different countries and at various times: interest in cancer management, initiation of the specialty during the 2nd cycle, job opportunities, low working hours, and quality of life. DISCUSSION: The literature on this topic is particularly scarce. No qualitative studies have been published in the English language. The limited data in the literature do not allow us to fully comprehend the problem.

Complete DPYD genotyping combined with dihydropyrimidine dehydrogenase phenotyping to prevent fluoropyrimidine toxicity: A retrospective study.

INTRODUCTION: In April 2019, French authorities mandated dihydropyrimidine dehydrogenase (DPD) screening, specifically testing uracilemia, to mitigate the risk of toxicity associated with fluoropyrimidine-based chemotherapy. However, this subject is still of debate as there is no consensus on a standardized DPD deficiency screening test. We conducted a real-life retrospective study with the aim of assessing the impact of DPD screening on the occurrence of severe toxicity and exploring the potential benefits of complete genotyping using next-generation sequencing. METHODS: All adult patients consecutively treated with 5-fluorouracil (5-FU) or its oral prodrug at six cancer centers between March 2018 and February 2019 were considered for inclusion. Dihydropyrimidine dehydrogenase deficiency screening included gene encoding DPD (DPYD) genotyping using complete genome sequencing and DPD phenotyping (uracilemia or dihydrouracilemia/uracilemia ratio) or both tests. Associations between each DPD screening method and (i) severe (grade ≥3) early toxicity and (ii) fluoropyrimidine dose reduction in the second chemotherapy cycle were evaluated using multivariable logistic regression analysis. Furthermore, we assessed the concordance between DPD genotype and phenotype using Cohen's kappa. RESULTS: A total of 551 patients were included. Most patients were tested for DPD deficiency (86%) including DPYD genotyping only (6%), DPD phenotyping only (8%), or both (72%). Complete DPD deficiency was not detected in the study population. Severe early toxicity events were observed in 73 patients (13%), with two patients (0.30%) presenting grade 5 toxicity. Despite the numerically higher toxicity rate in untested patients, the occurrence of severe toxicity was not significantly associated with the DPD screening method (p = 0.69). Concordance between the DPD genotype and phenotype was weak (Cohen's kappa of 0.14). CONCLUSION: Due to insufficient numbers, our study was not able to demonstrate any added value of DPYD genotyping using complete genome sequencing to prevent 5-FU toxicity. The optimal strategy for DPD screening before fluoropyrimidine-based chemotherapy requires further clinical evaluation.

Carboplatin in metastatic castration-resistant prostate cancer patients with molecular alterations of the DNA damage repair pathway: the PRO-CARBO phase II trial.

Introduction: DNA damage repair genes are altered in 20-35% of metastatic castration-resistant prostate cancer (mCRPC). Poly-ADP (Adénosine Diphosphate)-ribose polymerase inhibitors (PARPi) showed significant activity for these selected tumors, especially with homologous recombination repair (HRR) deficiency. These alterations could also predict platinum sensitivity. Although carboplatin was inconclusive in unselected mCRPC, the literature suggests an anti-tumoral activity in mCRPC with HHR gene alterations. We aimed to assess the efficacy of carboplatin monotherapy in mCRPC patients with HRR deficiency. Methods: This prospective multicenter single-arm two-stage phase II addressed mCRPC men with HRR somatic and/or germline alterations, pretreated with ⩾2 taxane chemotherapy regimens and one androgen receptor pathway inhibitor. Prior PARPi treatment was allowed. Enrolled patients received intravenous carboplatin (AUC5) every 21 days for 6-9 cycles. The primary endpoint was the best response rate according to adapted PCWG3 guidelines: radiological response (RECIST 1.1 criteria) and/or biological response [⩾50% prostate-specific antigen (PSA) decline]. Results: A total of 15 out of 16 enrolled patients started carboplatin treatment. Genomic alterations were identified for BRCA2 (n = 5), CDK12 (n = 3), ATM (n = 3) CHEK2 (n = 2), CHEK1 (n = 1), and BRCA1 (n = 1) genes. Objective response (partial biological response + stable radiological response) was achieved in one patient (6.7%), carrying a BRCA2 mutation and not pre-treated with PARPi; stable disease was observed for five patients (33.5%). Among seven patients (46.7%) with previous PARPi treatment, four patients (57.1%) had a stable disease. The median progression-free and overall survivals were 1.9 [95% confidence interval (95% CI), 1.8-9.5] and 8.6 months (95% CI, 4.3-19.5), respectively. The most common severe (grade 3-4) treatment-related toxicities were thrombocytopenia (66.7%), anemia (66.7%), and nausea (60%). Overall, 8 (53.3%) patients experienced a severe hematological event. Conclusion: The study was prematurely stopped as pre-planned considering the limited activity of carboplatin monotherapy in heavily pre-treated, HHR-deficient mCRPC patients. Larger experience is needed in mCRPC with BRCA alterations. Trial registration: NCT03652493, EudraCT ID number 2017-004764-35.

Handling missing covariates in observational studies: an illustration with the assessment of prognostic factors of survival outcomes in soft-tissue or visceral sarcomas in irradiated fields (SIF).

Background: Missing covariates are common in observational research and can lead to bias and loss of statistical power. Limited data regarding prognostic factors of survival outcomes of sarcomas in irradiated fields (SIF) are available. Because of the long lag time between irradiation of first cancer and scarcity of SIF, missing data are a critical issue when analyzing long-term outcomes. We assessed prognostic factors of overall (OS), progression-free (PFS), and metastatic-progression-free (MPFS) survivals in SIF using three methods to account for missing covariates. Methods: We relied on the NETSARC French Sarcoma Group database, Cox (OS/PFS), and competitive hazards (MPFS) survival models. Covariates investigated were age, sex, histological subtype, tumor size, depth and grade, metastasis, surgery, surgical resection, surgeon's expertise, imaging, and neo-adjuvant treatment. We first applied multiple imputation (MI): observed data were used to estimate the missing covariate. With the missing-data modality approach, a category missing was created for qualitative variables. With the complete-case (CC) approach, analysis was restricted to patients without missing covariates. Results: CC subjects (N = 167; 33%) presented more often with soft-tissue sarcoma (versus visceral sarcoma) and grade I-II tumors as compared to the 504 eligible cases. With MI (N = 504), factors associated with the worst outcome included metastasis (p = 0.04) and R1/R2 resection (p < 0.001) for OS; higher grade/non-gradable tumors (p = 0.002) and R1/R2 resection (p < 0.001) for PFS; and metastasis (p = 0.01) for M-PFS. The 'missing-data modality' approach (N = 504) led to different associations, including significance reached due to variables with the modality 'missing'. The CC analysis led to different results and reduced precision. Conclusion: The CC population was not representative of the eligible population, introducing bias, in addition to worst precision. The 'missing-data modality method' results in biased estimates in non-randomized studies, as outcomes may be related to variables with missing values. Appropriate statistical methods for missing covariates, for example, MI, should therefore be considered.

[Should we take into account the informational stress of the medical oncologist?] / Doit-on prendre en compte le stress informationnel de l'oncologue médical ?

Information overload, informational stress and its deleterious consequences constitute a subject of growing interest in the way of work. This is quite well documented among anesthesiologists. Studies have also been carried out on cancer patients or on the general public in terms of cancer prevention. After having defined the concepts and the consequences, we hypothesize the presence of informational stress among medical oncologists. We illustrate this hypothesis regarding adjuvant treatment of breast cancer. Specific studies (qualitative and quantitative ones) would be particularly interesting in oncology.

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA.

BACKGROUND: Darolutamide and enzalutamide are second-generation androgen receptor inhibitors with activity in men with castrate-resistant prostate cancer (CRPC) and different toxicity profiles. OBJECTIVE: ODENZA is a prospective, randomized, multicenter, cross-over, phase 2 trial designed to assess preference between darolutamide and enzalutamide in men with asymptomatic or mildly symptomatic metastatic CRPC (mCRPC). DESIGN, SETTING, AND PARTICIPANTS: Patients were randomized 1:1 to receive either darolutamide 1200 mg/d for 12 wk followed by enzalutamide 160 mg/d for 12 wk or enzalutamide followed by darolutamide. In both arms, the second treatment was given in absence of cancer progression. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was patient preference between the two drugs, as assessed by a preference questionnaire (p value calculated with the Prescott test). After week 24, patients entered an extension period during which they received their preferred treatment until progression or toxicity. The main secondary objectives included reasons for patient preference, response at week 12, tolerance of each drug, and measurement compared with baseline of cognitive outcomes assessed using tablet questionnaires. RESULTS AND LIMITATIONS: Overall, 249 patients, with a median age of 72 yr, were randomized. Among the 200 patients who fulfilled the preplanned criteria for the evaluation of the primary endpoint of preference, 97 (49% [41; 56]), 80 (40% [33; 47]), and 23 (12% [7; 16]) chose darolutamide, chose enzalutamide, and had no preference, respectively (p = 0.92). Reduced fatigue, easier administration, and better quality of life were the main criteria that influenced patient choice. A moderate benefit in episodic memory from darolutamide was observed for the acquisition of new information (least square [LS] means difference = 2.2, effect size = 0.5) and for the recall of that information after a brief delay (LS means difference = 0.7, effect size = 0.3). Using the Brief Fatigue Inventory questionnaire, patients reported greater fatigue with enzalutamide (3.3 [3.0; 3.6]) than with darolutamide (2.7 [2.4; 3.0]). There was no difference in terms of depression, seizures, and falls. CONCLUSIONS: The study did not show a difference in preference between the two treatments. In men with mCRPC, darolutamide was associated with a clinically meaningful benefit in episodic memory and less fatigue compared with enzalutamide. PATIENT SUMMARY: Preference between darolutamide and enzalutamide was well balanced in men with castrate-resistant prostate cancer. Darolutamide was associated with a significant benefit in verbal learning and less fatigue compared with enzalutamide.

Regorafenib in patients with advanced Ewing sarcoma: results of a non-comparative, randomised, double-blind, placebo-controlled, multicentre Phase II study.

BACKGROUND: The REGOBONE multi-cohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the Ewing sarcoma (ES) cohort. METHODS: Patients with relapsed ES progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progression. The primary endpoint was the progression-free rate at 8 weeks. With one-sided α of 0.05, and 80% power, at least 14/24 progression-free patients at 8 weeks were needed for success. RESULTS: From September 2014 to November 2019, 41 patients were accrued. 36 patients were evaluable for efficacy: 23 on regorafenib and 13 on placebo. Thirteen patients (56%; one-sided 95% CI [37.5%-[)) were progression-free at 8 weeks on regorafenib vs. 1 (7.7%; 95% CI [0.4%-[) on placebo. Median PFS was 11.4 weeks on regorafenib, and 3.9 weeks on placebo. Ten placebo patients crossed over to receive regorafenib after progression. The most common grade ≥3 regorafenib-related adverse events were pain (22%), asthenia (17%), thrombocytopenia (13%) and diarrhoea (13%). CONCLUSION: Although the primary endpoint was not met statistically in this randomised cohort, there is evidence to suggest that regorafenib might modestly delay tumour progression in relapsed ES after failure of prior chemotherapy.

Impact of the coronavirus disease 2019 pandemic on sarcoma management in France: a 2019 and 2020 comparison.

Background: The coronavirus disease 2019 (COVID-19) pandemic was an unprecedented shock to the healthcare systems, and its consequences on managing rare cancers are unknown. We investigated COVID-19's impact on the activity of sarcoma-labeled networks by comparing key indicators in 2019-2020 (before and during the pandemic, respectively). Methods: We compared the incidence of limb and trunk soft tissue sarcomas, surgery rate, surgery center, surgery quality, and surgery delays nationally and in various regions, focusing on the three most severely affected regions. Findings: In this study, sarcoma incidence did not decrease, and the tumor and patient characteristics were similar in both years. The number of patients who underwent surgery in the labeled centers increased significantly (63% versus 57%, p = 0.015), the rate of R0 resection increased (55% versus 47%, p = 0.004), and the rate of re-excision decreased (12% versus 21%, p < 0.0001). In the univariate analysis, the time to surgery was similar in both years. Cox regression analysis revealed that the factors associated with a longer time to surgery were age > 70 years (p = 0.003), retroperitoneal location (p > 0.001), tumor size (p < 0.001), deep tumors (p < 0.001), and regions (p < 0.001). However, we have observed an increase in the time before surgery in the regions most stroked by the COVID-19 pandemic. Interpretation: The model of the labeled center network for managing rare tumors was resilient. Paradoxically, the quality indicators improved during the pandemic due to the direct referral of patients with sarcomas to the labeled centers. Summary: This study shows that a nationwide network organization has made it possible to maintain care for these rare tumors during the pandemic.

Predictive biomarkers for immune checkpoint inhibitor response in urothelial cancer.

Immune checkpoint inhibitors (ICIs) are commonly used to treat patients with advanced urothelial cancer. However, a significant number of patients do not respond to ICI, and the lack of validated predictive biomarkers impedes the success of the ICI strategy alone or in combination with chemotherapy or targeted therapies. In addition, some patients experience potentially severe adverse events with limited clinical benefit. Therefore, identifying biomarkers of response to ICI is crucial to guide treatment decisions. The most evaluated biomarkers to date are programmed death ligand 1 expression, microsatellite instability/defective mismatch repair phenotype, and tumor mutational burden. Other emerging biomarkers, such as circulating tumor DNA and microbiota, require evaluation in clinical trials. This review aims to examine these biomarkers for ICI response in urothelial cancer and assess their analytical and clinical validation.

Initial Active Surveillance Strategy for Patients with Peripheral Sporadic Primary Desmoid-Type Fibromatosis: A Multicentric Phase II Observational Trial.

BACKGROUND: Stabilization or spontaneous regressions are demonstrated in more than half of patients affected by primary desmoid-type fibromatosis (DF) in retrospective studies. The objective of this phase II study was to prospectively assess the behavior of primary sporadic DT managed by active surveillance (AS). METHODS: This prospective, multicenter, observational study (NCT01801176) included patients ≥18 years of age with primary sporadic DF located in an extremity or the abdominal/thoracic wall. At inclusion, all patients were initially placed on AS. Follow-up was based on clinical and radiological evaluation by magnetic resonance imaging (MRI) performed at 1, 3, 6, 9, and 12 months, and then every 6 months for 3 years. The primary endpoint was progression-free survival (PFS) at 3 years according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as evaluated by a Central Review Board. RESULTS: Between 2012 and 2015, 100 patients were enrolled. The female/male ratio was 8 and the median age was 34 years (interquartile range [IQR] 30.8-43.9). Median follow-up was 46.6 months (IQR 36.8-61.1) and the 3-year PFS was 53.4% (95% confidence interval 43.5-63.1%). At progression (48 patients), 23 patients received active treatment. Fifty-eight patients (58%) presented with spontaneous tumor regression (decrease > 0% compared with the initial size) during the first 3 months (n = 35, 35%) or after an initial progression (n = 23, 23%), of whom 26 (26%) had partial responses (PRs). The median time to PR was 31.7 months (25.3-not available). CONCLUSIONS: These data support the use of AS as the primary approach to select patients with peripheral DF who require aggressive treatment.

Maintenance Therapy With Cetuximab After FOLFIRI Plus Cetuximab for RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial.

Importance: The optimal maintenance strategy after induction chemotherapy with anti-epidermal growth factor receptor antibody for patients with RAS wild-type metastatic colorectal cancer (mCRC) remains to be debated. Objective: To evaluate the efficacy and safety of maintenance therapy with single-agent cetuximab after FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) plus cetuximab induction therapy. Design, Setting, and Participants: The TIME (Treatment After Irinotecan-Based Frontline Therapy: Maintenance With Erbitux]) (PRODIGE 28 [Partenariat de Recherche en Oncologie Digestive]-UCGI 27 [UniCancer GastroIntestinal Group]) phase 2 noncomparative, multicenter randomized clinical trial was conducted from January 15, 2014, to November 23, 2018, among 139 patients with unresectable RAS wild-type mCRC. The cutoff date for analysis was July 21, 2022. Interventions: After first-line induction therapy with 8 cycles of FOLFIRI plus cetuximab, patients without disease progression were randomized (1:1) to biweekly maintenance with cetuximab or observation. On disease progression, the same induction regimen was recommended for 16 weeks followed by further maintenance with cetuximab or observation until disease progression under the full induction regimen. Main Outcomes and Measures: The primary end point was the 6-month progression-free rate from randomization. Analysis was performed on an intention-to-treat basis. An exploratory biomolecular analysis, using next-generation sequencing, investigated the putative prognostic value of the tumor mutation profile. Results: Of 214 patients enrolled (141 men [65.9%]; median age, 67 years [range, 23-85 years]), 139 were randomized to receive cetuximab (n = 67; 45 men [67.2%]; median age, 64 years [range, 34-85 years]) or to be observed (n = 72; 50 men [69.4%]; median age, 68 years [23-85 years]). The 6-month progression-free rate was 38.8% ([26 of 67] 95% CI, 27.1%-51.5%) in the cetuximab group and 5.6% ([4 of 72] 95% CI, 1.5%-13.6%) in the observation group. At a median follow-up of 40.5 months (95% CI, 33.6-47.5 months), median progression-free survival (PFS) from randomization was 5.3 months (95% CI, 3.7-7.4 months) in the cetuximab group and 2.0 months (95% CI, 1.8-2.7 months) in the observation group. Median overall survival (OS) was 24.8 months (95% CI, 18.7-30.4 months) in the cetuximab group and 19.7 months (95% CI, 13.3-24.4 months) in the observation group. In an exploratory multivariate analysis, any tumor-activating mutation in the mitogen-activated protein kinase (MAPK) pathway genes was associated with shorter PFS from randomization regardless of treatment group (hazard ratio, 1.63 [95% CI, 1.01-2.62]; P = .04). The most frequent grade 3 or 4 treatment-related toxic effect in the cetuximab group during maintenance therapy was rash (8 of 67 [11.9%]). Conclusion and Relevance: The randomized clinical trial did not meet its primary end point but suggests clinically meaningful PFS and OS benefits associated with cetuximab maintenance therapy. However, maintenance cetuximab or treatment breaks after first-line combination FOLFIRI-cetuximab therapy seems inappropriate for patients with MAPK-mutated independently of the side of primary tumor. A more complete assessment of MAPK pathway mutations warrants further investigation to the refine treatment strategy for patients with RAS wild-type mCRC. Trial Registration: ClinicalTrials.gov Identifier: NCT02404935.

[Contribution of whole-body MRI to the initial assessment of myxoid liposarcoma]. / Apport de l'IRM corps entier au bilan initial du liposarcome myxoïde.

INTRODUCTION: Myxoid liposarcoma is a soft tissue sarcoma associated with multifocal metastases at diagnosis. These metastases are asymptomatic and occult on CT and FDG-PET and can alter the therapeutic management and prognosis. In this context, we evaluated the contribution of whole-body MRI to the initial workup of patients with myxoid liposarcoma. METHOD: This retrospective study was conducted between January 2015 and December 2020 at the Oscar Lambret Center. We enrolled 22 patients who were diagnosed with myxoid liposarcoma and underwent whole-body MRI at diagnosis. The number of metastases at diagnosis, their location, and the visibility of these lesions on CT were evaluated. Associations between clinical features, presence of metastasis, and their impact on management were assessed. RESULTS: Sixteen patients (72.7%) had non-metastatic disease at the initial diagnosis, and 15 of these patients were managed using local treatment. Six patients (27.3%) had metastases at multiple locations and received chemotherapy. The main locations were the bones (n=5) and lungs (n=3). In five patients with metastases, whole-body MRI demonstrated additional lesions that were not visible on CT (bone and soft tissue lesions). Only the presence of a round cell contingent (P=0.009) was found as a criterion associated with the presence of metastases. CONCLUSION: The patients' young age, absence of reliable prognostic factors at diagnosis, asymptomatic nature of the lesions, and the benefits of early and targeted therapeutic management encourage the use of whole-body MRI as part of the initial work-up as it seems to provide a better initial staging compared with conventional imaging.

Pembrolizumab in patients with rare and ultra-rare sarcomas (AcSé Pembrolizumab): analysis of a subgroup from a non-randomised, open-label, phase 2, basket trial.

BACKGROUND: Sarcoma is a heterogeneous group of diseases with few treatment options. Immunotherapy has shown little activity in studies including unselected sarcomas, but immune checkpoint blockers have shown activity in specific histotypes. We evaluated the activity of pembrolizumab in rare and ultra-rare sarcomas. METHODS: AcSé Pembrolizumab is an ongoing phase 2, basket, multitumour study investigating the activity of pembrolizumab monotherapy in rare cancers. Here, we report the results obtained in patients with selected histotypes of rare sarcomas (incidence of less than one case per 1 000 000 people per year) recruited at 24 French hospitals. Key inclusion criteria were age 15 years or older, Eastern Cooperative Oncology Group performance status of 0-1, and advanced disease that was untreated and resistant to treatment. Patients were given pembrolizumab 200 mg intravenously on day 1 of every 21-day cycle for a maximum of 24 months. The primary endpoint was objective response rate at week 12 using Response Evaluation Criteria in Solid Tumours version 1.1, assessed by local investigators. The primary endpoint and safety were analysed in the intention-to-treat population. The AcSé Pembrolizumab study is registered with ClinicalTrials.gov, NCT03012620. FINDINGS: Between Sept 4, 2017, and Dec 29, 2020, 98 patients were enrolled, of whom 97 received treatment and were included in analyses (median age 51 years [IQR 35-65]; 53 [55%] were male; 44 [45%] were female; no data were collected on race or ethnicity). 34 (35%) patients had chordomas, 14 (14%) had alveolar soft part sarcomas, 12 (12%) had SMARCA4-deficient sarcomas or malignant rhabdoid tumours, eight (8%) had desmoplastic small round cell tumours, six (6%) had epithelioid sarcomas, four (4%) had dendritic cell sarcomas, three (3%) each had clear cell sarcomas, solitary fibrous tumours, and myxoid liposarcomas, and ten (10%) had other ultra-rare histotypes. As of data cutoff (April 11, 2022), median follow-up was 13·1 months (range 0·1-52·8; IQR 4·3-19·7). At week 12, objective response rate was 6·2% (95% CI 2·3-13·0), with no complete responses and six partial responses in the 97 patients. The most common grade 3-4 adverse events were anaemia (eight [8%] of 97), alanine aminotransferase and aspartate aminotransferase increase (six [6%]), and dyspnoea (five [5%]). 86 serious adverse events were reported in 37 patients. Five deaths due to adverse events were reported, none of which were determined to be related to treatment (two due to disease progression, two due to cancer, and one due to unknown cause). INTERPRETATION: Our data show the activity and manageable toxicity of pembrolizumab in some rare and ultra-rare sarcoma histotypes, and support the PD-1/PD-L1 pathway as a potential therapeutic target in selected histotypes. The completion of the basket study will provide further evidence regarding the activity and toxicity of pembrolizumab in identified rare types of cancer. FUNDING: The Ligue contre le cancer, INCa, MSD. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Taxanes Versus Androgen Receptor Therapy as Second-Line Treatment for Castrate-Resistant Metastatic Prostate Cancer After First-Line Androgen Receptor Therapy.

BACKGROUND: The optimal therapeutic sequence for metastatic castrate-resistance prostate cancer (mCRPC) is still debated. This study aimed to compare activity of taxanes (TAX) versus that of androgen-receptor therapy (ART) in men with mCRPC treated with first-line ART. PATIENTS AND METHODS: This retrospective study included all consecutive chemo-naive mCRPC patients who have received first-line ART treatment. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with second-line ART or TAX. RESULTS: Overall, 175 patients treated with first-line enzalutamide (ENZA, n = 75) or abiraterone (ABI, n = 100) were evaluated. Among them, 69 (39%) and 30 (17%) patients received second-line TAX and ART, respectively, while 76 (43%) patients did not receive further treatment. From the start of first-line therapy, the median PFS and OS were 13 months (95% CI: 11-15) and 34 months (95% CI: 29-39), respectively, without any significant difference between ENZA and ABI. From the start of second-line therapy, the median PFS and OS were 6 months (95% CI: 5-7) and 18 months (95% CI: 14-21), respectively. Compared with ART, docetaxel was associated with significantly higher prostate-specific antigen (PSA, ≥ 50%) (29% vs. 0%, P < .001) and radiological responses (21% vs. 0%, P < .001). PFS was longer in TAX than in ART (6.7 months vs. 4 months, HR: 0.63, 95% CI: 0.41-0.96, P = .034), but there was no significant difference in OS (19 months vs. 12 months, P = .1). After propensity score adjustment, PFS (P = .2) and OS (P = .1) were similar between second-line TAX and ART. CONCLUSION: In the second-line setting, TAX provides higher PSA and radiological responses than does ART for mCRPC patients who received first-line ART, but the PFS and OS are similar. This study provides new elements to help deciding the best treatment sequence.

Pain in desmoid-type fibromatosis: Prevalence, determinants and prognosis value.

The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected patients from the ALTITUDES cohort (NCT02867033), managed by surgery, active surveillance or systemic treatments, with pain assessment at diagnosis. Patients were invited to fill QLQ-C30 questionnaire and Hospital Anxiety Depression Scale. Determinants were identified using logistic models. Prognostic value on event-free survival (EFS) was evaluated using the Cox model. Overall, 382 patients were included in the current study (median age: 40.2 years; 117 men). The prevalence of pain was 36%, without significant difference according to first-line treatment (P = .18). In the multivariate analysis, pain was significantly associated with tumor size >50 mm (P = .013) and tumor site (P < .001); pain was more frequent in the neck and shoulder locations (odds ratio: 3.05 [1.27-7.29]). Pain at baseline was significantly associated with poor quality of life (P < .001), depression (P = .02), lower performance status (P = .03) and functional impairment (P = .001); we also observed a nonsignificant association with anxiety (P = .10). In the univariate analysis, baseline pain was associated with poor EFS; the 3-year EFS was 54% in patients with pain compared to 72% in those without pain. After adjustment for sex, age, size and line of treatment, pain was still associated with poor EFS (hazard ratio: 1.82 [1.23-2.68], P = .003). One third of recently diagnosed patients with DF experienced pain, especially those with larger tumors and neck/shoulder locations. Pain was associated with unfavorable EFS after adjustment for the confounders.

Intracranial Solitary Fibrous Tumour Management: A French Multicentre Retrospective Study.

BACKGROUND: Intracranial solitary fibrous tumour (iSFT) is an exceptional mesenchymal tumour with high recurrence rates. We aimed to analyse the clinical outcomes of newly diagnosed and recurrent iSFTs. METHODS: We carried out a French retrospective multicentre (n = 16) study of histologically proven iSFT cases. Univariate and multivariate Cox models were used to estimate the prognosis value of the age, location, size, WHO grade, and surgical extent on overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS). RESULTS: Eighty-eight patients were included with a median age of 54.5 years. New iSFT cases were treated with gross tumour resection (GTR) (n = 75) or subtotal resection (STR) (n = 9) and postoperative radiotherapy (PORT) (n = 32, 57%). The median follow-up time was 7 years. The median OS, PFS, and LRFS were 13 years, 7 years, and 7 years, respectively. Forty-two patients experienced recurrence. Extracranial metastasis occurred in 16 patients. Median OS and PFS after the first recurrence were 6 years and 15.4 months, respectively. A higher histological grade was a prognosis factor for PFS (p = 0.04) and LRFS (p = 0.03). GTR influenced LRFS (p = 0.03). CONCLUSION: GTR provided benefits as a first treatment for iSFTs. However, approximately 40% of patients experienced relapse, which remains a challenging state.

Effect of medical staff training on vaccination coverage in outpatients with cancer: An interventional multicenter before-and-after study.

Purpose: Despite widely disseminated guidelines, pneumococcal and influenza vaccination coverage (VC) remains insufficient in patients with cancer receiving cancer treatment. We performed an interventional study to evaluate VC in patients with cancer treated at the medical oncology departments of three North-of-France hospitals and to assess the effect of medical staff training on VC in these patients. Methods: A standardized questionnaire assessed VC in adult patients with cancer receiving anticancer treatment at three day hospitals during December 2-7, 2019. Subsequently (January 2020), we organized educational training sessions for medical staff from each hospital to discuss the current vaccination guidelines. To assess the impact of training on pneumococcal and influenza VC, we re-administered the same questionnaire in March 2020. Because there are no specific guidelines on Diphtheria-Tetanus-Pertussis (DTP) vaccination and no improvement was expected, DTP VC acted as an internal control. Results: In total, 272 patients from all three hospitals were enrolled in the "before study"; 156 patients from only two hospitals were enrolled in the "after study" as medical training and data collection at the third were impossible because of administrative reasons and COVID-19 pandemic. The predictors were age for DTP VC; treatment center for pneumococcal VC; and age, sex, and tumor histology (adenocarcinoma vs. others) for influenza VC. Neither influenza VC (42.6% vs. 55.1%, p = 0.08), nor pneumococcal VC were significantly improved post-intervention (11.8% vs. 15.4%, p = 1). There seems to be a small effect in the most fragile for influenza VC. Conclusion: As expected, VC was very low in patients with cancer, consistent with the literature. There was no impact of the intervention for pneumococcal and influenza VC.