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Glioblastoma (GBM) is frequent in elderly patients, but their frailty provokes debate regarding optimal treatment in general, and the standard 6-week chemoradiation (CRT) in particular, although this is the mainstay for younger patients. All patients with newly diagnosed GBM and age ≥ 70 who were referred to our institution for 6-week CRT were reviewed from 2004 to 2018. MGMT status was not available for treatment decision at that time. The primary endpoint was overall survival (OS). Secondary outcomes were progression-free survival (PFS), early adverse neurological events without neurological progression ≤ 1 month after CRT and temozolomide hematologic toxicity assessed by CTCAE v5. 128 patients were included. The median age was 74.1 (IQR: 72–77). 15% of patients were ≥ 80 years. 62.5% and 37.5% of patients fulfilled the criteria for RPA class I–II and III–IV, respectively. 81% of patients received the entire CRT and 28% completed the maintenance temozolomide. With median follow-up of 11.7 months (IQR: 6.5–17.5), median OS was 11.7 months (CI 95%: 10–13 months). Median PFS was 9.5 months (CI 95%: 9–10.5 months). 8% of patients experienced grade ≥ 3 hematologic events. 52.5% of patients without neurological progression had early adverse neurological events. Post-operative neurological disabilities and age ≥ 80 were not associated with worsened outcomes. 6-week chemoradiation was feasible for “real-life” elderly patients diagnosed with glioblastoma, even in the case of post-operative neurological disabilities. Old does not necessarily mean worse.

Hyperthermic intraperitoneal chemotherapy (HIPEC) at interval cytoreductive surgery for ovarian cancer improves overall survival but its role in recurrent disease is uncertain. We aimed to compare outcomes in patients treated with or without HIPEC during surgery for recurrent ovarian cancer. The multicentre, open-label, randomised, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada, and enrolled patients with first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Eligible patients were aged 18 years or older with WHO performance status of less than 2. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients amenable to complete cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimisation procedure, during surgery to receive HIPEC (cisplatin 75 mg/m2 in 2 L/m2 of serum at 41±1°C for 60 min) or not, stratified by centre, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly(ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analysed on an intention-to-treat basis in all randomly assigned patients. This ongoing trial is registered with ClinicalTrials.gov, NCT01376752. Between May 11, 2011, and May 14, 2021, 415 female patients were randomly assigned (207 HIPEC, 208 no HIPEC). At the primary analysis (median follow-up 6·2 years, IQR 4·1–8·1), 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group). Overall survival was significantly improved with HIPEC (stratified hazard ratio 0·73, 95% CI 0·56–0·96; p=0·024). Median overall survival was 54·3 months (95% CI 41·9–61·7) with HIPEC versus 45·8 months (38·9–54·2) without. Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC, the most common being anaemia (47 [23%] vs 30 [14%]), hepatotoxicity (23 [11%] vs 18 [9%]), electrolyte disturbance (28 [14%] vs two [1%]), and renal failure (20 [10%] vs three [1%]). There were three deaths within 60 days of surgery, all in the no-HIPEC group. Adding HIPEC to cytoreductive surgery after response to platinum-based chemotherapy at first epithelial ovarian cancer recurrence significantly improved overall survival. When treating patients with late first relapse of high-grade serous or high-grade endometrioid ovarian cancer amenable to complete cytoreductive surgery at specialist centres, platinum-based HIPEC should be considered to extend overall survival. French National Cancer Institute and French League Against Cancer.

Radiotherapy can diminish quality of life (QoL) for prostate cancer patients. Our objective was to evaluate the effect of radiotherapy on QoL in men aged 75 years or older treated with radiotherapy for a localized prostate cancer, and to identify predictors of reduced QoL. We prospectively administered a battery of geriatric (MNA, GDS, Get up and Go Test, CIRS-G, ADL, IADL, MMSE), toxicity (IPSS; IIEF 5), and QoL (QLQ C30) screening tests in 100 elderly patients before and two months after prostate cancer radiotherapy (NCT 02876237). Patients ≥ 75 years undergoing radiotherapy with a curative intent for localized prostate cancer with or without androgen deprivation therapy (ADL) were eligible for study inclusion. Correlations between patient-assessed QoL and tumor characteristics, radiotherapy treatment or CGA parameters were sought using the Fisher or the Mann and Whitney tests. Changes in QoL parameters over time were analyzed using the Wilcoxon signed-rank test. At study entry, scores for IADL impairments were present in 51%, reduced autonomy in activities of daily living in 16%, cognitive impairment found in 20%, depression-related symptoms in 31%, and 66% of patients had significant co-morbidities. Eight percent were judged to be at risk of fall and 2% were found to be undernourished. Severely impaired (IPSS ≥ 20) urinary function was observed in 11.2% and 13.5% of patients before and two months after completion of radiotherapy respectively. Significantly decreased QoL (> 20 points) at two months after treatment was found in 13% of patients and a moderate but clinically relevant reduction (10 to 20 points) in 17% of patients. No tumor characteristic, treatment, or oncogeriatric parameter was predictive of reduced QoL following prostate cancer radiotherapy. Despite sometimes markedly diminished oncogeriatric parameters, prostate cancer radiotherapy was generally well tolerated in these elderly patients. We found no predictive factor to determine which patients would experience impaired quality of life following radiotherapy.

Five‐year overall survival (OS) of localized RMS exceeds 70% in children (<18) but is very poor in adult patients. We analyzed the outcome and prognostic factors (PF) of a national series of adult patients with RMS in a large study. The study population consisted of two different cohorts: a retrospective cohort (157 adult patients treated in 13 reference centers between 05/1981 and 02/2010) and the prospective cohort (292 patients with RMS diagnosed and treated between 01/2010 and 12/2014 in France) included in the NetSarc database. A descriptive analysis of patients’ characteristics and prognostic factors was conducted on both series which were compared. In the retrospective series, histological subtypes were embryonal (E‐RMS) for 21% of patients, alveolar (A‐RMS) for 35% of patients, and “adult‐type” P‐RMS (pleomorphic, spindle cell RMS, not otherwise specified) (P) for 44% patients. This distribution significantly differed in the prospective cohort: A‐RMS: 18%; E‐RMS: 17%; and P‐RMS 65%. With a median follow‐up of 8.5 years, 5‐year OS for localized RMS and advanced RMS (with nodes and/or metastases) was 43% and 5%, respectively, (P < 0.0001), and median OS was 51, 33, and 16 months for E‐RMS, A‐RMS, and P‐RMS, respectively, in the retrospective cohort. The median OS was less than 40 months for the prospective nationwide cohort for the entire population. In a multivariate analysis of the retrospective study, independent prognostic factors for OS were A‐RMS, R0 resection, and adjuvant radiotherapy (RT). For localized RMS, age and use of pediatric chemotherapy (CT) regimen are independent prognostic factors. Adult patients with RMS have a poorer overall survival than pediatric patients, and survival varies considerably across histological subtypes. This is the largest study analyzing all factors in univariate analysis and multivariate analysis for localized and metastatic isease and for each histological subtype. Specific management for A‐RMS and E‐RMS using a pediatric protocol chemotherapy and carcinologic surgery is the cornerstone to improving survival. The FSG experience emphasizes the urgent need to build a worldwide clinical trial using these rare entities that exhibit a dismal prognosis.

The prognosis of medullary thyroid carcinoma (MTC) varies from long- to short-term survival based on such prognostic factors as serum calcitonin and carcinoembryonic antigen (CEA) doubling times (DTs). This prospective phase II multicenter trial evaluated the efficacy and safety of anti-CEA pretargeted radioimmunotherapy (pRAIT) in rapidly progressing metastatic MTC patients and also how serum biomarker DTs correlate with clinical outcome. From June 2004 to January 2008, 42 patients were treated with anti-CEA × anti-diethylenetriaminepentaacetic acid (DTPA) bispecific antibody (hMN-14 × m734) (40 mg/m(2)), followed by (131)I-di-DTPA-indium bivalent hapten (1.8 GBq/m(2)) 4-6 d later. The disease control rate (durable stabilization plus objective response) was 76.2%. Grade 3-4 hematologic toxicity was observed in 54.7% of patients and myelodysplastic syndrome in 2, including 1 heavily treated previously. After pRAIT, 21 of 37 assessed patients (56.7%) showed a significant impact on DT (≥100% increase of pre-pRAIT calcitonin or CEA DT or prolonged decrease of the biomarker concentration after pRAIT). Pre-pRAIT DT and post-pRAIT DT were significant independent predictors for overall survival (OS) from pRAIT (pre-pRAIT: hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24-0.86; P = 0.016; and post-pRAIT: HR, 5.32; 95% CI, 1.63-17.36; P = 0.006) and OS from diagnosis (pre-pRAIT: HR, 0.21; 95% CI, 0.08-0.51; P = 0.001; and post-pRAIT: HR, 6.16; 95% CI, 1.81-20.98; P = 0.004). pRAIT showed antitumor activity, with manageable hematologic toxicity in progressive MTC. Increased biomarker DT after treatment correlated with increased OS.

Background Anti-apoptotic signals induced downstream of HER2 are known to contribute to the resistance to current treatments of breast cancer cells that overexpress this member of the EGFR family. Whether or not some of these signals are also involved in tumor maintenance by counteracting constitutive death signals is much less understood. To address this, we investigated what role anti- and pro-apoptotic Bcl-2 family members, key regulators of cancer cell survival, might play in the viability of HER2 overexpressing breast cancer cells. Methods We used cell lines as an in vitro model of HER2-overexpressing cells in order to evaluate how anti-apoptotic Bcl-2, Bcl-xL and Mcl-1, and pro-apoptotic Puma and Bim impact on their survival, and to investigate how the constitutive expression of these proteins is regulated. Expression of the proteins of interest was confirmed using lysates from HER2-overexpressing tumors and through analysis of publicly available RNA expression data. Results We show that the depletion of Mcl-1 is sufficient to induce apoptosis in HER2-overexpressing breast cancer cells. This Mcl-1 dependence is due to Bim expression and it directly results from oncogenic signaling, as depletion of the oncoprotein c-Myc, which occupies regions of the Bim promoter as evaluated in ChIP assays, decreases Bim levels and mitigates Mcl-1 dependence. Consistently, a reduction of c-Myc expression by inhibition of mTORC1 activity abrogates occupancy of the Bim promoter by c-Myc, decreases Bim expression and promotes tolerance to Mcl-1 depletion. Western blot analysis confirms that naïve HER2-overexpressing tumors constitutively express detectable levels of Mcl-1 and Bim, while expression data hint on enrichment for Mcl-1 transcripts in these tumors. Conclusions This work establishes that, in HER2-overexpressing tumors, it is necessary, and maybe sufficient, to therapeutically impact on the Mcl-1/Bim balance for efficient induction of cancer cell death.

The aim of this multicentric study was to prospectively compare 68Ga-DOTANOC PET/CT versus somatostatin receptor scintigraphy (SRS) with SPECT/CT, combined with multiphasic CT scan and MRI in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET). Patients with histologically proven grade 1 or 2 GEP-NET with suspicion of recurrence or progression, or with typical aspects of GEP-NET on morphological imaging, were explored with conventional imaging (CI): SRS with SPECT/CT, multiphasic CT scan and/or liver MRI followed by 68Ga-DOTANOC PET/CT. The gold standard was based on histology and imaging follow-up. The data of 105 patients (45 woman and 60 men; median age) were analyzed. 68Ga-DOTANOC PET/CT sensitivity was significantly higher than CI sensitivity in per-patient (98.9% vs. 88.6%, p = 0.016) and per-region (97.6% vs. 75.6%, p < 0.001) analyses, in the detection of the primary (97.9% vs. 78.7%; p = 0.016), peritoneal carcinomatosis (95% vs. 30%, p < 0.001), and bone metastases (100% vs. 33.3%, p = 0.041). 68Ga-DOTANOC PET/CT had an impact on the therapeutic management of 41.9% (44/105) patients compared to decisions based on CI explorations. Our data confirm the superiority of 68Ga-DOTANOC PET/CT over CI in the detection of peritoneal carcinomatosis and bone metastasis, as well as its strong therapeutic impact on the management of patients with grade 1-2 GEP-NETs.

Introduction Triple-negative breast cancers need to be refined in order to identify therapeutic subgroups of patients. Methods We conducted an unsupervised analysis of microarray gene-expression profiles of 107 triple-negative breast cancer patients and undertook robust functional annotation of the molecular entities found by means of numerous approaches including immunohistochemistry and gene-expression signatures. A triple-negative external cohort ( n  = 87) was used for validation. Results Fuzzy clustering separated triple-negative tumours into three clusters: C1 (22.4%), C2 (44.9%) and C3 (32.7%). C1 patients were older (mean = 64.6 years) than C2 (mean = 56.8 years; P  = 0.03) and C3 patients (mean = 51.9 years; P  = 0.0004). Histological grade and Nottingham prognostic index were higher in C2 and C3 than in C1 ( P  < 0.0001 for both comparisons). Significant event-free survival ( P  = 0.03) was found according to cluster membership: patients belonging to C3 had a better outcome than patients in C1 ( P  = 0.01) and C2 ( P  = 0.02). Event-free survival analysis results were confirmed when our cohort was pooled with the external cohort ( n  = 194; P  = 0.01). Functional annotation showed that 22% of triple-negative patients were not basal-like (C1). C1 was enriched in luminal subtypes and positive androgen receptor (luminal androgen receptor). C2 could be considered as an almost pure basal-like cluster. C3, enriched in basal-like subtypes but to a lesser extent, included 26% of claudin-low subtypes. Dissection of immune response showed that high immune response and low M2-like macrophages were a hallmark of C3, and that these patients had a better event-free survival than C2 patients, characterized by low immune response and high M2-like macrophages: P  = 0.02 for our cohort, and P  = 0.03 for pooled cohorts. Conclusions We identified three subtypes of triple-negative patients: luminal androgen receptor (22%), basal-like with low immune response and high M2-like macrophages (45%), and basal-enriched with high immune response and low M2-like macrophages (33%). We noted out that macrophages and other immune effectors offer a variety of therapeutic targets in breast cancer, and particularly in triple-negative basal-like tumours. Furthermore, we showed that CK5 antibody was better suited than CK5/6 antibody to subtype triple-negative patients.

Gene prognostic meta-analyses should benefit from breast tumour genomic data obtained during the last decade. The aim was to develop a user-friendly, web-based application, based on DNA microarrays results, called “breast cancer Gene-Expression Miner” (bc-GenExMiner) to improve gene prognostic analysis performance by using the same bioinformatics process. bc-GenExMiner was developed as a web-based tool including a MySQL relational database. Survival analyses are performed with R statistical software and packages. Molecular subtyping was performed by means of three single sample predictors (SSPs) and three subtype clustering models (SCMs). Twenty-one public data sets have been included. Among the 3,414 recovered breast cancer patients, 1,209 experienced a pejorative event. Molecular subtyping by means of three SSPs and three SCMs was performed for 3,063 patients. Furthermore, three robust lists of stable subtyped patients were built to maximize reliability of molecular assignment. Gene prognostic analyses are done by means of univariate Cox proportional hazards model and may be conducted on cohorts split by nodal (N), oestrogen receptor (ER), or molecular subtype status. To evaluate independent prognostic impact of genes relative to Nottingham Prognostic Index and Adjuvant! Online, adjusted Cox proportional hazards models are performed. bc-GenExMiner allows researchers without specific computation skills to easily and quickly evaluate the in vivo prognostic role of genes in breast cancer by means of Cox proportional hazards model on large pooled cohorts, which may be split according to different prognostic parameters: N, ER, and molecular subtype. Prognostic analyses by molecular subtype may also be performed in three robust molecular subtype classifications.

The objective of this retrospective work was to evaluate the prognostic value on histological response and survival of quantitative indices derived from FDG-PET performed before and after chemotherapy (CHT), in a homogeneous pediatric Ewing sarcoma (EWS) and Osteosarcoma (OST) population. Thirty-one patients with EWS and 31 with OST were included. All patients were treated with neoadjuvant CHT, and underwent surgery for local control. All patients had FDG-PET at diagnosis and after CHT, prior to surgery. Several parameters were evaluated: SUVmax, SUVpeak, SUVmean, metabolic tumor volume, total lesion glycolysis, 7 textural features and 3 shape features (SF). The segmentation was performed using an adaptive approach. Results were compared to histopathological regression of the resected tumor and to clinical follow-up for survival evaluation. For EWS, univariate analysis did not highlight any prognostic value on histological response, or survival regardless of all the considered metrics. For OST, only one of the SF, namely elongation, was significantly associated with PFS and OS on both univariate and multivariate analysis (PFS: p = 0.019, HR = 5.583; OS: p = 0.0062, HR = 7.113). Only elongation determined on initial FDG-PET has a potential interest as a prognostic factor of PFS and OS in pediatric OST patients. Unlike recent studies of the literature realized in adult population, all the metrics reveal limited additional prognostic value in pediatric EWS patients. This seems to reinforce the question of whether children experience different subtypes of the same pathologies than older patients, with different outcomes.