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Background: Based on preclinical studies showing that IDH-mutant (IDHm) gliomas could be vulnerable to PARP inhibition we launched a multicenter phase 2 study to test the efficacy of olaparib monotherapy in this population., Methods: Adults with recurrent IDHm high-grade gliomas (HGGs) after radiotherapy and at least one line of alkylating chemotherapy were enrolled. The primary endpoint was a 6-month progression-free survival rate (PFS-6) according to response assessment in neuro-oncology criteria. Pre-defined threshold for study success was a PFS-6 of at least 50%., Results: Thirty-five patients with recurrent IDHm HGGs were enrolled, 77% at ≥ 2nd recurrence. Median time since diagnosis and radiotherapy were 7.5 years and 33 months, respectively. PFS-6 was 31.4% (95% CI [16.9; 49.3%]). Two patients (6%) had an objective response and 14 patients (40%) had a stable disease as their best response. Median PFS and median overall survival were 2.05 and 15.9 months, respectively. Oligodendrogliomas (1p/19q codeleted) had a higher PFS-6 (53.4% vs. 15.7%, P  = .05) than astrocytomas while an initial diagnosis of grade 4 astrocytoma tended to be associated with a lower PFS-6 compared to grade 2/3 gliomas (0% vs 31.4%, P  = .16). A grade 2 or 3 treatment-related adverse event was observed in 15 patients (43%) and 5 patients (14%), respectively. No patient definitively discontinued treatment due to side effects., Conclusions: Although it did not meet its primary endpoint, the present study shows that in this heavily pretreated population, olaparib monotherapy was well tolerated and resulted in some activity, supporting further PARP inhibitors evaluation in IDHm HGGs, especially in oligodendrogliomas., Competing Interests: I.E.: none. M.S.: none. O.C.: none. M.F.: research purposes from Servier company, benefits for interventions from Seagen and Novocure, and payment of congress fees from Gilead and Pfizer. R.R.: Advisory board (Daiichi Sankyo, Lilly), travel grants (Amgen, Astra Zeneca, Bayer HealthCare SAS, Daiichi Sankyo, Lilly, MSD France, Novartis Pharma SAS, Pfizer, Roche). S.C.: MSD (travel grant). E.T.: Gliocure, Leo Pharma (advisory board), Leo Pharma (research grant), Novocure, Servier (symposium. A.B-L.: none. A. D.: Servier, Novocure (advisory board), Servier (travel grants). D.M.: none. M.B.: none. F.G.: none. L.R.: none. D.M-B.: none. J.H.: Novocure (travel grants, advisory board). C.D.: none. F.D.: Servier, Novocure (advisory board, symposium)., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Introduction: MVAC (Methotrexate, Vinblastine, Adriamycin, and Cisplatin) neoadjuvant chemotherapy a standard treatment for invasive bladder cancer is associated with mainly haematological toxicities. Randomized clinical trials remain a gold standard for treatment outcomes and efficacy assessment. Patients enrolled in clinical trials are selected and tend to benefit from a stricter follow-up unlike everyday clinical practice patients. Conversely, real-life observational studies better define the effectiveness of treatments in clinical routine practice. The aim of this study is to analyse the impact of clinical trial monitoring on MVAC-related toxicities., Material and Methods: Patients with an infiltrative localized bladder cancer treated by MVAC neoadjuvant chemotherapy between 2013 and 2019 were enrolled, and divided into 2 groups: patients included in a clinical trial namely "VESPER study" during their treatment and patients treated in clinical routine practice., Results: Out of 59 patients were enrolled in this retrospective study, 13 patients were included in a clinical trial. Clinical characteristics were similar between the 2 groups. Comorbidities were more frequent in the nonclinical trial group (NCTG). Completed 6 cures treatment proportion was higher in the clinical trial group (CTG) (69.2% vs. 50%). Yet, in this group, patients had more doses reduction (38.5% vs. 19.6%). The proportion of complete pathologic response was higher in patients enrolled in clinical trial (53.8% vs. 39.1%). Statistically, the expected stricter monitoring due to clinical trial enrolment had no impact on the complete pathologic response and clinically relevant toxicities., Discussion: When compared to conventional clinical practice, clinical trial enrolment induced no significant difference on the pathologic complete response or toxicity rate. Further large prospective studies are needed to confirm these data., Competing Interests: Disclosure No conflicts of interest to disclose, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Pseudoprogression in gliomas has been extensively described after radiotherapy with or without chemotherapy, but not after chemotherapy alone. Here we describe the occurrence of pseudoprogression in patients with anaplastic oligodendrogliomas treated with postoperative procarbazine, lomustine and vincristine (PCV) chemotherapy alone., Methods: We retrospectively reviewed the medical and radiological files of patients with 1p/19q codeleted, IDH-mutant anaplastic oligodendrogliomas treated with PCV chemotherapy alone who presented magnetic resonance imaging (MRI) modifications suggestive of tumour progression and in whom the final diagnosis was a pseudoprogression., Results: We identified six patients. All patients underwent a surgical resection and were treated with PCV chemotherapy without radiotherapy. After a median of 11 months following the initiation of chemotherapy (range: 3-49 months), the patients developed asymptomatic white matter MRI modifications around the surgical cavity leading to the suspicion of a tumour progression. These modifications appeared as hyperintense on T2-fluid-attenuated inversion recovery (FLAIR) sequence, hypointense on T1 sequence, and lacked mass effect (0/6), contrast enhancement (0/6), restriction on diffusion-weighted imaging (0/4), relative cerebral blood volume (rCBV) increase on perfusion MRI (0/4), and hypermetabolism on 18 F-fluoro-L-dopa positron emission tomography ( 18 F-DOPA PET) scan (0/3). One patient underwent a surgical resection demonstrating no tumour recurrence; the five other patients were considered as having post-therapeutic modifications based on imaging characteristics. After a median follow-up of 4 years all patients were progression-free., Conclusions: Anaplastic oligodendroglioma patients treated with postoperative PCV chemotherapy alone occasionally develop T2/FLAIR hyperintensities around the surgical cavity that can wrongly suggest tumour progression. Multimodal imaging and close follow-up should be considered in this situation., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: PARP inhibitors (PARPi) have revolutionized the management of high-grade epithelial ovarian cancer (HGOC) treatment. However, a significant number of patients relapse or progress under PARPi, leading to the introduction of a new line of systemic therapy such as chemotherapy. In patients with a limited number of metastatic sites at progression, -referred to as an oligometastatic progression- a potential indication for local therapy followed by re-introduction or continuation of PARPi treatment rather than initiating a new line of chemotherapy could be proposed. However, the impact of such strategies on progression free survival (PFS) in these patients remains unknown., Methods: This international multicenter retrospective study evaluated the efficacy of PARPi continuation or re-introduction in patients with HGOC after local treatment for oligometastatic progression. The main objective was to assess PFS under PARPi after local therapy (PFS post-LT). Secondary objectives included safety and overall survival (OS)., Results: 74 patients were identified in 20 centers between April 2020 and November 2021. 65% of patients were BRCA mutated and 92% had received ≥2 lines of prior systemic chemotherapy before the initial introduction of PARPi. Main progression sites were lymph nodes (42%), peritoneum (27%), liver (16%), other visceral (16%) and abdominal wall (4%). Local therapies included radiotherapy (45%), surgery (43%), both (7%), percutaneous thermal ablation (4%) or chemoembolization (1%). Median PFS post-LT was 11.5 months [95% CI 7.4; 17.2]. After a median follow up of 14.8 months, 6 patients (8.1%) discontinued PARPi due to toxicity. The 1-year overall survival rate was 90.7% [95% CI 79.1; 96.0]., Conclusions: With close to one year without progression or introduction of a new line of systemic therapy, this study reports the feasibility and potential benefit of this original strategy in patients with oligometastatic progression under PARPi., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ganglioglioma, pleomorphic xanthoastrocytoma (PXA) and pilocytic astrocytoma are rare brain neoplasms with frequent activation of mitogen-activated protein (MAP) kinase pathway. A downstream marker of MAP-kinase pathway activation is cyclin D1. However, the expression of cyclin D1 has not been studied in the differential diagnosis between these brain tumors. The aim of this work is to compare the expression of cyclin D1 in ganglioglioma, PXA, pilocytic astrocytoma. We also compared cyclin D1 expression in giant cell glioblastoma and in IDH wild type glioblastoma. Our work shows that roughly half of gangliogliomas have ganglion cells stained by cyclin D1 while two third of PXA have pleormophic cells stained by cyclin D1 and 15% of giant cell glioblastoma have pleomorphic cells stained by cyclin D1 (p < 0.001). Cyclin D1 never stains normal neurons either in the adjacent cortex of circumscribed tumor, or in entrapped neurons in IDH wild type glioblastomas. The expression of cyclin D1 is correlated to the presence of BRAF V600E mutation in ganglioglioma and PXA (p = 0.002). To conclude, cyclin D1 positivity might be used to confirm the neoplastic nature of ganglion cells. Cyclin D1 is expressed in most cases of BRAF V600E mutated gangliogliomas but also in cases without BRAF mutations suggesting an activation of MAP-kinase pathway through another way. Cyclin D1 immunohistochemistry has currently no or little role in the differential diagnosis of pilocytic astrocytoma. Its role in the differential diagnosis between PXA and giant cell glioblastoma needs to be further investigated on external series., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The use of oral cancer drugs (OAD) has increased over the last two decades. The objective of this study was to measure the impact of a nurse-led telephone follow-up in the therapeutic management of patients treated with an OAD regarding toxicity, medication adherence and quality of life., Methods: A randomized, multicenter, controlled trial was conducted. All consecutive over 18-year-old patients, treated in medical oncology, radiotherapy, or hematology departments, receiving OAD for any cancer were invited to participate to the study. A total of 183 patients treated for solid or hematological cancers with an OAD were randomly assigned to receive a nurse-led telephone follow-up or standard care for 24 weeks. Data were collected between 2015 and 2018., Results: Nurse telephone follow-up did not improve the global score toxicity in the intervention group. However, telephone calls directed by trained nurses induced a significant decrease in number of patients with grade 3 adverse events throughout the follow-up [OR 0.45 (IC à 95%) (0.23, 0.9)](P = 0.03). There was no significant difference in quality of life and medication adherence between groups at any follow-up time point., Conclusions: In this first French real-life study, the advice provided by qualified nurses via phone calls improved the management of grade 3 toxicities but failed to demonstrate an improvement of all grades of toxicities. More prospective studies are needed to confirm the impact of telephone calls on the toxicities related to OAD., Trial Registration: Clinical trial registration is NCT02459483. Protection committee SUD-ESTI registration is 2015-A00527-42 on 13 April 2015. National Agency for the Safety of Medicines and Health Products registration is 150619-B on the 27 may 2015.

Meningioma grading relies on several pathological criteria (brain invasion, mitotic count, sheeting, small cell foci, necrosis, macronucleoli and hypercellularity) and histopathological subtypes. Regardless of histopathological subtype, the presence of these pathological parameters can be focally present and not present on each slide of a meningioma. We performed (1) a retrospective work comparing the frequency of parameters used for meningioma grading between two periods with different sampling techniques, and (2) we calculated the probability of presence of each criterion on resected meningiomas entirely processed included and examined. First, we compared two time periods: between 2002-2008 where meningiomas were not all entirely sampled, and between 2012-2018 where all meningiomas were entirely sampled. The frequency of tumour grades was not significantly different between the two periods (p=0.17). Mitosis ≥4/1.6mm 2 , small cell foci, macronucleoli and hypercellularity were more frequently found when meningiomas were entirely sampled (p<0.05). Second, we focused on 59 grade 2 meningiomas entirely sampled to highlight the distribution of histopathological parameters used for meningioma grading. We have shown that a correct grading of more than 95% of meningiomas can be achieved when at least six slides are examined. Our work suggests that meningioma sampling might be an issue and the sampling system must be specified in research works on grading., (Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Rationale: Meningeal melanocytoma is a rare benign melanocytic tumor of the central nervous system. We report for the first time a case of meningeal melanocytoma treated with immunotherapy., Patient Concerns: A 70-year-old man with no medical history was admitted to the Emergency Room. He suffered from a motor and sensory deficit in his left lower limb and a bilateral upper arm neuralgia., Diagnoses: A contrast-enhanced magnetic resonance imaging (MRI) was performed. It showed a C7-T1 bleeding intramedullary tumor. Laminectomy was decided and performed. The results of the pathologic examination showed a melanocytic tumor harboring GNAQ mutation. Meningeal melanocytoma was the final diagnosis., Interventions: The patient was treated with 10 radiotherapy sessions and 6 cycles of nivolumab. A year later, the patient experienced neuralgia again with severe pain and an increasing sensory motor deficit. He underwent a second surgery that was incomplete. As the tumor kept growing, he received temozolomide. But the 6th cycle had to be interrupted due to bedsore infection in the hip area., Outcomes: Disease progression finally led to the patient's death 3 years after diagnosis., Lessons: This case report is the first about a patient with meningeal melanocytoma treated with immunotherapy. Treatment based on biomolecular mutations will probably change spinal melanocytoma therapeutic approach in the next few years., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Immunotherapy is the current treatment in non-small cell lung cancer (NSCLC). 20% of patients treated with immunotherapy have a prolonged response. What about the remaining 80%? How can we explain that some patients get no benefit from immunotherapy?, Materiel and Methods: We retrospectively analyzed predictive factors of primary or secondary resistance to immunotherapy in NSCLC patients from 2 French hospitals between 2015 and 2018. Moreover, we evaluated whether PD1 inhibitor had an impact on the antitumor effects of salvage chemotherapy administered after immunotherapy. We chose to focus on taxanes., Results: Ninety-six patients were included in this cohort, 65(68%) patients were considered as having primary resistance and 31(32%) secondary resistance. Resistant populations did not differ. At immunotherapy initiation, median survival was 4.6 months for primary resistant patients (95%CI-4.6-6.8) and 15.6 months (95%CI-9.8-NA) for secondary resistant patients. The disease control rates with taxane were 15% in pre immunotherapy conditions vs 50% in post immunotherapy. Response rates improved regardless of the status of resistance., Conclusion: This study enriches data about immunotherapy in real-life in NSCLC. Prognostic resistance factors still seem complicated to identify. The high rate of taxane responders in post immunotherapy in this retrospective cohort support the use of taxane in therapeutic escape., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Immune checkpoint inhibitors (ICIs) have become part of cancer treatments. Their main side effects are immune-related adverse events (irAEs). So far, there has been no recommendation regarding routine vaccinations during ICIs treatment. Clinicians are aware of the risk of irAEs increases in this specific situation. The aim of this review of literature is to summarize the main studies about vaccination and ICIs interactions., Methods: A systematic assessment of literature articles was performed by searching in PubMed (MEDLINE), and major oncology meeting following PRISMA guidelines., Results: This review highlights the lack of literature. Indeed, most of the studies published were about influenza vaccination. Vaccination for patients under ICIs causes a humoral response and seems to be associated with an increase rate of seroconversion. Interestingly vaccination may provoke irAEs in ICIs-treated patients. So far, inactivated vaccines have not been contraindicated during ICI treatment., Conclusion: Larger prospective studies are needed in order to define a consensus on the use of vaccines under immunotherapy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Capping body surface area (BSA) at 2 m 2 is a routine clinical practice. It aims at reducing toxicities in over 2 m 2 BSA patients. 455,502 computerized chemotherapy prescriptions made between 2011 and 2017 were taken from BPC software. Chemotherapy computerized order entry is created by a senior physician prescribers before patient consultation. Only prescriptions with dose calculation involving BSA were selected. 51,179 chemotherapy prescriptions were analyzed; corresponding to 7206 patients who received intravenous chemotherapy. The number of chemotherapy prescriptions in over 2 m 2 BSA patients was nearly the same in the hematology as in the oncology departments. But, 79.1% of prescriptions were capped at 2 m 2 in the oncology department contrary to 21.9% in the hematology department. Practices analysis showed more dose limitation in palliative situations in both departments. Unexpectedly, 6.53% of capped prescriptions were performed in patients with normal BMI. The patients who received capped doses of chemotherapy had neither fewer dose reductions due to toxicity nor deterioration of their general condition. Capping did not induce fewer dose reductions in patients with BSA greater than 2 m 2 . Prospective studies in this population are needed to standardize chemotherapy administration in population with BSA > 2 m 2 .

Background: The increase in the number of cancer cases and the evolution of cancer care management have become a significant problem for the French health care system, thereby making patient empowerment as a long sought-after goal in chronic pathologies. The implementation of an activation measure via the Patient Activation Measure-13 item (PAM-13) in the course of cancer care can potentially highlight the patient's needs, with nursing care adapting accordingly., Objective: The objectives of this PARACT (PARAmedical Interventions on Patient ACTivation) multicentric study were as follows: (1) evaluate the implementation of PAM-13 in oncology nursing practices in 5 comprehensive cancer centers, (2) identify the obstacles and facilitators to the implementation of PAM-13, and (3) produce recommendations for the dissemination of such interventions in other comprehensive cancer centers., Methods: This study will follow the "Reach, Effectiveness, Adoption, Implementation, and Maintenance" framework and will consist of 3 stages. First, a robust preimplementation analysis will be conducted using the Theoretical Domains Framework (TDF) linked to the "Capability, Opportunity, Motivation, and Behavior" model to identify the obstacles and facilitators to implementing new nursing practices in each context. Then, using the Behavior Change Wheel, we will personalize a strategy for implementing the PAM-13, depending on the specificities of each context, to encourage acceptability by the nursing staff involved in the project. This analysis will be performed via a qualitative study through semistructured interviews. Second, the patient will be included in the study for 12 months, during which the patient care pathway will be studied, particularly to collect all relevant contacts of oncology nurses and other health professionals involved in the pathway. The axes of nursing care will also be collected. The primary goal is to implement PAM-13. Secondary factors to be measured are the patient's anxiety level, quality of life, and health literacy level. The oncology nurses will be responsible for completing the questionnaires when the patient is at the hospital for his/her intravenous chemotherapy/immunotherapy treatment. The questionnaires will be completed thrice in a year: (1) at the time of the patient's enrollment, (2) at 6 months, and (3) at 12 months. Third, a postimplementation analysis will be performed through semistructured interviews using the TDF to investigate the implementation problems at each site., Results: This study was supported by a grant from the French Ministry of Health (PHRIP PARACT 2016-0405) and the Lucien Neuwirth Institute of Cancerology of Saint-Etienne, France. Data collection for this study is ongoing., Conclusions: This study would improve the implemented targeted nursing interventions in cancer centers so that a patient is offered a personalized cancer care pathway. Furthermore, measuring the level of activation and the implementation of measures intended to increase such activation could constitute a significant advantage in reducing social health inequalities., Trial Registration: ClinicalTrials.gov NCT03240341; https://clinicaltrials.gov/ct2/show/NCT03240341., International Registered Report Identifier (irrid): DERR1-10.2196/17485., (©Elise Verot, Wafa Bouleftour, Corinne Macron, Romain Rivoirard, Franck Chauvin. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 08.12.2020.)

Pleomorphic xanthoastrocytoma (PXA) is classified as an astrocytic glioma occurring most often in children or young adults. Molecular alterations in PXA are not fully known, especially those associated with tumor progression. We describe a patient with several relapses of a PXA. The tumor showed an acquired ATRX loss through tumor evolution. We tested alternative lengthening of telomeres (ALT) with the C-circle test. While the test was negative in the first tumor, a high circle activity was detected in the last relapse, suggesting an acquired ALT phenotype. Our data not only confirm previous findings of the possible occurrence of ATRX mutations in PXA but also suggest that this alteration is linked to PXA progression. In small biopsies, tumors with ATRX loss, without IDH or histone mutation, pathologists should consider the diagnosis of PXA, especially if associated with BRAF V600E mutation, CDKN2A deletion, and ALT., (© 2020 American Association of Neuropathologists, Inc. All rights reserved.)

Introduction: Obesity is a major risk factor for chronic disease and cancer development. Therapeutic management of obese patients with cancer is a real challenge for physician because of the alteration of antineoplastic pharmacokinetics parameters in this population. In routine clinical practices, chemotherapy doses in obese patients are arbitrarily capped or adjusted to an ideal weight to minimize excessive toxicities. Material and methods: The main goal of this review is to describe the current state of knowledge concerning the correlation between the adjustment of BSA (capping or ideal weight) and the rates of global toxicities and survival outcomes in obese patients under chemotherapy in different types of cancer. We searched in the Medline database (via PubMed) in order to identify all publications of literature reviews whose subject chemotherapy dosing in obese population. Results: Only a single study was pointing toward increased of global toxicities of full weight dosing. Furthermore, some studies suggests that the practice of limiting doses in overweight and obese patients may negatively influence the quality of care and outcomes in a constantly increasing population. Conclusion: This review highlights the lack of prospective studies focusing on chemotherapy methods of administration in obese patients. At this time, there is no prospective study comparing capping and full weight dose chemotherapy administration in obese patient population.

Leptomeningeal metastasis (LM) in solid tumors are rare, even more in renal cell carcinoma (RCC). To date there is a lack of consensual treatment modalities of leptomeningeal metastasis. Furthermore, with the improvement of outcomes and more effective systemic targeted therapies, the management of leptomeningeal metastasis becomes a real challenge. We here report two cases of RCC with leptomeningeal metastasis at initial diagnosis. Both patients had concurrent adjacent skull bone metastasis. Therapeutic management of both patients consisted in surgical resection, followed by radiotherapy in one case. Systemic treatment was delayed according to current recommendations for the management of metastatic RCC. The aim of this work is to report the therapeutic approach and related outcomes and also provide a review of the currently available literature on leptomeningeal disease in renal cell carcinoma. Indeed, local treatment with curative outcome of meningeal location in RCC should be performed specially in LM at initial diagnosis.

Introduction: The announcement of cancer coupled with initiation of its treatment impacts patients' psychological and physical states as well as their lifestyles. The objective of this study was to identify and confirm the needs of patients starting off on anticancer chemotherapy treatment., Methods: This study was based on a qualitative-quantitative mixed method. In 2009, a qualitative study was conducted at the Lucien Neuwirth Cancer Institut for cancer patients undergoing intravenous chemotherapy for the first time. Exploratory and semi-directed interviews were carried out by a sociologist. In 2014, a questionnaire was hetero-administered to 100 patients starting off on chemotherapy., Results: Forty patients were interviewed in 2009. Ninety-seven patients answered the questionnaire in 2014. Food was a theme that was identified by a majority of patients in 2009 (13/40) and confirmed in 2014: 63% needed help in identifying favorable food and 67% in identifying those that had to be avoided. The other needs identified were those linked to better understanding of the treatment, of how it may affect the couple, its side effects, hygiene and beauty, and knowledge about other treatments. These needs were confirmed in 2014. New needs were elicited in 2014: activities and leisure (33%), psychological needs (32.6%), and family relations (29.9%)., Conclusion: This study enabled us to identify, confirm, and enrich our knowledge of the needs of cancer patients starting off on intravenous chemotherapy. These results led to the modification of an existing patient education program for these patients, in order to fulfill their needs in an updated and tailored manner., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: To describe the current state of knowledge concerning the quality of reporting in phase II clinical trials in oncology and to describe the various methods published allowing this quality evaluation., Methods: databases including MEDLINE and COCHRANE were searched. Reviews and meta-analyses analyzing the quality of the reporting of phase II trials in oncology were included. Descriptive analysis of the results was performed., Results: Thirteen publications were retained. Only 2 publications adopted a systematic approach of evaluation of the quality of reporting by overall scores. The Key Methodological Score (KMS), proposed by Grellety et al., gathering 3 items, seemed adapted for such an evaluation. A score of 3/3 was found in 16.1% of the 156 phase II trials analysed by this score. The other reviews used a qualitative analysis to evaluate the reporting, via an analysis of a single criterion, generally the statistical plan of the study. This item was considered as having been correctly reported in less than 50% of the analysed articles., Conclusion: The quality of reporting in phase II trials in oncology is a field that has been investigated very little (13 publications). When it is studied, the estimated level of quality is not satisfactory, whatever the method employed. The use of an overall score of evaluation is a path which should be pursued, in order to get reliable results. It also seems necessary to propose strong recommendations, which would create a consensus for the methodology and the reporting of these studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Glioblastoma is one of the most common types of primary brain tumor. In situations of local recurrence, physicians can suggest either specific palliative anticancer treatments (SPAT; surgery, chemotherapy, radiotherapy) or best supportive care (BSC). The objective of the present study was to identify clinical factors that may have influenced the continuation or cessation of SPAT during the final 3 months of life in patients with glioblastoma. In the present retrospective single-center study, all records of patients treated for glioblastoma, who succumbed to the disease between June 2006 and February 2014, were assessed. All selected patients were divided into two groups, according to treatments received during the last 3 months of life: The SPAT and BSC groups. A total of 148 patients were included: 81 patients in the SPAT group (group A) and 67 patients in the BSC group (group B). A performance status equal to 0 was observed for 17.3% of patients in group A vs. 6% in group B. Following progression, chemotherapy was administered in 39.5% of cases in group A vs. 20.9% of cases in group B (P=0.0149). The mean number of lines of chemotherapy administered in group A was equal to 1.44±0.77 as compared with 1.06±0.67 in group B (P=0.0017). SPAT are utilized frequently among patients approaching mortality due to a glioblastoma. Certain factors, including the utilization of novel chemotherapy after the first progression or number of lines of chemotherapy previously administered, may have influenced physicians' decisions whether to continue with the SPAT or not.

Background: Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials., Data Sources: A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010-2015)., Study Eligibility Criteria: All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer., Intervention: Quality of reporting was assessed using the Key Methodological Score., Results: 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001)., Limitations: Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate., Conclusions & Implications of Key Findings: This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles.

The present review gives an overview of systematic reviews published in peer reviewed Journals analysing quality of reporting in oncology studies. PUBMED and Cochrane library were searched to identify systematic reviews assessing quality of reporting for randomized controlled trials (RCTs) and observational studies (OBS). Recommendations and primary endpoints used to assess the quality of reporting were described. Intrinsic quality of reporting was analyzed using an Overall Quality Score for literature Reviews (OQSR). Main evaluation themes were overall quality of reporting (20/58) and reporting of Health-Related Quality Of Life (HRQOL) in RCTs (7/58). Reporting recommendations used were not detailed in 56.9% of reviews. Insufficient reporting for the methodological description (randomization, blinding details, and allocation concealment) and the rationale for using specific measure of HRQOL were highlighted. OQSR was significantly higher for reviews published between 2010 and 2014 (after the PRISMA Publication), as compared to those published between 1996-2009 (median OQSR 10 (10-11) versus median OQSR 9 (6-10) respectively, p=0.0053). Intrinsic quality of reporting is satisfactory and has been improved in the last years., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In clinical research, biostatistical methods allow the rigorous analysis of data collection and should be defined from the trial design to obtain the appropriate experimental approach. Thus, if the main purpose of phase I is to determine the dose to use during phase II, methodology should be finely adjusted to experimental treatment(s). Today, the methodology for chemotherapy and targeted therapy is well known. For radiotherapy and chemoradiotherapy phase I trials, the primary endpoint must reflect both effectiveness and potential treatment toxicities. Methodology should probably be complex to limit failures in the following phases. However, there are very few data about methodology design in the literature. The present study focuses on these particular trials and their characteristics. It should help to raise existing methodological patterns shortcomings in order to propose new and better-suited designs., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: Quality of reporting for Randomized Clinical Trials (RCTs) in oncology was analyzed in several systematic reviews, but, in this setting, there is paucity of data for the outcomes definitions and consistency of reporting for statistical tests in RCTs and Observational Studies (OBS). The objective of this review was to describe those two reporting aspects, for OBS and RCTs in oncology., Methods: From a list of 19 medical journals, three were retained for analysis, after a random selection: British Medical Journal (BMJ), Annals of Oncology (AoO) and British Journal of Cancer (BJC). All original articles published between March 2009 and March 2014 were screened. Only studies whose main outcome was accompanied by a corresponding statistical test were included in the analysis. Studies based on censored data were excluded. Primary outcome was to assess quality of reporting for description of primary outcome measure in RCTs and of variables of interest in OBS. A logistic regression was performed to identify covariates of studies potentially associated with concordance of tests between Methods and Results parts., Results: 826 studies were included in the review, and 698 were OBS. Variables were described in Methods section for all OBS studies and primary endpoint was clearly detailed in Methods section for 109 RCTs (85.2%). 295 OBS (42.2%) and 43 RCTs (33.6%) had perfect agreement for reported statistical test between Methods and Results parts. In multivariable analysis, variable "number of included patients in study" was associated with test consistency: aOR (adjusted Odds Ratio) for third group compared to first group was equal to: aOR Grp3 = 0.52 [0.31-0.89] (P value = 0.009)., Conclusion: Variables in OBS and primary endpoint in RCTs are reported and described with a high frequency. However, statistical tests consistency between methods and Results sections of OBS is not always noted. Therefore, we encourage authors and peer reviewers to verify consistency of statistical tests in oncology studies., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: B. Mery, G. Moriceau, R. Rivoirard et O. Collard déclarent n’avoir aucun lien d’intérêts.

Introduction: The aim of this study was to appreciate the place and role of geriatric assessment in elderly patients with prostate cancer., Materials and Methods: We performed a retrospective analysis of prostate cancer patients who underwent geriatric assessment during the therapeutic management from 2008 to 2014. Patient, tumor, treatment characteristics and their associated toxicity as well as the parameters of geriatric assessment were studied. The occurrence of geriatric assessment within the 3 months preceding a therapeutic decision was reviewed., Results: Data of seventy-four patients were analyzed with a median follow-up of 15.6 years. The average age at diagnosis was 74.3 and 80.6 at the geriatric assessment. At the time of the geriatric assessment 64 patients had metastatic disease, 39 were in poor condition more than 50% of patients had walking ability disorders. Thirteen patients underwent radical surgery, 28 received radiotherapy, 30 patients had chemotherapy and hormonotherapy was prescribed for 72 patients. The geriatric assessment, requested on average 15 years after diagnosis, was not carried out within the 3 months preceding treatment decision for 55 patients., Conclusion: The recourse to geriatric assessment is predominantly used to endorse a decision of supportive care for elderly patients with prostate cancer. An early intervention by a geriatrician consultant for the initial management and then at each therapeutic event is a sine qua non condition for efficient personalized therapeutic management suitable to every patient according to physiological age., Level of Evidence: 4., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Competing Interests: B. Mery, G. Moriceau, R. Rivoirard et O. Collard déclarent n’avoir aucun lien d’intérêts.

Background: Despite radiotherapy (RT) technical improvements, high salivary dysfunction rates are still reported in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of the present study was to report salivary glands dosimetry with volumetric-modulated arc therapy (VMAT) and intensity-modulated RT (IMRT)., Methods: Dosimetry of consecutive patients receiving IMRT or VMAT for proven HNSCC between 2007 and 2013 were retrospectively reviewed., Results: Data of 609 patients were studied. Mean dose, mean maximum dose, and mean percentage of salivary gland volume receiving at least 26 Gy (V26) of the contralateral parotid were 24.50 Gy (range, 0-70.4 Gy), 39.08 Gy (range, 0.38-76.45 Gy), and 40.92% (range, 0% to 100%), respectively. Mean and maximum dose on contralateral submandibular gland were 48.18 Gy (range, 0.19-70.73 Gy), and 61.25 Gy (range, 0-75.8 Gy), respectively., Conclusion: Target volume coverage still has to be prioritized over organs at risk (OAR) sparing with new RT techniques. Submandibular glands are not sufficiently taken into account in guidelines. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1028-1034, 2016., (© 2016 Wiley Periodicals, Inc.)

Molecular targeted therapies (TT) are the cornerstone of metastatic renal cell carcinoma (RCC) treatment. There is a paucity of data on the safety of the radiotherapy (RT)-TT association in a sequential or a concomitant setting. The aim of the present study is to retrospectively assess the safety of the RT-TT association. From 2006 to 2014, data from 84 consecutive patients treated with RT and TT for metastatic RCC were retrospectively collected. RT-TT sequential and concomitant associations were, respectively, defined by a time interval of more than five TT half-lives and less than or equal to five TT half-lives between the last TT administration and RT initiation. Toxicities in the fields of RT were assessed systematically. As many patients received several TT and RT courses, 136 RT-TT associations were analyzed, with 66 sequential and 70 concomitant schemes. RT was mainly delivered on bone (75%) and brain metastases (14.7%). TT were tyrosine kinase inhibitors (73.5%), mTOR inhibitors (19.8%), and monoclonal antibodies (6.7%). With a median follow-up of 9.5 months, whatever the sequence, no grade≥4 toxicity was reported. Two grade 3 toxicities were reported with sequential (3%) and concomitant (2.9%) RT-TT, respectively. Sequential or concomitant RT-TT associations in metastatic RCC do not seem to cause major toxicity.

Introduction: The score of the MASCC, by means of clinical criteria, estimates the risk of serious complications in patients with neutropenic fever induced by chemotherapy., Methods: We retrospectively studied a cohort of patients hospitalized for a neutropenic fever and analyzed complications according to the criteria defined by the MASCC., Results: Eighty-one neutropenic fevers in 71 patients were identified. Microbiological documentation was obtained in 33% of cases only. Fifty-eight patients (72%) presented with a MASCC score≥21 and were considered as low risk of complications. In the total population, 10 patients died during their hospitalizations for neutropenic fever, 7 in the high-risk group versus 3 in the low risk group, including 2 patients suffering from significant comorbidities not taken into account by MASCC score. Within the low risk group, presence of a metastatic disease and existence of 2 or more comorbidities were associated with a longer duration of hospitalization., Conclusion: This analysis suggests that the criteria of the MASCC are not always enough to thoroughly identify which patients were at risk of complications or could be treated through outpatient management. By better taking into account the comorbidities and tumoral stage, a better selection of the patients who are likely to receive an ambulatory treatment could be made. To date, hospitalization remains frequently necessary in neutropenic fevers, at least in its initial steps, and the place of the general practitioner remains to be better defined., (Copyright © 2016. Published by Elsevier Masson SAS.)

Radiochemotherapy is undergoing a complete expansion. Currently, possibilities of treatment combination are skyrocketting, with different anticancer and targeted molecules, different radiotherapy techniques, and dose escalation with each therapy. The development of a modern phase I radiochemotherapy trial becomes more and more complex and should be fully investigated. In the literature, there are no exhaustive reviews describing the necessity of their characteristics. The present article explores historical and current phase I clinical trials involving a combination of radiation therapy and anticancer therapies. Selected trials were identified by searching in PubMed databases. A total of 228 studies were identified in the last three decades, and a portrait of their characteristics is presented. As expected, most frequently studied malignancies were head and neck cancers, followed by non-small cell lung cancer and brain cancer. Toxicity is reported in more than 90% of the studies. Most studies were published since 2010, at the area of targeted therapies, but mainly concerned classical chemotherapies (cisplatin and 5-fluorouracil). The present review highlights some limits. Indeed, methodology seems not optimised and could be based on more accurate methods of dose-escalation. The present portrait of phase I radiochemotherapy trials suggests that radiochemotherapy notion must be reinvented and trials should be adapted to its complexity. Step by step method does not sound like an option anymore. Let us build the future of radiochemotherapy on past evidences., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Carcinomatous meningitis complicates 5 to 10% of cancers, essentially with breast cancers, lung cancers and melanomas. The incidence probably increased because of therapeutic advances in oncology. Treatment is based on external beam radiotherapy, systemic treatment, intrathecal chemotherapy and supportive care. The aim of this work was to review data on external radiation therapy and carcinomatous meningitis. There are few evidences on the subject, but it is a major topic of interest. A whole brain radiation therapy is indicated in case of brain metastases or clinical encephalitis. Focal radiation therapy is recommended on symptomatic, bulky or obstructive sites. The dose depends on performance status (20 to 40 Gy in five to 20 fractions), volume to treat and available techniques (classic fractionation or hypofractionation via stereotactic radiosurgery). The objective of radiation therapy is to improve quality of life. Association with systemic therapy improves overall survival. Administration of sequential intrathecal chemotherapy may also improve overall survival, but induces more toxicity. The use of new radiotherapy techniques and development of radiosensitizing molecules in patients with good performance status could improve survival in this frequent complication of cancer., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Objectives: Glioblastoma is one of the most frequent primitive brain tumors. Patients who experience tumor relapse after surgery and concomitant radiochemotherapy have a dismal prognosis. The objective of this study is to analyze efficacy data in terms of overall survival (OS) and progression- free survival (PFS) following combination therapy with bevacizumab (BVZ) and irinotecan among patients with relapsed glioblastoma. Safety data will also be reviewed and all results will be compared with data of the literature., Methods: In this single-center retrospective study, all records of patients treated with BVZ and irinotecan for a relapsed glioblastoma were analyzed. Each chemotherapy cycle was repeated every 15 days until progression. Magnetic resonance imaging and neurologic examination were repeated every 6 weeks during treatment., Results: Forty-five patients were analyzed. The median number of BVZ-irinotecan cycles was 8 (range 1-38). Median PFS was 26 weeks and median OS was 28 weeks. Eighteen of the 45 patients (40% of cases) had an objective response 6 months after initiation of treatment. Two patients had to discontinue treatment due to toxicity., Conclusions: The results of the SV1 study are consistent with those found in phase II studies evaluating the same treatment. The irinotecan-BVZ combination is effective in relapsed glioblastoma with acceptable toxicity. Biomarkers predictive of response to BVZ should help in the selection of patients who could benefit from treatment., (© 2016 S. Karger AG, Basel.)

Background: The elderly population in Western countries is growing and constitutes a public health issue. Concomitantly, age-related diseases such as cancer increase. There are few data on the efficacy, tolerability and toxicity of specific anticancer therapy in the very elderly patients; therefore, their management is not standardized., Methods: In this bi-institutional study, we reviewed medical records of patients who received or continued specific anticancer therapy beyond the age of 90 years. Geriatric assessment was not reported for our patients. Twelve patients were enrolled. Their general health condition was good, and half of them were living in elderly institutions. Ten patients had a solid tumor and 2 were treated for hematological malignancies. Most were diagnosed with a locally advanced or metastatic disease, and the goal of treatment was curative for only 1 patient. Six patients received chemotherapy as first-line treatment, 4 patients received targeted therapy and 2 received concomitant chemoradiation. Four patients received a second-line treatment., Results: Despite a significant reduction in treatment posology in half of the patients, 8 acute grade 3/4 toxicities were reported and 2 patients died of treatment-related septic shock. Median duration of first-line treatment was 3.2 months, and progression-free survival ranged from 18 to 311 days. Overall survival ranged from 18 days to 11 years., Conclusion: Aging is a heterogeneous process, and management of elderly patients is a multidisciplinary approach. Geriatric assessment helps to identify older patients with a higher risk of morbidity/mortality and allows to assess the risks and benefits of specific anticancer therapy. The choice of treatment should be based primarily on the expected symptomatic benefit, and treatment should not compromise the quality of life., (© 2015 S. Karger AG, Basel.)

Background: Trabectedin plus pegylated liposomal doxorubicin (PLD) proved efficacious as second-line treatment for patients with recurrent ovarian cancer (ROC)., Methods: We report a single-center retrospective analysis of the efficacy and tolerance of trabectedin 1.1 mg/m2 every 3 weeks in a cohort of real-life ROC patients., Results: From February 2012 to January 2014, 17 patients were treated with trabectedin alone or combined with PLD. Median age was 61 years (range: 48-78). Performance status was 0-1 in 16 patients (94%). Disease response rate was 53% and disease control rate was 76%. At the end of the follow-up, 8 patients (47%) were alive. Median overall survival was 17.6 months (95% CI 13.6 to not reached). Median progression-free survival was 6.7 months (95% CI 5.4-10.0). The most frequent grade 3-4 toxicities were neutropenia (n = 4, 24%) and nausea/vomiting (n = 4, 24%)., Conclusion: Trabectedin combined with PLD seems efficient in and well tolerated by real-life ROC patients., (© 2016 S. Karger AG, Basel.)

Purpose: Intravenous vinflunine 320 mg/m(2) every 3 weeks plus best supportive care resulted in better overall survival in comparison with best supportive care alone for eligible patients with failure of prior therapy with locally advanced or metastatic transitional cell cancer of urothelial tract (TCCU). The objective of the present study was to describe our real-life experience of vinflunine for treatment of patients with TCCU., Patients and Methods: We retrospectively investigated all patients with TCCU who received at least 1 cycle of vinflunine., Results: Nineteen patients were treated between May 2010 and March 2014 in a compassionate-use program. Performance status was poor in our real-life cohort, with 6 patients (32%) with an Eastern Cooperative Oncology Group performance status of 2. Median duration of vinflunine treatment was 2.4 months (range, 0-4.3 months), and median number of cycles was 3 (range, 1-6). Total response rate was 32%, with partial responses only. Disease control rate was 53%, with a median duration of 7.7 months (range, 6.0-9.4 months). Median progression-free survival was 87 days, or 2.9 months (range, 0.7-11.7 months). After vinflunine treatment, 42% of patients received from 1 to 3 additional lines of chemotherapy. The most frequent grade 4 toxicities were constipation (26%), with 3 intestinal obstructions (16%) and 1 mechanical ileus (5%); and asthenia and fatigue (21%)., Conclusion: Vinflunine, as a TCCU second-line chemotherapy, brings benefits, particularly in cases where there is no alternative treatment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Lung cancer is a major public health concern worldwide. Progress in improving 5-year survival is lagging behind comparable survival rates in other common cancers. The majority of patients with locally advanced non-small cell lung cancer (NSCLC) are not suitable for surgical resection, hence the major role of radical radiotherapy. Advances in radiotherapy techniques allow targeted treatment of the disease, whilst minimizing the dose to organs at risk. Recent research into fractionation schedules, with hyperfractionated and accelerated radiotherapy regimens has been promising. Platinum-based chemotherapy has long been the standard of care for the initial treatment of advanced NSCLC. However, if radical radiotherapy remains the cornerstone of treatment for patients with unresectable advanced NSCLC either as single modality treatment or with concomitant chemotherapy, advances in understanding of tumor molecular biology and targeted drug development should bring targeted agents into the NSCLC management. The development of numerous therapeutic approaches has made the locally advanced NSCLC world change. An up-to-date overview of the current literature on updated chemotherapeutic agents, targeted therapy, immunotherapy, radiotherapy in stage III NSCLC is provided., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Trabectedin proved its efficacy in relapsed advanced soft tissue sarcomas (STS) in 3 multicenter phase II studies with selected patients. The aim of the present study is to investigate trabectedin efficacy and tolerance in a cohort of "real-life" unselected patients with sarcoma., Methods: A single-center analysis was carried out on all consecutive patients with histologically proven unresectable advanced or metastatic STS, who received at least one cycle of trabectedin. Data on efficacy and tolerance were retrospectively reported., Results: From 2004 to 2014, data of 59 patients were reviewed. Median age was 62 years (from 23 to 87). A total of 317 cycles of trabectedin were administered. Twenty-five patients (42%) suffered grade 3-4 hematological toxicity, mainly with neutropenia (22 patients, 37%). Disease control rate was 24%, mainly with stable disease, and 45 patients (76%) experienced disease progression. Median overall survival was 6.6 months (95%CI [4.9-12.6])., Conclusion: Trabectedin might be an option for patients without any other validated alternative, but phase III study evaluating trabectedin+best supportive care (BSC) versus BSC is necessary., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: There are only scarce data on the optimal management of patients who present with a bladder carcinoma and who are aged 90 years and older., Patients and Methods: We retrospectively reviewed records from radiotherapy departments from two university hospitals, two private centers and one public center to identify patients who underwent radiotherapy for bladder cancer over the past decade and who were aged 90 years or older. From 2003 to 2013, 14 patients aged 90 years or older receiving RT for bladder malignant tumors were identified., Results: Mean age was 92.7 years. Ten patients (71 %) had a general health status altered (PS 2-3) at the beginning of RT. A total of 14 RT courses were delivered, including six treatments (43 %) with curative intent and eight treatments (57 %) with palliative intent. Palliative intent mainly encompassed hemostatic RT (36 %). At last follow-up, two patients (14 %) experienced complete response, one patient (7 %) experienced partial response, three patients (21 %) had their disease stable, and three patients (21 %) experienced tumor progression, of whom two patients with the progression of symptoms. There was no reported high-grade acute local toxicity in 14 patients (100 %). One patient experienced delayed grade 2 toxicity with pain and lower urinary tract symptoms. At last follow-up, seven patients (50 %) were deceased. Cancer was the cause of death for five patients., Conclusion: Hypofractionated radiotherapy remains feasible for nonagenarians with bladder cancer. Further investigations including analysis of geriatric comorbidities and impact of treatments on quality of life should be conducted.

The ageing of French population imposes to radiotherapists the challenge to treat older patients and to adjust their treatment. Unthinkable 30 years ago, radiation therapy concerns nowadays patients aged more than 90 years old. Oncogeriatric scales have been improved those last years without necessarily making sure that the right treatment is given to the right patient: if oncogeriatric scales use influences the final therapeutic decision, it does not define new target volumes, new doses, or new fractionation protocols. Except for some organs, there is not, for the moment, any consensus concerning geriatric population adapted treatments. This makes any therapeutic decision difficult. The present review has for objective to realise a report of the studies about favorable and unfavorable effects of radiation therapy amongst aged (>70 years old) or very aged (>90years old) population., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)