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Purpose: With the promising results of immunotherapy in patients with stage III melanoma, the role of adjuvant radiotherapy after resection and complete lymph-node dissection must be reassessed. We evaluate the outcomes and safety of adjuvant radiotherapy and immunotherapy compared to immunotherapy only in patients with resected stage III melanoma., Patients and Methods: This retrospective and single institution study included patients treated for a stage III melanoma with complete lymph-node dissection and adjuvant immunotherapy from January 2019 to December 2022. The radiotherapy associated with immunotherapy group was defined by completion of immunotherapy and adjuvant radiotherapy in the lymph-node dissection area. The primary endpoint was disease-free survival. The secondary endpoints were locoregional progression, incidence of adverse events grade 3 or above and disease-free survival rate in patients with high risk of locoregional recurrence., Results: Thirty-three patients were included. Among them, twelve received adjuvant lymph-node field radiotherapy. The median duration of follow-up was 17months (range: 8-45months). Patients receiving radiotherapy and immunotherapy had a significantly higher disease stage and more frequent extracapsular extension. At 12months, the disease-free survival rate was 66.7% for the patients receiving immunotherapy alone (95% CI: 42.5-82.5%) and 83.3% for those receiving radiotherapy and immunotherapy (95% CI: 48.2-95.6%; P=0.131). The locoregional progression rate was 24% in patients receiving immunotherapy and 8% in patients receiving immunotherapy and radiotherapy (P=0.379). After adjuvant treatment, 6% of patients developed grade 3 or above immunotherapy-related events and none developed grade 3 or above radiation-related adverse events., Conclusion: In patients with stage III melanoma, adjuvant lymph-node field radiotherapy combined with immunotherapy seems to be associated with longer disease-free survival, with acceptable tolerance. However, these results need to be confirmed by long-term and prospective studies., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: The French healthcare system has been affected by the COVID-19 pandemic in 2020, including cancer care., Methods: In order to evaluate the impact of this pandemic on cancer incidence, the Isere Departmental Cancer Registry compared the actual 2020 incidence of melanoma, breast, colorectal, prostate and lung cancers with the expected 2020 incidence based on data collected by the Registry between 2015 and 2019, taking into account periods of lockdown and reopening. When available, cancer stages and/or prognostic scores were recorded., Results: During the period of initial confinement, a 54%, 50% and 36,8% drop in incidence was observed for breast, prostate and colorectal cancer respectively. Although their annual incidence remained stable, a worsening trend emerged as a decline in the number of low stages/scores at diagnosis in favour of higher stages/scores towards the end of 2020. In contrast, a significant 17,8% drop was observed in annual incidence of melanoma, particularly for Breslow scores < 1 (-27,4%). However, this trend was noticeable before the lockdown, as well as the 14% reduction in the incidence of lung cancer in women, but not in men., Conclusion: The incidence of certain cancers was caught up over the year but the COVID-19 pandemic seems to be associated with a change in their severity at diagnosis throughout 2020. The downward trends in female lung cancer and melanoma incidence point to complex underlying phenomena. Further analysis is still needed to assess the global impact of the COVID-19 pandemic on cancer incidence., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objective: In many countries, the first line response to an emergency call is decided by the emergency dispatch center EMS clinician. Our main objective was to compare the pre-hospital response to calls received from cancer and non-cancer patients. We also compared the reasons for calling, for each group., Methods: We conducted a retrospective cohort study of data collected between January 1, 2016 and December 31, 2020, from emergency dispatch center records of the Isère county, France. Statistical tests were conducted after matching one cancer patient with two non-cancer patients, resulting in a cohort of 44,022 patients. We used multivariate logistic regression to determine the impact of patient cancer status on the medical decision taken in response to the emergency call., Results: Overall, data on 849,110 patients were extracted, including 16,451 patients with a diagnosis of cancer and 29,348 non-cancer patients. In the matched cohort, cancer was associated with a higher odd of having a mobile intensive care unit (MICU) [odds ratio (OR)=2.02 (1.81-2.26), p<0.001] or an ambulance being dispatched to the patient's home or other location [OR=2.36 (2.24-2.48), p<0.001]. The two most frequent medical responses were to send an ambulance (58.6%) and giving advice only (36.8%). The five main reasons for the emergency call for the cancer group were cardiovascular disease symptoms (13.5%), respiratory problems (10.6%), digestive disorders (10.4%), infections (8.9%) and neurological disorders (6.0%)., Conclusion: An MICU or an ambulance was more often dispatched for cancer patients than for others. Considering that cancer is a very frequent comorbidity in Western countries, knowledge of the patient's cancer status should be sought and taken into consideration when a patient seeks emergency help., (Copyright © 2024. Published by Elsevier Masson SAS.)

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment in recent years, but have led to the emergence of new so-called immune-related adverse events (irAE). The objective of this study was to determine whether cancer type is a potential predictive factor of irAEs., Methods: This retrospective study included patients who had started an ICI treatment between 2019 and 2020 at the Grenoble Alpes University Hospital. A logistic regression model and a Fine and Gray survival model with death as a competing risk were used to identify variables associated with grade≥2 irAEs and grade≥2 irAEs-free survival., Results: Of the 512 patients included, 160 (31.2%) had a grade≥2 irAE. Grade≥2 irAEs were less frequent in head and neck cancer compared to other cancers. Ipilimumab (odds ratio [OR]: 6.05; 95% confidence interval [CI]: 2.81-13.7), treatment duration (OR: 1.01; 95% CI: 1.01-1.02), and history of autoimmune disease (OR: 6.04; 95% CI: 2.45-16.5) were independently associated with grade≥2 irAEs. With death as a competing risk, grade≥2 irAEs-free survival was independently improved with treatment duration (subdistribution hazard ratio [sdHR]: 0.93; 95% CI: 0.92-0.94), ipilimumab (sdHR: 0.24; 95% CI: 0.1-0.59) and history of autoimmune disease (sdHR: 0.23; 95% CI: 0.08-0.69) whereas it was poorer for patients with performance status≥2 (sdHR: 2.04; 95% CI: 1.5-2.76) and an older age (sdHR: 1.02; 95% CI: 1.00-1.03)., Conclusion: Ipilimumab and history of autoimmune disease were both associated with the presence of grade≥2 irAEs and grade≥2 irAEs-free survival. The different cancer groups were not., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Bone metastases (BM) in renal cell carcinoma (RCC) are associated with a poor prognosis based on retrospective studies evaluating antiangiogenic agents. Few data are available regarding immune checkpoint inhibitors (ICI) in patients with bone metastatic RCC. NIVOREN is a multicentre prospective study in which patients were treated with nivolumab after the failure of antiangiogenic agents. We aim to assess the impact of BM on prognosis, and the efficacy and safety of nivolumab in patients enrolled in the NIVOREN trial., Materials and Methods: All patients with BM at inclusion were included in our study. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), safety, and skeletal-related events (SRE)., Results: Among 720 patients treated with nivolumab, 194 presented BM at inclusion. The median follow-up was 23.9 months. Median OS was 17.9 months in patients with BM versus 26.1 months in patients without BM (p = 0.0023). The difference was not statistically significant after adjustment (p = 0.0707). The median PFS was shorter in patients with BM even after adjustment (2.8 versus 4.6 months, p = 0.0045), as well as the ORR (14.8% versus 23.3%). SRE occurred for 36% of patients with BM. A post-hoc analysis evaluating the impact of bone-targeting agents (BTA) on SRE incidence showed a significant benefit of BTA on the incidence of SRE (OR = 0.367, CI95% [0.151-0.895])., Conclusion: Nivolumab is associated with shorter PFS, and lower ORR in RCC patients with BM. Our study suggests that BTA in association with immunotherapy decreases the incidence of SRE., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MaudVELEV, Cecile Dalban, Florence Joly, Mathieu Laramas, Berangère Narciso, Jean-François BERDAH, Victoria FERRARI, Quentin Dominique THOMAS, Cecile Mione, Florence Tantot and Sylvie Chabaud have nothing to disclose. Christine Chevreau: consulting or advisory role – BMS; Ipsen; Novartis; Pfizer. Travel, accommodations, and expenses – AstraZeneca, BMS, Pfysez-Ipsen. Gwenaelle Gravis: AstraZeneca (Inst); Bayer (Inst); BMS (Inst); IPSEN (Inst); Janssen (Inst); MSD Oncology (Inst); Pfizer (Inst); Sanofi/Aventis (Inst). Speaker's: Amgen (Inst); Astellas Pharma (Inst); BMS (Inst); Ipsen (Inst); Janssen Oncology (Inst); MSD Oncology (Inst); Sanofi/Aventis (Inst), Research Funding: BMS. Sylvie Negrier: Honoraria: Bristol-Myers Squibb; Ipsen; MSD Oncology; Novartis; Pfizer. Consulting or advisory role – Bristol-Myers Squibb; Ipsen; MSD Oncology; Novartis; Pfizer. Research Funding: IPSEN (Inst); Pfizer (Inst). Travel, accommodations, and expenses – Bristol-Myers Squibb; IPSEN; Novartis; Pfizer. Brigitte Laguerre: Honoraria: Astellas Pharma; AstraZeneca; Ipsen; Ipsen; Ipsen; Janssen-Cilag; MSD Oncology. Travel, accommodations, and expenses – Astellas Pharma; Janssen; Janssen Oncology; Novartis; Pfizer. Marine Gross-Goupil: consulting or advisory role – Amgen; Astellas Medivation; AstraZeneca; Bayer/Onyx; Bristol-Myers Squibb; Ipsen; Janssen-Cilag; MSD Oncology; Pfizer; Roche; Sanofi. Research Funding – AstraZeneca (Inst); AstraZeneca (Inst); BMS (Inst); Ipsen (Inst); Janssen-Cilag (Inst); Merck (Inst); MSD Oncology (Inst); Pfizer (Inst); Roche (Inst). Sylvain Ladoire: Expert testimony – Astellas Pharma; Bristol-Myers Squibb; Ipsen; Janssen Oncology; Lilly; Novartis; Pfizer; Roche; Sanofi. Travel, accommodations, and expenses – Astellas Pharma; AstraZeneca; Bristol-Myers Squibb; Ipsen; Janssen Oncology; Novartis; Pfizer; Sanofi. Delphine Borchiellini has received consulting and advisory fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, MSD Oncology, Novartis, Pfizer, and Sanofi; research funding from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Infinity Pharmaceuticals, Janssen, MSD, and Roche; and travel and accommodations expenses from Bristol-Myers Squibb, Janssen, Pfizer, and Roche. Lionnel Geoffrois: Honoraria: BMS; Ipsen; Merck serono; Pfizer. Consulting or advisory role – Ipsen. Frank Priou: consulting or advisory role – AstraZeneca. Philippe Barthélémy: Honoraria Astellas Pharma; BMS; IPSEN; Janssen-Cilag; Merck KGaA; MSD; Novartis; Pfizer. Consulting or advisory role – Amgen; AstraZeneca; BMS; Eisai; Ipsen; Janssen-Cilag; Merck KGaA; MSD Oncology; Pfizer. Travel, accommodations, and expenses – Astellas Pharma; BMS; IPSEN; Janssen-Cilag; MSD; Pfizer. Antoine Thiery-Vuillemin has received honoraria from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche/Genentech, and Sanofi; consulting and advisory fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, and Sanofi; research funding from Pfizer; and travel and accommodations expenses from AstraZeneca, Bristol-Myers Squibb, Janssen, MSD, Pfizer, and Roche. Hubert Curcio: Honoraria or consultation fees: Bristol Myers Squibb. Stephane Oudard has received honoraria from Astellas Pharma, Bayer, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche/Genentech, and Sanofi; consulting and advisory fees from Astellas Pharma, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, MSD Oncology, Novartis, Pfizer, Roche, Roche, and Sanofi; research funding from Ipsen and Sanofi; and travel and accommodation expenses from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Merck, MSD Oncology, Novartis, Pfizer, and Roche. Bernard Escudier: Honoraria Bristol-Myers Squibb; Ipsen; Oncorena; Pfizer. Consulting or Advisory Role – AVEO; Bristol-Myers Squibb; Ipsen; Oncorena; Pfizer. Research Funding - BMS France (Inst). Travel, accommodations, and expenses - Bristol-Myers Squibb; Ipsen; MSD. Laurence Albiges: consulting or advisory role – Amgen (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Bristol-Myers Squibb (Inst); Corvus Pharmaceuticals (Inst); Exelixis (Inst); Ipsen (Inst); Janssen (Inst); Merck (Inst); MSD (Inst); Novartis (Inst); Peloton therapeutics (Inst); Pfizer (Inst); Roche (Inst). Research Funding – Bristol-Myers Squibb (Inst). Travel, accommodations, and expenses – Bristol-Myers Squibb; MSD. Constance Thibault: consulting or advisory role – Astellas/Agensys; AstraZeneca; Bristol-Myers Squibb; Ipsen; Janssen; Merck; MSD; Pfizer; Sanofi. Travel, accommodations, and expenses - Astellas/Agensys; Janssen; Sanofi., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Recent studies suggest improvements in response to salvage chemotherapy (CT) after immune checkpoint inhibitors (ICIs) in several types of cancer. Our objective was to assess the efficacy of chemotherapy re-challenge after ICI, compared with second-line chemotherapy without previous ICI in patients with locally advanced or metastatic urothelial carcinoma (la/mUC)., Methods: In this multicentre retrospective study, we included all patients with la/mUC initiating second or third-line chemotherapy from January 2015 to June 2020. We compared patients treated with second-line chemotherapy without previous ICI (CT2) and patients treated with third-line chemotherapy after ICI (CT3). The primary end-point was objective response rate (ORR) in CT3 compared with CT2. Secondary end-points included progression-free survival (PFS) and toxicities., Results: Overall, 553 patients were included. ORRs were 31.0% (95% CI, 26.5 to 35.5) and 29.2% (95% CI, 21.9 to 36.6), respectively, in CT2 and CT3, with no statistically significant differences (P = 0.62). In subgroup analyses, no differences in ORR were observed by Bellmunt risk group, type of chemotherapy (platinum or taxanes), duration of response to first-platinum-based chemotherapy (&lt; or ≥ 12 months) or FGFR-status. Median PFS was 4.6 months (95% CI, 3.9 to 5.1) and 4.9 months (95% CI, 4.1 to 5.5) in CT2 and CT3, respectively, and grade 3-4 hematologic toxicity occurred in 35.0% and 22.4% of patients., Conclusion: This large multicentre retrospective study provides clinically relevant real-world data. Chemotherapy re-challenge after ICI in la/mUC achieves ORR and PFS comparable with those obtained in CT2 with an acceptable safety profile. These updated results offer more promising outcomes than historically reported with second-line chemotherapy data., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Ntrk: rearrangements represent a very rare genomic abnormality among all cancers but can be detected in thyroid cancer with a non-negligible frequency of 2%. Dramatic clinical responses to therapies targeting NTRK chimeric proteins are now well described in the literature. SQSTM1-NTRK1fusions have not yet been described in a full clinical case report. We report a patient with a papillary thyroid carcinoma harboring this unique rearrangement, with an impressive clinical and radiologic response to larotrectinib, a highly specific inhibitor.

Sarcomas are rare tumours that represent less than 1% of all malignant tumours in adults. Liposarcomas are among the most common malignant mesenchymal tumours. They are preferentially located in the limbs and the retroperitoneum. Liposarcomas primarily arising in the digestive tract are exceptional with a few cases reported in the literature. Their clinical presentation is variable and the symptoms are not specific. Anatomopathological examination remains the gold standard for the diagnosis and the classification of these tumours, which are divided into 5 histological types according to the 5th edition of the WHO classification of soft tissue tumours. We report two observations of unusual digestive liposarcomas, located in the oesophagus and the colon, emphasizing the variability of the diagnostic challenges, depending on the clinical presentation, the histological type and the analysed material., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Abstract: Prostate cancer bone metastases usually appear as osteosclerotic lesions. However, atypical lesions have also been described. We report herein the case of a 65-year-old man treated since 2013 for prostate cancer with early bone metastases. This asymptomatic patient was referred for 18F-choline PET/CT due to a major elevation of prostate-specific antigen to >1500 ng/mL. The results indicated multiple bone lesions, disseminated on the axial skeleton, girdles, and upper extremities of femurs. Interestingly, we described the development of an intensely hypermetabolic spiculated periosteal reaction, evidencing a rapidly progressive disease., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: At intensive care unit (ICU) admission, the issue about prognosis of critically ill cancer patients is of clinical interest, especially after ICU discharge. Our objective was to assess the factors associated with 3- and 6-month survival of ICU cancer survivors., Methods: Based on the French OutcomeRea™ database, we included solid cancer patients discharged alive, between December 2005 and November 2013, from the medical ICU of the university hospital in Grenoble, France. Patient characteristics and outcome at 3 and 6 months following ICU discharge were extracted from available database., Results: Of the 361 cancer patients with unscheduled admissions, 253 (70%) were discharged alive from ICU. The main primary cancer sites were digestive (31%) and thoracic (26%). The 3- and 6-month mortality rates were 33 and 41%, respectively. Factors independently associated with 6-month mortality included ECOG performance status (ECOG-PS) of 3-4 (OR,3.74; 95%CI: 1.67-8.37), metastatic disease (OR,2.56; 95%CI: 1.34-4.90), admission for cancer progression (OR,2.31; 95%CI: 1.14-4.68), SAPS II of 45 to 58 (OR,4.19; 95%CI: 1.76-9.97), and treatment limitation decision at ICU admission (OR,4.00; 95%CI: 1.64-9.77). Interestingly, previous cancer chemotherapy prior to ICU admission was independently associated with lower 3-month mortality (OR, 0.38; 95%CI: 0.19-0.75). Among patients with an ECOG-PS 0-1 at admission, 70% (n = 66) and 61% (n = 57) displayed an ECOG-PS 0-2 at 3- and 6-months, respectively. At 3 months, 74 (55%) patients received anticancer treatment, 13 (8%) were given exclusive palliative care., Conclusions: Factors associated with 6-month mortality are almost the same as those known to be associated with ICU mortality. We highlight that most patients recovered an ECOG-PS of 0-2 at 3 and 6 months, in particular those with a good ECOG-PS at ICU admission and could benefit from an anticancer treatment following ICU discharge.

Background: To assess whether whole-body (WB) bone SPECT/CT provides additional diagnostic information over [18F]-FCH PET/CT for the detection of bone metastases in the setting of prostate cancer biochemical recurrence (PC-BR)., Methods: Patients referred for a PC-BR and whom benefited from a WB bone SPECT/CT and FCH PET/CT were retrospectively included. Tests were classified as positive, equivocal, or negative for bone metastases. A best valuable comparator (BVC) strategy including imaging and follow-up data was used to determine the metastatic status in the absence of systematic histological evaluation., Results: Between January 2011 and November 2017, 115 consecutive patients with a PC-BR were evaluated. According to the BVC, 30 patients had bone metastases and 85 patients did not present with bone lesions. The sensitivity, specificity, positive and negative predictive values were respectively 86.7% [69.3-96.2], 98.8% [93.6-100.0], 96.3% [78.7-99.5], and 95.5% [89.4-98.1] for WB bone SPECT/CT and 93.3% [77.9-99.2], 100.0% [95.8-100.0], 100.0 and 97.7% [91.8-99.4] for FCH PET/CT. There was no significant difference in diagnostic accuracy of bone metastases between WB Bone SPECT/CT (AUC 0.824 [0.74-0.90]) and FCH PET/CT (AUC 0.829 [0.75-0.90], p = 0.41)., Conclusion: Despite good performances for the diagnosis of bone metastases in PC-BR, WB bone SPECT/CT does not provide additive diagnostic information over concomitant FCH PET/CT.

Background: Pharmacists play a key role in ensuring the safe use of injectable antineoplastics, which are considered as high-alert medications. Pharmaceutical analysis of injectable antineoplastic prescriptions aims to detect and prevent drug related problems by proposing pharmacist interventions (PI). The impact of this activity for patients, healthcare facilities and other health professionals is not completely known. This study aimed at describing the clinical, economic, and organizational impacts of PIs performed by pharmacists in a chemotherapy preparation unit., Methods: A prospective 10-week study was conducted on PIs involving injectable antineoplastic prescriptions. Each PI was assessed by one of the four multidisciplinary expert committees using a multidimensional tool with three independent dimensions: clinical, economic and organizational. An ancillary quantitative evaluation of drug cost savings was conducted., Results: Overall, 185 patients were included (mean age: 63.5 ± 13.7 years; 54.1% were male) and 237 PIs concerning 10.1% prescriptions were recorded. Twenty one PIs (8.9%) had major clinical impact (ie: prevented hospitalization or permanent disability), 49 PIs (20.7%) had moderate clinical impact (ie: prevented harm that would have required further monitoring/treatment), 62 PIs (26.2%) had minor clinical impact, 95 PIs (40.0%) had no clinical impact, and 9 PIs (3.8%) had a negative clinical impact. For one PI (0.4%) the clinical impact was not determined due to insufficient information. Regarding organizational impact, 67.5% PIs had a positive impact on patient management from the healthcare providers' perspective. A positive economic impact was observed for 105 PIs (44.3%), leading to a saving in direct drug costs of 15,096 €; 38 PIs (16.0%) had a negative economic impact, increasing the direct drug cost by 11,878 €. Overall cost saving was 3218€., Conclusions: PIs are associated with positive clinical, economic and organizational impacts. This study confirms the benefit of pharmacist analysis of injectable antineoplastic prescriptions for patient safety with an overall benefit to the healthcare system.

Purpose: Nivolumab is standard of care for patients with metastatic clear cell renal cell carcinoma (ccRCC) after failure of antiangiogenic therapies, but its activity on brain metastases from ccRCC remains unknown, because these patients were excluded from pivotal studies. We aimed to assess the activity of nivolumab in this population., Methods: The GETUG-AFU 26 NIVOREN phase II trial assessed the activity and safety of nivolumab in patients with metastatic ccRCC who failed vascular endothelial growth factor-directed therapies (ClinicalTrials.gov identifier: NCT03013335). Patients with asymptomatic brain metastases were prospectively identified and underwent dedicated brain evaluation. Two cohorts were constituted: cohort A comprised patients with previously untreated brain metastases, and cohort B comprised patients whose brain metastases underwent prior therapy. The primary end point was intracranial response rate in cohort A., Results: Seventy-three patients with brain metastases were included: 39 in cohort A and 34 in cohort B. Intracranial response rate was 12% in cohort A; no objective response was reported in patients with brain lesions that were multiple or larger than 1 cm. Median intracranial progression-free survival was 2.7 months (95% CI, 2.3 to 4.6 months) in cohort A and 4.8 months (95% CI, 3.0 to 8.0 months) in cohort B, with adjusted hazard ratio of 2.04 (95% CI, 1.08 to 3.83). Overall survival rate at 12 months was 67% (95% CI, 49.6% to 79.1%) in cohort A and 59% (95% CI, 40.6% to 73.2%) in cohort B. Most patients in cohort A (72%) needed subsequent focal brain therapy. Nivolumab was well tolerated, with no unexpected toxicity., Conclusion: Nivolumab activity is limited in patients with untreated brain metastases from ccRCC. Brain imaging and focal therapy should be considered before immune checkpoint inhibitors in patients with metastatic ccRCC.

Background: The French EMS study prospectively collected exhaustive data from STS patients diagnosed in the Rhone-Alpes region from 2005 to 07., Methods: The database included diagnosis/histology, surgery, radiotherapy, systemic treatments and treatment response. Treatment patterns and outcomes of patients with metastatic disease, excluding adipocytic sarcoma and GIST were analyzed., Results: Of 888 total patients, 145 were included based on having metastatic disease and appropriate subtypes. All patients received treatment with systemic therapy being most common (74%, n = 107), followed by radiotherapy (30%, n = 44) and surgery (23%, n = 33). Doxorubicin, alone or in combination, was the most common first line systemic therapy (65%, n = 46). Drugs without license in sarcoma were used in 38-83% of treatments depending on treatment line. 24% of frontline patients demonstrated an objective response, decreasing to 11% objective responses in second line but no responses were documented beyond second line, with median PFS declining with each additional line. Median PFS also declined in patients receiving surgery compared to those receiving no surgery (8-15 m vs 5 m). Median OS from metastatic diagnosis for patients receiving systemic therapy was double that of patients without systemic treatment (24 m vs 12 m, p = 0.007)., Conclusions: Outcomes in this population were poor and declined with successive treatment. However, results suggest that further anticancer therapies in recurrent sarcoma might be beneficial.

Aim: To assess the efficacy and tolerability of sunitinib rechallenge in the third-line or later setting in patients with metastatic renal cell carcinoma (mRCC)., Patients and Methods: This observational study comprised 61 mRCC patients at 19 centres in France who received sunitinib rechallenge between January 2006 and May 2013. Patients received first-line sunitinib, ≥1 different targeted therapies, and then sunitinib rechallenge. Patient/disease characteristics, tolerability, treatment modalities, and outcomes of therapeutic lines were recorded. The primary end-point was progression-free survival (PFS) in sunitinib rechallenge., Results: Analyses included 52 patients; median age was 59 years, 75% were male, and 98% had clear-cell mRCC and prior nephrectomy. At sunitinib rechallenge versus first-line, patients had poorer performance (Karnofsky performance status 90-100: 30% versus 81%) and Memorial Sloan Kettering Cancer Centre prognostic risk (poor risk: 18% versus 3%). Overall, 20%, 65%, 12%, and 4% received sunitinib rechallenge as third-, fourth-, fifth-, and sixth-line therapy, respectively, at 14.6 months (median) after stopping initial treatment. With first-line sunitinib and rechallenge, median PFS was 18.4 and 7.9 months, respectively; objective response rate was 54% and 15%. Two of eight rechallenge responders had not achieved first-line response. Median overall survival was 55.9 months. The sunitinib rechallenge safety profile was as expected, with no new adverse events reported., Conclusions: Sunitinib rechallenge is a feasible treatment option with potential clinical benefit for mRCC patients. Disease progression with first-line sunitinib may not be associated with complete or irreversible resistance to therapy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The transferability of economic evaluation in health care is of increasing interest in today's globalized environment. Here, we propose a methodology for assessing the variability of data elements in cost evaluations in oncology. This method was tested in the context of the European Network of Excellence "Connective Tissues Cancers Network"., Methods: Using a database that was previously aimed at exploring sarcoma management practices in Rhône-Alpes (France) and Veneto (Italy), we developed a model to assess the transferability of health cost evaluation across different locations. A nested data structure with 60 final factors of variability (e.g., unit cost of chest radiograph) within 16 variability areas (e.g., unit cost of imaging) within 12 objects (e.g., diagnoses) was produced in Italy and France, separately. Distances between objects were measured by Euclidean distance, Mahalanobis distance, and city-block metric. A hierarchical structure using cluster analysis (CA) was constructed. The objects were also represented by their projections and area of variability through correlation studies using principal component analysis (PCA). Finally, a hierarchical clustering based on principal components was performed., Results: CA suggested four clusters of objects: chemotherapy in France; follow-up with relapse in Italy; diagnosis, surgery, radiotherapy, chemotherapy, and follow-up without relapse in Italy; and diagnosis, surgery, and follow-up with or without relapse in France. The variability between clusters was high, suggesting a lower transferability of results. Also, PCA showed a high variability (i.e. lower transferability) for diagnosis between both countries with regard to the quantities and unit costs of biopsies., Conclusion: CA and PCA were found to be useful for assessing the variability of cost evaluations across countries. In future studies, regression methods could be applied after these methods to elucidate the determinants of the differences found in these analyses.

Resulting medical decision from a multidisciplinary team (MDT) meeting has to be accurate regarding to various patient criteria and relevant specialists participation. The target is to optimize treatment or management options for patients taking into account patients' benefit. The aim of our study was to examine quality criteria of MDT meeting processes, implementation of the MDT decision, and the follow-up of national or regional clinical guidelines. The results lead us to discuss about care management in cancer. Ten various medical specialities of MDT meetings were studied. Relevant multidisciplinarity varied between MDT meetings specialities and was effective between 55 and 100%. Implementation of the decisions that arise from MDT meetings was 86.3%. The most frequent grounds of non-application were patient refusal and new or previous unknown clinical data. The percentage of MDT meetings decisions following national or regional recommendations was 74%. The main reason of not following was the complexity of clinical patient circumstances. Participation in MDT meetings is more and more time-consuming related to enforce the completeness referred to the Plan Cancer (National recommendations). Leading to completeness raises questions about medical time employment and meaning of the MDT meeting for standard clinical cases. The priority seems to enforce multidisciplinarity rather than reach completeness.

Neoadjuvant chemotherapy or chemoradiotherapy is an important concept in the treatment of colorectal liver metastasis, gastric cancer, and esophageal or rectal tumors. This treatment strategy improves disease-free survival and sometimes overall survival. It allows surgical resection of lesions that where not resectable at diagnosis. The new standards of neoadjuvant treatments in gastrointestinal oncology are described in this article.

Many genomic abnormalities have been identified in various subsets of prostate cancer, but until now, few genes have been associated with the progression of this cancer. High activity of protein serine/threonine kinase CK2 has been observed in various solid tumours and this alteration has been linked both to growth-related functions and to suppression of cellular apoptosis. Here, we provide the first evidence for a strong association between a nuclear localization of CK2alpha, evaluated by immunohistochemistry, and poor prognostic factors in a retrospective cohort of 131 human prostate adenocarcinomas. Nuclear CK2alpha localization is significantly correlated with higher Gleason score, more locally advanced disease (cT3-T4) and more perineural or lymphatic invasion (p<0.0019 to 0.046). In contrast, despite a strong trend, no significant relationship was found between higher initial PSA and nuclear CK2alpha localization. Thus, this previously undescribed molecular heterogeneity is the first step in defining CK2 as both a potential biomarker and a promising target in human prostate cancer.

A 33 year old female had febrile aplasia following a first chemotherapy treatment for acute T lymphoid leukaemia. She was transferred to intensive care for acute respiratory distress due to bilateral pneumonia with Stenotrophomonas maltophilia septicaemic shock. After an initial improvement with antibiotic treatment, she developed multiple necrotic cutaneous lesions. A skin biopsy showed the presence of Aspergillus flavus in large quantities in the vascular lumina. Echocardiography revealed a voluminous vegetation on the mitral valve supporting aspergillus endocarditis. Despite antifungal treatment, shock and coma developed rapidly. Cerebral CT scan suggested multiple septic emboli. Within several hours, the scenario progressed towards multiorgan failure leading the death of the patient. Aspergillus endocarditis is exceptional and usually only occurs in immunosuppressed patients. The diagnosis is difficult, and the prognosis is appalling with a mortality greater than 90% despite treatment.