Consore: A Powerful Federated Data Mining Tool Driving a French Research Network to Accelerate Cancer Research.

BACKGROUND: Real-world data (RWD) related to the health status and care of cancer patients reflect the ongoing medical practice, and their analysis yields essential real-world evidence. Advanced information technologies are vital for their collection, qualification, and reuse in research projects. METHODS: UNICANCER, the French federation of comprehensive cancer centres, has innovated a unique research network: Consore. This potent federated tool enables the analysis of data from millions of cancer patients across eleven French hospitals. RESULTS: Currently operational within eleven French cancer centres, Consore employs natural language processing to structure the therapeutic management data of approximately 1.3 million cancer patients. These data originate from their electronic medical records, encompassing about 65 million medical records. Thanks to the structured data, which are harmonized within a common data model, and its federated search tool, Consore can create patient cohorts based on patient or tumor characteristics, and treatment modalities. This ability to derive larger cohorts is particularly attractive when studying rare cancers. CONCLUSIONS: Consore serves as a tremendous data mining instrument that propels French cancer centres into the big data era. With its federated technical architecture and unique shared data model, Consore facilitates compliance with regulations and acceleration of cancer research projects.

Triplet chemotherapy plus cetuximab as first-line treatment in extended RAS wild-type metastatic colorectal cancer patients.

BACKGROUND: Triplet chemotherapy plus cetuximab showed promising results in phase II trials in unsystematically selected RAS population. We evaluated FOLFIRINOX+cetuximab efficacy as first-line treatment in extended RAS wild-type metastatic colorectal cancer (mCRC) patients. METHODS: We retrospectively analyzed patients treated with FOLFIRINOX+cetuximab, using data from clinical trials and real-life practice. Extended mutation analysis was performed when RAS/BRAF status was unavailable. The primary endpoint was progression-free survival (PFS). RESULTS: Seventy patients (61.4 % male, median age 58.7 years) were analyzed. Eighty percent had left-sided mCRC and 97.1 % had liver metastases. Median PFS and overall survival (OS) were 13.3 and 48.5 months, respectively. The objective response rate was 85.7 %, with 20 % complete response. Primary tumor location did not affect OS and PFS. BRAF wild-type patients (n = 65) had longer PFS (13.3 vs. 6.0 months; p = 0.005) and OS (50.1 vs. 21.2 months; p = 0.007) than BRAF mutated patients (n = 5, including four BRAFV600E). Median OS was significantly longer in resected patients (n = 39, 55.1 vs. 30.7 months; p = 0.030). Main toxicities were diarrhea (31.4 %) and neutropenia (21.4 %). CONCLUSION: FOLFIRINOX+cetuximab provides good PFS, high response rate and prolonged disease control in initially unresectable extended RAS wild-type mCRC. This combination is particularly interesting for selected patients with liver-limited disease eligible to secondary resection.

Identification of 18F-FDG PET/CT Parameters Associated with Weight Loss in Patients with Esophageal Cancer.

18F-FDG PET-CT is routinely performed as part of the initial staging of numerous cancers. Other than having descriptive, predictive and prognostic values for tumors, 18F-FDG PET-CT provides full-body data, which could inform on concurrent pathophysiological processes such as malnutrition. To test this hypothesis, we measured the 18F-FDG uptake in several organs and evaluated their association with weight loss in patients at diagnosis of esophageal cancer. Forty-eight patients were included in this retrospective monocentric study. 18F-FDG uptake quantification was performed in the brain, the liver, the spleen, bone marrow, muscle and the esophageal tumor itself and was compared between patients with different amounts of weight loss. We found that Total Lesion Glycolysis (TLG) and peak Standardized Uptake Values (SUVpeak) measured in the brain correlated with the amount of weight loss: TLG was, on average, higher in patients who had lost more than 5% of their usual weight, whereas brain SUVpeak were, on average, lower in patients who had lost more than 10% of their weight. Higher TLG and lower brain SUVpeak were associated with worse OS in the univariate analysis. This study reports a new and significant association between 18F-FDG uptake in the brain and initial weight loss in patients with esophageal cancer.

BRCA1-methylated triple negative breast cancers previously exposed to neoadjuvant chemotherapy form RAD51 foci and respond poorly to olaparib.

Background: About 15% of Triple-Negative-Breast-Cancer (TNBC) present silencing of the BRCA1 promoter methylation and are assumed to be Homologous Recombination Deficient (HRD). BRCA1-methylated (BRCA1-Me) TNBC could, thus, be eligible to treatment based on PARP-inhibitors or Platinum salts. However, their actual HRD status is discussed, as these tumors are suspected to develop resistance after chemotherapy exposure. Methods: We interrogated the sensitivity to olaparib vs. carboplatin of 8 TNBC Patient-Derived Xenografts (PDX) models. Four PDX corresponded to BRCA1-Me, of which 3 were previously exposed to NeoAdjuvant-Chemotherapy (NACT). The remaining PDX models corresponded to two BRCA1-mutated (BRCA1-Mut) and two BRCA1-wild type PDX that were respectively included as positive and negative controls. The HRD status of our PDX models was assessed using both genomic signatures and the functional BRCA1 and RAD51 nuclear foci formation assay. To assess HR restoration associated with olaparib resistance, we studied pairs of BRCA1 deficient cell lines and their resistant subclones. Results: The 3 BRCA1-Me PDX that had been exposed to NACT responded poorly to olaparib, likewise BRCA1-WT PDX. Contrastingly, 3 treatment-naïve BRCA1-deficient PDX (1 BRCA1-Me and 2 BRCA1-mutated) responded to olaparib. Noticeably, the three olaparib-responsive PDX scored negative for BRCA1- and RAD51-foci, whereas all non-responsive PDX models, including the 3 NACT-exposed BRCA1-Me PDX, scored positive for RAD51-foci. This suggested HRD in olaparib responsive PDX, while non-responsive models were HR proficient. These results were consistent with observations in cell lines showing a significant increase of RAD51-foci in olaparib-resistant subclones compared with sensitive parental cells, suggesting HR restoration in these models. Conclusion: Our results thus support the notion that the actual HRD status of BRCA1-Me TNBC, especially if previously exposed to chemotherapy, may be questioned and should be verified using the BRCA1- and RAD51-foci assay.

Correlation of the TIGIT-PVR immune checkpoint axis with clinicopathological features in triple-negative breast cancer.

Background: T cell immunoreceptor with Ig and ITIM domains (TIGIT) interacts with poliovirus receptor (PVR) to contribute to cancer immune escape. Recently, TIGIT and PVR have been identified as promising immunotherapy targets. Their gene expression is upregulated in many solid tumors, but their protein expression level is not well documented, particularly in triple negative breast cancer (TNBC), the breast cancer subtype that most benefit from immunotherapy. Methods: TIGIT and PVR expression levels were assessed by immunohistochemistry in 243 surgically resected localized TNBC and then their relationship with clinical-pathological features and clinical outcome was analyzed. Results: TIGIT expression was observed in immune cells from the tumor microenvironment, whereas PVR was mainly expressed by tumor cells. High TIGIT expression was significantly associated with age (p=0.010), histological grade (p=0.014), non-lobular histology (p=0.024), adjuvant chemotherapy (p=0.006), and various immune cell populations (tumor infiltrating lymphocytes (TILs), CD3+, CD8+, PD-1+ cells; all p<0.0001), PD-L1+ tumor cells (p<0.0001), and PD-L1+ stromal cells (p=0.003). Infiltration by TIGIT+ cells tended to be higher in non-molecular apocrine tumors (p=0.088). PVR was significantly associated with histological grade (p<0.0001), the basal-like (p=0.003) and non-molecular apocrine phenotypes (p=0.039), high TILs infiltration (p=0.011), CD3+ (p=0.002), CD8+ (p=0.024) T cells, and PD-L1 expression in tumor (p=0.003) and stromal cells (p=0.001). In univariate analysis, only known prognostic factors (age, tumor size, lymph node status, adjuvant chemotherapy, TILs and CD3+ T-cell infiltrate) were significantly associated with relapse-free survival (RFS) and overall survival. High TIGIT and PVR expression levels tended to be associated with longer RFS (p=0.079 and 0.045, respectively). The analysis that included only non-molecular apocrine TNBC revealed longer RFS for tumors that strongly expressed TIGIT or PVR (p=0.025 for TIGIT and 0.032 for PVR). Conclusions: These results indicated that in TNBC, TIGIT+ cells can easily interact with PVR to exert their inhibitory effects. Their wide expression in TNBC and their association with other immune checkpoint components suggest the therapeutic interest of the TIGIT-PVR axis.

Detection of Circulating Tumor Cells in Cerebrospinal Fluid of Patients with Suspected Breast Cancer Leptomeningeal Metastases: A Prospective Study.

BACKGROUND: The diagnosis of breast cancer (BC)-related leptomeningeal metastases (LM) relies on the detection of tumor cells in cerebrospinal fluid (CSF) using conventional cytology (gold standard). However, the sensitivity of this technique is low. Our goal was to evaluate whether circulating tumor cell (CTC) detection in CSF using the CellSearch® system could be used for LM diagnosis. METHODS: This prospective, monocentric study included adult patients with suspected BC-related LM. The clinical sensitivity and specificity of CTC detection in CSF for LM diagnosis were calculated relative to conventional CSF cytology. RESULTS: Forty-nine eligible patients were included and 40 were evaluable (CTC detection technical failure: n = 8, eligibility criteria failure: n = 1). Cytology was positive in 18/40 patients. CTCs were detected in these 18 patients (median: 5824 CTC, range: 93 to 45052) and in 5/22 patients with negative cytology (median: 2 CTC, range: 1 to 44). The detection of ≥1 CSF CTC was associated with a clinical sensitivity of 100% (95% CI, 82.4-100) and a specificity of 77.3% (95% CI, 64.3-90.3) for LM diagnosis. HER2+ CTCs were detected in the CSF of 40.6% of patients with HER2- BC (median: 500 CTC, range: 13 to 28 320). CONCLUSIONS: The clinical sensitivity of CTC detection in CSF with the CellSearch® system for LM diagnosis is higher than that of CSF cytology. CTC detection in patients with negative cytology, however, must be further investigated. The finding of HER2+ CTCs in patients with HER2- BC suggests that the HER2 status of LM should be evaluated to increase the treatment opportunities for these patients.

Chemotherapy (doublet or triplet) plus targeted therapy by RAS status as conversion therapy in colorectal cancer patients with initially unresectable liver-only metastases. The UNICANCER PRODIGE-14 randomised clinical trial.

BACKGROUND: Colorectal cancer (CRC) patients have a better prognosis if metastases are resectable. Initially, unresectable liver-only metastases can be converted to resectable with chemotherapy plus a targeted therapy. We assessed which of chemotherapy doublet (2-CTx) or triplet (3-CTx), combined with targeted therapy by RAS status, would be better in this setting. METHODS: PRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. The primary endpoint was to increase the R0/R1 liver-resection rate from 50 to 70% with the 3-CTx. RESULTS: Patients (n = 256) were mainly men with an ECOG PS of 0, and a median age of 60 years. In total, 109 patients (42.6%) had RAS-mutated tumours. After a median follow-up of 45.6 months, the R0/R1 liver-resection rate was 56.9% (95% CI: 48-66) with the 3-CTx versus 48.4% (95% CI: 39-57) with the 2-CTx (P = 0.17). Median overall survival was 43.4 months with 3-CTx versus 40 months with 2-CTx. CONCLUSION: We failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.

Perioperative FOLFOX in Patients With Locally Advanced Oesogastric Adenocarcinoma.

BACKGROUND: We hypothesized that perioperative FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) might be used as an alternative to standard FLOT (docetaxel, 5-fluorouracil, leucovorin, and oxaliplatin) in patients with locally advanced oesogastric adenocarcinomas (OGA), particularly those with frailties. PATIENTS AND METHODS: We reviewed the charts of 61 consecutives patients treated with FOLFOX for resectable OGA to estimate overall survival, recurrence-free survival, and safety. RESULTS: The median follow-up was 69.7 (range=3.6-97.9) months. Few patients experienced grade 3 adverse events during the preoperative (n=6; 10%) and postoperative (n=6; 16%) phases. One patient experienced a fatal grade 5 adverse events (cardiogenic shock). Median overall survival was 51.7 months [95% confidence interval (CI)=31.6-93.2 months] and the 5-year survival rate was 44.4% (95% CI=30.3%-57.5%). CONCLUSION: Regarding its comparable efficacy and its favourable toxicity profile, perioperative FOLFOX is a reasonable alternative to FLOT for frail patients with resectable OGA.

A Truncated NRIP1 Mutant Amplifies Microsatellite Instability of Colorectal Cancer by Regulating MSH2/MSH6 Expression, and Is a Prognostic Marker of Stage III Tumors.

Microsatellite instability (MSI) is related to the alteration of mismatch repair (MMR) genes and plays a key role in colorectal cancer (CRC) pathogenesis. We previously reported that the transcription factor Nuclear Receptor Interacting Protein 1 (NRIP1) is involved in sporadic intestinal tumorigenesis. The aim of this study was to decipher its role in MSI CRC. By using different mouse models and engineered cell lines, we demonstrated that NRIP1 increased MSH2 and MSH6 MMR gene transcription and mRNA/protein levels. In human CRC cells, NRIP1 expression was associated with decreased MSI and the hypermutator phenotype, and with resistance to chemotherapy drugs. Using a cohort of 194 CRC patients, we detected in 22% of the cases a MSI-induced frameshift mutation in the NRIP1 coding sequence. This genetic alteration generates a truncated protein with a dominant negative activity that increased human CRC cell proliferation and impaired the regulation of MSH2 and MSH6 gene expression. Moreover, the NRIP1 mutant correlated with a decreased overall survival of patients with advanced CRC, especially when MLH1-deficient. By decreasing the expression of MSH2 and MSH6 gene expression, the NRIP1 variant may amplify MLH1-dependent CRC progression and behave as a new prognostic marker of advanced MSI CRC.

Sunitinib Alone or After Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Is There Still a Role for Cytoreductive Nephrectomy?

BACKGROUND: The CARMENA trial in patients with metastatic renal cell carcinoma (mRCC) demonstrated that treatment with sunitinib alone was noninferior to cytoreductive nephrectomy (CN) followed by sunitinib (nephrectomy⬜sunitinib). OBJECTIVE: The objective of this study was to provide updated overall survival (OS) outcomes of CARMENA and assess whether some subgroups may still benefit from upfront CN. DESIGN, SETTING, AND PARTICIPANTS: CARMENA was a phase III trial in 450 patients with mRCC enrolled from 2009 to 2017. INTERVENTION: Patients in the intention-to-treat population received nephrectomy⬜sunitinib (standard of care [SOC]; n = 226) or sunitinib alone (n = 224). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint was OS, assessed using an updated data cut-off (October 2018; median OS event-free follow-up, 36.6 mo). Patients were reclassified by risk using International Metastatic RCC Database Consortium (IMDC) criteria. RESULTS AND LIMITATIONS: Sunitinib alone was noninferior to nephrectomy⬜sunitinib (hazard ratio [HR], 0.97; 95% confidence interval, 0.79⬜1.19; p = 0.8) and demonstrated longer median OS (19.8 mo vs 15.6 mo, respectively). For patients with two or more IMDC risk factors, OS was significantly longer with sunitinib alone than with nephrectomy⬜sunitinib (31.2 mo vs 17.6 mo, respectively; HR, 0.65; p = 0.03). For patients with one IMDC risk factor, OS was longer for nephrectomy⬜sunitinib versus sunitinib alone although not significantly (31.4 mo vs 25.2 mo; HR, 1.30; p = 0.2). The post hoc nature of the subgroup analyses may limit their interpretation. CONCLUSIONS: Sunitinib alone was noninferior compared with nephrectomy⬜sunitinib, suggesting that CN should not be considered SOC in patients with mRCC requiring systemic treatment. Certain subgroups, including patients with one IMDC risk factor, may still benefit from upfront CN. PATIENT SUMMARY: We assessed the survival of patients with metastatic kidney cancer in a clinical trial. Patients treated with sunitinib on its own had the same survival as patients who had surgery before sunitinib treatment. We conclude that surgery may not be necessary for some patients with metastatic kidney cancer.

Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin With or Without Panitumumab in Patients With Advanced Urothelial Carcinoma: Multicenter, Randomized, French Unicancer GETUG/AFU 19 Study.

This study looked at whether epidermal growth factor receptor inhibition by the monoclonal antibody panitumumab could increase the efficacy of standard chemotherapy in advanced urothelial cancer. Results were disappointing, with higher toxicity and no improvement in efficacy in the combination arm. BACKGROUND: Epidermal growth factor receptor (EGFR) overexpression is frequent and associated with poor outcome in urothelial carcinoma. EGFR inhibition could improve the antitumor activity of chemotherapy. PATIENTS AND METHODS: Patients with advanced, treatment-naïve, histologically confirmed advanced urothelial carcinoma and no HRAS or KRAS mutation in the primary tumor received dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) without or with the anti-EGFR monoclonal antibody panitumumab (Pmab). A randomized (1:2) phase II design was used with progression-free survival (PFS) as the primary endpoint. RESULTS: Ninety-seven eligible patients were randomized; 96 patients were evaluable for toxicity and 87 for efficacy. The median PFS were 6.8 months (95% confidence interval [CI], 6.3-9.2) for dd-MVAC and 5.7 months (95% CI, 4.6-6.4 months) for dd-MVAC+Pmab. For both immunohistochemical and molecular definition of basal/squamous-like (BASQ) tumors, no difference was observed in objective response rates or PFS between the two arms in BASQ and non-BASQ tumors. CONCLUSION: dd-MVAC+Pmab was associated with more serious adverse events and no improvement in efficacy outcomes.

A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX.

BACKGROUND: In a previous phase II study an immunonutrient supplement was found to reduce severe acute toxicities for head and neck squamous cell cancer (HNSCC) patients treated with concomitant cisplatin and radiotherapy. OBJECTIVES: The primary objective of the present study was to evaluate efficacy of the same immunonutrient supplement on severe mucositis. Secondary objectives included tolerance, compliance to oral supplementation, chemotherapy interruptions and delays, quality of life, and progression-free survival (PFS) and overall survival (OS) at 1, 2, and 3 y. METHODS: Between November 2009 and June 2013, 180 HNSCC patients eligible for adjuvant chemotherapy after surgery with curative intent were included in our double-blind phase III multicenter trial. They were assigned to receive oral supplementation (3 sachets/d) of either a formula enriched with l-arginine and omega-3 (n-3) fatty and ribonucleic acids (experimental arm), or an isocaloric isonitrogenous control (control arm), for 5 d before each of 3 cycles of cisplatin. Intention-to-treat (ITT) and per-protocol (PP) analyses were undertaken, along with subgroup analyses of ≥75% compliant patients, to compare the incidence of acute mucositis (Radiation Therapy Oncology Group and WHO scales) and 36-mo survival. RESULTS: At 1 mo after terminating chemoradiotherapy (CRT), no differences were observed in the incidence of grade 3-4 mucositis between treatment groups, in the ITT, PP (172 patients), and subgroup (≥75% compliance, n = 112) analyses. The immunomodulating supplement did not significantly improve survival in the ITT and PP analyses at 3 y after CRT. Among ≥75% compliant patients, however, OS at 3 y was significantly improved in the immunomodulating formula group (81%; 95% CI: 67%, 89%) compared with controls (61%; 95% CI: 46%, 73%; P = 0.034), as well as PFS (73%; 95% CI: 58%, 83% compared with 50%; 95% CI: 36%, 63%; P = 0.012). CONCLUSIONS: Although this immunomodulating formula failed to reduce severe mucositis during CRT, the findings suggest that the long-term survival of compliant HNSCC patients was improved.This trial was registered at clinicaltrials.gov as NCT01149642.

Inflammatory Blood Markers as Prognostic and Predictive Factors in Early Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

BACKGROUND: Inflammatory blood markers, such as neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), have been reported as putative prognostic factors for survival and predictive factors for pathological complete response and toxicity in cancers, however with conflicting results. METHODS: We retrospectively analyzed data of 280 patients with early breast cancer receiving neo-adjuvant chemotherapy between 2005 and 2013 in our center. Neutrophil count, lymphocyte count and platelet count before treatment were collected as well as data on pathological complete response, toxicity, recurrence and survival. RESULTS: In multivariate analysis, high PLR was an independent prognostic factor for relapse-free survival (hazard ratio [HR] = 1.91; 95%CI = 1.15-3.16; p = 0.012) and for shorter overall survival (HR = 1.83; 95%CI = 1.03-3.24; p = 0.039). NLR was an independent predictive factor for febrile neutropenia (HR = 0.28; 95%CI = 0.13-0.58; p = 0.001). In triple negative breast cancer molecular subtype, low white blood cell count (<6.75 G/L) was predictive for a higher pathological complete response rate (odds ratio [OR] = 0.29; 95%CI = 0.14-0.61; p < 0.01). CONCLUSION: In the present study, PLR was found as an independent prognostic factor for survival, while NLR was an independent predictive factor for febrile neutropenia.

Sorafenib Plus Irinotecan Combination in Patients With RAS-mutated Metastatic Colorectal Cancer Refractory To Standard Combined Chemotherapies: A Multicenter, Randomized Phase 2 Trial (NEXIRI-2/PRODIGE 27).

BACKGROUND: No treatment option was available for patients with RAS-mutated (RASmt) metastatic colorectal cancer (mCRC) who progress after standard combined chemotherapies at the time of the study. After promising results in phase II, the aim of the present NEXIRI-2/PRODIGE 27 trial was to assess the 2-month non-progression rate for sorafenib (NEX) plus irinotecan (IRI), that is, NEXIRI, treatment. METHODS: Patients with RASmt mCRC after failure of oxaliplatin, IRI, fluoropyrimidines, and bevacizumab were randomized between NEXIRI (IRI 120-180 mg/m2 intravenous, D1 = D15 plus oral NEX 400 mg twice a day) versus IRI (180 mg/m2) versus NEX. Primary endpoint was the 2-month non-progression rate. Secondary endpoints included progression-free and overall survival (PFS and OS), safety, and germline cyclin D1 (CCND1) rs9344 polymorphisms analyses. RESULTS: A total of 173 patients were included, 59 in NEXIRI, 57 in IRI, and 57 in NEX arms. The 2-month non-progression rate was 52.6% (95% confidence interval [CI]: 39%-66%), 21.4% (10%-33%), and 19.3% (9%-30%) for NEXIRI, IRI, and NEX. Median PFS was 3.6 (95% CI: 2-4.2), 1.7 (1.7-1.8), and 2 (1.8-2.3) months and the median OS was 7.2 (5.8-9.4), 6.3 (4.8-8), and 5.6 (3.9-7.7) months for NEXIRI, IRI, and NEX, respectively. For NEXIRI rs9344CCND1 A/A genotype patients, OS was 19.6 months (95% CI: 4.8-not reached). Main grade 3 toxicities included neutropenia, febrile neutropenia, diarrhea, hand-foot syndrome, and hypertension. CONCLUSIONS: In patients with RASmt mCRC who progressed after standard combined chemotherapies, the results of 2-month non-progression rate and median PFS in the NEXIRI arm were in favor of an increase of the time before progression.

[The role of the specialist nurse in parenteral nutrition : An observational study of complications with home parenteral nutrition in adult cancer patients] / Étude observationnelle prospective des complications chez l'adulte atteint de cancer et bénéficiant d'une nutrition parentérale à domicile.

Background : In France, home parenteral nutrition (HPN) is managed by two parallel healthcare systems : in approved specialist centers (HPN > 12 weeks), and outside of these approved specialist centers (HPN<12 weeks). Objective : To prospectively evaluate infectious and vascular complications in adult cancer patients undergoing HPN administered via a central venous line, outside of approved specialist HPN centers. Methods : Our observational prospective study included adult patients with cancer, hospitalized for 48 hours or more, and under HPN. They had a WHO performance status of ≤ 2 and had had a nutritional consultation before discharge. Results : 25 patients were included in the study, with a median age of 63 years [19­74]. Weight loss of ≥ 5% was reported in 79% of patients. The Ingesta score was < 7 in 96% of cases. 87% of patients presented chill or body temperature variation episodes, with a median of 2 episodes [1­6] per patient. The median delay between end of hospitalization and the first chill episode was 11 days [1­85]. A vascular complication (obstruction without thrombosis) was reported in one patient. Discussion : This high number of infectious episodes requires improvement of patient care when it comes to strictly adhering to the recommendations. Getting the approved specialist HPN centers to work together and share care protocols could be the first important step.

Intraoperative partial irradiation for highly selected patients with breast cancer: Results of the INTRAOBS prospective study.

PURPOSE: To evaluate our long-term experience on one-day breast intraoperative radiotherapy (IORT) given as sole radiation treatment to selected patients with breast cancer. METHODS AND MATERIALS: Inclusion criteria of INTRAOBS study (prospective observational study) were: ER+ T1N0 unifocal ductal carcinoma; absence of lymphovascular invasion or of extensive intraductal component (Scarff-Bloom-Richardson grade III and HER2+++ excluded). Two different linacs were used (20Gy/1 fraction): one dedicated electron linac (

Impact of time to radiation therapy in adjuvant settings in endometrial carcinoma: A multicentric retrospective study.

OBJECTIVE: Time to adjuvant treatment could have an impact on cancer prognosis. It is possible that robotic surgery lengthens the healing time of vaginal cuff after minimally invasive hysterectomy. The objective of this study was to state the impact of time to RT (TTR) on prognosis in endometrial carcinoma (EC) patients and to assess variables associated with TTR. STUDY DESIGN: We conducted a multicentric retrospective study in two cancer centers. We included EC patients, between January 1996 and January 2016. We searched variables associated with TTR and impact of TTR on end-points: local recurrence-free survival, metastatic-free survival, event-free survival and overall survival. RESULTS: 329 patients were included and 279 were analyzed for TTR impact. Robotic surgery was associated with shorter TTR (8 weeks, 8.9 w for laparotomy, 9.2 w for laparoscopy). Pelvic lymphadenectomy, para-aortic lymphadenectomy, discussion in multidisciplinary meeting and treatment center was independently associated with TTR. No impact of TTR was shown on metastatic-free survival, event-free survival and overall survival but there was a trend of a decreased local recurrence rate in case of prolonged TTR (HRcontinuous variable = 1.08; CI95 %: 0.97-1.2). CONCLUSION: Our study did not show any impact of treatment delay on survival end-points although prolonged TTR could moderate the benefit of radiotherapy on local control rate. Surgical route was not associated with TTR, particularly robot-associated laparoscopy did not lengthen treatment delay. TTR seems dependent of health-care organization and could represent a quality criterion of EC care for institutions.

Surgical Margins and Adjuvant Therapies in Malignant Phyllodes Tumors of the Breast: A Multicenter Retrospective Study.

BACKGROUND: The optimal threshold of surgical margins for breast malignant phyllodes tumors (MPTs) and the impact of adjuvant chemotherapy and radiotherapy were investigated. PATIENTS AND METHODS: We conducted a multicenter nationwide retrospective study of all MPT cases with central pathological review within the French Sarcoma Group. Endpoints were local recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) rates. RESULTS: Overall, 212 patients were included in the study. All non-metastatic patients underwent primary surgical treatment, including 58.6% of conservative surgeries. An R0 resection was achieved in 117 patients (59.4%: 26.9% of patients with 1-2 mm margins, 12.2% of patients with 3-7 mm margins, 20.3% of patients with ≥ 8 mm margins). Ninety-four patients (45%) underwent a second surgery (SS) to obtain R0 margins, with a final mastectomy rate of 72.6%. Radiotherapy and chemotherapy were performed in 91 (43.1%) and 23 patients (10.9%), respectively, but were not associated with better outcomes. Mastectomy was significantly associated with better LRFS (p < 0.001). Margins of 0, 1, or 2 mm with SS were associated with better MFS (hazard ratio [HR] 0.3, p = 0.005) and OS (HR 0.32, p = 0.005) compared with margins of 0-1-2 mm without SS. Wider margins (> 8 mm) were not superior to margins of 3-7 mm (3-7 mm vs. > 8 mm; HR 0.81, p = 0.69). Age (HR 2.14, p = 0.038) and tumor necrosis (HR 1.96, p = 0.047) were found to be poor prognostic factors and were associated with MFS. CONCLUSIONS: This study suggests that 3 mm margins are necessary and sufficient for surgical management of MPTs, and emphasizes the importance of SS to obtain clear margins in case of 0-1-2 mm margins. No impact of adjuvant chemotherapy or radiotherapy was detected in this study.

Long-term follow-up experience in anal canal cancer treated with Intensity-Modulated Radiation Therapy: Clinical outcomes, patterns of relapse and predictors of failure.

BACKGROUND AND PURPOSE: To assess the long-term outcomes of patients with squamous cell carcinoma of the anal canal (SCCAC) treated with Intensity-Modulated Radiation Therapy (IMRT). MATERIAL AND METHODS: From 2007 to 2015, 193 patients were treated by IMRT for SCCAC. Radiotherapy delivered 45 Gy in 1.8 Gy daily-fractions to the primary tumor and elective nodal areas, immediately followed by a boost of 14.4-20 Gy to the primary tumor and involved nodes. Concurrent chemotherapy with 5-FU-mitomycin (MMC) or cisplatin was added for locally advanced tumors. Survivals were estimated by Kaplan-Meier method. Locoregional (LR) relapses were precisely assessed. Prognostic factors were evaluated by uni- and multivariate analyses. Late toxicity was scored according to the Common Toxicity Criteria for Adverse Events v4.0. RESULTS: Median follow-up was 70 months (range, 1-131). Forty-nine men (25%) and 144 women (75%) were analyzed. Median age was 62 years. Tumor stages were I, II, III and IV in 7%, 24%, 63% and 6% of cases, respectively. Chemotherapy was delivered in 167 patients (87%), mainly MMC (80%). Five-year OS, DFS, CFS and LR control rates were 74%, 68%, 66% and 85%, respectively. Forty-one patients (21%) had a relapse: 22 were LR, mostly in-field (68%). Predictors for LR failure were exclusive radiotherapy, chemotherapy lacking MMC and treatment breaks >3 days. Overall late toxicity ≥grade 2 occurred in 43% of patients, with 24% grade 3 and one case of grade 4 (hematuria). CONCLUSION: CRT with IMRT assures excellent local control in locally advanced SCCAC with manageable long-term toxicity. Multicentric prospective trials are required to reinforce those results.