FOLFIRINOX De-Escalation in Advanced Pancreatic Cancer: A Multicenter Real-Life Study.

BACKGROUND: Our study describes the feasibility and efficacy of a first-line FOLFIRINOX (5-fluorouracil [5FU], folinic acid, irinotecan, and oxaliplatin) induction chemotherapy (CT) followed by de-escalation as a maintenance strategy for advanced pancreatic cancer. MATERIALS AND METHODS: This multicenter retrospective study was conducted from January 2011 to December 2018. FOLFIRINOX de-escalation was defined as stopping oxaliplatin and/or irinotecan after at least four cycles of FOLFIRINOX, without evidence of disease progression. Maintenance schedules were fluoropyrimidine monotherapy (intravenous or oral [capecitabine]), FOLFOX (5FU, oxaliplatin), or FOLFIRI (5FU, irinotecan). Primary endpoint was overall survival (OS). Secondary endpoints were first progression-free survival (PFS1), second progression-free survival (PFS2), and toxicity. RESULTS: Among 321 patients treated with FOLFIRINOX, 147 (45.8%) were included. Median OS was 16.1 months (95% confidence interval [CI], 13.7-20.3) and median PFS1 was 9.4 months (95% CI, 8.5-10.4). The preferred maintenance regimen was FOLFIRI in 66 (45%) patients versus 5FU monotherapy in 52 (35%) and FOLFOX in 25 (17%) patients. Among 118 patients who received maintenance CT with FOLFIRI or 5FU, there was no difference in PFS1 (median, 9.0 vs. 10.1 months, respectively; p = .33) or OS (median, 16.6 vs. 18.7 months; p = .86) between the two maintenance regimens. Reintroduction of FOLFIRINOX was performed in 20.2% of patients, with a median PFS2 of 2.8 months (95% CI, 2.0-22.3). The rates of grade 3-4 toxicity were significantly higher with FOLFIRI maintenance CT than with 5FU (41% vs. 22%; p = .03), especially for neuropathy (73% vs. 9%). CONCLUSION: 5FU monotherapy maintenance appeared to be as effective as FOLFIRI, in a FOLFIRINOX de-escalation strategy, which is largely used in France. IMPLICATIONS FOR PRACTICE: FOLFIRINOX de-escalation and maintenance is a feasible strategy in advanced pancreatic cancer that decreases chemotherapy toxicity to improve both survival and quality of life. Survivals in patients with maintenance therapy are clinically meaningful. Fluoropyrimidine monotherapy maintenance seems to be as efficient as FOLFIRI and should be a reference arm in future pancreatic cancer maintenance trials.

Clinical Relevance of Alternative Endpoints in Colorectal Cancer First-Line Therapy With Bevacizumab: A Retrospective Study.

BACKGROUND: We studied the relationship between intermediate criteria and overall survival (OS) in metastatic colorectal cancer (mCRC) patients who received first-line chemotherapy with bevacizumab. PATIENTS AND METHODS: We assessed OS, progression-free survival (PFS), duration of disease control (DDC), the sum of the periods in which the disease did not progress, and the time to failure of strategy (TFS), which was defined as the entire period before the introduction of a second-line treatment. Linear correlation and regression models were used, and Prentice criteria were investigated. RESULTS: With a median follow-up of 57.6 months for 216 patients, the median OS was 24.5 months (95% confidence interval [CI], 21.3-29.7). The median PFS, DDC, and TFS were 8.9 (95% CI, 8.4-9.7), 11.0 (95% CI, 9.8-12.4), and 11.1 (95% CI, 10.0-13.0) months, respectively. The correlations between OS and DDC (Pearson coefficient, 0.79 [95% CI, 0.73-0.83], determination coefficient, 0.62) and OS and TFS (Pearson coefficient, 0.79 [95% CI, 0.73-0.84], determination coefficient, 0.63) were satisfactory. Linear regression analysis showed a significant association between OS and DDC, and between OS and TFS. Prentice criteria were verified for TFS as well as DDC. CONCLUSION: DDC and TFS correlated with OS and are relevant as intermediate criteria in the setting of patients with mCRC treated with a first-line bevacizumab-based regimen.

[Incidence and risk factors for ifosfamide-related encephalopathy in sarcoma patients]. / Incidence et facteurs de risque de l'encéphalopathie à l'ifosfamide chez les patients suivis pour un sarcome.

CONTEXT: Ifosfamide remains one of the major cytotoxic drugs for sarcoma management. Ifosfamid-related encephalopathy (IRE) is a rare but severe adverse event, without clearly identified risk factors. METHOD: We have carried out a single-center, retrospective study to assess the occurrence and the risk factors for IRE after the two first cycles of chemotherapy. We have collected the data-describing patients, biological data, tumors characteristics (histology, leptomeningeal metastasis) and ifosfamide administration modalities. RESULTS: From September 2008 to November 2013, we have identified 8 IRE out of 187 patients (4.2% [CI95%: 1.8-8.2]). The median age was 27 (0-78). Histologies were adult soft tissue sarcomas (78 patients), osteosarcoma (48), ewing sarcoma (41) and rhabdomyosarcoma (26). Most of factors were not associated with IRE. Only 8 patients have received aprepitant, none of them experienced IRE. Under univariate analysis, the risk factors for IRE were: PS≥2 (OR=9.52 [CI95%: 2.38-38.80]), albumin≤36g/L (OR=9.79 [CI95%: 1.19-80.26]), leptomeningeal metastasis (OR=13.20 [CI95%: 2.76-63.19]), 4 or 5 successive days of ifosfamide administration (OR=6.00 [CI95%: 1.40-25.60]). Under multivariate analysis, the risk factors for IE were: PS≥2 (OR=16.00 [IC95%: 2.80-67.00]), leptomeningial metastasis (OR=23.56 [IC95%: 2.01-456.80]) and 4 or 5 days of ifosfamide administration (OR=57.45 [IC95%: 1.66-35.00]). CONCLUSION: Ifosfamide administration must be given with caution in patients with poor performans status. A 4 to 5 days fractioned ifosfamide and leptomeningeal metastasis seems associated with increased risk for IRE, whatever the total administered dose.

First-Line Chemotherapy for Metastatic Esophageal Squamous Cell Carcinoma: Clinico-Biological Predictors of Disease Control.

OBJECTIVE: This study aimed to identify predictors of tumor control (TC) in metastatic esophageal squamous cell carcinoma patients receiving first-line chemotherapy. METHODS: A development cohort of 68 patients from a prospective multicenter trial (NCT01248299) was used to identify predictors of TC at first radiological tumor assessment and to generate a predictive score for TC. That score was applied in an independent retrospective single-center validation cohort of 60 consecutive patients. RESULTS: Multivariate analysis identified three predictors of TC: body mass index ≥18.5 (OR 4.5, 95% CI 0.91-22.5), absence of bone metastasis (OR 4.6, 95% CI 0.91-23.2) and albumin ≥35 g/l (OR 3.5, 95% CI 1.0-12.1). Based on the presence or absence of these three independent prognosticators, we built a predictive model using a score from 0 to 3. In the development cohort, the TC rates were 14.3 and 78.0% and in the validation cohort 12.5 and 44.2%, for scores of 0-1 and 2-3, respectively. With negative predictive values of 85 and 88% in the development and validation cohorts, respectively, we were able to identify patients with a very low probability of TC. CONCLUSION: We have developed and validated a score that can be easily determined at the bedside to predict TC in metastatic esophageal squamous cell carcinoma patients.

Comparison of response evaluation criteria in solid tumours and Choi criteria for response evaluation in patients with advanced soft tissue sarcoma treated with trabectedin: a retrospective analysis.

BACKGROUND: To assess the additional value of density measurement using contrast-enhancement sequences (Choi assessment) in a real-life cohort of adult soft tissue sarcoma patients treated with trabectedin. METHODS: Eligibility criteria included adults (age ⩾18) treated between 01/2007 and 12/2011, with at least two trabectedin cycles after failure or intolerance to doxorubicin/ifosfamide. Baseline and first computed tomography (CT)-scans were centrally reviewed by an experienced radiologist. RESULTS: The retrospective cohort consists of 134 (73 female) patients treated with trabectedin 1.5 mg/m(2) given as a 24-h infusion every 3 weeks. Patients received a median of five trabectedin cycles (range: 2-33) and the main cause of discontinuation was progressive disease (PD) (n = 105, 78.4%). Response Evaluation Criteria in Solid Tumours (RECIST) assessment was feasible in 128 (95.5%) patients, with Choi assessment performed in 92 (68.7%) patients, generally due to inadequate sequences or exclusive lung metastases. Concordance between both methods was fair (Kappa = 0.290). We identified five patients with false PD (i.e. PD according to RECIST but stable disease/partial response as per Choi). Univariate analysis did not identify any predictive factors for false PD. Median overall survival (OS) of patients with PD as per RECIST but stable disease/partial response (SD/PR) according to Choi was better than for patients with PD according to both RECIST and Choi (14 months versus 8 months; p = 0.052). CONCLUSIONS: Choi assessment may identify patients with false PD who achieved improved efficacy outcomes, suggesting that trabectedin may delay tumour progression even in the case of non-dimensional response. Dual size and tumour density assessment may be more suitable to evaluate responses to trabectedin in sarcoma patients as well as to improve the decision-making strategies for the continuation of trabectedin therapy.

[Urachal cancers]. / Les cancers de l'ouraque.

Urachal cancer is a rare pathology (less than 1% among all bladder tumors) with a poor prognosis for all stages, because of clinical delay leading to a late diagnosis, difficult differential diagnosis with bladder cancer, and no consensus for the treatment, mostly about the chemotherapy for advanced stages, because there are no data from prospective studies. A surgical treatment can be performed for the localized stages, but there are no real guidelines for local relapses and metastatic progression treatment. Those cancers are not radio- or chemosensitive; nevertheless data from fundamental research are missing. As this pathology is really uncommon, there are no clinical studies with targeted therapies. The purpose of this review is to introduce the most important clinical and paraclinical features of those cancers, and the usual treatment performed.

Return to work after treatment for breast cancer: single center experience in a cohort of 273 patients.

BACKGROUND: An increasing number of patients is treated for breast cancer during their professional life. The aim of this study was to assess factors impacting return to work and time to return to work after treatment. PATIENTS AND METHODS: One thousand and sixty-seven patients less than 60 years of age, and surgically treated in our institution between January 1st, 2004 and December 31st, 2005 received a questionnaire with medical, sociodemographic and professional items. An answer was obtained in 586 cases. Two hundred and seventy-three patients were evaluable. All the clinical files of these patients were reviewed. RESULTS: Overall, 79.8% of the patients returned to work after a median delay of 11.5 months. In the multivariate analysis, the factors affecting the return to work were: age (P<0.0001), educational level (P<0.001), colleagues' support (P<0.001), chemotherapy (P<0.05), lymphedema (P<0.01), and the physical (P=0.01) and psychological (P<0.01) constraints of the job. The factors affecting the time until return to work were very quite similar. No significant difference was observed according to the type of surgery, radiation therapy or not, hormonotherapy or not. CONCLUSION: Eighty percent of the patients with a professional activity before treatment returned to work; the factors affecting return to work were medical, demographic and socio-professional.

Use of conventional fractionation with cyberknife in children: a report of 5 cases.

SUMMARY: The use of stereotactic radiotherapy with CyberKnife (Accuray Incorporated, Sunnyvale, CA) in adults is becoming more and more established. For children, there is no such consensus and the appropriate approach to this type of treatment is still debated. In the meantime, there seems to be a number of certain pediatric cases in which the use of CyberKnife within very strict limits is potentially justified. Here, we report the feasibility of and acute tolerance to radiotherapy with CyberKnife using conventional fractionation in 5 children.

Factors related to return to work by women with breast cancer in northern France.

INTRODUCTION: Earlier diagnosis and better treatment have increased the survival rates of breast cancer patients. This warrants research on return to work of cancer survivors, especially about subjective factors because they affect the mental desire to return to work. Moreover, knowledge in this issue is very limited in France. OBJECTIVES: This study aims to explore the objective and subjective factors that affect whether and when women with breast cancer return to work. METHODS: 379 women with breast cancer aged 18-60 years who were working at the time of diagnosis responded to a 45 item questionnaire. The questionnaire had personal characteristics, disease-related characteristics and work-related ones. Multivariate logistic regressions were run to determine the association of these factors and return to work and time until return to work. RESULTS: During a median follow-up of 36 months, 82.1% of the 379 women who had worked before their diagnosis returned to work after a median sick leave of 10.8 months. Older age, lower educational level, chemotherapy, radiotherapy, lymphoedema, psychological or organizational self-perceived constraints related to their former job, and the lack of moral support from work colleagues both limited and delayed return to work. CONCLUSION: The resumption of work by women with breast cancer depends on many factors, not all of them medical. The self-perceived factors must be considered: first to help support these women during their sick leave, while taking into account elements that may hinder early return to work; second to initiate a work resumption support process which takes into account both the person and her environment.