Motor disorders related to oxaliplatin-induced peripheral neuropathy: long-term severity and impact on quality of life.

PURPOSE: Sensory chemotherapy-induced peripheral neuropathy (CIPN) is well-recognized, but motor CIPN remains understudied. This secondary analysis focused on the long-term severity and impact of motor disorders, their relation to sensory CIPN, neuropathic pain, psychological distress, and health-related quality of life (HRQoL) after oxaliplatin-based chemotherapy in colorectal cancer (CRC) survivors. METHODS: Data from a multicenter, cross-sectional study were re-analyzed to explore motor CIPN among CRC survivors up to 5 years post-chemotherapy, with no longitudinal follow-up. Questionnaires assessed sensory and motor CIPN (QLQ-CIPN20), neuropathic pain (DN4), anxiety and depression (HADS), and HRQoL (QLQ-C30). RESULTS: Among 405 CRC survivors, 31.1% had sensory CIPN as previously described. When categorizing the 405 CRC survivors based on the years since their last oxaliplatin-based chemotherapy, the motor scores derived from the QLQ-CIPN20 showed no significant difference between years (p = 0.08). Motor CIPN scores correlated with female gender, higher oxaliplatin dose intensity, sensory CIPN, and neuropathic pain. Motor CIPN also linked to decreased HRQoL and increased psychological distress. CONCLUSION: The study underscores the detrimental impact of motor disorders on CRC survivors post-oxaliplatin-based chemotherapy. Oncologists should prioritize assessing and managing motor manifestations alongside sensory symptoms to enhance post-cancer quality of life. TRIAL REGISTRATION: NCT02970526 (2016-11-22). https://classic. CLINICALTRIALS: gov/ct2/show/NCT02970526?term=NCT02970526&draw=2&rank=1 .

Effect of Adapted Physical Activity in Patients With Advanced Pancreatic Cancer: The APACaP GERCOR Randomized Trial.

BACKGROUND: The impact of adapted physical activity (APA) on health-related quality of life (HRQoL) in patients with advanced pancreatic ductal adenocarcinoma (aPDAC) is unknown. This study evaluated whether APA in addition to standard care improved HRQoL in patients who have aPDAC who are receiving first-line chemotherapy. PATIENTS AND METHODS: Patients with locally advanced/metastatic PDAC and an ECOG performance status of 0 to 2 were randomized (1:1) to receive standard care (standard arm) or standard care plus a home-based 16-week APA program (APA arm). The primary objective was the effect of the APA program on 3 dimensions of the EORTC QLQ-C30: global health status, physical function, and fatigue at week 16 (W16), with a one-sided type I error of 0.017 for each dimension. The primary HRQoL analysis was performed in patients with available baseline and W16 scores for the dimensions (ie, the modified intention-to-treat population 1 [mITT1]), and secondary longitudinal HRQoL analyses using the mixed model for repeated measures (MMRM) and time until definitive deterioration (TUDD) methods were performed in the mITT1 population and in patients with baseline and at least one follow-up questionnaire (mITT2 population). A difference of ≥5 points was considered to be clinically relevant. RESULTS: Of 326 included patients, 313 were randomized to the standard (n=157) or APA (n=156) arms. In the mITT1 population (n=172), the mean differences in global health status, physical function, and fatigue at W16 adjusted from baseline were -0.98 (SD, 23.9; P=.39), -2.08 (SD, 21.3; P=.26), and 4.16 (SD, 29.2; P=.17), respectively, showing a non-statistically significant benefit with APA. In the mITT2 population (n=259), APA was associated with statistically significant and clinically relevant improvement in 5 and 8 dimensions of the HRQoL in the longitudinal MMRM and TUDD analyses, respectively. CONCLUSIONS: APA improved several dimensions of HRQoL in patients with aPDAC receiving first-line chemotherapy and standard care.

Colorectal Cancer Survivors Suffering From Sensory Chemotherapy-Induced Peripheral Neuropathy Are Not a Homogenous Group: Secondary Analysis of Patients' Profiles With Oxaliplatin-Induced Peripheral Neuropathy.

Oxaliplatin, a pivotal drug in the management of colorectal cancer, causes chemotherapy-induced peripheral neuropathy (CIPN) in a third of cancer survivors. Based on a previous cross-sectional study assessing oxaliplatin-related sensory CIPN in colorectal cancer survivors, a secondary analysis was designed to explore the possibility that different clusters of patients may co-exist among a cohort of patients with oxaliplatin-related CIPN. Other objectives were to characterize these clusters considering CIPN severity, anxiety, depression, health-related quality of life (HRQOL), patients' characteristics and oxaliplatin treatments. Among the 96 patients analyzed, three clusters were identified (cluster 1: 52, cluster 2: 34, and cluster 3: 10 patients). Clusters were significantly different according to CIPN severity and the proportion of neuropathic pain (cluster 1: low, cluster 2: intermediate, and cluster 3: high). Anxiety, depressive disorders and HRQOL alteration were lower in cluster 1 in comparison to clusters 2 and 3, but not different between clusters 2 and 3. This study underlines that patients with CIPN are not a homogenous group, and that CIPN severity is associated with psychological distress and a decline of HRQOL. Further studies are needed to explore the relation between clusters and CIPN management.

Long-Term Prevalence of Sensory Chemotherapy-Induced Peripheral Neuropathy for 5 Years after Adjuvant FOLFOX Chemotherapy to Treat Colorectal Cancer: A Multicenter Cross-Sectional Study.

(1) Background: Oxaliplatin is among the most neurotoxic anticancer drugs. Little data are available on the long-term prevalence and consequences of chemotherapy-induced peripheral neuropathy (CIPN), even though the third largest population of cancer survivors is made up of survivors of colorectal cancer. (2) Methods: A multicenter, cross-sectional study was conducted in 16 French centers to assess the prevalence of CIPN, as well as its consequences (neuropathic pain, anxiety, depression, and quality of life) in cancer survivors during the 5 years after the end of adjuvant oxaliplatin chemotherapy. (3) Results: Out of 406 patients, the prevalence of CIPN was 31.3% (95% confidence interval: 26.8-36.0). Little improvement in CIPN was found over the 5 years, and 36.5% of patients with CIPN also had neuropathic pain. CIPN was associated with anxiety, depression, and deterioration of quality of life. None of the patients with CIPN were treated with duloxetine (recommendation from American Society of Clinical Oncology), and only 3.2%, 1.6%, and 1.6% were treated with pregabalin, gabapentin, and amitriptyline, respectively. (4) Conclusions: Five years after the end of chemotherapy, a quarter of patients suffered from CIPN. The present study showed marked psychological distress and uncovered a failure in management in these patients.

Single-arm phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients over 70 with previously treated metastatic colorectal adenocarcinoma FFCD 1404 - REGOLD.

BACKGROUND: Regorafenib significantly increases overall survival (OS) in patients with metastatic colorectal cancer previously treated but gives toxicities. OBJECTIVES: to assess the efficacy and safety of regorafenib at it's approved dose in the older population. PATIENTS AND METHODS: This multicenter single-arm phase II enrolled patients ≥70 years old after the failure of fluoropyrimidine-based chemotherapy, anti-VEGF, and anti-EGFR treatment. The primary endpoint was disease control rate (DCR) 2 months after initiation of regorafenib (160 mg/day, 3 weeks on/1 week off). RESULTS: Forty-three patients were enrolled, with a median age of 77 years. The 2 months DCR was 31.4% in the 35 evaluable patients. For the 42 patients that received at least one dose of regorafenib, median progression-free survival and OS were 2.2 and 7.5 months. The median time to autonomy degradation and quality of life degradation was 3.1 and 3.2 months, respectively. A grade 3-4 treatment-related adverse events was observed in 35/42 patients, notably: fatigue (45.2%), hand-foot skin reaction (19.0%), hypertension (21.4%), and diarrhea (7.1%). There is a trend to achieve DCR in patients ≤80 years and a trend to discontinue the study due to toxicity in patients with ECOG ≥1, over 80 years and with impaired baseline autonomy. CONCLUSION: Treatment with regorafenib in pretreated patients ≥70 years is feasible and demonstrate similar efficacy that was observed in previous studies in young patients. Fatigue is the most frequent severe adverse event. However, caution should be taken for older patients with ECOG ≥1, over 80 years, and with impaired baseline autonomy.

Quality of life in cancer patients undergoing anticoagulant treatment with LMWH for venous thromboembolism: the QUAVITEC study on behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

BACKGROUND: Clinical guidelines recommend at least 3-months low molecular weight heparin (LMWH) treatment for established venous thromboembolism (VTE) in cancer patients. However, no study has analyzed the impact of 3-6 months of LMWH therapy on quality-of-life (QoL) in cancer patients. RESULTS: Among 400 cancer patients included at M0, 88.8% received long-term LMWH. Using a random-effects linear regression model with time as covariate, QoL scores in the MOS SF-36 (Global HRQoL, 1.3-fold per month [95% confidence interval (CI) 0.81-1.79], p < 0.0001) and EORTC QLQ-C30 (global health status/qol, 2.25-fold per month [95% CI 1.63-2.88]; p < 0.0001) questionnaires significantly improved over the 6-month study period in patients treated with LMWH, while VEINES-QOL scores did not change. In the MOS SF-36 and EORTC QLQ-C30, the following factors were associated with change in QoL: symptomatic VTE, cancer dissemination and histological type. Factors pertaining to reduced mobility were also identified as significant predictors of QoL outcomes, including being bedridden in the MOS SF-36 and ECOG score ≥ 2 in the EORTC QLQ-C30. Presence of acute infection and not undergoing anti-angiogenic therapy were additional factors associated with QoL improvement in the EORTC QLQ-C30. METHODS: QUAVITEC, a prospective, longitudinal, multicenter study, recruited all consecutive eligible adult cancer patients with objectively confirmed VTE between February 2011 and 2012. Patients were asked to answer three QoL questionnaires at anticoagulant treatment initiation (M0) and at 3 (M3) and 6 (M6)-month follow-ups. CONCLUSION: QUAVITEC is the first study to show that QoL was improved in cancer patients receiving long-term LMWH treatment for established VTE.

Adenoma detection with blue-water infusion colonoscopy: a randomized trial.

Background and aims Colonoscopy is currently the reference method to detect colorectal neoplasia, yet some adenomas remain undetected. The water infusion technique and dying with indigo carmine has shown interesting results for reducing this miss rate. The aim of this study was to compare the adenoma detection rate (adenoma and adenocarcinoma; ADR) and the mean number of adenomas per patient (MAP) for blue-water infusion colonoscopy (BWIC) versus standard colonoscopy. Methods We performed a multicenter, randomized controlled trial in eight units, including patients with a validated indication for colonoscopy (symptoms, familial or personal history, fecal occult blood test positive). Consenting patients were randomized 1:1 to BWIC or standard colonoscopy. All colonoscopies were performed by experienced colonoscopists. All colonoscopy quality indicators were prospectively recorded. Results Among the 1065 patients included, colonoscopies were performed completely for 983 patients (514 men; mean age 59.1). The ADR was not significantly different between the groups; 40.4 % in the BWIC group versus 37.5 % in the standard colonoscopy group (odds ratio [OR] 1.13; 95 % confidence interval [CI] 0.87 - 1.48; P = 0.35). MAP was significantly greater in the BWIC group (0.79) than in the standard colonoscopy group (0.64; P = 0.005). For advanced adenomas, the results were 50 (10.2 %) and 36 (7.3 %), respectively (P = 0.10). The cecal intubation rate was not different but the time to cecal intubation was significantly longer in BWIC group (9.9 versus 6.2 minutes; P < 0.001). Conclusion Despite the higher MAP with BWIC, the routine use of BWIC does not translate to a higher ADR. Whether increased detection ultimately results in a lower rate of interval carcinoma is not yet known. CLINICAL TRIALS REGISTRATION: EudraCT 2012-A00548 - 35; NCT01937429.

Feasibility of preoperative and postoperative chemoradiotherapy in gastric adenocarcinoma. Two phase II studies done in parallel. Fédération Francophone de Cancérologie Digestive 0308.

BACKGROUND: For resectable gastric cancer, both postoperative chemoradiotherapy and perioperative chemotherapy demonstrate high-level evidence for improved survival in Western populations. To evaluate the feasibility of pre- or postoperative chemoradiotherapy, we proposed two multicentre phase II studies. PATIENTS AND METHODS: Patients with localised, histologically confirmed gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status <2 judged suitable for curative resection were eligible. Eligible patients were assigned to either preoperative chemoradiotherapy followed by surgical resection or surgical resection followed by chemoradiotherapy depending on each centre. Chemoradiotherapy regimen included four courses of FOLFIRI (5 Fluorouracil, Leucovorin, Irinotecan) regimen then Concurrent fluorouracil at 200 mg/m2/d by continuous infusion 5 days each week. A dose of 50 Gy in 25 fractions in the preoperative study, or 45 Gy in 25 fractions in the postoperative study, was delivered. The primary end-point for both studies was the proportion of patients, who completed the therapeutic sequence. RESULTS: Between September 2007 and January 2010, 63 patients were included in both studies. The postoperative study was stopped for futility at the first step. In the preoperative study, 31 patients (73.8%, confidence interval (CI) 95%: 65.8-90.1%) received complete therapeutic sequence. Serum albumin and dietary restriction evaluated by QLQ-STO22 (Quality of Life-Stomach module) score were significantly linked with chemoradiotherapy feasibility in univariate analysis with respectively Odds-ratio (OR) 1.16 [CI 95%: 1.01-1.33] and 0.17 [0.03-0.89], p=0.04. Median overall survival time was 26.4 months in the preoperative study. CONCLUSION: Feasibility of chemoradiotherapy was not achieved for these studies: 73.8% (CI 95%: 65.8-90.1) and 42.9% (CI 95%: 21.8-66%) in preoperative and postoperative settings respectively.

Totally implantable central venous access port infections in patients with digestive cancer: incidence and risk factors.

BACKGROUND: Central venous access port-related bloodstream infection (CVAP-BSI) is associated with morbidity and mortality in patients with cancer. This study examined the incidence rates and risk factors for CVAP-BSI in adult patients with digestive cancer. METHODS: This prospective observational cohort study was performed from 2007 to 2011 in 2 oncology units of a university hospital. Incidence rate was expressed as number of CVAP-BSI per 1,000 catheter-days. A Cox regression model was used to identify risk factors for CVAP-BSI. RESULTS: A total of 315 patients were included. CVAP-BSI occurred in 41 patients (13.0%). The overall incidence rate was 0.76/1,000 catheter-days. The rate was higher in patients with esophageal cancer (1.28. P = .05) and pancreatic cancer (1.24; P = .007). Risk factors independently associated with CVAP-BSI were World Health Organization performance status between 2 and 4, catheter utilization-days in the previous month, pancreatic cancer, and parenteral nutrition. Coagulase-negative Staphylococci and enterobacteria were the main microorganisms isolated. CONCLUSIONS: In adult patients with digestive cancer, pancreatic cancer, cumulative catheter utilization-days, World Health Organization performance status, and parenteral nutrition were identified as independent risk factors for CVAP-BSI. Patients with any of these risk factors could be candidates for preventive strategies.

FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.

BACKGROUND: Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer. METHODS: We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival. RESULTS: The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001). CONCLUSIONS: As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.).

[Ano-rectal symptoms, related to Epstein-Barr Virus-Associated Burkitt's lymphoma in an immunocompetent patient]. / Manifestations anorectales, en rapport avec un lymphome de Burkitt associé au virus Epstein Barr, chez une malade immunocompétente.

We report the case of an immunocompetent 23-year-old Caucasian woman, with symptoms including rectal bleeding, tenesmus and epreint, 6 months after an anal sexual trauma. The rectal examination showed a hardened, inflammatory and painful anal margin, associated with stenosis of the anal canal, suggesting abscess. The neurological examination showed numbing of the chin. Pelvic MRI and CT scan confirmed a bulky posterior tissular pelvic mass more than 7 cm in diameter, infiltrating the rectum and the anal canal. Final diagnosis confirmed by biopsy performed during rectosigmoidoscopy was an Epstein-Barr Virus-Associated Burkitt's lymphoma. Chemotherapy resulted in rapid regression of the tumoral mass.