Preoperative chemosensitivity testing as Predictor of Treatment benefit in Adjuvant stage III colon cancer (PePiTA): protocol of a prospective BGDO (Belgian Group for Digestive Oncology) multicentric study.

BACKGROUND: Surgery is a curative treatment for patients with locally advanced colon cancer, but recurrences are frequent for those with stage III disease. FOLFOX adjuvant chemotherapy has been shown to improve recurrence-free survival and overall survival by more than 20% and is nowadays considered a standard of care. However, the vast majority of patients will not benefit from receiving cytotoxic drugs because they have either already been cured by surgery or because their tumor cells are resistant to the chemotherapy, for which predictive factors are still not available. METHODS/DESIGN: PePiTA is a prospective, multicenter, non-randomised trial built on the hypothesis that preoperative chemosensitivity testing using FDG-PET/CT before and after one course of FOLFOX can identify the patients who are unlikely to benefit from 6 months of adjuvant FOLFOX treatment for stage III colon cancer. DISCUSSION: PePiTA is the first study to use the primitive tumor chemosensitivity assessed by metabolic imaging as a guidance for adjuvant therapy in colon cancer. It could pave the way for tailoring the treatment and avoiding useless toxicities for the patients and inadequate expenses for the society. It could also give an interesting insight into tumoral heterogeneity, resistance to chemotherapy, genetic predisposants to oxaliplatin toxicity and immune response to cancer. EUDRACT NUMBER: 2009-011445-13 TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00994864.

Fortnightly or fractionated weekly docetaxel-cisplatin-5-FU as first-line treatment in advanced gastric and gastroesophageal junction adenocarcinoma: The randomized phase II DoGE study.

BACKGROUND: While docetaxel/cisplatin/5-fluorouracil (DCF) outperforms CF in first-line gastric adenocarcinoma, toxicity remains an issue. METHODS: This multicenter phase II trial randomized chemonaïve metastatic gastric adenocarcinoma patients to fractionated weekly DCF (D 40 mg/m2 , C 35 mg/m², F 1800 mg/m² over 24 h, on days 1 and 8 every 3 weeks, arm (1) or fortnightly DCF (D 50 mg/m2 , C 50 mg/m², F 2000 mg/m² over 48 h every 2 weeks, arm (2). Prophylactic granulocyte colony-stimulating factor (G-CSF) was not allowed. The primary endpoint was the rate of febrile neutropenia within the first six treatment weeks (early FN). RESULTS: A total of 106 eligible patients were recruited. The early and overall FN rates were 9.5% and 17% in arm 1, respectively, and 5.9% and 8% in arm 2, respectively. Grade ≥3 toxicities occurred in 81% of patients in arm 1 and 90% of patients in arm 2, the most common being neutropenia (33% vs. 61%), fatigue (27% vs. 25%), vomiting (21% vs. 12%), anorexia (19% vs. 18%), and diarrhea (17% vs. 10%). Median progression-free survival and overall survival were 5.1 (95% CI, 3.2-6.5) and 8.2 months (95% CI, 6.0-14.5), respectively, in arm 1 and 5.2 (95% CI, 3.0-6.9) and 11.9 months (95% CI, 7.4-15.9), respectively, in arm 2. CONCLUSIONS: Fractionated weekly and fortnightly DCF regimens are associated with a low risk of early FN, and a better hematological toxicity profile as compared to historical DCF without compromising efficacy. Both regimens offer greater convenience removing the need for systematic use of prophylactic G-CSF.

Dietetic and Psychological Mindfulness Workshops for the Management of Cachectic Cancer Patients. A Randomized Study.

AIM: To determine if actively-treated cancer patients developing cachexia could benefit from participation to mindfulness workshops. PATIENTS AND METHODS: Subjects developing cachexia signs while treated for cancer were randomized in a trial aiming to compare an experimental group that would participate to specific workshops based on mindfulness alternating dietetic and psychological approaches, and a control group managed in accordance to usual practice. RESULTS: The recruitment was difficult (12% of the approached population). Finally 53 patients accepted to participate. Despite an unpredictable compliance of workshop participants, the final satisfaction score attained 75%. In comparison with the control group, patients randomized to the experimental group showed a significant benefit with an increase of their body weight and an improvement of their WHO status score. They also experienced an improvement of emotional function and observation faculty as well as a relief of fatigue and some digestive disorders. CONCLUSION: Selected cachectic cancer patients may benefit from this experimental approach. This approach may, however, be difficult to implement on a large scale.

The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer.

BACKGROUND: Tumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR) heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC). METHODS: Standardized FDG-PET/CT was performed at baseline and after the first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day) and capecitabine (1700 mg/m²/day administered D1-14 every 21 days). MR assessment was categorized according to the proportion of metabolically non-responding (non-mR) lesions (stable FDG uptake with SUVmax decrease <15%) among all measurable lesions. RESULTS: Ninety-two patients were included. The median overall survival (OS) and progression-free survival (PFS) were 8.2 months (95% CI: 6.8-10.5) and 4.2 months (95% CI: 3.4-4.8) respectively. In the 79 assessable patients, early PET-CT showed no metabolically refractory lesion in 47%, a heterogeneous mR with at least one non-mR lesion in 32%, and a consistent non-mR or early disease progression in 21%. On exploratory analysis, patients without any non-mR lesion showed a significantly longer PFS (HR 0.34; 95% CI: 0.21-0.56, P-value <0.001) and OS (HR 0.58; 95% CI: 0.36-0.92, P-value 0.02) compared to the other patients. The proportion of non-mR lesions within the tumor load did not impact PFS/OS. CONCLUSION: The presence of at least one metabolically refractory lesion is associated with a poorer outcome in advanced mCRC patients treated with combined sorafenib-capecitabine. Early detection of treatment-induced mR heterogeneity may represent an important predictive efficacy biomarker in mCRC. TRIAL REGISTRATION: ClinicalTrials.gov NCT01290926.

Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study.

PURPOSE: The addition of radiation to adjuvant 5-fluorouracil for the treatment of pancreatic cancer has not yet shown any definite benefit. Gemcitabine (GEM) has potential activity in advanced pancreatic cancer and is a powerful radiosensitizer. We evaluated the feasibility of postoperative administration of GEM alone, followed by concurrent GEM and irradiation (RT) after curative resection for pancreatic adenocarcinoma. METHODS AND MATERIALS: GEM 1000 mg/m(2) on Days 1 and 8 every 21 days for three courses was given within 8 weeks after surgery and was followed by GEM 300 mg/m(2) weekly +40 Gy in a split course. Twenty-two patients (median age 59 years, range 39-74, Performance Status 0-1) with Stage II and III curatively resected pancreatic head adenocarcinoma were included. RESULTS: For GEM alone, all patients received the three planned courses, with dose reductions in 7 (32%) of 22 patients. All patients, except two, completed full chemoradiation; one received only 20 Gy because of both World Health Organization Grade 4 vomiting and thrombopenia and the other stopped RT after 32 Gy because of early disease progression. No reduction in GEM during RT was necessary; no toxic death was noted; and World Health Organization Grade 3-4 hematologic and nonhematologic toxicities occurred in 8 (36%) and 7 (nausea, vomiting) (32%) of 22 patients respectively. No late toxicity developed. After a median follow-up of 15 months, 11 patients were alive, and 2 patients had died of causes unrelated to their disease or toxicity, The median disease-free survival and overall survival was 6 and 15 months, respectively. CONCLUSION: This adjuvant regimen was well tolerated and can be easily administered after curative surgery for pancreatic cancer. Its intensification with continuous RT is currently being investigated.

Endoscopic findings in case of incidental colonic uptake in PET-CT how to improve PET-CT specificity?

Unexpected colonic 18FDG focal uptakes (UCFU) in PET CT occur in 1.3-3.3% of cases in retrospective study and are often associated with significant colorectal findings in endoscopy, especially neoplastic lesions. The purpose of our prospective study was to evaluate the significance of UCFU and to assess criteria improving PET CT specificity for advanced adenoma and neoplasia. This study was conducted in a single institution from April 2012 to September 2013. In the 2904 patients who benefit from PET CT, 52 had an UCFU and 43 were referred for colonoscopy. After endoscopy, 8 examinations showed no colonic abnormality (18.6%), 7 showed benign lesion (16.3%), 18 showed advanced adenoma (42.9%) and 10 showed carcinoma (23.3%). There were more false positives results in the proximal colon compared to distal colon. Eighteen patients had UCFU and tomodensitometric abnormalities in the same colonic area. This pathological combination was strongly associated to the diagnosis of malignancy. Comparing standardized uptake values (SUV), we showed statistically significant difference between the adenocarcinoma and advanced adenoma groups and a difference at the margin of statistical significance between adenocarcinoma and benign lesion groups. Any cut off value could be determined. In conclusion, we confirmed that UCFU are often associated to endoscopic findings and neoplastic lesions and justify systematic endoscopic exploration. Considering the fragility of oncologic patients, criteria improving PET CT specificity are needed to select endoscopies which should be performed quickly from those who could be delayed. We showed that associated tomodensitometric abnormality and high focal FDG activity are more predictive of a neoplastic lesion.