The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer

Background: In the phase III RECOURSE trial, trifluridine/tipiracil (TAS-102) extended overall survival (OS) and progression-free survival (PFS) with an acceptable toxicity profile in patients with metastatic colorectal cancer refractory or intolerant to standard therapies. The present analysis investigated the efficacy and safety of trifluridine/tipiracil in RECOURSE subgroups. Methods: Primary and key secondary end-points were evaluated using a Cox proportional hazards model in prespecified subgroups, including geographical subregion (United States of America [USA], European Union [EU], Japan), age (<65 years, ≥65 years) and v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue (KRAS) status (wild type, mutant). Safety and tolerability were reported with descriptive statistics. Results: Eight-hundred patients were enrolled: USA, n = 99; EU, n = 403; Japan, n = 266. Patients aged ≥65 years and those with mutant KRAS tumours comprised 44% and 51% of all patients in the subregions, respectively. Final OS analysis (including 89% of events, compared with 72% in the initial analysis) confirmed the survival benefit associated with trifluridine/tipiracil, with a hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.59–0.81; P = 0.0001). Median OS in the three regions was 6.5–7.8 months in the trifluridine/tipiracil arm and 4.3–6.7 months in the placebo arm (USA: HR 0.56; 95% CI 0.34–0.94; P = 0.0277; EU: HR 0.62; 95% CI 0.48–0.80; P = 0.0002; Japan: HR 0.75; 95% CI 0.57–1.00; P = 0.0470). Median PFS was 2.0–2.8 months for trifluridine/tipiracil and 1.7–1.8 months for placebo; HRs favoured trifluridine/tipiracil in all regions. Similar clinical benefits of trifluridine/tipiracil were observed in elderly patients and in those with mutant KRAS tumours. There were no marked differences among subregions in terms of safety and tolerability. Conclusions: Trifluridine/tipiracil was effective in all subgroups, regardless of age, geographical origin or KRAS status

Bevacizumab plus FOLFIRI or FOLFOX in chemotherapy-refractory patients with metastatic colorectal cancer: a retrospective study

<p>Abstract</p> <p>Background</p> <p>The anti-VEGF antibody bevacizumab associated with an irinotecan or oxaliplatin-based chemotherapy was proved to be superior to the chemotherapy alone in first or second line treatment of metastatic colorectal cancer (mCRC). However, it was reported to have no efficacy in 3^rdor later-line, alone or with 5FU. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI or FOLFOX in mCRC who have failed prior chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin.</p> <p>Methods</p> <p>Thirty one consecutive patients treated between May 2005 and October 2006 were included in this retrospective study. All of them have progressed under a chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin and received bevacizumab (5 mg/kg) in combination with FOLFIRI or simplified FOLFOX4 every 14 days.</p> <p>Results</p> <p>Ten patients (32.2%) had an objective response (1 CR, 9 PR) and 12 (38.8%) were stabilized. The response and disease control rates were 45.4% and 100% when bevacizumab was administered in 2^ndor 3^rdline and 25% and 55% in 4^thor later line respectively (p = 0.024 and p = 0.008). Among the patients who had previously received the same chemotherapy than that associated with bevacizumab (n = 28) the overall response rate was 35.7% and 39.3% were stabilized. Median progression free survival (PFS) and overall survival (OS) were of 9.7 and 18.4 months respectively. Except a patient who presented a hypertension associated reversible posterior leukoencephalopathy syndrome, tolerance of bevacizumab was acceptable. A rectal bleeding occurred in one patient, an epistaxis in five. Grade 1/2 hypertension occurred in five patients.</p> <p>Conclusion</p> <p>This study suggests that bevacizumab combined with FOLFOX or FOLFIRI may have the possibility to be active in chemorefractory and selected mCRC patients who did not receive it previously.</p

La Biopsie guidée sous échoendoscopie (faisabilité et rentabilité diagnostique au bout d'un an d'expérience)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Bone metastases in gastrointestinal cancer.

International audienceColorectal (CRC) and gastroesophageal (GEC) cancers unusually spread to the bone. However, bone metastases (BM) are responsible for skeletal-related events (SREs) associated with an altered quality of life. Aiming to describe the characteristics and prognostic influence of BM from gastro-intestinal cancers, we performed a retrospective analysis of prospectively collected data in patients treated in our institution (1996-2006). 189 patients (5.5 %) developed BM: 79 with GEC and 110 with CRC. 57 patients had bone-exclusive metastases. In univariate analyses, the median time to BM occurrence was correlated with the primary tumour (PT) localisation, surgery, histology and TNM staging. However, in multivariate analyses, the occurrence delay was significantly shorter only for patients with GEC (HR 2.1), N1-2 status (HR 1.9), M1 status (HR 2.4), and epidermoid carcinoma (HR 6.0). Pain was the most frequent clinical sign leading to BM diagnosis (77.2 %). SRE occurred in 55 % of patients. Median overall survivals (OSs) of patients with CRC and GEC were 9.4 months [95 % confidence interval (95 % CI) 6.4-11.1] and 3.4 months (95 % CI 2.5-9.0), respectively. In univariate analyses, OS was correlated with PT surgery and NM staging, and the number of BM. In multivariate analyses, only the PT surgery and the number of BM remained correlated with OS. Our results suggest that there may be a subset of patients associated with a quicker development of BM. Given their higher risk of SRE, they could benefit from an early screening, calling for further prospective studies encompassing patients with and without BM

The Colofight feasibility study protocol : Hypnosis and Cognitive Behavioral Therapy with online sessions to reduce fatigue in patients undergoing chemotherapy for a metastatic colorectal cancer

International audienceBackground. This study aims to implement two interventions (CBT and hypnosis) for the management of cancer-related fatigue. Although CBT is known to be effective in treating cancer-related side effects, it requires specific training often reserved for psychologists. On the other hand, hypnosis has the advantage of being increasingly practiced by caregivers and is therefore less expensive, but it is more difficult to standardize.Implementing an intervention in a healthcare setting is complex and recruiting participants can be challenging. Thus, we aim to evaluate the feasibility of implementing this type of intervention.Methods and design. A prospective, single-center, randomized interventional feasibility study, using mixed methods (both quantitative and qualitative). 60 patients will be randomized and allocated to each intervention group (Hypnosis (n=30) and CBT (n=30)). Both programs will consist of 6 weekly sessions focusing on the fatigue management over a period of 6 weeks. Trained therapists will conduct the program combining 3 face-to-face sessions and 3 online sessions. The feasibility and experience of interventions will be evaluated by qualitative interviews. Quality of Life and daily fatigue will be self-assessment using an online application from the cancer center.Discussion. Inclusions are ongoing but the oral presentation could focus on the overview of the two interventions and in particular how the authors standardized the hypnosis sessions. Specific exercises are proposed to target the determinants of fatigue (eg. distress). The next step in this project is the opening of a multi-center RCT. An opportunity to discuss with clinicians and researchers interested in the interventions

Determinants of distinct trajectories of fatigue in patients undergoing chemotherapy for a metastatic colorectal cancer: 6-month follow-up using Growth Mixture Modeling

OBJECTIVE: This longitudinal prospective and observational study was designed to identify fatigue trajectories during a 6-month period of chemotherapy in patients with metastatic colorectal cancer, and examine the psychosocial factors predicting these trajectories. Associations between fatigue and survival were also investigated. METHODS: A total of 169 patients (M(age)=64.36 years, SD=10.5) reported their fatigue levels every 2 weeks for 6 months. Psychological variables (anxiety, depression, internal control, and coping) were assessed at baseline. A Growth Mixture Model was used to identify latent trajectories of fatigue, and a multinomial logistic regression tested covariate predictors of patients' trajectories. RESULTS: Four clinically distinct fatigue trajectories were identified: intense fatigue (6.51%), moderate fatigue (48.52%), no fatigue (33%), and increasing fatigue (11.83%). Fatigue severity was directly associated with overall survival. High depression levels were associated with fatigue severity over time for intense (OR=1.80 [1.32-2.47]) and for moderate (OR=1.58 [1.25-2.00]) fatigue, compared to patients reporting no fatigue. Patients who did not report fatigue were better adjusted, and had more resources, such as better internal control over the disease and less emotion-focused coping (guilt and avoidance), than those who reported intense (OR(control)=0.77 [0.65-0.92]) or moderate (OR(control)=0.89 [0.79-0.99] and OR(coping)=1.13 [1.02-1.24]) fatigue. CONCLUSIONS: Fatigue trajectories differed considerably across patients with metastatic colorectal cancer. This first longitudinal study on colorectal cancer patients involving transactional variables suggests that psychosocial interventions should target these specific outcomes, in order to help patients manage their fatigue

The Colofight feasibility study protocol : Hypnosis and Cognitive Behavioral Therapy with online sessions to reduce fatigue in patients undergoing chemotherapy for a metastatic colorectal cancer

International audienceBackground. This study aims to implement two interventions (CBT and hypnosis) for the management of cancer-related fatigue. Although CBT is known to be effective in treating cancer-related side effects, it requires specific training often reserved for psychologists. On the other hand, hypnosis has the advantage of being increasingly practiced by caregivers and is therefore less expensive, but it is more difficult to standardize.Implementing an intervention in a healthcare setting is complex and recruiting participants can be challenging. Thus, we aim to evaluate the feasibility of implementing this type of intervention.Methods and design. A prospective, single-center, randomized interventional feasibility study, using mixed methods (both quantitative and qualitative). 60 patients will be randomized and allocated to each intervention group (Hypnosis (n=30) and CBT (n=30)). Both programs will consist of 6 weekly sessions focusing on the fatigue management over a period of 6 weeks. Trained therapists will conduct the program combining 3 face-to-face sessions and 3 online sessions. The feasibility and experience of interventions will be evaluated by qualitative interviews. Quality of Life and daily fatigue will be self-assessment using an online application from the cancer center.Discussion. Inclusions are ongoing but the oral presentation could focus on the overview of the two interventions and in particular how the authors standardized the hypnosis sessions. Specific exercises are proposed to target the determinants of fatigue (eg. distress). The next step in this project is the opening of a multi-center RCT. An opportunity to discuss with clinicians and researchers interested in the interventions

Distal Pancreatectomy with Celiac Axis Resection (Modified Appleby Procedure) and Arterial Reconstruction for Locally Advanced Pancreatic Adenocarcinoma After FOLFIRINOX Chemotherapy and Chemoradiation Therapy

International audienceBackground: Resectability of pancreatic carcinoma (PC) is directly linked to vascular extension (Tempero MA et al. in J Natl Compr Canc Netw 15(8):1028–1061, 2017. https://doi.org/10.6004/jnccn.2017.0131; Isaji S et al. in Pancreatology 18(1):2–11, 2018. https://doi.org/10.1016/j.pan.2017.11.011). Involvement of the celiac axis (CA) is typically a contraindication to surgery. High postoperative morbidity and subsequent poor prognosis have been observed in this case, especially for contact > 180° requiring arterial resection (Tempero MA et al. 2017). Recent medical advances in PC treatment, such as FOLFIRINOX-based chemotherapy eventually followed by chemoradiation therapy, offer the potential to select tumour for surgery and to obtain a negative-margin resection even in case of unresectable PC at diagnosis (Suker M et al. in Lancet Oncol 17(6):801–10, 2016. https://doi.org/10.1016/s1470-2045(16)00172-8; Pietrasz D et al. in Ann Surg Oncol 26(1):109–117, 2019. https://doi.org/10.1245/s10434-018-6931-6). A major pathologic response has been observed in more than 20% of patients after this treatment and is associated with an improved survival (Suker M et al. 2016; Pietrasz D et al. 2019). This evolution allows aggressive surgical strategies with the possibility of long-term disease control for patients showing a good response to induction treatment.Patient: This video presents the case of a 66-year-old man diagnosed with a locally advanced ductal adenocarcinoma of the pancreatic body with a 360° involvement of the CA and the hepatic artery. After eight courses of FOLFIRINOX chemotherapy and a capecitabin-based chemoradiation, a surgical exploration was planned for potential resection.Technique: The key steps of the procedure are presented, i.e. surgical exposition, assessment of resectability with frozen sections of peri-arterial tissues, en bloc resection (Strasberg SM et al. in Surgery 133(5):521–527, 2003. https://doi.org/10.1067/msy.2003.146), and primary end-to-end arterial reconstruction.Conclusion: A modified Appleby operation for locally advanced PC is a technically challenging but feasible procedure in experienced teams. It offers the possibility of en bloc R0 resection of a locally advanced PC with the potential of long-term disease local control. This video may help surgeons to perform this complex intervention

Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study)

Abstract Background At time of diagnosis, less than 10% of patients with pancreatic adenocarcinomas (PDAC) are considered to be immediately operable (i.e. resectable). Considering their poor overall survival (OS), only tumours without vascular invasion (NCCN 2017) should be considered for resection, i.e. those for which resection with disease-free margins (R0) is theoretically possible in absence of presurgery treatment. With regard to high R1 rates and undetectable locoregional and/or metastatic spreading prior to surgery explain (at least in part) the observed 1-year relapse and mortality rates of 50 and 25%, respectively. Today, upfront surgery followed by adjuvant chemotherapy is the reference treatment in Europe. The main limitation of the adjuvant approach is the low rate of completion of the full therapeutic sequence. Indeed, only 47 to 60% patients received any adjuvant therapy after resection compared to more than 75% for neoadjuvant therapy. No previous prospective study has compared this approach to a neoadjuvant FOLFIRINOX or FOLFOX chemotherapy for resectable PDAC. Methods PANACHE01-PRODIGE48 is a prospective multicentre controlled randomized non comparative Phase II trial, evaluating the safety and efficacy of two regimens of neo-adjuvant chemotherapy (4 cycles of mFOLFIRINOX or FOLFOX) relative to the current reference treatment (surgery and then adjuvant chemotherapy) in patients with resectable PDAC. The main co-primary endpoints are OS rate at 12 months and the rate of patients undergoing the full therapeutic sequence. Discussion The “ideal” cancer treatment for resectable PDAC would have the following characteristics: administration to the highest possible proportion of patients, ability to identify fast-progressing patients (i.e. poor candidates for surgery), a low rate of R1 resections (through optimisation of local disease control), and an acceptable toxicity profile. The neoadjuvant approach may meet all these criteria. With respect to published data on the efficacy of FOLFOX and mFOLFIRINOX, these two regimens are potential candidates for neoadjuvant use in the aim to optimising oncological outcomes in resectable PDAC. Trial registration ClinicalTrials.gov, NCT02959879. Trial registration date: November 9, 2016