This study compared chemotherapy discontinuation with maintenance therapy with leucovorin and fluorouracil after six cycles of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy in the ...first-line treatment of metastatic colorectal cancer.
Two hundred two patients with untreated metastatic colorectal cancer were randomly assigned to receive six cycles of modified FOLFOX7 (mFOLFOX7) followed by simplified leucovorin plus bolus and infusional fluorouracil until progression (arm 1 or maintenance arm, n = 98) or six cycles of mFOLFOX7 before a complete stop of chemotherapy (arm 2 or chemotherapy-free interval CFI arm, n = 104). Reintroduction of mFOLFOX7 was scheduled after tumor progression in both arms. The primary study end point was duration of disease control (DDC).
Median DDC was 13.1 months in patients assigned to the maintenance arm and 9.2 months in patients assigned to the CFI arm (P = .046). Median progression-free survival (PFS) and overall survival were 8.6 and 23.8 months, respectively, in the maintenance arm and 6.6 and 19.5 months, respectively, in the CFI arm. Median duration of maintenance therapy (arm 1) and CFIs (arm 2) were 4.8 months and 3.9 months, respectively. Overall response rates were 59.2% and 59.6% for the initial FOLFOX chemotherapy and 20.4% and 30.3% for FOLFOX reintroduction in arms 1 and 2, respectively.
The planned complete discontinuation of chemotherapy had a negative impact on DDC and PFS compared with the maintenance therapy strategy. These results suggest that chemotherapy discontinuation cannot be decided before therapy is initiated in patients with advanced colorectal cancer.
Small bowel adenocarcinoma (SBA) is a rare tumour. Large genomic analyses with prognostic assessments are lacking. The NADEGE cohort has enrolled 347 patients with all stage SBA from 2009 to 2012. ...Next‐generation sequencing investigates the presence of 740 hotspot somatic mutations in a panel of 46 genes involved in carcinogenesis. The mismatch repair (MMR) status was assessed by immunochemistry. We have collected 196 tumour samples and 125 had conclusive results for mutation analysis. The number of mutations was 0 in 9.6% of tumours, only 1 in 32.0%, 2 in 26.4% and ≥3 in 32.0%. Overall, at least one genomic alteration was observed in 90.4% of tumour. The most frequent genomic alteration was in KRAS (44.0%), TP53 (38.4%), PIK3CA (20.0%), APC (18.4%), SMAD4 (14.4%) and ERBB2 (7.2%) genes. KRAS mutations were more frequent in synchronous metastatic tumours than in localised tumours (72.7% vs 38.2%, P = .003). There was no significant difference in the mutation rates according to primary location for the most frequently altered gene. ATM, FGFR3 and FGFR1 gene alterations were associated with Lynch syndrome and IDH1 mutations with Crohn disease. dMMR tumours were associated with younger age, localised tumours, less KRAS but more SMARCB1 mutations. No genomic alteration was associated with overall survival. There is a trend for better survival in patient with dMMR tumours. In conclusion, there is a different genomic alteration profile in SBA according to predisposing diseases. No association between genomic alterations and prognoses was observed except for a trend of better prognoses associated with dMMR.
What's new?
Because small bowel adenocarcinomas (SBAs) are quite rare, genomic analyses and prognostic biomarkers are lacking. In this study, the authors found at least one genomic alteration in 90.4% of SBAs. The most frequent alterations occurred at KRAS, TP53, PIK3CA, APC, SMAD4 and ERBB2. Additional alterations were specific to SBAs from patients with Lynch syndrome, while IDH1 mutations were associated with Crohn disease. No association was found between SBA prognosis and specific genomic alterations, except for a trend toward better prognosis with tumors deficient in mismatch repair (dMMR).
Poorly differentiated neuroendocrine carcinomas (NEC) are rare diseases with a poor prognosis. Platinum-etoposide (PE) has been the recommended first-line treatment for decades. FOLFIRINEC ...(NCT04325425) is a national multicenter randomized phase II study which aims to challenge this standard regimen.
The primary objective is to compare the median progression-free survival (PFS) under mFOLFIRINOX versus PE. The secondary objectives are to evaluate the objective response rates (ORR), median overall survival (OS), safety and quality of life. The associated real-time translational study will establish a molecular profile for each patient enrolled.
NEC of gastroenteropancreatic (GEP) or unknown origin, metastatic and RECIST 1.1 evaluable disease, tumor sample available and no contraindication to chemotherapy. Patients will be randomized 1:1 between PE every 21 days for 6–8 cycles and mFOLFIRINOX every 14 days for up to 12 cycles and stratified according to center, performance status, Ki67 and pathological subtype.
This trial will randomize 218 patients (24 months of follow-up) to have 80% power to detect an improvement of the median PFS from 5 months under PE to 7.5 months under mFOLFIRINOX (HR of 0.67, α =5%, two-sided). An intermediate analysis is planned at 50% of events.
Recruitment started on October 20, 2020.
Small Bowel Adenocarcinoma Aparicio, Thomas; Zaanan, Aziz; Mary, Florence ...
Gastroenterology clinics of North America,
09/2016, Letnik:
45, Številka:
3
Journal Article
Recenzirano
Small bowel adenocarcinomas (SBAs) are rare tumors, but their incidence is increasing. The most common primary location is the duodenum. Even though SBAs are more often sporadic, some diseases are ...risk factors. Early diagnosis of small bowel adenocarcinoma remains difficult, despite significant radiologic and endoscopic progress. After R0 surgical resection, the main prognostic factor is lymph node invasion. An international randomized trial (BALLAD Benefit of Adjuvant Chemotherapy For Small Bowel Adenocarcinoma study) will evaluate the benefit of adjuvant chemotherapy. For metastatic disease, retrospectives studies suggest that platinum-based chemotherapy is the most effective treatment. Phase II studies are ongoing to evaluate targeted therapy in metastatic SBA.
Cyclosporine is an effective rescue therapy in steroid-refractory ulcerative colitis (UC) and may avoid immediate colectomy. However, the individual's response to cyclosporine is poorly predictable. ...The aim of this study was to identify predictive factors of the response to cyclosporine in steroid-refractory UC.
One hundred thirty-five patients with steroid-refractory UC, admitted consecutively between 1992 and 2004, were included. Data were collected on the first day of the cyclosporine therapy. Colonoscopy was performed within 2 days preceding or following the cyclosporine treatment in 118 patients for assessing the presence of severe endoscopic lesions.
The actuarial rate of colectomy was 0.45 at 6 months. Cox analysis in the whole population selected three predictive criteria of colectomy: body temperature >37.5 degrees C (adjusted hazard ratio = 1.94, 95% confidence interval 1.51-2.49), heart rate >90 bpm (1.86, 1.45-2.38), and C-reactive protein (CRP) >45 mg/L (1.70, 1.34-2.16). In the 118 patients who underwent colonoscopy, the presence of severe endoscopic lesions was an independent predictive factor of colectomy (2.38, 1.80-3.14). Colonoscopy was decisive and changed the therapeutic decision in patients with one or two criteria: 71% of the patients with severe endoscopic lesions were colectomized versus 17% of the patients without severe endoscopic lesions (P < 0.001). Finally, the clinical, biological, and endoscopic criteria allowed the classification of the patients into two different groups (80%vs 20% colectomy at 6 months).
In patients with steroid-refractory UC, the combination of simple criteria is useful to predict the response to cyclosporine. Colonoscopy is crucial in patients with intermediate clinical and biological severity.
Introduction Bilobar colorectal metastases may be treated by a 2-stage surgical strategy. The risk of drop out after the first stage hepatectomy remains high and is associated with a nearly zero ...survival rate at 3 years. Our goal was to evaluate the factors predictive of the feasibility of the strategy and long-term survival, based on simple clinical and histologic features obtained from the first stage specimen. Patients and Methods Patients who underwent a first stage hepatectomy with curative intent were included. Preoperative clinical parameters and histologic features of the primary neoplasm and metastases obtained at the first stage hepatectomy were analyzed and compared between patients who did or did not undergo the second stage operation. A group of comparable patients treated only by chemotherapy was used as a control group. Results The feasibility rate of this 2-stage resection was 76% (38/50 patients). Median survival was greater in patients treated with chemotherapy alone than for those who failed the second stage. A clinicopathologic score including male sex, segment 1 metastasis, need for >3 resection(s)/radiofrequency ablation(s), vascular invasion in the primary, need for change in type of chemotherapy, and microscopic biliary invasion by the metastasis was predictive of feasibility of the second stage and disease-free survival in patients achieving the second stage. Conclusion Combining preoperative clinical parameters with pathologic features of the primary and the metastatic lesions obtained during first stage hepatectomy predicted accurately patients who failed the second stage, and the long-term outcomes. Considering both clinical and pathologic parameters may help to define the best oncologic strategy by choosing between an exclusive chemotherapeutic or a surgical strategy.
According to previously reported Groupe Coordinateur Multidisciplinaire en Oncologie (GERCOR) studies in locally advanced pancreatic cancer (LAPC), concomitant chemoradiotherapy (CCRT) may be ...recommended for patients who do not experience disease progression after systemic induction chemotherapy (CT). To further improve patient outcome with classical fluorouracil (FU)-based CCRT, this study was designed to prospectively investigate a CCRT with FU infusion and weekly oxaliplatin after 2 months of gemcitabine and oxaliplatin (GEMOX) induction chemotherapy.
Nonpretreated patients with LAPC having WHO performance status (PS) of 0 to 2 received four induction cycles of GEMOX (gemcitabine 1 g/m(2) on day 1 and oxaliplatin 100 mg/m(2) on day 2; day 1 of a 15-day cycle). One month after cycle 4, patients who did not experience disease progression with PS 0 to 2 received 45 Gy over 5 weeks + 10 Gy (as a concomitant boost during the last 2 weeks) of radiotherapy (RT), with daily 250 mg/m(2) FU as a continuous infusion and 60 mg/m(2)of oxaliplatin weekly.
Of 59 patients, 50 patients (84.7%) received CCRT, whereas nine patients did not because of disease progression (seven patients), CT toxicity (one patient), or personal decision (one patient). Forty-four patients (74.5%) completed the fully planned CCRT. Median progression-free survival and overall survival durations were 7.6 and 12.2 months, respectively, for the whole population and 9.4 and 12.6 months, respectively, for patients who completed CCRT. CCRT grade 3 to 4 toxicities (National Cancer Institute Common Toxicity Criteria) were neutropenia (10.4%), thrombocytopenia (8.4%), nausea and vomiting (16.7%), and diarrhea (12.5%).
Concomitant administration of weekly oxaliplatin, continuous-infusion FU, and RT in patients with LAPC is feasible, with an acceptable acute and late safety profile. The encouraging results observed despite a nonoptimal patient selection (owing to the short induction time) indicates that further randomized evaluation to better define the specific role of oxaliplatin in CCRT is deserved.
Log odds of positive lymph nodes (LODDS) classification showed superiority over 8th edition N staging in predicting survival of small bowel adenocarcinoma (SBA) patients. The aim of this study was to ...develop and validate the Tumor, LODDS, and Metastasis (TLM) staging of SBA.
Totally 1789 SBA patients from the Surveillance, Epidemiology, and End Results (SEER) database between 1988–2010, 437 patients from SEER database between 2011–2013 and 166 patients from multicenters were categorized into development, validation and test cohort, respectively. The TLM staging was developed in the development cohort using Ensemble Algorithm for Clustering Cancer Data (EACCD) method. C-index was used to assess the performance of the TLM staging in predicting cancer-specific survival (CSS) and was compared with the traditional 8th edition TNM staging.
Four-category TLM staging designed for the development cohort showed higher discriminatory power than TNM staging in predicting CSS in the development cohort (0.682 vs. 0.650, P < 0.001), validation cohort (0.682 vs. 0.654, P = 0.022), and test cohort (0.659 vs. 0.611, P = 0.023), respectively. TLM staging continued to show its higher predictive efficacy than the 8th TNM in TNM stage II/III patients or in patients with lymph node yield less than 8.
TLM staging showed a better prognostic performance than the 8th TNM staging especially TNM stage II/III or patients with lymph node yield less than 8 and therefore, could serve to complement the TNM staging in patients with SBA.
A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
Abstract Small bowel adenocarcinomas are rare tumours, but their incidence is increasing. Their most common primary location is the duodenum. The few studies that have collected data regarding small ...bowel adenocarcinoma are not homogeneous and are widely spread over time. Even though these tumours are most often sporadic, some predisposing diseases have been identified, among which Crohn's disease and genetic syndromes. Early diagnosis of small bowel adenocarcinoma remains difficult despite significant radiological and endoscopic progress. After surgical resection the main prognostic factor is node invasion; in this case, adjuvant chemotherapy can be expected to be beneficial, although this has not been established by randomised trials. For metastatic disease, platinum-based chemotherapy seems to be the most effective treatment. Targeted therapies have not yet been evaluated in this type of cancer.
The main purpose of this retrospective study was to determine the diagnostic performance of 68GaGa-DOTA-D-Phe1-Try3-octreotide(DOTA-TOC) positron emission tomography/computed tomography (PET/CT) in ...patients with well-differentiated colorectal Neuroendocrine Tumours (NETs) originating from the hindgut. The other aims were to assess the impact of the examination on patient management and to analyze the results of 2-18FFDG and/or 6-18FFDOPA PET/CT when they were performed. 68GaGa-DOTA-TOC PET/CT and clinical data from 30 patients with biopsy-proven well-differentiated NETs originating from the hindgut were retrospectively reviewed and analyzed by comparing the 68GaGa-DOTA-TOC PET/CT findings with pathological and/or follow-up data. We also compared the 68GaGa-DOTA-TOC PET/CT results with 2-18FFDG and/or 6-18FFDOPA PET/CT results in 6 patients. The impact on management was determined in hindsight by comparing the patient management decided before and after the TEP examination based on data from multidisciplinary team meetings. On a patient basis, 68GaGa-DOTA-TOC PET/CT was accurate in 30 of the 30 examinations. 68GaGa-DOTA-TOC PET/CT correctly identified the primary tumor in all patients with primary tumors not resected before the examination and allowed the detection of unexpected distant metastases in 36% of the patients referred for initial staging. 68GaGa-DOTA-TOC PET/CT findings affected patient management in 57% of cases with generally major intermodality changes. Intraindividual comparison of the results of the different PET radiopharmaceuticals showed a clear superiority of 68GaGa-DOTA-TOC PET/CT considering both the number of lesions and the intensity of uptake. 68GaGa-DOTA-TOC PET/CT is an accurate imaging modality for the assessment of well-differentiated colorectal NETs that highly impact patient management. Thus, we suggest that 68GaGa-DOTA-TOC PET/CT be employed as a first choice for the assessment of these tumors in nuclear medicine.
PDF
