Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial

Background: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. Methods/Design: The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 °C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA. Discussion: Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival. Trial registration number: NCT02231086 (Clinicaltrials.gov)

RAS and BRAF mutations in cell-free DNA are predictive for outcome of cetuximab monotherapy in patients with tissue-tested RAS wild-type advanced colorectal cancer

In metastatic colorectal cancer, RAS and BRAF mutations cause resistance to anti-EGFR therapies, such as cetuximab. Heterogeneity in RAS and BRAF mutations might explain nonresponse in a subset of patients receiving cetuximab. Analyzing mutations in plasma-derived circulating tumor DNA (ctDNA) could provide a more comprehensive overview of the mutational landscape as compared to analyses of primary and/or metastatic tumor tissue. Therefore

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial

Background: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay. Methods/Design: The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 degrees C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA. Discussion: Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: A stepped-wedge cluster randomised trial

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion: If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care

Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: The CHARISMA randomized multicenter clinical trial

Background: Efforts to improve the outcome of liver surgery by combining curative resection with chemotherapy have failed to demonstrate de

Group medical consultations (GMCs) and tablet-based online support group sessions in the follow-up of breast cancer: A multicenter randomized controlled trial

Objective: Group medical consultations (GMCs) provide individual medical visits in the presence of ≤7 peer-patients. In the follow-up of breast cancer, we evaluated the efficacy of a new type of blended care My-GMC, a GMC combined with a tablet-based online app, consisting of three online support group sessions (SGS) and additional information. Methods: This randomized controlled trial compared the effect of My-GMC (n = 59) with one individual medical visit (n = 50) (care as usual). Between-group differences on the outcomes distress and empowerment were analyzed 1 week, 3 and 6 months after the visit. Results: No between-group differences were found for the primary outcomes distress and empowerment. More themes were discussed in GMCs compared to individual visits. Significantly more patients experienced peer-support in GMCs (78%) than via the online app (29%). Satisfaction with the online app was low. Conclusions: My-GMC did not result in improvements in distress or empowerment, which might partly be explained by low baseline distress levels. This paper provides valuable information concerning factors on organizational level as well as individual level influencing the evaluation of a blended care intervention. Practice implications: My-GMC provided an innovative alternative, combining professional and peer-support in face-to-face and online SGS, resulting in additional information provision and peer-support. Further improvement of the apps is needed to improve user satisfaction. Netherlands Trial Register: NTR3771

Dietary intake of magnesium or calcium and chemotherapy-induced peripheral neuropathy in colorectal cancer patients

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe side-effect in colorectal cancer (CRC) patients. This study assessed the association between habitual dietary intake of magnesium or calcium and prevalence and severity of chronic CIPN in CRC patients receiving adjuvant chemotherapy. For this prospective cohort study, 196 CRC patients were considered. Magnesium and calcium intake was determined using a food frequency questionnaire at diagnosis, during and after chemotherapy. Chronic CIPN was assessed 12 months after diagnosis using the quality of life questionnaire CIPN20. Prevalence ratios were calculated to assess the association between magnesium or calcium intake and the prevalence of CIPN. Multivariable linear regression analysis was used to assess the association between magnesium or calcium intake and severity of CIPN. CIPN was reported by 160 (82%) patients. Magnesium intake during chemotherapy was statistically significantly associated with lower prevalence of CIPN (prevalence ratio (PR) 0.53, 95% confidence interval (CI) 0.32, 0.92). Furthermore, higher dietary intake of magnesium during (β-1.08, 95% CI -1.95, -0.22) and after chemotherapy (β-0.93, 95% CI -1.81, -0.06) was associated with less severe CIPN. No associations were found for calcium intake and the prevalence and severity of CIPN. To conclude, we observed an association between higher dietary magnesium intake and lower prevalence and severity of CIPN in CRC patients

Traditional ecological knowledge of fruit trees used for fishery at Estirão Comprido Community, Barão de Melgaço - Panatanal Matogrossense

Esta pesquisa aborda o conhecimento ecológico tradicional de fruteiras na comunidade de Estirão Comprido, localizada às margens do Rio Cuiabá, Barão de Melgaço, Pantanal Matogrossense. Foram entrevistados 20 pescadores, utilizando-se a técnica de listagem livre, a qual foi analisada pelo índice de saliência de Smith e análise de consenso cultural, com o programa ANTHROPAC 4.0. Os resultados mostraram que o conhecimento ecológico tradicional sobre fruteiras foi de 30 espécies distribuídas em 21 famílias de plantas. A análise de índice de saliência de Smith mostrou quatro rupturas quanto à ordenação e frequência de respostas, sendo que a primeira contemplou uma espécie, a segunda oito espécies, a terceira quatro espécies e a quarta ruptura 17 espécies. O consenso cultural dos pescadores sobre o conhecimento ecológico tradicional concentrou-se em nove espécies de fruteiras: parada, coquinho, marmelada, roncador, sardinha, timbó, acaiá, jenipava e taiuiá, verificado pela relação entre fatores, onde o primeiro fator foi aproximadamente nove vezes maior que o segundo fator com probabilidade = 0,951. O estudo evidenciou que esta comunidade pantaneira apresenta um conhecimento sobre as fruteiras que são a base da cadeia alimentar das espécies de peixes de valor comercial.This study deals with traditional ecological knowledge on fruit trees at Estirão Comprido community, located on the banks of Cuiabá River, in Barão de Melgaço, Pantanal Matogrossense. Twenty fishermen were interviewed, using free lists, which were evaluated by Smith's Salience Index and cultural consensus analysis, using the software ANTHROPAC 4.0. Results indicated that traditional ecological knowledge on fruit trees involves 30 species distributed in 21 families. Smith's Salience Index showed four ruptures on the rank and frequency of answers; the first rupture included one species, the second eight species, the third four species and fourth 17 species. The cultural consensus of fishermen on such traditional knowledge concentrated on nine fruit tree species: parada, coquinho, marmelada, roncador, sardinha, timbó, acaiá, jenipava and taiuiá, verified by the relationship between factors, where the first factor was approximately nine-fold higher than the second one, pseudo-reliability = 0.951. This study indicated that Pantanal community presents knowledge about fruit trees, the base of the food chain for commercially important fish