Palliation of dysphagia in metastatic oesogastric cancers: An international multidisciplinary position.

Malignant dysphagia is the most common symptom in advanced oesogastric cancers patients. Relief of dysphagia allows quality of life improvement, nutritional replenishment and potentially improves prognosis. Chemotherapy alone is effective and should be prioritised in patients with metastatic disease a good performance status, and its impact on dysphagia should be determined before further interventions are planned. Regarding local treatments, the insertion of a covered self-expandable metallic stent is the most commonly used alternative, as it allows for the rapid relief of severe dysphagia. Although several randomised trials have highlighted the role of oesophageal brachytherapy, this technique is often not easily accessible. Contemporary trials are ongoing to better define the role of external radiation therapy. While awaiting these results, external radiation therapy can be considered as a second-best option for patients with a life-expectancy > 3 months. It is important to offer nutritional support and to integrate quality of life measures in the palliative management of dysphagia. This multidisciplinary international position paper aims to propose a decision-making process and highlight randomised trials for the management of malignant dysphagia in metastatic oesogastric cancer patients.

Preclinical assessment of JNJ-26854165 (Serdemetan), a novel tryptamine compound with radiosensitizing activity in vitro and in tumor xenografts.

Serdemetan (JNJ-26854165) is a novel tryptamine compound with antiproliferative activity in various p53 wild-type (WT) tumor cell lines. We investigated its potential as radiosensitizer using four human cancer cell lines: H460, A549, p53-WT-HCT116, and p53-null-HCT116. Serdemetan inhibited clonogenic survival in all cell lines, but in a lower extent in p53-null-HCT116. In the combination studies, Serdemetan treatment at 0.25µM in H460 and at 5µM in A549 cells resulted in a sensitivity-enhancement ratio of 1.18 and 1.36, respectively. At 2Gy, surviving fractions were 0.72 and 0.97 for p53-WT HCT116 and p53-null cells exposed to 0.5µM of Serdemetan, respectively (p<0.05). Radiosensitization of H460 and A549 cells was associated with G2/M cell cycle arrest and with an increased expression of p53 and p21. In vivo, Serdemetan caused a greater than additive increase in tumor growth delay. The dose enhancement factor was 1.9 and 1.6 for H460 and A549 tumors, respectively. Serdemetan inhibited proliferation, capillary tube formation and migration of HMEC-1 cells. These effects were more marked concurrently with irradiation. These results in tumor and endothelial cells suggest that Serdemetan has potential as a radiosensitizer. Further investigations are warranted with regard to the molecular mechanisms underlying its actions and its dependency regarding p53 status.

Special focus on cardiac toxicity of different sequences of adjuvant doxorubicin/docetaxel/CMF regimens combined with radiotherapy in breast cancer patients.

BACKGROUND AND PURPOSE: Cardiac toxicity associated with anthracyclines and taxanes and/or radiotherapy (RT) can be life-threatening and can adversely affect quality of life. The aim was to evaluate treatment-related cardiac toxicity in breast cancer patients treated with doxorubicin/docetaxel/CMF sequential or combined regimens and RT. METHODS AND MATERIALS: From 1996 to 1998, 64 patients with stages II-III breast cancer were included in a pilot study that investigated the efficacy/feasibility of sequential and combined doxorubicin/docetaxel/CMF regimens. No patients had any cardiovascular history or ECG abnormalities. The same RT technique was performed in all patients. LVEF measurements were obtained at baseline, during, at the end of chemotherapy, at the end of radiotherapy and subsequently during the follow-up. A cardiac event was defined as a myocardial infraction or clinical evidence of congestive heart failure. RESULTS: Median age was 48 years (range 29-65 years). The median follow-up was 6 years. Significant drop in the post-treatment LVEF occurred in 21 patients (median decrease of 10%). Notwithstanding, all patients have preserved normal cardiac function and regained their initial LVEF value during follow-up. No cardiac events were reported. CONCLUSION: Sequential and combined doxorubicin/docetaxel/CMF regimens plus conventional RT in selected non high-risk cardiac patients are relatively safe without cardiac toxicity at mid-term follow-up.

Nutritional support during oncologic treatment of patients with gastrointestinal cancer: who could benefit?

INTRODUCTION: In patients with gastrointestinal (GI) cancer, severe malnutrition is associated with increased morbidity and mortality, reduction of treatment efficacy, and increased length of hospital stay. Therefore, systematic screening and care of malnutrition is mandatory. MATERIALS AND METHODS: Data for this review were identified by searches of Medline with and without MeSH database and Cancerlit. Studies were selected only if they were randomised clinical trials or historical reports. References were also identified from reference lists in relevant previously published articles. Recent guidelines and meta-analyses were included. Only articles published in English were taken into consideration. RESULTS: For surgical patients, practical information such as weight loss or subjective global assessment would provide a better basis for deciding whether or not to delay surgery. At least 10 days of nutritional support is recommended in severely malnourished patients before major digestive surgery. In non-severely malnourished patients, preoperative oral immunonutrition is associated with a 50% decrease in postoperative complications. The benefit of immune-enhancing diets in severely malnourished patients remains to be proven. For patients undergoing radiochemotherapy, dietary counselling should be proposed to all patients. In cases of severely malnourished patients or if dietary counselling suffers a setback, enteral nutrition should be recommended. Parenteral nutrition should be reserved for patients with severe digestive intolerance when enteral nutrition is not possible. CONCLUSION: Propose an adaptive nutritional support at each step of a multimodal GI oncological treatment is essential. These recommendations should be used in daily practice but should also be included in all clinical research protocols.