A DNA vaccine, SCIB1, incorporating two CD8 and two CD4 epitopes from TRP-2/gp100 was evaluated in patients with metastatic melanoma. Each patient received SCIB1 via intramuscular injection with electroporation. The trial was designed to find the safest dose of SCIB1 which induced immune/clinical responses in patients with or without tumour. Fifteen patients with tumor received SCIB1 doses of 0.4-8 mg whilst 20 fully-resected patients received 2–8 mg doses. Twelve patients elected to continue immunization every 3 months for up to 39 months. SCIB1 induced dose-dependent T cell responses in 88% of patients with no serious adverse effects or dose limiting toxicities. The intensity of the T cell responses was significantly higher in patients receiving 4 mg doses without tumor when compared to those with tumor (p < 0.01). In contrast, patients with tumor showed a significantly higher response to the 8 mg dose than the 4 mg dose (p < 0.03) but there was no significant difference in the patients without tumor. One of 15 patients with measurable disease showed an objective tumor response and 7/15 showed stable disease. 5/20 fully-resected patients have experienced disease recurrence but all remained alive at the cut-off date with a median observation time of 37 months. A positive clinical outcome was associated with MHC-I and MHC-II expression on tumors prior to therapy (p = 0.027).We conclude that SCIB1 is well tolerated and stimulates potent T cell responses in melanoma patients. It deserves further evaluation as a single agent adjuvant therapy or in combination with checkpoint inhibitors in advanced disease.

Our patient population is older than the patients in the MAGIC trial (age 66 years vs. 62 years) with a much higher proportion of esophageal and GEJ tumours. Overall, curative resection rate was comparable to the MAGIC trial. Overall survival is superior to that found in the MAGIC trial.

The association between venous thromboembolism and chemotherapy for esophagogastric cancer is well known in patients treated with palliative intent. Whether this risk extends to the neoadjuvant and perioperative setting is unclear. A retrospective interrogation of databases of patients receiving perioperative chemotherapy for potentially curative intent at the Leicester (2006-2011) and Nottingham (2004-2011) esophagogastric cancer centers was performed. Thromboembolic events were diagnosed in 48 of 384 patients (12.5%), 21 (5.5%) at presentation, 12 (3%) during neoadjuvant chemotherapy, and 15 (3.9%) in the postoperative period. There were no deaths from thromboembolic disease. By site these comprised catheter-related axillary vein thrombosis in 7 patients, deep venous thrombosis in 12 patients, and pulmonary embolism in 29 patients. Twenty-five of the 29 pulmonary emboli were incidental findings on staging computed tomography imaging. Combination chemotherapy with epirubicin, cisplatin, and capecitabine appeared to carry the greatest risk for the development of thromboembolism. Seven of the 12 patients (58%) who developed thromboembolism during neoadjuvant chemotherapy did not proceed to surgery because of deterioration in performance status. Preoperative thromboembolic disease resulted in a significant increase in the interval between chemotherapy and surgery, but did not influence either length of hospital stay or survival. Venous thromboembolism will develop in 12.5% of patients treated with potentially curative intent. This adverse event can occur at any time during the patient journey. In contrast to the commonly held view, this did not translate into a poorer prognosis.

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Objectives: To assess the efficacy of the second measured glomerular filtration rate (GFR) during the course of weekly cisplatin-based chemoradiotherapy in head and neck cancer. Methods: Data was collected on consecutive 221 head and neck cancer patients who underwent cisplatin-based chemoradiotherapy. Results: 68% patients managed to complete at least five out six proposed cycles of cisplatin, with a cumulative dose of ≥200 mg/m 2 . 181 patients underwent second measured GFR and it showed a mean fall in measured GFR by 12.0 ml/min/1.73 m 2 (p < 0.0001). Out of these 181 patients, in 16 patients (9%), the decision to discontinue cisplatin was purely based on a low second measured GFR (below 50 ml/min/1.73 m 2 ). Conclusion: Our study has shown that obtaining a second measured GFR is valuable in 9% of these patients. We propose that this should be considered as a standard procedure in these settings and also should be considered incorporating this additional safety measure, into future clinical trials as a mandatory procedure. Advances in knowledge: To the best of author’s knowledge, this is first study of its kind. The results of our study suggest that it should be a standard procedure of obtaining a second GFR in these settings.

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