This study aimed to evaluate the feasibility of and immune response to Wilms tumor gene 1 (WT1) peptide-pulsed dendritic cell vaccination combined with gemcitabine (DCGEM) as a first-line therapy among patients with advanced pancreatic cancer. Ten HLA-A*2402 patients were treated with WT1 peptide-pulsed DC vaccination (1 × 107 cells) on days 8 and 22 and gemcitabine (1000 mg/m2) on days 1, 8 and 15. Induction of a WT1-specific immune response was evaluated using the delayed-type hypersensitivity (DTH) skin test, interferon-γ enzyme-linked immunospot and HLA tetramer assays, along with assays for various immunological factors. DCGEM was well-tolerated, and the relative dose intensity of gemcitabine was 87%. Disease control associated with a low neutrophil/lymphocyte ratio was observed in all three patients with DTH positivity; it was also correlated with a low percentage of granulocytic myeloid derived suppressor cells in the pretreatment peripheral blood (P = 0.017). Patients with liver metastases and high levels of inflammatory markers such as C-reactive protein and interleukin-8 (IL-8) showed poor survival even though a WT1-specific immune response was induced in them. WT1 peptide-pulsed DCGEM is feasible and effective for inducing anti-tumor T-cell responses. Our results support future investigations for pancreatic cancer patients with non-liver metastases and favorable immunological conditions. This trial was registered with the University hospital Medical Information Network (UMIN) Clinical Trials Registry (http://www.umin.ac.jp/ctr/ number: UMIN-000004855).
This study assessed the impact of postoperative complications on the colorectal cancer survival and recurrence after curative surgery using pooled individual patients’ data from three large phase III randomized trials. In total, 5530 patients were included in this study. The patients were classified as those with postoperative complications (C group) and those without postoperative complications (NC group). The risk factors for the overall survival (OS) and the disease‐free survival (DFS) were analyzed. Postoperative complications were found in 861 (15.6%) of the 5530 patients. The OS and DFS rates at 5 years after surgery were 68.9% and 74.8%, respectively, in the C group and 75.8% and 82.2%, respectively, in the NC group, values that were significantly different between the two groups (P < 0.001). The multivariate analysis demonstrated that postoperative complications were a significant independent risk factor for the OS and DFS. Postoperative complications can worsen the colorectal cancer survival and risk of recurrence. Surgical morbidity must be considered as a stratification factor in future phase III trials evaluating the effects of adjuvant chemotherapy on colorectal cancer.
BackgroundSkeletal muscle wasting during curative treatment is an important issue faced by esophageal cancer patients. However, it has not been clarified whether skeletal muscle change during neoadjuvant chemotherapy followed by surgery adversely affects prognosis. This study aimed to determine the relation between skeletal muscle change and survival for patients with advanced esophageal cancer who underwent neoadjuvant chemotherapy followed by surgery.MethodsThis study retrospectively analyzed 66 patients with thoracic esophageal cancer who had undergone neoadjuvant chemotherapy followed by esophagectomy. The study investigated the correlation between the change in the total muscle cross-sectional area at the third lumbar vertebra before and 4 months after surgery as well as the postoperative recurrence and overall survival (OS).ResultsOf the 66 patients, 39 (59%) showed a skeletal muscle decrease from baseline to 4 months after esophagectomy. The change in the skeletal muscle index from baseline to 4 months after surgery was −1.2 cm2/m2. Multivariable analysis showed that nonsquamous cell carcinoma subtype (hazard ratio [HR] 2.57; p = 0.029), pathologic stage (HR 5.73; p < 0.01), and skeletal muscle wasting (HR per 1 unit decrease in skeletal muscle index, 1.16; p = 0.015) were the independent prognostic factors associated with worse OS. Additionally, pathologic stage (HR 6.03; p < 0.01) and skeletal muscle wasting (HR per 1 unit decrease in skeletal muscle index, 1.11; p = 0.048) also were found to be independent prognostic factors associated with worse recurrence-free survival.ConclusionsThe study findings suggest that skeletal muscle wasting from baseline has a negative impact on cancer recurrence and survival.
The present study demonstrates the long-term outcomes and risk factors for mortality of salvage esophagectomy. To improve OS after salvage surgery, the development of a means of decreasing pulmonary complications is needed.
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