Purpose: The aim of this study is to find a laboratory marker for overall survival in advanced cancer patients who were vaccinated with peptides based on pre-existing, peptide-specific CTL precursors in the circulation.Experimental Design: A group of 113 patients with advanced cancer (28 colorectal, 22 prostate, 15 lung, 14 gastric, and 34 other cancers) was enrolled in a Phase I clinical study of peptide vaccination in which peptidespecific CTL precursors of prevaccination peripheral blood mononuclear cells were measured, followed by vaccination with these peptides (maximum of four). For cellular responses, pre and postvaccination (sixth) peripheral blood mononuclear cells were provided for measurement of both peptide-specific CTL precursors by IFN-␥ release assay and tumor reactivity by 51 Cr release assay. Delayed type hypersensitivity was also measured. For humoral response, pre and postvaccination (sixth) sera were provided for measurement of peptide-reactive IgG by an ELISA.Results: The median survival time and 1-year survival rate of the total cases were 346 ؎ 64.9 days and 44.6%, respectively, and those of patients vaccinated more than six times (n ‫؍‬ 91) were 409 ؎ 15 days and 54.4%, respectively. In these 91 patients, the overall survival of patients whose sera showed increased levels of peptide-reactive IgG (n ‫؍‬ 60) was significantly more prolonged (P ‫؍‬ 0.0003) than that of patients whose sera did not (n ‫؍‬ 31), whereas none of cellular responses correlated with overall survival.Conclusions: Peptide-specific IgG in postvaccination sera could be a suitable laboratory maker for the prediction of prolonged survival in advanced cancer patients vaccinated with peptides based on pre-existing CTL precursors.

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Pulmonary resection for colorectal metastases is well accepted. However, the main cause of death after pulmonary resection is recurrence in the lung. The aim of this study was to clarify whether a repeat pulmonary resection was warranted in patients with recurrent lung metastases. The records of 76 patients undergoing initial pulmonary resection, including 14 patients undergoing a repeat operation for lung metastases, were reviewed for survival, operative morbidity, and mortality. Overall, pulmonary resection was performed 96 times in this group of patients. The operative mortality was 0%, morbidity involved only one case of major postoperative hemorrhage associated with the first operation. The cumulative 5-year survival rate for the 76 patients was 32%. After the second pulmonary operation, recurrence was identified in 79% (11 of 14) of the patients. In 10 patients with isolated lung recurrence after a first pulmonary resection, who showed no extrapulmonary disease before or at the time of first thoracotomy, the 3-year, and 5-year-survival rate after the second pulmonary resection was 67%, and 33%, respectively, comparing favorably with the survival rate in those who underwent primary pulmonary resection. In contrast, all 4 patients with extrapulmonary disease before or at the time of thoracotomy had poor prognosis. Repeat pulmonary operation for isolated recurrent colorectal metastases to the lung yielded results comparable to those after the first pulmonary resection in terms of operative mortality and survival in the absence of hilar/mediastinal lymph node or extrathoracic involvement.

Patients with an elevated preoperative CEA may be candidates for adjuvant chemotherapy after curative resection in stage II colon cancer. These findings warrant clinical trials to test out the efficacy of adjuvant chemotherapy in stage II colon cancer with an elevated preoperative CEA.

In most protocols of peptide-based vaccination, no consideration has been paid to whether or not peptide-specific cytotoxic Tlymphocyte (CTL) precursors are pre-existent in cancer patients. Initiation of immune boosting through vaccination is better than that of immune priming to induce prompt and strong immunity. In this study, 10 human histocompatibility leukocyte antigen-A24 þ patients with advanced colorectal carcinomas were treated with up to four peptides that had been positive for pre-vaccination measurement of peptide-specific CTL precursors in the circulation (CTL precursor-oriented peptide vaccine). No severe adverse effect was observed, although local pain and fever of grade I or II were observed. Post-vaccination peripheral blood mononuclear cells (PBMCs) from five patients demonstrated an increased peptide-specific immune response to the peptides. Increased CTL response to cancer cells was detected in post-vaccination PBMCs of five patients. Antipeptide immunoglobulin G became detectable in postvaccination sera of seven patients. Three patients developed a positive delayed-type hypersensitivity response to at least one of the peptides administrated. One patient was found to have a partial response; another had a stable disease, sustained through 6 months. These results encourage further development of CTL precursor-oriented vaccine for colorectal cancer patients.