High-dose radiotherapy with intensity-modulated radiation therapy for advanced hepatocellular carcinoma.

AIMS AND BACKGROUND: We report the results of intensity-modulated radiotherapy for patients with advanced hepatocellular carcinoma who were not candidate for local ablative therapies, transarterial chemoembolization or hepatic arterial infusion chemotherapy. METHODS AND STUDY DESIGN: Between 2003 and 2008, 27 patients were treated with high-dose radiotherapy (median dose, 50.4 Gy). The equivalent sphere size of tumors was 11.4 ± 2.6 cm. Nineteen and 8 patients were Child-Pugh class A and B, respectively. Eighteen patients had thromboses in large veins. Six patients were treated with radiotherapy as the initial treatment modality, and 21 patients received other treatments before radiotherapy. RESULTS: The overall response rate was 44.4% (1 pathologic complete response and 11 partial responses). The primary failure pattern was intrahepatic disease progression. Until the last follow-up, the primary liver masses and vein thromboses did not progress in 63.6% and 60.0% of the patients, respectively. The median progression-free survival and overall survival after radiotherapy rate were 3 and 5 months, respectively. Based on univariate analyses, response, Child-Pugh classification, and vein thrombosis were significant factors for overall survival, and tumor response, tumor size, vein thrombosis, and multiplicity were significant factors for progression-free survival. Tumor response was the only significant prognostic factor for overall survival and progression-free survival based on multivariate analyses. CONCLUSIONS: Radiotherapy with intensity-modulated radiotherapy achieved a good response rate in patients with advanced hepatocellular carcinoma, and patients who had a good response lived longer than patients who did not have a good response.

Comparison of concurrent chemoradiotherapy with cisplatin plus 5-fluorouracil versus cisplatin plus paclitaxel in patients with locally advanced cervical carcinoma.

OBJECTIVE: The aim of this study was to compare survival outcomes and toxicities between concurrent radiotherapy with cisplatin plus 5-fluorouracil and that with cisplatin plus paclitaxel in patients with locally advanced cervical carcinoma. METHODS: We retrospectively reviewed data from 93 locally advanced cervical carcinoma patients (stage IB to IVA) who had been treated by concurrent radiotherapy with cisplatin plus 5-fluorouracil (CF, n=45) vs. cisplatin plus paclitaxel (CP, n=48) as primary therapy. Toxicities and survival outcomes were compared. RESULTS: In the CP group, there were higher frequencies of severe (grade 3 or 4) leukopenia (79.2%, as compared to 11.1% in the CF group), severe neutropenia (77.1%, as compared to 8.9% in the CF group) and severe peripheral neuropathy (12.5%, as compared to 2.2% in the CF group). In the CF group, there were higher frequencies of severe nausea (33.3%, as compared to 14.6% in the CP group) and severe hyponatremia (11.1%, as compared to 0% in the CP group). Five-year DFS of the CF and CP groups was 67.4% and 79.1%, respectively (p=NS). Five year OS of the CF and CP groups was 79.6% and 80.9%, respectively (p=NS). CONCLUSION: Concurrent radiotherapy with cisplatin plus paclitaxel showed increased leukopenia, neutropenia and peripheral neuropathy, but less gastrointestinal toxicity (nausea) than that with cisplatin plus 5-fluorouracil. Survival outcome between these two groups was not statistically different in this study. Large prospective randomized controlled studies will be needed to confirm this result.

Increased sensitivity of radiated murine cervical cancer tumors to E7 subunit vaccine-driven CTL-mediated killing induces synergistic anti-tumor activity.

The development of therapeutic vaccines has important implications for the treatment of cancer patients. Here we investigate whether human papillomavirus (HPV) E7 subunit vaccines can enhance tumor radioresponse using an established cervical cancer animal model. Radiation plus E7 subunit vaccines improved complete response, cure, and recurrence rates of tumors dramatically compared with single therapy alone. In particular, both components of the E7 subunit vaccines (E7 protein and CpG-oligodeoxynucleotide) were required for the induction of antigen (Ag)-specific cytotoxic T-lymphocyte (CTL) responses and for therapeutic synergy with radiotherapy. Moreover, with combined therapy the radiation dose could be reduced by 16 Gy to achieve an equivalent anti-tumor efficacy to radiation treatment alone. This therapeutic synergy was found to be mediated by CD8(+) CTLs and was concomitant with histological changes (presence of apoptotic bodies and multinucleated giant cells; heavy infiltration of lymphocytes), as determined by in vivo T-cell depletion and histological analysis. Finally, phenotypic changes of radiated tumors and their increased sensitivity to CTL-mediated killing appeared to be responsible for therapeutic synergy. These results show that E7 subunit vaccines act as a potent enhancer of tumor radioresponse and that this is mediated by increased sensitivity of radiated tumors to CTL-mediated killing. This study further suggests that E7-targeted therapeutic vaccines have the potential to improve radiotherapy in patients with cervical cancer.

Survival benefits of neoadjuvant chemotherapy followed by radical surgery versus radiotherapy in locally advanced chemoresistant cervical cancer.

The aim of this study was to analyze long-term survivals in patients with stage IB to IIA cervical cancer treated by neoadjuvant chemotherapy setting. Between February 1989 and January 1998, 94 women with previously untreated stage IB to IIA carcinoma of the uterine cervix who received cisplatin based neoadjuvant chemotherapy were enrolled in this study. All of patients with chemoresponse (complete response, n=15; partial response, n=47) and 16 patients with chemoresistance received radical surgery (RS group). The other 16 patients with chemoresistance received radiotherapy for definite treatment (RT group). In the RS group, the 10 yr survival estimation in patients with bulky tumors (diameter > or =4 cm, n=26) was similar to that with non-bulky tumors (83.3% vs. 89.3%, p=NS). In selected patients with chemoresistance, those treated by radiotherapy (n=16) showed significantly poorer survivals than those treated by radical surgery (n=16) (10 yr survival rates of RT (25%) vs. RS (76.4%), p=0.0111). Our results support that a possible therapeutic benefit of neoadjuvant chemotherapy plus radical surgery is only in patients with bulky stage IB to IIA cervical cancer. In cases of chemoresistance, radical surgery might be a better definite treatment option.