Survival Rates For Radiotherapy Research Articles

Phase I/II Study of Concurrent Chemoradiotherapy for Newly-Diagnosed, Localized Nasal NK/T-Cell Lymphoma: Results of a Phase I Portion of JCOG0211-DI.

Nasal NK/T-cell lymphoma is a rare lymphoid neoplasm, and its standard therapy has not been established. It is one of the Epstein-Barr virus (EBV) - associated lymphoid malignancies, and lymphoma cells express P-glycoprotein concerning multi-drug resistance (MDR) of the disease. Anthracycline-containing chemotherapy followed by radiotherapy (RT) has been established as the standard care for localized aggressive NHL; however this strategy is not effective for localized nasal NK/T-cell lymphoma. The 5-year overall survival rates of RT alone are only 30–40%. To explore a more effective treatment for newly-diagnosed localized nasal NK/T-cell lymphoma, we conducted a multicenter phase I/II study of concurrent chemoradiotherapy consisted of 50 Gy of RT and 3 courses of DeVIC chemotherapy [carboplatin (CBDCA) 300mg/m2 d1 IV, etoposide (ETP) 100mg/m2 d1-3 IV, ifosfamide (IFM) 1.5g/m2 d1-3 IV, dexamethasone (DMS) 40mg/body d1-3 IV; every 21 days]. DeVIC comprised of MDR-non-related agents and ETP that shows both in vitro and in vivo efficacy for NK-cell neoplasms, and is well-known to be effective for EBV-associated hemophagocytic syndrome. Pts with newlydiagnosed, localized (IE and contiguous IIE with cervical node involvement) diseases, 20–69 years of age and PS 0–2 were eligible. The protocol requests the CT based 2 or 3 dimensional RT planning that the volume with appropriate margin (2 cm) to gross tumor, entire nasal cavities and nasopharynx should be irradiated. In the phase I portion, a standard 3+3 design was used to evaluate dose-limiting toxicities (DLTs). The doses of RT and DMS were fixed. Two dose levels of CBDCA/ETP/IFM were evaluated: Level 1 (2/3-dose DeVIC) CBDCA 200mg/m2, ETP 67mg/m2, IFM 1.0g/m2 and Level 2 (100%-dose DeVIC). Enrolled 10 pts showed the following features: age 30–61 yrs (median 44.5), M:F=5:5, stage IE 6, stage IIE 4, B symptom(+) 4, elevated serum LDH 2, PS0 6, PS1 4. No treatment-related death occurred, and no grade 4 non-hematologic toxicities other than transient hypokalemia were observed. Grade 4 neutropenia and grade 3 mucositis due to RT were common. At Level 2, grade 4 leukopenia/anemia/thrombocytopenia and grade 3 infection were more frequent than Level 1. In summary, at Level 1, 1 pt developed PD before evaluation of DLT. Remaining 3 pts did not develop DLT. At Level 2, 4 out of 6 pts developed DLT. Thus, we decided to select the Level 1 for the subsequent phase II portion. Of all 10 enrolled pts, 7 achieved CR, 2 PD, and 1 not evaluable. Of note, all 10 pts achieved local control. Our results suggest that concurrent chemoradiotherapy using MDR-non-related agents and ETP is a promising treatment strategy for localized nasal NK/T-cell lymphoma. Feasibility and efficacy of Level 1 will be evaluated further in the phase II portion.

Thermoradiotherapy combined with adenoviral p53 gene therapy in head and neck squamous cell carcinoma cell lines

We examined effects of recombinant p53-expressing adenovirus combined with thermoradiotherapy in 8 head and neck squamous cell carcinoma (SCC) cell lines to improve the outcomes of the treatment of advanced head and neck cancer. The p53 gene therapy did not improve the discrepancy between thermoradiosensitivities among the 8 SCC cell lines. However, p53 gene therapy improved the effects of thermoradiotherapy in all 8 cell lines, and there were significant differences in four situations of the HSC4 44 degrees C (p=0.032), SAS at 44 degrees C (p=0.029), the KB at 43 degrees C (p=0.025), and the Ca9-22 43 degrees C (p=0.020). In comparing the survival rates of thermoradiotherapy with those of thermotherapy and radiotherapy, thermoradiotherapy demonstrated actual survival rates less than theoretical survival rates based on the survival rates of thermotherapy multiplied by the survival rates of radiotherapy in almost all treatments of thermoradio-gene therapy of the 8 SCC cell lines. These results demonstrate that thermoradiotherapy combined with p53 gene therapy may be a useful tool in treating SCC cells.

Thermoradiotherapy combined with p53 gene therapy of human salivary gland adenocarcinoma cell line

We report on thermoradiotherapy combined with p53 gene therapy in the human salivary gland adenocarcinoma cell line HSG. HSG cells were successfully infected at a rate of 62.3% with MOIs of 20 of either AxCAip53 or AxCAiLacZ. The AxCAiLacZ did not inhibit the survival of the HSG cells. The survival fractions of AxCAip53-infected HSG cells were lower than those of the AxCAiLacZ-infected HSG cells, but there was no significant difference (p=0.30). AxCAip53 decreased the survival rates of thermotherapy (43 degrees C; p=0.084 and 44 degrees C; p=0.18), radiotherapy (6 Gy; p=0.20) and thermoradiotherapy (6 Gy plus 43 degrees C; p=0.24 and 6 Gy plus 44 degrees C; p=0.96), but there were no significant differences. In comparing the survival rates of thermoradiotherapy with those of thermotherapy and radiotherapy, thermoradiotherapy, regardless of the combination with p53 gene therapy, demonstrated actual survival rates lower than theoretical survival rates based on survival rates of thermotherapy multiplied by survival rates of radiotherapy. This result indicates that thermoradiotherapy is effective in the treatment of HSG cells. Thermoradiotherapy combined with p53 gene therapy was the most effective therapy among the combinations of therapies demonstrating that thermoradiotherapy combined with p53 gene therapy may be a useful tool in the treatment of HSG cells.

Multivariate prognostic analysis of stage I(E) primary non-Hodgkin's lymphomas of the nasal cavity.

From January 1968 to December 1997, a total of 71 patients with stage I(E) (Ann Arbor staging system, 1971) primary non-Hodgkin's lymphomas of the nasal cavity received treatment in the Cancer Center of Sun Yat-Sen University of Medical Sciences. Thirty-seven lesions were limited to the nasal cavity (limited I(E)), whereas the other 34 were extended to the structure out of the nasal cavity (extended I(E)). Forty-four patients were treated with radiochemotherapy and 27 with radiotherapy alone. Kaplan-Meier methods were used in the survival analysis. Multivariate analysis was carried out using the Cox proportional hazard model. The 5- and 10-year survival rates were 71.85% and 59.67% for the patients with a complete response to irradiation, and both were 13.89% for the patients with residue lesions (p = 0.0004). The 5- and 10-year survival rates were 69.81% and 56.72% for limited I(E), and 40.65% and 35.57% for extended I(E) (p = 0.0047). The prognosis was better for those younger than 44 years (p = 0.0003). The 10-year survival rates for radiotherapy alone and combined radiochemotherapy are 52% and 75% for limited I(E) versus 37.58% and 45% for extended I(E) (p = 0.0644). B symptoms did not significantly affect clinical outcome (p = 0.729). Multivariate analysis showed that complete response of local lesion after radiotherapy, invasion of the primary tumor to adjacent structures, and patients' age were independent prognostic factors. Our study showed that radiotherapy is the main treatment method for the primary non-Hodgkin's lymphomas of the nasal cavity; the addition of chemotherapy may improve long-term survival. The local tumor response to radiotherapy, whether the extranasal structures were invaded, and patients' age were independent prognostic factors.