Role of vaginal brachytherapy boost following adjuvant external beam radiotherapy in cervical cancer: Turkish Society for Radiation Oncology Gynecologic Group Study (TROD 04-002).

OBJECTIVE: There are a limited number of studies supporting vaginal brachytherapy boost to external beam radiotherapy in the adjuvant treatment of cervical cancer. The aim of this study was to assess the impact of the addition of vaginal brachytherapy boost to adjuvant external beam radiotherapy on oncological outcomes and toxicity in patients with cervical cancer. METHODS: Patients treated with post-operative external beam radiotherapy ± chemotherapy ± vaginal brachytherapy between January 2001 and January 2019 were retrospectively evaluated. The treatment outcomes and prognostic factors were analyzed in patients treated with external beam radiotherapy with or without vaginal brachytherapy. RESULTS: A total of 480 patients were included in the analysis. The median age was 51 years (range 42-60). At least two intermediate risk factors were observed in 51% of patients, while 49% had at least one high-risk factor. The patients in the external beam radiotherapy + vaginal brachytherapy group had worse prognostic factors than the external beam radiotherapy alone group. With a median follow-up time of 56 months (range 33-90), the 5-year overall survival rate was 82%. There was no difference in 5-year overall survival (87% vs 79%, p=0.11), recurrence-free survival (74% vs 71%, p=0.49), local recurrence-free survival (78% vs 76%, p=0.16), and distant metastasis-free survival (85% vs 76%, p=0.09) rates between treatment groups. There was no benefit of addition of vaginal brachytherapy to external beam radiotherapy in patients with positive surgical margins. In multivariate analysis, stage (overall survival and local recurrence-free survival), tumor histology (recurrence-free survival, local recurrence-free survival and distant metastasis-free survival), parametrial invasion (recurrence-free survival and distant metastasis-free survival), lymphovascular space invasion (recurrence-free survival), and lymph node metastasis (distant metastasis-free survival) were found as negative prognostic factors. CONCLUSION: Adding vaginal brachytherapy boost to external beam radiotherapy did not provide any benefit in local control or survival in patients with cervical cancer.

Impact of the Charlson Comorbidity Index on dose-limiting toxicity and survival in locally advanced and metastatic renal cell carcinoma patients treated with first-line sunitinib or pazopanib.

BACKGROUND: Anti-angiogenic tyrosine kinase inhibitors, sunitinib and pazopanib, have proven efficacy in advanced renal cell carcinoma, with specific adverse events occurring during treatment process. Comorbidities can reflect functional status and have prognostic value in oncology patients. We aimed to assess the association of the Charlson Comorbidity Index with severe toxicities and mortality in renal cell carcinoma cases treated with front-line sunitinib or pazopanib. METHODS: Files of locally advanced and metastatic renal cell carcinoma patients who received first-line sunitinib or pazopanib were retrospectively examined. Charlson Comorbidity Index of each patient was calculated. Patients were also stratified into Memorial Sloan-Kettering Cancer Center risk groups. Predictors of dose-limiting toxicity were evaluated with binomial logistic regression analysis. Univariate and multivariate Cox regression models were utilized to determine prognostic factors for survival. RESULTS: The study included 102 patients, 64 were treated with first-line sunitinib and 38 with pazopanib. In 42 patients (41.9%), Charlson Comorbidity Index was 9 or more. Dose-limiting toxicities were significantly more frequent in Charlson Comorbidity Index ≥9 group (69% vs. 40%, p = 0.004), and Charlson Comorbidity Index independently predicted dose-limiting toxicity (Hazard ratio (HR) = 4.30, p = 0.002). After adjusting for other variables, a Charlson Comorbidity Index of ≥9 is also a significant prognostic factor for progression-free (HR = 1.76, p = 0.02) and overall survival (HR = 1.75, p = 0.03). CONCLUSIONS: Charlson Comorbidity Index may be a valuable method to estimate prognosis and optimize therapy in patients with advanced renal cell carcinoma receiving first-line sunitinib or pazopanib.

A Diet Containing Beta-Hydroxy-Beta-Methylbutyrate, L-Glutamine and L-Arginine Ameliorates Chemoradiation-Induced Gastrointestinal Injury in Rats.

The aim of this study was to investigate the effects of a specific diet, containing beta-hydroxy-beta-methylbutyrate, L-glutamine and L-arginine (HMB/Glu/Arg), on chemoradiation-induced injuries of the rat gastrointestinal mucosa. Wistar albino rats were divided into 4 groups: control (n = 5); radiation (n = 14); 5-fluorouracil treatment (5-FU; n = 14); and radiation and 5-FU treatment (n = 14). Rats were fed either a standard diet or a specific diet (SpD) containing HMB/Glu/Arg supplementation for 7 days prior to radiation exposure and/or 5-FU treatment. The irradiated groups were exposed to an 1 Gy dose of 6 MV x rays delivered to the who-abdominal. The animals receiving 5-FU treatment were given a 100 mg/kg dose of the drug. In the radiation and 5-FU treatment group, the 5-FU was administered 30 min prior to irradiation. After irradiation and/or 5-FU treatment, feeding with either the standard rat diet or specific diet continued as before. All animals were sacrificed on day 4 after irradiation and 5-FU treatment. Data collected included microbiological, histological and immunohistochemical end points. We found that bacterial colony counts in the ceca and mesenteric lymph nodes of irradiated rats treated with 5-FU were significantly lower in the specific diet (SpD) group than in the standard diet group (P = 0.002-0.05). Morphometrically, gastric, duodenal and colonic mucosal injuries were less severe in the irradiated animals fed the specific diet, as well as the 5-FU-treated animals fed the specific diet, compared to the similarly treated standard diet groups. Apoptosis, measured by TUNEL, revealed significantly lower numbers of TUNEL positive cells in irradiated animals fed the specific diet, and irradiated animals treated with 5-FU and fed the specific diet compared to irradiated animals fed the standard diet, and irradiated animals treated with 5-FU and fed the standard diet. In the 5-Fu-treated and SpD group, the extent of apoptosis was significantly lower than that of the 5-Fu-treated and standard diet group in both the stomach and duodenum (P = 0.0001), but not in the colon. Apoptosis, measured by caspase 3 staining, was significantly less in all three organs of the SpD groups. In conclusion, these findings suggest that a diet supplemented with HMB/Glu/Arg may ameliorate the effect of radiation-induced gastrointestinal injury, coinciding with reduced bacterial growth.