Radiotherapy dose escalation with concurrent chemotherapy in locally advanced cervix cancer is feasible

Background. To test the feasibility of radiotherapy dose escalation using volumetric arc therapy (VMAT) and image-guided radiotherapy (IGRT) with concurrent chemotherapy in locally advanced cervix cancer (LACC) and compare this with whole-pelvis three-dimensional conformal radiation therapy (CRT) in terms of clinical toxicity. Methods. Database was reviewed for all LACC patients treated during 2011 and 2012. Twenty patients who were treated with escalated dose of radiotherapy using VMAT were selected for analysis. A matched cohort of 40 patients who had 3DCRT between 2005 and 2008 was selected as control. Mean basal hemoglobin, average weekly hemoglobin, and maximal drop in hemoglobin were measured for both 3DCRT and VMAT groups and treatment toxicity scored according to RTOG criteria. Charts were also reviewed for other acute and late toxicities including the rate of compliance with prescribed treatment. Results. Mean age was 46 (30-63) and 47 years (33-67), mean tumor size was 5.5 and 5 cm and blood transfusion rate was 55 and 45 % in CRT and VMAT groups, respectively. Hemoglobin toxicity (Grade I-II) was encountered in 97.5 and 90 % (p 0.0.3) while Grade I-III Leukopenia was 90 and 70 % (p 0.02), respectively. There was no Grade 3 or 4 GI or GU toxicity. Conclusion. VMAT/IGRT with dose escalation is feasible in LACC without excessive toxicity as compared to CRT "Box". We propose a randomized control trial of this novel approach of higher radiation dose and volume against the standard prescription based on CRT (AU)

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Radiotherapy dose escalation with concurrent chemotherapy in locally advanced cervix cancer is feasible.

BACKGROUND: To test the feasibility of radiotherapy dose escalation using volumetric arc therapy (VMAT) and image-guided radiotherapy (IGRT) with concurrent chemotherapy in locally advanced cervix cancer (LACC) and compare this with whole-pelvis three-dimensional conformal radiation therapy (CRT) in terms of clinical toxicity. METHODS: Database was reviewed for all LACC patients treated during 2011 and 2012. Twenty patients who were treated with escalated dose of radiotherapy using VMAT were selected for analysis. A matched cohort of 40 patients who had 3DCRT between 2005 and 2008 was selected as control. Mean basal hemoglobin, average weekly hemoglobin, and maximal drop in hemoglobin were measured for both 3DCRT and VMAT groups and treatment toxicity scored according to RTOG criteria. Charts were also reviewed for other acute and late toxicities including the rate of compliance with prescribed treatment. RESULTS: Mean age was 46 (30-63) and 47 years (33-67), mean tumor size was 5.5 and 5 cm and blood transfusion rate was 55 and 45 % in CRT and VMAT groups, respectively. Hemoglobin toxicity (Grade I-II) was encountered in 97.5 and 90 % (p 0.0.3) while Grade I-III Leukopenia was 90 and 70 % (p 0.02), respectively. There was no Grade 3 or 4 GI or GU toxicity. CONCLUSION: VMAT/IGRT with dose escalation is feasible in LACC without excessive toxicity as compared to CRT "Box". We propose a randomized control trial of this novel approach of higher radiation dose and volume against the standard prescription based on CRT.

Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies.

BACKGROUND: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. PATIENTS AND METHODS: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS). RESULTS: Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82). CONCLUSION: Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches. TRIAL REGISTRATION: NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA.