Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: Results of a phase III randomised controlled trial.

AIM: To determine equivalence of modified gemcitabine and oxaliplatin compared with gemcitabine and cisplatin in unresectable gallbladder cancer (GBC). Primary end-point was overall survival (OS). METHODS: Open label, prospective, randomised phase III equivalence study. Inclusion criteria included histologically proven unresectable GBC, 18 years or older, adequate organ functions and Eastern Cooperative Oncology Group ≤2. SAMPLE SIZE: 108 patients were required in each arm to have an equivalence margin of ±2 months with power of 80%. TREATMENT: Modified gemcitabine and oxaliplatin (mGemOx)-gemcitabine 900 mg/m2, oxaliplatin 80 mg/m2, maximum 6 cycles; gemcitabine + cisplatin (CisGem)-gemcitabine 1000 mg/m2, cisplatin 25 mg/m2, maximum 8 cycles, all day 1 and 8 every 3 weeks. RESULTS: Two hundred sixty subjects were recruited between February 2011 and July 2015. Two hundred forty-three patients (119, mGemOx and 124, CisGem) received at least 1 dose and analysed for safety and efficacy (modified intention to treat). Median OS was 8·5 months for whole group (95% confidence interval [CI]: 7·9-9·1). Median OS in mGemOx was 9 months and 8·3 months in CisGem; p = 0·057 (hazard ratio = 0·78; 95% CI = 0·60-1·02). Restricted mean OS for follow-up limited to 30 months was 11·2 months (95% CI: 9·8-12·6) in mGemOx and 10·4 months (95% CI: 9·1-11·7) in CisGem. Difference of the mean was 0·8 months with 95% CI, exceeding 2 months (-1·1 to 2·7), hence rejecting equivalence. Peripheral neuropathy, thrombocytopaenia in mGemOx and nephrotoxicity was higher with CisGem. CONCLUSION: This trial failed to show equivalence of eight cycles of CisGem to six cycles of mGemOx. Numerically OS was better with mGemOx. Toxicities were different. The trial was not powered to answer superiority. CLINICAL TRIAL REGISTRATION: CTRI/2010/091/001406.

Technical Note: Rotational positional error corrected intrafraction set-up margins in stereotactic radiotherapy: A spatial assessment for coplanar and noncoplanar geometry.

PURPOSE: The aim of this study is to calculate setup margin based on six-dimensional (6D) corrected residual positional errors from kV cone beam computed tomography (CBCT) and from intrafraction projection kV imaging in coplanar and in noncoplanar couch positions in stereotactic radiotherapy. METHODS: Six dimensional positional corrections were carried out before patient treatments, using a robotic couch and CBCT matching. A CBCT and stereoscopic ExacTrac image were acquired post-table position correction. Further, a series of intrafraction ExacTrac images were obtained for the variable couch position. Translational and rotational errors were identified as lateral (X), longitudinal (Y), vertical (Z); roll (Ɵ°), pitch (Φ°) and yaw (Ψ°). A total of 699 intrafraction image sets (361 coplanar and 338 noncoplanar) for 51 SRS/SRT patients were analysed. Rotational errors were corrected in terms of translational coordinates. Residual set-up margins were calculated from CBCT shifts. ExacTrac shifts give residual + intrafraction setup margins as a function of coplanar and noncoplanar couch positions. RESULTS: The average residual positional error obtained from CBCT in X, Y, Z, Ɵ, Φ, Ψ were 0.1 ± 0.4 mm, 0.0 ± 0.6 mm, 0.0 ± 0.5 mm, 0.2 ± 0.8°, 0.1 ± 0.6° and -0.1 ± 0.7° respectively. For ExacTrac, the shits were -0.5 ± 0.9 mm, -0.0 ± 1mm, -0.6 ± 1.0mm, 0.4 ± 0.9°, -0.2 ± 0.6°, and -0.0 ± 0.8°. CBCT calculated linear setup margins in X, Y, Z direction were 0.5, 1.2, and 1 mm respectively. ExacTrac yielded coplanar and noncoplanar linear setup margins were 1.2, 1.3, 1.5, 1.4, 1.5, and 2.1 mm respectively. CONCLUSION: CBCT-based gross residual set-up margin is equal to 1 mm. ExacTrac calculated residual plus intrafraction setup margin falls within a 2 mm range; attributed to intrafraction patient movement, table position inaccuracies, and poor image fusion in noncoplanar geometry. There could be variations in the required additional margin between centers and between machines, which require further studies.

Short tangential arcs in VMAT based breast and chest wall radiotherapy lead to conformity of the breast dose with lesser cardiac and lung doses: a prospective study of breast conservation and mastectomy patients.

Volumetric modulated arc therapy (VMAT) is modern rotational intensity modulated therapy used for treatment of several sites. The study aimed to analyze partial tangential arc VMAT treatment planning and delivery, including analyzing the cardiac and contralateral breast doses resulting from this technique. A total of 153 consecutively treated breast cancer (conservation as well as mastectomy) patients were taken for this dosimetric study. All patients were planned using partial arc VMAT in the Monaco treatment planning system using two partial arc beams. All patients were divided into seven different categories: (1) all the patients in the study, (2) left sided whole breast and chest wall patients, (3) left Chest wall patients, (4) left whole breast patients, (5) right sided whole breast and chest wall patients, (6) right chest wall patients, and (7) right whole breast patients. We evaluated each treatment plan for PTV coverage and doses to OARs. SPSS version 16.0 software was used for statistical analysis. There were 91 left sided and 62 right sided breast cancer patients in the overall analysis. The percentage of PTV volume receiving 95% of the prescription dose (PTV V95%, mean ± SD) varied in the range of 91.2 ± 5.2-94.8 ± 2.1% with mean dose of 92.4 ± 5.2% for all cases. The (mean ± SD) cardiac dose for all the patients was 289 ± 23 cGy. The (mean ± SD) cardiac doses were higher for left sided patients (424 ± 33.8 cGy) as compared to right sided patients (123.9 ± 80 cGy) (p < 0.001). Cardiac mean doses were higher with arc angles >30° versus 30° (324.5 ± 247.1 vs. 234.4 ± 188.4 cGy) (p = 0.001). Similarly contralateral breast mean dose was higher with arc angles >30° versus 30° (126 ± 115 vs. 88.6 ± 76.1 cGy) (p = 0.001). However cardiac V20, V30 and V40 Gy did not exhibit any statistical difference between the two groups (p = 0.26, 0.057 and 0.054 respectively). This is the first large study of its kind that assesses the dosimetric outcome of tangential partial arc VMAT treatments in a large group of mastectomy and breast conservation patients. Our study demonstrates the efficacy of this technique in dose coverage of PTV as well as in minimizing dose to OARs. Further, based on our results, we conclude that the arc length for the bi-tangential arcs should be 30° since it helps to achieve the most optimal balance between target coverage and acceptable OAR doses.