Feasibility of Stereotactic Body Radiation Therapy on Unresectable Stage III NSCLC with Peripheral Primary Tumor: A Prospective Study (GFPC 01-14).

Concomitant radiochemotherapy (RTCT) is the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, in patients with a peripheral primary tumor, the irradiated volume may include a large portion of normal lung and RT-CT is not possible. This multicenter phase II trial in unresectable stage III NSCLC with peripheral primary tumor evaluated the feasibility of stereotactic body radiation therapy (SBRT) in peripheral tumor after concomitant radio-chemotherapy (RT-CT). Nineteen patients were included and analyzed (median age, 60.9 years; male, 78%; adenocarcinoma, 74%; median size of peripheral primary tumor, 19 mm). At 6 months, the disease control rate was 79% (15/19). SBRT toxicity was generally mild with one (5%) patient having grade 3 lung toxicity. Recruitment for this study was stopped prior to completion, firstly due to the approval of adjuvant durvalumab after RT-CT, which was not anticipated in the design, and secondly due to the small number of stage III NSCLC patients with a peripheral tumor that was accessible to SBRT. Nevertheless, the combination of RT-CT and SBRT appeared to be feasible and safe.

A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX.

BACKGROUND: In a previous phase II study an immunonutrient supplement was found to reduce severe acute toxicities for head and neck squamous cell cancer (HNSCC) patients treated with concomitant cisplatin and radiotherapy. OBJECTIVES: The primary objective of the present study was to evaluate efficacy of the same immunonutrient supplement on severe mucositis. Secondary objectives included tolerance, compliance to oral supplementation, chemotherapy interruptions and delays, quality of life, and progression-free survival (PFS) and overall survival (OS) at 1, 2, and 3 y. METHODS: Between November 2009 and June 2013, 180 HNSCC patients eligible for adjuvant chemotherapy after surgery with curative intent were included in our double-blind phase III multicenter trial. They were assigned to receive oral supplementation (3 sachets/d) of either a formula enriched with l-arginine and omega-3 (n-3) fatty and ribonucleic acids (experimental arm), or an isocaloric isonitrogenous control (control arm), for 5 d before each of 3 cycles of cisplatin. Intention-to-treat (ITT) and per-protocol (PP) analyses were undertaken, along with subgroup analyses of ≥75% compliant patients, to compare the incidence of acute mucositis (Radiation Therapy Oncology Group and WHO scales) and 36-mo survival. RESULTS: At 1 mo after terminating chemoradiotherapy (CRT), no differences were observed in the incidence of grade 3-4 mucositis between treatment groups, in the ITT, PP (172 patients), and subgroup (≥75% compliance, n = 112) analyses. The immunomodulating supplement did not significantly improve survival in the ITT and PP analyses at 3 y after CRT. Among ≥75% compliant patients, however, OS at 3 y was significantly improved in the immunomodulating formula group (81%; 95% CI: 67%, 89%) compared with controls (61%; 95% CI: 46%, 73%; P = 0.034), as well as PFS (73%; 95% CI: 58%, 83% compared with 50%; 95% CI: 36%, 63%; P = 0.012). CONCLUSIONS: Although this immunomodulating formula failed to reduce severe mucositis during CRT, the findings suggest that the long-term survival of compliant HNSCC patients was improved.This trial was registered at clinicaltrials.gov as NCT01149642.

Is mean heart dose a relevant surrogate parameter of left ventricle and coronary arteries exposure during breast cancer radiotherapy: a dosimetric evaluation based on individually-determined radiation dose (BACCARAT study).

BACKGROUND: Intra-individual heterogeneity of cardiac exposure is an issue in breast cancer (BC) radiotherapy that was poorly considered in previous cardiotoxicity studies mainly based on mean heart dose (MHD). This dosimetric study analyzes the distribution of individually-determined radiation doses to the heart and its substructures including coronary arteries and evaluate whether MHD is a relevant surrogate parameter of dose for these substructures. METHODS: Data were collected from the BACCARAT prospective study that included left or right unilateral BC patients treated with 3D-Conformal Radiotherapy (RT) between 2015 and 2017 and followed-up for 2 years with repeated cardiac imaging examinations. A coronary computed tomography angiography (CCTA) was performed before RT for all patients. Registration of the planning CT and CCTA images allowed delineation of the coronary arteries on the planning CT images. Using the 3D dose matrix generated during treatment planning and the added coronary contours, dose distributions were generated for whole heart and the following substructures: left ventricle (LV), left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA). A descriptive analysis of the physical doses in Gray (Gy) was performed, Dmean was the volume-weighted mean dose. RESULTS: Dose distributions were generated for 89 left-sided BC patients (MHD = 2.9 ± 1.5 Gy, Dmean_LAD = 15.7 ± 3.1 Gy) and 15 right-sided BC patients (MHD = 0.5 ± 0.1 Gy; Dmean_RCA = 1.2 ± 0.4 Gy). For left-sided BC patients, the ratio Dmean_LAD/MHD was around 5. Pearson correlation coefficients between MHD and Dmean for delineated substructures were all statistically significant. However, for all substructures, the coefficient of determination R2 indicated that the proportion of the variance in Dmean of the substructure predictable from MHD was moderate to low (in particular R2 = 0.45 for LAD). Among left-sided BC patients with MHD < 3Gy, 56% of patients could nevertheless receive LAD doses above 40Gy (V40 > 0). CONCLUSION: Our study illustrates that MHD is not enough to predict with confidence individual patient dose to the LV and coronary arteries, in particular the LAD. For precise radiotherapy-induced cardiotoxicity studies it would be necessary to consider the distribution of doses within these cardiac substructures rather than just the MHD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02605512 , Registered 6 November 2015 - Retrospectively registered.

Cost Analysis of Complex Radiation Therapy for Patients With Head and Neck Cancer.

PURPOSE: This cost analysis aimed to prospectively assess differences in costs between TomoTherapy and volumetric modulated arc therapy (VMAT) in patients with head and neck cancer. METHODS AND MATERIALS: Economic data were gathered from a multicenter study. However, randomization was not possible due to the availability of equipment. Costs were calculated using the microcosting technique from the hospital's perspective (in 2013 euros), and the time horizon was radiation therapy. Only resources that entered the hospital production process and which were likely to vary between the strategies being compared were considered. Acute adverse events observed within the time horizon were also assessed. RESULTS: The cost analysis was based on a total of 173 patient treatments given between 2010 and 2012 in 14 French cancer centers: 73 patients were treated with TomoTherapy, 92 with VMAT RapidArc, and 8 with VMAT SmartArc. Estimated costs of SmartArc were removed from the comparison due to the small sample size. The mean ± SD cost per patient of the treatment planning phase was €314 (±€214) for TomoTherapy and €511 (±€590) for RapidArc. Mean costs ± SD per patient of irradiation reached €3144 (±€565) for TomoTherapy and €1350 (±€299) for RapidArc. The most sensitive parameter of irradiation was the annual operating time of accelerators. Ninety-five percent confidence intervals for the mean costs of irradiation were €3016 to €3272 for TomoTherapy and €1281 to €1408 for RapidArc. The number of acute adverse events during radiation therapy was not significantly different between strategies. CONCLUSIONS: TomoTherapy appeared to be more expensive than RapidArc mainly due to the higher price of the accelerator, the higher costs of maintenance, and the longer duration of treatment sessions. Because strategies were not significantly different in clinical effect, RapidArc appeared to be the strategy to be recommended at this stage of knowledge.