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Simultaneous multitarget radiotherapy using helical tomotherapy and its combination with sorafenib for pulmonary metastases from hepatocellular carcinoma.

ABSTRACT: We evaluated radiotherapy using helical tomotherapy (HT) combined with sorafenib for treatment of pulmonary metastases from hepatocellular carcinoma (HCC). We also analyzed potential prognostic factors and further validated the combination treatment. The objective response rate in the total cohort of 45 patients treated with HT (with or without sorafenib) was 66.7% (complete response, n = 1; partial response, n = 29), with no adverse events > grade 2 in severity. Median progression-free survival (PFS) and overall survival (OS) were 7.50 ± 0.53 and 26.40 ± 2.66 months, respectively. The addition of sorafenib was associated with increased PFS (11.80 ± 1.55 vs 5.80 ± 0.52 months, p = 0.006) and increased OS (29.60 ± 5.23 vs 21.90 ± 5.17 months, p = 0.007). After multivariate adjustment, the risk of disease progression associated with combination treatment was significantly lower (p = 0.022) compared with HT only, and survival was significantly longer (p = 0.014). Further validation confirmed the benefit of combination treatment. Prognostic factors were number of pulmonary metastases for PFS (19.00 ± 7.15 months for ?3 lesions vs 5.80 ± 0.26 months for >3 lesions, p < 0.001) and intrahepatic tumor status for OS (28.50 ± 2.76 months for well-controlled tumors vs 15.60 ± 6.38 months for uncontrolled tumors, p = 0.011). In conclusion, radiotherapy with HT for pulmonary metastases is feasible without major complications, and its combination with sorafenib may be a promising approach in a subgroup of patients.

SUBMITTER: Sun T

PROVIDER: S-EPMC5217040 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Simultaneous multitarget radiotherapy using helical tomotherapy and its combination with sorafenib for pulmonary metastases from hepatocellular carcinoma.

Sun Taiwei T He Jian J Zhang Shumin S Sun Jing J Zeng Mengsu M Zeng Zhaochong Z

Oncotarget 20160701 30

We evaluated radiotherapy using helical tomotherapy (HT) combined with sorafenib for treatment of pulmonary metastases from hepatocellular carcinoma (HCC). We also analyzed potential prognostic factors and further validated the combination treatment. The objective response rate in the total cohort of 45 patients treated with HT (with or without sorafenib) was 66.7% (complete response, n = 1; partial response, n = 29), with no adverse events > grade 2 in severity. Median progression-free survival ...[more]

PMID: 27191894

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Project description:Our research group has previously published a dosimetric planning study that demonstrated that a 60 Gy/10 fractions intralesional boost with whole-brain radiotherapy (WBRT) to 30 Gy/10 fractions was biologically equivalent with a stereotactic radiosurgery (SRS) boost of 18 Gy/1 fraction with 30 Gy/10 fractions WBRT. Helical tomotherapy (HT) was found to be dosimetrically equivalent to SRS in terms of target coverage and superior to SRS in terms of normal tissue tolerance. A phase I trial has been now completed at our institution with a total of 60 enrolled patients and 48 evaluable patients. The phase II dose has been determined to be the final phase I cohort dose of 60 Gy/10 fractions.The objective of this clinical trial is to subject the final phase I cohort dose to a phase II assessment of the endpoints of overall survival, intracranial control (ICC) and intralesional control (ILC). We hypothesize HT would be considered unsuitable for further study if the median OS for patients treated with the HT SIB technique is degraded by 2 months, or the intracranial progression-free rates (ICC and ILC) are inferior by 10% or greater compared to the expected results with treatment by whole brain plus SRS as defined by the RTOG randomized trial. A sample size of 93 patients was calculated based on these parameters as well as the statistical assumptions of alpha = 0.025 and beta = 0.1 due to multiple statistical testing. Secondary assessments of toxicity, health-related quality-of-life, cognitive changes, and tumor response are also integrated into this research protocol.To summarize, the purpose of this phase II trial is to assess this non-invasive alternative to SRS in terms of central nervous system (CNS) control when compared to SRS historical controls. A follow-up phase III trial may be required depending on the results of this trial in order to definitively assess non-inferiority/superiority of this approach. Ultimately, the purpose of this line of research is to provide patients with metastatic disease to the brain a shorter course, dose intense, non-invasive radiation treatment with equivalent or improved CNS control/survival and health-related quality-of-life/toxicity profile when compared to SRS radiotherapy.Clinicaltrials.gov - NCT01543542.

Project description:BACKGROUND AND PURPOSE:Radiotherapy (RT) is persistently gaining significance in the treatment of pediatric tumors. However, individual features of a growing body and multifocal stages complicate this approach. Tomotherapy offers advantages in the treatment of anatomically complex tumors with low risks of side effects. Here we report on toxicity incidence and outcome of tomotherapy with a focus on multitarget RT (mtRT). MATERIALS AND METHODS:From 2008 to 2017, 38 children diagnosed with sarcoma were treated with tomotherapy. The median age was 15 years (6-19 years). Toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03 and classified into symptoms during RT, acutely (0-6 months) and late (>6 months) after RT, and long-term sideeffects (>24 months). RESULTS:The main histologies were Ewing sarcoma (n?=?23 [61%]) and alveolar rhabdomyosarcoma (n?=?5 [13%]). RT was performed with a median total dose of 54?Gy (40.5-66.0?Gy) and a single dose of 2?Gy (1.80-2.27?Gy). Twenty patients (53%) received mtRT. Median follow-up was 29.7 months (95% confidence interval 15.3-48.2 months) with a 5-year survival of 55.2% (±9.5%). The 5?year survival rate of patients with mtRT (n?=?20) was 37.1?±?13.2%, while patients who received single-target RT (n?=?18) had a 5-year survival rate of 75?±?10.8%. Severe toxicities (grade 3 and 4) emerged in 14 patients (70%) with mtRT and 7 patients (39%) with single-target RT. Two non-hematological grade 4 toxicities occurred during RT: one mucositis and one radiodermatitis. After mtRT 5 patients had grade 3 toxicities acute and after single-target RT 4 patients. One patient had acute non-hematological grade 4 toxicities (gastritis, pericarditis, and pericardial effusion) after mtRT. Severe late effects of RT occurred in 2 patients after mtRT and in none of the single-target RT patients. No severe long-term side effects appeared. CONCLUSION:Our results showed acceptable levels of acute and late toxicities, considering the highly advanced diseases and multimodal treatment. Hence, tomotherapy is a feasible treatment method for young patients with anatomically complex tumors or multiple targets. Especially mtRT is a promising and innovative treatment approach for pediatric sarcomas, delivering unexpectedly high survival rates for patients with multifocal Ewing sarcomas in this study, whereby the limited number of patients should invariably be considered in the interpretation.

Project description:BackgroundLeft-sided post-mastectomy radiotherapy (PMRT) certainly precedes some radiation dose to the cardiopulmonary organs causing many side effects. To reduce the cardiopulmonary dose, we created a new option of the breathing adapted technique by using abdominal compression applied with a patient in deep inspiration phase utilizing shallow breathing. This study aimed to compare the use of abdominal compression with shallow breathing (ACSB) with the free breathing (FB) technique in the left-sided PMRT.Materials and methodsTwenty left-sided breast cancer patients scheduled for PMRT were enrolled. CT simulation was performed with ACSB and FB technique in each patient. All treatment plans were created on a TomoTherapy planning station. The target volume and dose, cardiopulmonary organ volume and dose were analyzed. A linear correlation between cardiopulmonary organ volumes and doses were also tested.ResultsRegarding the target volumes and dose coverage, there were no significant differences between ACSB and FB technique. For organs at risk, using ACSB resulted in a significant decrease in mean (9.17 vs 9.81 Gy, p<0.0001) and maximum heart dose (43.79 vs 45.45 Gy, p = 0.0144) along with significant reductions in most of the evaluated volumetric parameters. LAD doses were also significantly reduced by ACSB with mean dose 19.24 vs 21.85 Gy (p = 0.0036) and the dose to 2% of the volume (D2%) 34.46 vs 37.33 Gy (p = 0.0174) for ACSB and FB technique, respectively. On the contrary, the lung dose metrics did not show any differences except the mean V5 of ipsilateral lung. The positive correlations were found between increasing the whole lung volume and mean heart dose (p = 0.05) as well as mean LAD dose (p = 0.041) reduction.ConclusionsThe ACSB technique significantly reduced the cardiac dose compared with the FB technique in left-sided PMRT treated by Helical TomoTherapy. Our technique is uncomplicated, well-tolerated, and can be applied in limited resource center.

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Simultaneous multitarget radiotherapy using helical tomotherapy and its combination with sorafenib for pulmonary metastases from hepatocellular carcinoma.

Publications

Simultaneous multitarget radiotherapy using helical tomotherapy and its combination with sorafenib for pulmonary metastases from hepatocellular carcinoma.

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