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Optimal time of tumour response evaluation and effectiveness of hypofractionated proton beam therapy for inoperable or recurrent hepatocellular carcinoma.

ABSTRACT: To evaluate the optimal time of tumour response and effectiveness of hypofractionated proton beam therapy (PBT) for hepatocellular carcinoma (HCC).Overall, treatment was well tolerated with no grade toxicity ?3. Of 71 patients, 66 patients (93%) eventually reached complete response (CR) after PBT: 93.9% (62 of 66) of patients who reached CR within 12 months, and the remaining 4 patients (6.1%) reached CR at 12.5, 16.2, 19.1 and 21.7 months, respectively. The three-year local progression-free survival (LPFS), relapse-free survival (RFS) and OS rates were 89.9%, 26.8%, and 74.4%, respectively. Multivariate analysis revealed that the tumour response was an independent prognostic factor for LPFS, RFS, and OS.Most CR was achieved within 1 year after PBT and further salvage treatments in PBT field might be postponed up to approximately 18-24 months. Hypofractionated PBT could be good alternative for HCC patients who are unsuitable for surgical or invasive treatments with curative intent.Seventy-one inoperable or recurrent HCC patients underwent hypofractionated PBT using 66 GyE in 10 fractions. The tumour responses were defined as the maximal tumour response observed during the follow-up period using the modified Response Evaluation Criteria in Solid Tumors criteria.

SUBMITTER: Kim TH

PROVIDER: S-EPMC5790519 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Optimal time of tumour response evaluation and effectiveness of hypofractionated proton beam therapy for inoperable or recurrent hepatocellular carcinoma.

Kim Tae Hyun TH Park Joong-Won JW Kim Bo Hyun BH Kim Dae Yong DY Moon Sung Ho SH Kim Sang Soo SS Lee Ju Hee JH Woo Sang Myung SM Koh Young-Hwan YH Lee Woo Jin WJ Kim Chang-Min CM

Oncotarget 20171219 3

<h4>Objective</h4>To evaluate the optimal time of tumour response and effectiveness of hypofractionated proton beam therapy (PBT) for hepatocellular carcinoma (HCC).<h4>Results</h4>Overall, treatment was well tolerated with no grade toxicity ≥3. Of 71 patients, 66 patients (93%) eventually reached complete response (CR) after PBT: 93.9% (62 of 66) of patients who reached CR within 12 months, and the remaining 4 patients (6.1%) reached CR at 12.5, 16.2, 19.1 and 21.7 months, respectively. The thr ...[more]

PMID: 29423102

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Project description:Background: Retroperitoneal sarcomas (RPS) are rare and primarily managed with surgery, which improves local recurrence-free and overall survival. Radiation can improve local control or provide palliation for inoperable or metastatic RPS by eliciting tumor cell death via irreparable DNA damage. In extraordinary circumstances radiation-induced cell death promotes immune-mediated regression of non-irradiated lesions in a process termed the abscopal effect. Abscopal effects are rare and incompletely understood, involving a balance of radiation's immunogenic and immunosuppressive effects. There are currently no methods to predict abscopal responses following radiotherapy. Case reports documenting post-radiotherapy abscopal effects provide additional information to better characterize these responses and to inform ongoing and future clinical trials attempting to harness radiation-induced immune responses to improve outcomes with systemic therapy, such as SARC-032, a cooperative group trial of pre-operative radiation ± pembrolizumab. We present a case of inoperable metastatic RPS treated with proton radiotherapy with complete responses of un-irradiated metastases. Case Presentation: A 67 year-old female with inoperable metastatic unclassified round cell RPS was treated with palliative proton radiotherapy only to the primary tumor. Following completion of radiotherapy, the patient demonstrated complete regression of all un-irradiated metastases, and near complete response of the primary lesion without additional therapy. Conclusions: Metastatic RPS is typically managed with first-line chemotherapy, with objective response rates <50%. We present a case of inoperable metastatic RPS treated with palliative proton radiotherapy for rapidly progressive disease who had complete regression of non-irradiated metastases consistent with the abscopal effect. To our knowledge this is the first case report describing abscopal effects in inoperable metastatic RPS treated with proton radiation and is among the first case reports of an abscopal effect in a patient treated with proton therapy regardless of disease site. Further investigation is warranted regarding the benefit of proton radiation to primary tumors for inoperable metastatic RPS.

Project description:PurposeProton beam therapy is a commonly accepted treatment for intraocular melanomas, but the literature is lacking in descriptions of patient preferences of clinical outcomes and economic impact. In addition, no economic evaluations have been published regarding the incremental cost-effectiveness of proton beam therapy compared with enucleation or plaque brachytherapy, typical alternative treatments. We, therefore, conducted a cost-utility analysis of these three approaches for the treatment of intraocular melanomas.Materials and methodsA Markov model was constructed. Model parameters were identified from the published literature and publicly available data sources. Cost-effectiveness of each treatment was calculated in 2011 US Dollars per quality-adjusted life-year. Incremental cost-effectiveness ratios were calculated assuming enucleation as reference. One-way sensitivity analyses were conducted on all model parameters. A decision threshold of $50,000/quality-adjusted life-year was used to determine cost-effectiveness.ResultsEnucleation had the lowest costs and quality-adjusted life-years, and plaque brachytherapy had the highest costs and quality-adjusted life-years. Compared with enucleation, the base-case incremental cost-effectiveness ratios for plaque brachytherapy and proton beam therapy were $77,500/quality-adjusted life-year and $106,100/quality-adjusted life-year, respectively. Results were highly sensitive to multiple parameters. All three treatments were considered optimal, and even dominant, depending on the values used for sensitive parameters.ConclusionBase-case analysis results suggest enucleation to be optimal. However, the optimal choice was not robust to sensitivity analyses and, depending on the assumption, both plaque brachytherapy and proton beam therapy could be considered cost-effective. Future clinical studies should focus on generating further evidence with the greatest parameter uncertainty to inform future cost-effectiveness analyses.

Dataset Information

Optimal time of tumour response evaluation and effectiveness of hypofractionated proton beam therapy for inoperable or recurrent hepatocellular carcinoma.

Publications

Optimal time of tumour response evaluation and effectiveness of hypofractionated proton beam therapy for inoperable or recurrent hepatocellular carcinoma.

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