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Efficacy and feasibility of proton beam radiotherapy using the simultaneous integrated boost technique for locally advanced pancreatic cancer.

ABSTRACT: To evaluate the clinical efficacy and feasibility of proton beam radiotherapy (PBT) using the simultaneous integrated boost (SIB) technique in locally advanced pancreatic cancer (LAPC), 81 LAPC patients receiving PBT using SIB technique were analyzed. The prescribed doses to planning target volume (PTV)1 and PTV2 were 45 or 50 GyE and 30 GyE in 10 fractions, respectively. Of 81 patients, 18 patients received PBT without upfront and maintenance chemotherapy (group I), 44 received PBT followed by maintenance chemotherapy (group II), and 19 received PBT after upfront chemotherapy followed by maintenance chemotherapy (n?=?16) (group III). The median follow-up time was 19.6 months (range 2.3-57.6 months), and the median overall survival (OS) times of all patients and of those in groups I, II, and III were 19.3 months (95% confidence interval [CI] 16.8-21.7 months), 15.3 months (95% CI 12.9-17.7 months), 18.3 months (95% CI 15.9-20.7 months), and 26.1 months (95% CI 17.8-34.3 months), respectively (p?=?0.043). Acute and late grade???3 toxicities related to PBT were not observed. PBT with the SIB technique showed promising OS for LAPC patients with a safe toxicity profile, and intensive combinations of PBT and chemotherapy could improve OS in these patients.

SUBMITTER: Kim TH

PROVIDER: S-EPMC7729854 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Efficacy and feasibility of proton beam radiotherapy using the simultaneous integrated boost technique for locally advanced pancreatic cancer.

Kim Tae Hyun TH Lee Woo Jin WJ Woo Sang Myung SM Oh Eun Sang ES Youn Sang Hee SH Jang Hye Young HY Han Sung-Sik SS Park Sang-Jae SJ Suh Yang-Gun YG Moon Sung Ho SH Kim Sang Soo SS Kim Dae Yong DY

Scientific reports 20201210 1

To evaluate the clinical efficacy and feasibility of proton beam radiotherapy (PBT) using the simultaneous integrated boost (SIB) technique in locally advanced pancreatic cancer (LAPC), 81 LAPC patients receiving PBT using SIB technique were analyzed. The prescribed doses to planning target volume (PTV)1 and PTV2 were 45 or 50 GyE and 30 GyE in 10 fractions, respectively. Of 81 patients, 18 patients received PBT without upfront and maintenance chemotherapy (group I), 44 received PBT followed by ...[more]

PMID: 33303947

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Project description:Objectives: To compare treatment plans of intensity modulated radiotherapy (IMRT), volumetric modulated arc radiotherapy (VMAT), and helical tomotherapy (HT) with simultaneous integrated boost (SIB) technique for esophageal cancer (EC) of different locations using dosimetry and radiobiology. Methods: Forty EC patients were planned for IMRT, VMAT, and HT plans, including 10 cases located in the cervix, upper, middle, and lower thorax, respectively. Dose-volume metrics, conformity index (CI), homogeneity index (HI), tumor control probability (TCP), and normal tissue complication probability (NTCP) were analyzed to evaluate treatment plans. Results: HT showed significant improvement over IMRT and VMAT in terms of CI (p = 0.007), HI (p < 0.001), and TCP (p < 0.001) in cervical EC. IMRT yielded more superior CI, HI and TCP compared with VMAT and HT in upper and middle thoracic EC (all p < 0.05). Additionally, V30 (27.72 ± 8.67%), mean dose (1801.47 ± 989.58cGy), and NTCP (Niemierko model: 0.44 ± 0.55%; Lyman-Kutcher-Burman model: 0.61 ± 0.59%) of heart in IMRT were sharply reduced than VMAT and HT in middle thoracic EC. For lower thoracic EC, the three techniques offered similar CI and HI (all p > 0.05). But VMAT dramatically lowered liver V30 (9.97 ± 2.84%), and reduced NTCP of lungs (Niemierko model: 0.47 ± 0.48%; Lyman-Kutcher-Burman model: 1.41 ± 1.07%) and liver (Niemierko model: 0.10 ± 0.08%; Lyman-Kutcher-Burman model: 0.17 ± 0.17%). Conclusions: HT was a good option for cervical EC with complex target coverage but little lungs and heart involvement as it achieved superior dose conformity and uniformity. Due to potentially improving tumor control and reducing heart dose with acceptable lungs sparing, IMRT was a preferred choice for upper and middle thoracic EC with large lungs involvement. VMAT could ameliorate therapeutic ratio and lower lungs and liver toxicity, which was beneficial for lower thoracic EC with little thoracic involvement but being closer to heart and liver. Individually choosing optimal technique for EC in different location will be warranted.

Project description:PurposeTo assess the feasibility of accelerated hypofractionated radiotherapy with simultaneous integrated boost (SIB) in patients with breast cancer.Materials and methodsA total of 27 patients after breast-conserving surgery were included in this study. Patients were planned on a four-dimensional computerized tomogram, and contouring was done using RTOG guidelines. The dose was 34 Gy/10#/2 week to the breast and 40 Gy/10#/2 week to the tumor bed as SIB with volumetric modulated arc technique. The primary endpoint was grade 2 acute skin toxicity. Doses to the organs-at-risk were calculated. Toxicities and cosmesis were assessed using RTOG/LENT/SOMA and HARVARD/NSABP/RTOG grading scales, respectively. Disease-free survival (DFS) and overall survival (OS) were calculated with Kaplan-Meier curves.ResultsThe mean age of the patients was 42 years. Left and right breast cancers were seen in 17 (63%) and 10 (37%) patients, respectively. The mean values of ipsilateral lung V16 and contralateral lung V5 were 16.01% and 3.74%, respectively. The mean heart doses from the left and right breast were 7.25 Gy and 4.37 Gy, respectively. The mean doses to the contralateral breast, oesophagus, and Dmax to brachial plexus were 2.64 Gy, 3.69 Gy, and 26.95 Gy, respectively. The mean value of thyroid V25 was 19.69%. Grade 1 and 2 acute skin toxicities were observed in 9 (33%) and 5 (18.5%) patients, respectively. Grade 2 hyperpigmentation, edema, and induration were observed in 1 (3.7%), 2 (7.4%), and 4 (14.8%) patients, respectively. Mild breast pain and arm/shoulder discomfort were reported by 1 (3.4%) patient. The median follow-up was 51 months (range, 12 to 61 months). At four years, breast induration, edema, and fibrosis were observed in 1 (3.7%) patient. Cosmesis was excellent and good in 21 (78%) and 6 (22%) patients, respectively. Local recurrence and distant metastases occurred in 1 (3.7%) and 2 (7.4%) patients, respectively. DFS and OS at four years were 88% and 92%, respectively.ConclusionWith this radiotherapy schedule, acute and late toxicity rates were acceptable with no adverse cosmesis. Local control, DFS, and OS were good.

Project description:PurposeWe evaluate the feasibility of the elective nodal irradiation strategy in stereotactic body radiotherapy (SBRT) for pancreatic cancer.MethodsThree simultaneous integrated boost (SIB)-SBRT plans (Boost1, Boost2, and Boost3) were retrospectively generated for each of 20 different patients. Boost1 delivered 33 and 25 Gy to PTV1 and PTV2, respectively. Boost2 delivered 40, 33, and 25 Gy to boostCTV, PTV1, and PTV2, respectively. Boost3 delivered 33 and 25 Gy to PTV1 and PTV3, respectively. PTV1 covered the initial standard SBRT plan (InitPlan) gross tumor volume (GTV). PTV2 covered CTVgeom which was created by a 10-mm expansion (15 mm posterior) of GTV. PTV3 covered CTVprop which included elective nodal regions. The boostCTV included GTV as well as involved vasculature. The planning feasibility in each scenario and dose-volume histograms (DVHs) were analyzed and compared with the InitPlan (delivered 33 Gy only to PTV1) by paired t-test. Next, a novel DVH prediction model was developed and its performance was evaluated according to the prediction accuracy (AC) of planning violations. Then, the model was used to simulate the impacts of GTV-to-organs at risk (OAR) distance and gastrointestinal (GI) OAR volume variations on planning feasibility.ResultsSignificant dose increases were observed in GI-OARs in SIB-SBRT plans when compared with InitPlan. All dose constraints were met in 63% of cases in InitPlan, Boost1, and Boost2, whereas Boost3 developed DVH violations in all cases. Utilizing previous patient anatomy, the novel DVH prediction model achieved a high AC in the prediction of violations for GI-OARs; the positive predictive value, negative predictive value, and AC were 66%, 90%, and 84%, respectively. Experiments with the model demonstrated that the larger proximity volume of GI-OAR at the shorter distance substantially impacted on planning violations.ConclusionsSIB-SBRT plan with geometrically defined prophylactic areas can be dosimetrically feasible, but including all nodal areas with 25 Gy in five fractions appears to be unrealistic.

Project description:BackgroundNeoadjuvant radio(chemo)therapy of non-metastasized, borderline resectable or unresectable locally advanced pancreatic cancer is complex and prone to cause side-effects, e.g., in gastrointestinal organs. Intensity-modulated proton therapy (IMPT) enables a high conformity to the targets while simultaneously sparing the normal tissue such that dose-escalation strategies come within reach. In this in silico feasibility study, we compared four IMPT planning strategies including robust multi-field optimization (rMFO) and a simultaneous integrated boost (SIB) for dose-escalation in pancreatic cancer patients.MethodsFor six pancreatic cancer patients referred for adjuvant or primary radiochemotherapy, four rMFO-IMPT-SIB treatment plans each, consisting of two or three (non-)coplanar beam arrangements, were optimized. Dose values for both targets, i.e., the elective clinical target volume [CTV, prescribed dose Dpres =?51Gy(RBE)] and the boost target [Dpres =?66Gy(RBE)], for the organs at risk as well as target conformity and homogeneity indexes, derived from the dose volume histograms, were statistically compared.ResultsAll treatment plans of each strategy fulfilled the prescribed doses to the targets (Dpres(GTV,CTV) =?100%, D95%,(GTV,CTV) ??95%, D2%,(GTV,CTV) ??107%). No significant differences for the conformity index were found (p >?0.05), however, treatment plans with a three non-coplanar beam strategy were most homogenous to both targets (p <?0.045). The median value of all dosimetric results of the large and small bowel as well as for the liver and the spinal cord met the dose constraints with all beam arrangements. Irrespective of the planning strategies, the dose constraint for the duodenum and stomach were not met. Using the three-beam arrangements, the dose to the left kidney could be significant decreased when compared to a two-beam strategy (p <?0.045).ConclusionBased on our findings we recommend a three-beam configuration with at least one non-coplanar beam for dose-escalated SIB with rMFO-IMPT in advanced pancreatic cancer patients achieving a homogeneous dose distribution in the target while simultaneously minimizing the dose to the organs at risk. Further treatment planning studies on aspects of breathing and organ motion need to be performed.

Project description:ImportanceEffective treatment options for locally advanced esophageal cancer are limited, and rates of local recurrence after standard chemoradiotherapy remain high.ObjectiveTo evaluate toxic effects, local control, and overall survival rates after chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose to the gross tumor and nodal disease for patients with unresectable locally advanced esophageal cancer.Design, setting, and participantsA phase 1/2, single-arm trial was conducted in 46 patients from April 28, 2010, to April 9, 2015 (median follow-up, 52 months [range, 2-86 months]), at a tertiary academic cancer center. Outcomes of the study patients were compared with those of 97 similar patients treated at the same institution from January 10, 2010, to December 5, 2014, as part of the interim analysis. Statistical analysis was performed from December 15, 2018, to February 12, 2019.InterventionsChemoradiotherapy with a simultaneous integrated boost of radiotherapy dose (50.4 Gy to subclinical areas at risk and 63.0 Gy to the gross tumor and involved nodes, all given in 28 fractions) with concurrent docetaxel and capecitabine or fluorouracil.Main outcomes and measuresToxic effects, local (in-field) control, and overall survival rates.ResultsAll 46 patients (11 women and 35 men; median age, 65.5 years [range, 37.3-84.4 years]) received per-protocol therapy, as intensity-modulated photon therapy (39 [85%]) or intensity-modulated proton therapy (7 [15%]); 11 patients (24%) ultimately underwent resection. No patients experienced grade 4 or 5 toxic effects; the 10 acute grade 3 toxic events were esophagitis (4), dysphagia (3), and anorexia (3) and the 3 late grade 3 toxic events were all esophageal strictures. The actuarial local recurrence rates were 22% (95% CI, 11%-35%) at 6 months, 30% (95% CI, 18%-44%) at 1 year, and 33% (95% CI, 20%-46%) at 2 years. Overall, 15 patients (33%) experienced local failure, at a median interval of 5 months (range, 1-24 months). The median overall survival time was 21.5 months (range, 2.3-86.4 months). Exploratory comparison with a 97-patient contemporaneous institutional cohort receiving standard-dose (non-simultaneous integrated boost) chemoradiotherapy showed superior local control (hazard ratio, 0.49; 95% CI, 0.26-0.92; P = .03) and overall survival (hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .02) in the group that received chemoradiotherapy with a simultaneous integrated boost.Conclusions and relevanceThese findings suggest that chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose for locally advanced esophageal cancer is well tolerated, with encouraging local control, and thus warrants further study.Trial registrationClinicalTrials.gov identifier: NCT01102088.

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Efficacy and feasibility of proton beam radiotherapy using the simultaneous integrated boost technique for locally advanced pancreatic cancer.

Publications

Efficacy and feasibility of proton beam radiotherapy using the simultaneous integrated boost technique for locally advanced pancreatic cancer.

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