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A Dosimetric Comparison of Dose Escalation with Simultaneous Integrated Boost for Locally Advanced Non-Small-Cell Lung Cancer.

ABSTRACT: Many studies have demonstrated that a higher radiotherapy dose is associated with improved outcomes in non-small-cell lung cancer (NSCLC). We performed a dosimetric planning study to assess the dosimetric feasibility of intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) in locally advanced NSCLC.We enrolled twenty patients. Five different dose plans were generated for each patient. All plans were prescribed a dose of 60?Gy to the planning tumor volume (PTV). In the three SIB groups, the prescribed dose was 69?Gy, 75?Gy, and 81?Gy in 30 fractions to the internal gross tumor volume (iGTV).The SIB-IMRT plans were associated with a significant increase in the iGTV dose (P < 0.05), without increased normal tissue exposure or prolonged overall treatment time. Significant differences were not observed in the dose to the normal lung in terms of the V5 and V20 among the four IMRT plans. The maximum dose (Dmax) in the esophagus moderately increased along with the prescribed dose (P < 0.05).Our results indicated that escalating the dose by SIB-IMRT is dosimetrically feasible; however, systematic evaluations via clinical trials are still warranted. We have designed a further clinical study (which is registered with ClinicalTrials.gov, number NCT02841228).

SUBMITTER: Yang W

PROVIDER: S-EPMC5467291 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A Dosimetric Comparison of Dose Escalation with Simultaneous Integrated Boost for Locally Advanced Non-Small-Cell Lung Cancer.

Yang Wenjuan W Zeng Biao B Qiu Yanfang Y Tan Jianfeng J Xu Shilei S Cai Yilong Y Zhou Yujuan Y Liu Zhigang Z Luo Junming J Wang Hui H

BioMed research international 20170528

<h4>Background</h4>Many studies have demonstrated that a higher radiotherapy dose is associated with improved outcomes in non-small-cell lung cancer (NSCLC). We performed a dosimetric planning study to assess the dosimetric feasibility of intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) in locally advanced NSCLC.<h4>Methods</h4>We enrolled twenty patients. Five different dose plans were generated for each patient. All plans were prescribed a dose of 60 Gy t ...[more]

PMID: 28630876

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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.

Project description:ObjectiveThis study aimed to evaluate the efficacy and safety of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) versus standard-dose intensity-modulated radiotherapy (SD-IMRT) in the treatment of locally advanced esophageal squamous cell carcinoma.MethodsFrom July 2003 to March 2014, 1748 patients in a single center who received definitive chemoradiotherapy were included in the analysis. A total of 109 patients who underwent SIB-IMRT and fulfilled all inclusion and exclusion criteria were identified as the study group. A total of 266 patients who underwent SD-IMRT (60 Gy/30 fractions, 2 Gy/fraction, 1 time/day, 5 times/week) during the same period were selected as the control group. Propensity score matching (PSM) was used to balance the baseline characteristics. Survival status, treatment failure mode, and the occurrence of adverse events were compared between the two groups.ResultsThere were more women and more cervical and upper thoracic cancers (P = 0.038, < 0.001, respectively) in the SIB-IMRT group before case matching. The median progression-free survival (PFS) in the SD-IMRT and SIB-IMRT groups was 22 and 19 months, respectively, and the median overall survival duration was 24 and 22 months, respectively, with χ2 = 0.244 and P = 0.621. After PSM of 1:1, 138 patients entered the final analysis (69 cases from each group). The median PFS of the SD-IMRT group and the SIB-IMRT group was 13 and 18 months, respectively, with χ2 = 8.776 and P = 0.003. The 1‑, 3‑, and 5‑year overall survival rates were 66.7, 21.7, and 8.7% and 65.2, 36.2, and 27.3%, respectively, and the median overall survival duration was 16 and 22 months, respectively, with χ2 = 5.362 and P = 0.021. Treatment failure mode: 5‑year local regional recurrence rates of SD-IMRT and SIB-IMRT were 50.7 and 36.2%, respectively, with χ2 = 2.949 and P = 0.086. The 5‑year distant metastasis rates of the two groups were 36.2 and 24.6%, respectively, with χ2 = 2.190 and P = 0.139.Adverse events3 patients experienced grade 4-5 toxicity (2.2%), including one case of grade 4 radiation esophagitis and two cases of grade 5 radiation pneumonitis, all in the SD-IMRT group; 14 patients experienced grade 3 adverse events (10.1%), primarily including radiation esophagitis, radiation pneumonitis, and hematological toxicity.ConclusionThe technique of SIB-IMRT was safe and reliable compared with SD-IMRT. In addition, SIB-IMRT had locoregional control advantages and potential survival benefits.

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:BACKGROUND:Treatment for locally advanced rectal cancer (LARC) consists of chemoradiation therapy (CRT) and surgery. Approximately 15% of patients show a pathological complete response (pCR). Increased pCR-rates can be achieved through dose escalation, thereby increasing the number patients eligible for organ-preservation to improve quality of life (QoL). A randomized comparison of 65 versus 50Gy with external-beam radiation alone has not yet been performed. This trial investigates pCR rate, clinical response, toxicity, QoL and (disease-free) survival in LARC patients treated with 65Gy (boost + chemoradiation) compared with 50Gy standard chemoradiation (sCRT). METHODS/DESIGN:This study follows the 'cohort multiple randomized controlled trial' (cmRCT) design: rectal cancer patients are included in a prospective cohort that registers clinical baseline, follow-up, survival and QoL data. At enrollment, patients are asked consent to offer them experimental interventions in the future. Eligible patients-histologically confirmed LARC (T3NxM0 <1 mm from mesorectal fascia, T4NxM0 or TxN2M0) located ?10 cm from the anorectal transition who provided consent for experimental intervention offers-form a subcohort (n = 120). From this subcohort, a random sample is offered the boost prior to sCRT (n = 60), which they may accept or refuse. Informed consent is signed only after acceptance of the boost. Non-selected patients in the subcohort (n = 60) undergo sCRT alone and are not notified that they participate in the control arm until the trial is completed. sCRT consists of 50Gy (25 × 2Gy) with concomitant capecitabine. The boost (without chemotherapy) is given prior to sCRT and consists of 15 Gy (5 × 3Gy) delivered to the gross tumor volume (GTV). The primary endpoint is pCR (TRG 1). Secondary endpoints include acute grade 3-4 toxicity, good pathologic response (TRG 1-2), clinical response, surgical complications, QoL and (disease-free) survival. Data is analyzed by intention to treat. DISCUSSION:The boost is delivered prior to sCRT so that GTV adjustment for tumor shrinkage during sCRT is not necessary. Small margins also aim to limit irradiation of healthy tissue. The cmRCT design provides opportunity to overcome common shortcomings of classic RCTs, such as slow recruitment, disappointment-bias in control arm patients and poor generalizability. TRIAL REGISTRATION:The Netherlands Trials Register NL46051.041.13. Registered 22 August 2013. ClinicalTrials.gov NCT01951521 . Registered 18 September 2013.

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A Dosimetric Comparison of Dose Escalation with Simultaneous Integrated Boost for Locally Advanced Non-Small-Cell Lung Cancer.

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A Dosimetric Comparison of Dose Escalation with Simultaneous Integrated Boost for Locally Advanced Non-Small-Cell Lung Cancer.

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