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PurposePatients with centrally located early-stage non-small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC.Materials and methodsMedically inoperable patients with biopsy-proven, positron emission tomography-staged T1 to 2 (≤ 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it.ResultsOne hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively.ConclusionThe MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.

PurposeTo present long-term results of RTOG 0915/NCCTG N0927, a randomized lung stereotactic body radiation therapy trial of 34 Gy in 1 fraction versus 48 Gy in 4 fractions.Methods and materialsThis was a phase 2 multicenter study of patients with medically inoperable non-small cell lung cancer with biopsy-proven peripheral T1 or T2 N0M0 tumors, with 1-year toxicity rates as the primary endpoint and selected failure and survival outcomes as secondary endpoints. The study opened in September 2009 and closed in March 2011. Final data were analyzed through May 17, 2018.ResultsEighty-four of 94 patients accrued were eligible for analysis: 39 in arm 1 and 45 in arm 2. Median follow-up time was 4.0 years for all patients and 6.0 years for those alive at analysis. Rates of grade 3 and higher toxicity were 2.6% in arm 1 and 11.1% in arm 2. Median survival times (in years) for 34 Gy and 48 Gy were 4.1 versus 4.6, respectively. Five-year outcomes (95% confidence interval) for 34 Gy and 48 Gy were a primary tumor failure rate of 10.6% (3.3%-23.1%) versus 6.8% (1.7%-16.9%); overall survival of 29.6% (16.2%-44.4%) versus 41.1% (26.6%-55.1%); and progression-free survival of 19.1% (8.5%-33.0%) versus 33.3% (20.2%-47.0%). Distant failure as the sole failure or a component of first failure occurred in 6 patients (37.5%) in the 34 Gy arm and in 7 (41.2%) in the 48 Gy arm.ConclusionsNo excess in late-appearing toxicity was seen in either arm. Primary tumor control rates at 5 years were similar by arm. A median survival time of 4 years for each arm suggests similar efficacy, pending any larger studies appropriately powered to detect survival differences.

IntroductionNRG Oncology RTOG 0937 is a randomized phase II trial evaluating 1-year overall survival (OS) with prophylactic cranial irradiation (PCI) or PCI plus consolidative radiation therapy (PCI+cRT) to intrathoracic disease and extracranial metastases for extensive-disease SCLC.MethodsPatients with one to four extracranial metastases were eligible after a complete response or partial response to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included partial response versus complete response after chemotherapy and one versus two to four metastases; age younger than 65 years versus 65 years or older was added after an observed imbalance. PCI consisted of 25 Gy in 10 fractions. cRT consisted of 45 Gy in 15 fractions. To detect an improvement in OS from 30% to 45% with a 34% hazard reduction (hazard ratio = 0.66) under a 0.1 type 1 error (one sided) and 80% power, 154 patients were required.ResultsA total of 97 patients were randomized between March 2010 and February 2015. Eleven patients were ineligible (nine in the PCI group and two in the PCI+cRT group), leaving 42 randomized to receive PCI and 44 to receive PCI+cRT. At planned interim analysis, the study crossed the futility boundary for OS and was closed before meeting the accrual target. Median follow-up was 9 months. The 1-year OS was not different between the groups: 60.1% (95% confidence interval [CI]: 41.2-74.7) for PCI and 50.8% (95% CI: 34.0-65.3) for PCI+cRT (p = 0.21). The 3- and 12-month rates of progression were 53.3% and 79.6% for PCI and 14.5% and 75% for PCI+cRT, respectively. Time to progression favored PCI+cRT (hazard ratio = 0.53, 95% CI: 0.32-0.87, p = 0.01). One patient in each arm had grade 4 therapy-related toxicity and one had grade 5 therapy-related pneumonitis with PCI+cRT.ConclusionsOS exceeded predictions for both arms. cRT delayed progression but did not improve 1-year OS.

Treating multiple lung lesions synchronously via single‐isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) improves treatment efficiency and patient compliance. However, aligning multiple lung tumors accurately on single pretreatment cone beam CTs (CBCTs) can be problematic. Tumors misaligned could lead to target coverage loss. To quantify this potential target coverage loss due to small, clinically realistic setup errors, a novel simulation method was developed. This method was used on 26 previously treated patients with two metastatic lung lesions. Patients were treated with 4D CT‐based, highly conformal noncoplanar VMAT plans (clinical VMAT) with 6MV‐flattening filter free (FFF) beam using AcurosXB dose calculation algorithm with heterogeneity corrections. A single isocenter was placed approximately between the lesions to improve patient convenience and clinic workflow. Average isocenter to tumor distance was 5.9 cm. Prescription dose was 54 Gy/50 Gy in 3/5 fractions. For comparison, a plan summation (simulated VMAT) was executed utilizing randomly simulated, clinically relevant setup errors, obtained from pretreatment setup, per treatment fraction, in Eclipse treatment planning system for each of the six degrees of freedom within ± 5.0 mm and ± 2°. Simulations yielded average deviations of 27.4% (up to 72% loss) (P < 0.001) from planned target coverage when treating multiple lung lesions using a single‐isocenter plan. The largest deviations from planned coverage and desired biological effective dose (BED10, with α/β = 10 Gy) were seen for the smallest targets (<10 cc), some of which received < 100 Gy BED10. Patient misalignment resulted in substantial decrease in conformity and increase in the gradient index, violating major characteristics of SBRT. Statistically insignificant differences were seen for normal tissue dose. Although, clinical follow‐up of these patients is ongoing, the authors recommend an alternative treatment planning strategy to minimize the probability of a geometric miss when treating small lung lesions synchronously with single‐isocenter VMAT SBRT plans. [ABSTRACT FROM AUTHOR]

Purpose: To develop a robust and adaptable knowledge‐based planning (KBP) model with commercially available RapidPlanTM for early stage, centrally located non‐small‐cell lung tumors (NSCLC) treated with stereotactic body radiotherapy (SBRT) and improve a patient's"simulation to treatment" time. Methods: The KBP model was trained using 86 clinically treated high‐quality non‐coplanar volumetric modulated arc therapy (n‐VMAT) lung SBRT plans with delivered prescriptions of 50 or 55 Gy in 5 fractions. Another 20 independent clinical n‐VMAT plans were used for validation of the model. KBP and n‐VMAT plans were compared via Radiation Therapy Oncology Group (RTOG)–0813 protocol compliance criteria for conformity (CI), gradient index (GI), maximal dose 2 cm away from the target in any direction (D2cm), dose to organs‐at‐risk (OAR), treatment delivery efficiency, and accuracy. KBP plans were re‐optimized with larger calculation grid size (CGS) of 2.5 mm to assess feasibility of rapid adaptive re‐planning. Results: Knowledge‐based plans were similar or better than n‐VMAT plans based on a range of target coverage and OAR metrics. Planning target volume (PTV) for validation cases was 30.5 ± 19.1 cc (range 7.0–71.7 cc). KBPs provided an average CI of 1.04 ± 0.04 (0.97–1.11) vs. n‐VMAT plan'saverage CI of 1.01 ± 0.04 (0.97–1.17) (P < 0.05) with slightly improved GI with KBPs (P < 0.05). D2cm was similar between the KBPs and n‐VMAT plans. KBPs provided lower lung V10Gy (P = 0.003), V20Gy (P = 0.007), and mean lung dose (P < 0.001). KBPs had overall better sparing of OAR at the minimal increased of average total monitor units and beam‐on time by 460 (P < 0.05) and 19.2 s, respectively. Quality assurance phantom measurement showed similar treatment delivery accuracy. Utilizing a CGS of 2.5 mm in the final optimization improved planning time (mean, 5 min) with minimal or no cost to the plan quality. Conclusion: The RTOG‐compliant adaptable RapidPlan model for early stage SBRT treatment of centrally located lung tumors was developed. All plans met RTOG dosimetric requirements in less than 30 min of planning time, potentially offering shorter "simulation to treatment" times. OAR sparing via KBPs may permit tumorcidal dose escalation with minimal penalties. Same day adaptive re‐planning is plausible with a 2.5‐mm CGS optimizer setting. [ABSTRACT FROM AUTHOR]

Purpose: To develop a knowledge‐based planning (KBP) routine for stereotactic body radiotherapy (SBRT) of peripherally located early‐stage non‐small‐cell lung cancer (NSCLC) tumors via dynamic conformal arc (DCA)‐based volumetric modulated arc therapy (VMAT) using the commercially available RapidPlanTM software. This proposed technique potentially improves plan quality, reduces complexity, and minimizes interplay effect and small‐field dosimetry errors associated with treatment delivery. Methods: KBP model was developed and validated using 70 clinically treated high quality non‐coplanar VMAT lung SBRT plans for training and 20 independent plans for validation. All patients were treated with 54 Gy in three treatments. Additionally, a novel k‐DCA planning routine was deployed to create plans incorporating historical three‐dimensional‐conformal SBRT planning practices via DCA‐based approach prior to VMAT optimization in an automated planning engine. Conventional KBPs and k‐DCA plans were compared with clinically treated plans per RTOG‐0618 requirements for target conformity, tumor dose heterogeneity, intermediate dose fall‐off and organs‐at‐risk (OAR) sparing. Treatment planning time, treatment delivery efficiency, and accuracy were recorded. Results: KBPs and k‐DCA plans were similar or better than clinical plans. Average planning target volume for validation was 22.4 ± 14.1 cc (7.1–62.3 cc). KBPs and k‐DCA plans provided similar conformity to clinical plans with average absolute differences of 0.01 and 0.01, respectively. Maximal doses to OAR were lowered in both KBPs and k‐DCA plans. KBPs increased monitor units (MU) on average 1316 (P < 0.001) while k‐DCA reduced total MU on average by 1114 (P < 0.001). This routine can create k‐DCA plan in less than 30 min. Independent Monte Carlo calculation demonstrated that k‐DCA plans showed better agreement with planned dose distribution. Conclusion: A k‐DCA planning routine was developed in concurrence with a knowledge‐based approach for the treatment of peripherally located lung tumors. This method minimizes plan complexity associated with model‐based KBP techniques and improve plan quality and treatment planning efficiency. [ABSTRACT FROM AUTHOR]