ABSTRACT
Purpose: Non-small cell lung cancer (NSCLC) is a deadly malignancy that is frequently diagnosed in patients with significant medical comorbidities. When delivering local and regional therapy, an exceedingly narrow therapeutic window is encountered, which often precludes patients from receiving aggressive curative therapy. Radiation therapy advances including particle therapy have been employed in an effort to expand this therapeutic window. Here we report outcomes with the use of proton therapy with curative intent and immunotherapy to treat patients diagnosed with high-risk NSCLC. Methods and Materials: Patients were determined to be high risk if they had severe underlying cardiopulmonary dysfunction, history of prior thoracic radiation therapy, and/or large volume or unfavorable location of disease (eg, bilateral hilar involvement, supraclavicular involvement). As such, patients were determined to be ineligible for conventional x-ray-based radiation therapy and were treated with pencil beam scanning proton beam therapy (PBS-PBT). Patients who demonstrated excess respiratory motion (ie, greater than 1 cm in any dimension noted on the 4-dimensional computed tomography simulation scan) were deemed to be ineligible for PBT. Toxicity was reported using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Overall survival and progression-free survival were calculated using the Kaplan-Meier method. Results: A total of 29 patients with high-risk NSCLC diagnoses were treated with PBS-PBT. The majority (55%) of patients were defined as high risk due to severe cardiopulmonary dysfunction. Most commonly, patients were treated definitively to a total dose of 6000 cGy (relative biological effectiveness) in 30 fractions with concurrent chemotherapy. Overall, there were a total of 6 acute grade 3 toxicities observed in our cohort. Acute high-grade toxicities included esophagitis (n = 4, 14%), dyspnea (n = 1, 3.5%), and cough (n = 1, 3.5%). No patients developed grade 4 or higher toxicity. The majority of patients went on to receive immunotherapy, and high-grade pneumonitis was rare. Two-year progression-free and overall survival was estimated to be 51% and 67%, respectively. COVID-19 was confirmed or suspected to be responsible for 2 patient deaths during the follow-up period. Conclusions: Radical PBS-PBT treatment delivered in a cohort of patients with high-risk lung cancer with immunotherapy is feasible with careful multidisciplinary evaluation and rigorous follow-up.
ABSTRACT
The purpose of this study was to perform comprehensive measurements and testing of a Novalis Tx linear accelerator, and to develop technical guidelines for com-missioning from the time of acceptance testing to the first clinical treatment. The Novalis Tx (NTX) linear accelerator is equipped with, among other features, a high-definition MLC (HD120 MLC) with 2.5 mm central leaves, a 6D robotic couch, an optical guidance positioning system, as well as X-ray-based image guidance tools to provide high accuracy radiation delivery for stereotactic radiosurgery and stereotactic body radiation therapy procedures. We have performed extensive tests for each of the components, and analyzed the clinical data collected in our clinic. We present technical guidelines in this report focusing on methods for: (1) efficient and accurate beam data collection for commissioning treatment planning systems, including small field output measurements conducted using a wide range of detectors; (2) commissioning tests for the HD120 MLC; (3) data collection for the baseline characteristics of the on-board imager (OBI) and ExacTrac X-ray (ETX) image guidance systems in conjunction with the 6D robotic couch; and (4) end-to-end testing of the entire clinical process. Established from our clinical experience thus far, recommendations are provided for accurate and efficient use of the OBI and ETX localization systems for intra- and extracranial treatment sites. Four results are presented. (1) Basic beam data measurements: Our measurements confirmed the necessity of using small detectors for small fields. Total scatter factors varied significantly (30% to approximately 62%) for small field measurements among detectors. Unshielded stereotactic field diode (SFD) overestimated dose by ~ 2% for large field sizes. Ion chambers with active diameters of 6 mm suffered from significant volume averaging. The sharpest profile penumbra was observed for the SFD because of its small active diameter (0.6 mm). (2) MLC commissioning: Winston Lutz test, light/radiation field congruence, and Picket Fence tests were performed and were within criteria established by the relevant task group reports. The measured mean MLC transmission and dynamic leaf gap of 6 MV SRS beam were 1.17% and 0.36 mm, respectively. (3) Baseline characteristics of OBI and ETX: The isocenter localization errors in the left/right, posterior/anterior, and superior/inferior directions were, respectively, -0.2 ± 0.2 mm, -0.8 ± 0.2 mm, and -0.8 ± 0.4 mm for ETX, and 0.5 ± 0.7 mm, 0.6 ± 0.5 mm, and 0.0 ± 0.5 mm for OBI cone-beam computed tomography. The registration angular discrepancy was 0.1 ± 0.2°, and the maximum robotic couch error was 0.2°. (4) End-to-end tests: The measured isocenter dose differences from the planned values were 0.8% and 0.4%, measured respectively by an ion chamber and film. The gamma pass rate, measured by EBT2 film, was 95% (3% DD and 1 mm DTA). Through a systematic series of quantitative commissioning experiments and end-to-end tests and our initial clinical experience, described in this report, we demonstrate that the NTX is a robust system, with the image guidance and MLC requirements to treat a wide variety of sites - in particular for highly accurate delivery of SRS and SBRT-based treatments.
