br Corresponding author at Department of Radiation Oncology Unit
⇑ Corresponding author at: Department of Radiation Oncology, Unit 1422, The University of Texas MD Anderson Cancer Center, 1220 Holcombe Blvd, Houston, TX 77030-4004, USA.
E-mail address: [email protected] (Q.-N. Nguyen).
volume layer by layer [3,4]. IMPT allows tight control and confor-mality of dose distributions and has dosimetric advantages over both passively scattered Necrostatin-1 therapy (PSPT) and intensity-modulated photon radiation therapy (IMRT) [5,6].
Despite the dosimetric advantages of IMPT, skepticism has been expressed regarding the accuracy of dose modeling in the thorax arising from uncertainties in the relative biological effectiveness (RBE) of protons at the distal edge of the beam, the heterogeneity of tissues in the beam trajectory, and interplay between motion of the scanning beam and lung aeration and diaphragmatic move-ment . Despite these uncertainties, treatment of locally advanced NSCLC with IMPT is becoming more widely adopted as the numbers of proton therapy centers continue to grow world-wide . Given the limited number of proton centers with com-missioned IMPT for the treatment of lung malignancies, however, there exists a shortage of clinical outcomes on patients with NSCLC treated with IMPT.
Herein we report disease control, survival, and treatment-related toxicity after IMPT with concurrent chemotherapy for locally advanced inoperable NSCLC at a single institution.
Materials and methods
Patients with newly diagnosed or recurrent stage II or III NSCLC who received definitive chemotherapy with IMPT at a single insti-tution from 2012 through 2016 were followed. Patients with recur-rent disease were included only if the primary treatment was surgery. Patients with prior thoracic radiation were excluded. A total of 51 patients were included, of whom 3 had recurrent dis-ease after surgical resection. All patients were enrolled on a reg-istry protocol designed to assess normal tissue effects of proton therapy (clinicaltrials.gov NCT00991094).
Disease was staged according to the 7th (2010) edition of the American Joint Commission on Cancer staging system and con-firmed histopathologically in all cases. All patients were evaluated with thoracic computed tomography (CT) and positron emission tomography (PET)/CT, bronchoscopy with endobronchial ultra-sonography, or mediastinoscopy for mediastinal node staging. Inoperability for medical reasons or for unresectability was evalu-ated and confirmed by thoracic surgeons. All patients received con-current chemotherapy, most often with carboplatin and paclitaxel, as weekly intravenous infusions during proton therapy. The type of chemotherapy, timing, and dose was at the discretion of the treat-ing physician. In the event of toxicity, chemotherapy was withheld, also at the discretion of the treating physician. Toxicity related to treatment was assessed according to the Common Terminology Criteria for Adverse Effects version 4.0.
Proton therapy treatment planning and delivery
All patients underwent 4D CT-based treatment simulation to account for respiratory motion. Patients were immobilized while supine in an upper body cradle with arms overhead. All patients were treated with image-guided IMPT. Tumors were contoured over all phases of the respiratory cycle to form the internal gross tumor volume (iGTV). A 7- to 8-mm expansion of the iGTV was used to create the clinical target volume (CTV), and an additional 5-mm expansion of the CTV was used to create the planning target volume (PTV). For patients treated with a simultaneous integrated boost (SIB), an SIB volume (SIBV) was defined as the iGTV + 5 mm and was treated to a higher dose. Orthogonal kilovoltage image guidance was used for daily set-up.