Stereotactic body radiation therapy for stage IIA to IIIA inoperable non-small cell lung cancer: A phase 1 dose-escalation trial Journal Article
| Authors: | Rimner, A.; Gelblum, D. Y.; Wu, A. J.; Shepherd, A. F.; Mueller, B.; Zhang, S.; Cuaron, J.; Shaverdian, N.; Flynn, J.; Fiasconaro, M.; Zhang, Z.; von Reibnitz, D.; Li, H.; McKnight, D.; McCune, M.; Gelb, E.; Gomez, D. R.; Simone, C. B. 2nd; Deasy, J. O.; Yorke, E. D.; Ng, K. K.; Chaft, J. E. |
| Article Title: | Stereotactic body radiation therapy for stage IIA to IIIA inoperable non-small cell lung cancer: A phase 1 dose-escalation trial |
| Abstract: | Purpose: Larger tumors are underrepresented in most prospective trials on stereotactic body radiation therapy (SBRT) for inoperable non-small cell lung cancer (NSCLC). We performed this phase 1 trial to specifically study the maximum tolerated dose (MTD) of SBRT for NSCLC >3 cm. Methods and Materials: A 3 + 3 dose-escalation design (cohort A) with an expansion cohort at the MTD (cohort B) was used. Patients with inoperable NSCLC >3 cm (T2-4) were eligible. Select ipsilateral hilar and single-station mediastinal nodes were permitted. The initial SBRT dose was 40 Gy in 5 fractions, with planned escalation to 50 and 60 Gy in 5 fractions. Adjuvant chemotherapy was mandatory for cohort A and optional for cohort B, but no patients in cohort B received chemotherapy. The primary endpoint was SBRT-related acute grade (G) 4+ or persistent G3 toxicities (Common Terminology Criteria for Adverse Events version 4.03). Secondary endpoints included local failure (LF), distant metastases, disease progression, and overall survival. Results: The median age was 80 years; tumor size was >3 cm and ≤5 cm in 20 (59%) and >5 cm in 14 patients (41%). In cohort A (n = 9), 3 patients treated to 50 Gy experienced G3 radiation pneumonitis (RP), thus defining the MTD. In the larger dose-expansion cohort B (n = 25), no radiation therapy–related G4+ toxicities and no G3 RP occurred; only 2 patients experienced G2 RP. The 2-year cumulative incidence of LF was 20.2%, distant failure was 34.7%, and disease progression was 54.4%. Two-year overall survival was 53%. A biologically effective dose (BED) <100 Gy was associated with higher LF (P = .006); advanced stage and higher neutrophil/lymphocyte ratio were associated with greater disease progression (both P = .004). Conclusions: Fifty Gy in 5 fractions is the MTD for SBRT to tumors >3 cm. A higher BED is associated with fewer LFs even in larger tumors. Cohort B appears to have had less toxicity, possibly due to the omission of chemotherapy. © 2023 Elsevier Inc. |
| Keywords: | cancer chemotherapy; clinical article; aged; aged, 80 and over; middle aged; primary tumor; overall survival; clinical trial; fatigue; mortality; cancer growth; chemotherapy; cancer staging; nuclear magnetic resonance imaging; follow up; neoplasm staging; prospective study; lung toxicity; esophagitis; carcinoma, non-small-cell lung; lung neoplasms; radiotherapy dosage; dehydration; radiotherapy; cohort analysis; patient monitoring; pathology; distant metastasis; high risk patient; coughing; dyspnea; lung tumor; thorax pain; karnofsky performance status; tumors; radiation dose fractionation; pneumothorax; disease progression; adjuvant chemotherapy; radiosurgery; fluorodeoxyglucose f 18; pleura effusion; inoperable cancer; maximum tolerated dose; phase 1 clinical trial; toxicity; acute toxicity; lung infection; stereotactic body radiation therapy; lung function test; lung fibrosis; disease exacerbation; biological organs; biologically effective dose; diseases; radiation dermatitis; radiation pneumonia; phase 1; pericarditis; blood examination; non small cell lung cancer; cumulative incidence; adverse event; local failure; radiation pneumonitis; lung emphysema; procedures; dose escalation; charlson comorbidity index; very elderly; four dimensional computed tomography; humans; human; male; female; article; neutrophil lymphocyte ratio; positron emission tomography-computed tomography; dose fractionation, radiation |
| Journal Title: | International Journal of Radiation Oncology, Biology, Physics |
| Volume: | 119 |
| Issue: | 3 |
| ISSN: | 0360-3016 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-07-01 |
| Start Page: | 869 |
| End Page: | 877 |
| Language: | English |
| DOI: | 10.1016/j.ijrobp.2023.12.018 |
| PUBMED: | 38154510 |
| PROVIDER: | scopus |
| PMCID: | PMC12094679 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus |
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