Phase 1 dose escalation study of SBRT using 3 fractions for locally advanced pancreatic cancer Journal Article
| Authors: | Reyngold, M.; Karam, S. D.; Hajj, C.; Wu, A. J.; Cuaron, J.; Lobaugh, S.; Yorke, E. D.; Dickinson, S.; Jones, B.; Vinogradskiy, Y.; Shukla-Dave, A.; Do, R. K. G.; Sigel, C.; Zhang, Z.; Crane, C. H.; Goodman, K. A. |
| Article Title: | Phase 1 dose escalation study of SBRT using 3 fractions for locally advanced pancreatic cancer |
| Abstract: | Purpose: The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC. Methods and Materials: Two parallel phase 1 dose escalation trials were conducted from 2016 to 2019 at Memorial Sloan Kettering Cancer Center and University of Colorado. Patients with histologically confirmed LAPC without distant progression after at least 2 months of induction chemotherapy were eligible. Patients received 3-fraction linear accelerator–based SBRT at 3 dose levels, 27, 30, and 33 Gy, following a modified 3+3 design. Dose-limiting toxicity, defined as grade ≥3 gastrointestinal toxicity within 90 days, was scored by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The secondary endpoints included cumulative incidence of local failure (LF) and distant metastasis (DM), as well as progression-free and overall survival PFS and OS, respectively, toxicity, and quality of life (QoL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ‐C30) and the pancreatic cancer–specific QLQ‐PAN26 questionnaire. Results: Twenty-four consecutive patients were enrolled (27 Gy: 9, 30 Gy: 8, 33 Gy: 7). The median (range) age was 67 (52-79) years, and 12 (50%) had a head/uncinate tumor location, with a median tumor size of 3.8 (1.1-11) cm and CA19-9 of 60 (1-4880) U/mL. All received chemotherapy for a median of 4 (1.4-10) months. There were no grade ≥3 toxicities. Two-year rates (95% confidence interval) of LF, DM, PFS, and OS were 31.7% (8.6%-54.8%), 70.2% (49.7%-90.8%), 20.8% (4.6%-37.1%), and 29.2% (11.0%-47.4%), respectively. Three- and 6-month QoL assessment showed no detriment. Conclusions: For select patients with LAPC, dose escalation to 33 Gy in 3 fractions resulted in no dose-limiting toxicities, no detriments to QoL, and disease outcomes comparable with conventional RT. Further exploration of SBRT schemes to maximize tumor control while enabling efficient integration with systemic therapy is warranted. © 2023 |
| Keywords: | adult; cancer survival; clinical article; aged; cancer surgery; survival rate; overall survival; clinical trial; fatigue; histopathology; intensity modulated radiation therapy; fluorouracil; advanced cancer; cancer combination chemotherapy; diarrhea; cancer patient; cancer radiotherapy; pancreatic neoplasms; chemotherapy; pancreaticoduodenectomy; pancreas; progression free survival; quality of life; pain; tumor volume; esophagitis; nausea; vomiting; radiotherapy dosage; radiotherapy; ca 19-9 antigen; cohort analysis; distant metastasis; irinotecan; cancer center; tumors; folinic acid; pancreas tumor; radiosurgery; pancreas adenocarcinoma; pancreatectomy; pleura effusion; maximum tolerated dose; phase 1 clinical trial; neoplasms, second primary; toxicity; oxaliplatin; radiation safety; stereotactic body radiation therapy; flatulence; diseases; national health organization; induction chemotherapy; phase 1; parallel design; volumetric modulated arc therapy; cumulative incidence; dose limiting toxicity; decreased appetite; bloating; local failure; dose-escalation study; dose escalation; gastrointestinal toxicities; body weight loss; colorado; Common Terminology Criteria for Adverse Events; radiation dose escalation; humans; human; male; female; article; locally advanced pancreatic cancers; lower gastrointestinal bleeding; european organization for research and treatment of cancer quality of life questionnaire core 30; second primary neoplasm; gemcitabine plus paclitaxel |
| Journal Title: | International Journal of Radiation Oncology, Biology, Physics |
| Volume: | 117 |
| Issue: | 1 |
| ISSN: | 0360-3016 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2023-09-01 |
| Start Page: | 53 |
| End Page: | 63 |
| Language: | English |
| DOI: | 10.1016/j.ijrobp.2023.03.036 |
| PUBMED: | 36918130 |
| PROVIDER: | scopus |
| PMCID: | PMC11229378 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PubMed and PDF -- Corresponding author is MSK author: Marsha Reyngold -- Source: Scopus |
