TY - JOUR
T1 - Phase I Study of Accelerated Hypofractionated Proton Therapy and Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer
AU - Contreras, Jessika
AU - Srivastava, Amar
AU - Samson, Pamela
AU - DeWees, Todd
AU - Govindan, Ramaswamy
AU - Baggstrom, Maria Q.
AU - Morgensztern, Daniel
AU - Roach, Michael
AU - Badiyan, Shahed N.
AU - Bradley, Jeffrey
AU - Waqar, Saiama
AU - Robinson, Clifford
N1 - Funding Information:
This study was funded in part by the Siteman Cancer Center Early Phase Clinical Research Support (EPCRS) program through the NCI Cancer Center Support grant #P30 CA91842.
Funding Information:
J.C. has consulting fees from Boston Scientific. R.G. has consulting fees from Bristol-Myers Squibb, Abbvie, and Geneplus, and participation on the DSMB or advisory board for Roche Genentech. M.Q.B. is on the ASCO digital education editorial board and the Lung Cancer Connection board of directors. D.M. has grants to the university from Arcus, Eli Lilly, Bristol-Myers Squibb, Merck, Epicentrix, Surface, Boehringer, Heat Biologics, Abbvie, and Novartis, and participation on the DSMB or advisory board for Bristol-Myers Squibb, Abbvie, Eli Lilly, G1 Therapeutics, PharmaMar, Gilead, and Takeda. S.N.B. has speaker's honoraria from MEVION. J.B. has a research grant from Varian and consulting fees from Varian, PrecisCa, and AstraZeneca. S.W. has a grant from SWOG-Clinical Trials Partnership, honoraria from ASCO, and participation on DSMB for the Hoosier Cancer Research Network. C.R. has grants to the university from Varian and Merck, consulting fees from Varian, EMD Serono, AstraZeneca, and Radialogica, and equity in Radialogica and QRS.
Funding Information:
J.C. has consulting fees from Boston Scientific. R.G. has consulting fees from Bristol-Myers Squibb, Abbvie, and Geneplus, and participation on the DSMB or advisory board for Roche Genentech. M.Q.B. is on the ASCO digital education editorial board and the Lung Cancer Connection board of directors. D.M. has grants to the university from Arcus, Eli Lilly, Bristol-Myers Squibb, Merck, Epicentrix, Surface, Boehringer, Heat Biologics, Abbvie, and Novartis, and participation on the DSMB or advisory board for Bristol-Myers Squibb, Abbvie, Eli Lilly, G1 Therapeutics, PharmaMar, Gilead, and Takeda. S.N.B. has speaker's honoraria from MEVION. J.B. has a research grant from Varian and consulting fees from Varian, PrecisCa, and AstraZeneca. S.W. has a grant from SWOG-Clinical Trials Partnership, honoraria from ASCO, and participation on DSMB for the Hoosier Cancer Research Network. C.R. has grants to the university from Varian and Merck, consulting fees from Varian, EMD Serono, AstraZeneca, and Radialogica, and equity in Radialogica and QRS. Research data are stored in an institutional repository and will be shared upon request to the corresponding author. We thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, Missouri, for the pilot funding for this study. This study was funded in part by the Siteman Cancer Center Early Phase Clinical Research Support (EPCRS) program through the NCI Cancer Center Support grant #P30 CA91842.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/7/15
Y1 - 2022/7/15
N2 - Purpose: Our purpose was to evaluate the maximum tolerated dose of hypofractionated proton beam radiation therapy with concurrent weekly carboplatin/paclitaxel in patients with stage II-III non-small cell lung cancer. Methods and Materials: A phase I trial was designed using the time-to-event continuous reassessment method. Maximum tolerated dose was defined as the dose associated with a 20% probability of Common Terminology Criteria for Adverse Events protocol-specified serious adverse events (SAEs). Starting dose was 3.5 Gy/fx for 15 fractions with 2 potential escalation and de-escalation levels in 0.25 Gy/fx increments. Chemotherapy was weekly concurrent carboplatin/paclitaxel with 2 cycles of optional consolidation carboplatin/paclitaxel. Results: From May 2015 to September 2016, 23 patients enrolled at a single institution. Of 20 evaluable, median age was 66.5 years (range, 54-89) and 12 were male (60%). Fourteen (70%) had squamous cell and 15 (75%) were stage IIIA. Nineteen (95%) completed all 3 cycles of concurrent chemotherapy, and 16 (80%) received at least 1 cycle of consolidation chemotherapy. Within the 6-month time-to-event continuous reassessment method assessment window, no SAEs were reported, and most patients were treated at the highest dose level. Dose level assignment was 52.5 Gy (n = 2), 56.25 Gy (n = 4), and 60 Gy (n = 14). The posterior probability of dose-limiting toxicity for 60 Gy was 5.3% (95% confidence interval, 1%-18.1%). Acute, nonserious AEs included grade 2 esophagitis in 7 patients (35%) and grade 2 pneumonitis in 1 patient (5%). At a median follow-up of 20.3 months for all and 44.9 months for living patients, there were no grade 4 or 5 AEs, though there were 3 (21% at 24 months) SAEs outside of the dose-escalation window. The 2-year overall survival, local, regional, and distant control rates were 48%, 84%, 77%, and 79%, respectively. Conclusions: Hypofractionated proton beam radiation therapy and chemotherapy up to 60 Gy in 15 fractions is acutely well tolerated, with high rates of locoregional control and overall survival, though late SAEs were noted.
AB - Purpose: Our purpose was to evaluate the maximum tolerated dose of hypofractionated proton beam radiation therapy with concurrent weekly carboplatin/paclitaxel in patients with stage II-III non-small cell lung cancer. Methods and Materials: A phase I trial was designed using the time-to-event continuous reassessment method. Maximum tolerated dose was defined as the dose associated with a 20% probability of Common Terminology Criteria for Adverse Events protocol-specified serious adverse events (SAEs). Starting dose was 3.5 Gy/fx for 15 fractions with 2 potential escalation and de-escalation levels in 0.25 Gy/fx increments. Chemotherapy was weekly concurrent carboplatin/paclitaxel with 2 cycles of optional consolidation carboplatin/paclitaxel. Results: From May 2015 to September 2016, 23 patients enrolled at a single institution. Of 20 evaluable, median age was 66.5 years (range, 54-89) and 12 were male (60%). Fourteen (70%) had squamous cell and 15 (75%) were stage IIIA. Nineteen (95%) completed all 3 cycles of concurrent chemotherapy, and 16 (80%) received at least 1 cycle of consolidation chemotherapy. Within the 6-month time-to-event continuous reassessment method assessment window, no SAEs were reported, and most patients were treated at the highest dose level. Dose level assignment was 52.5 Gy (n = 2), 56.25 Gy (n = 4), and 60 Gy (n = 14). The posterior probability of dose-limiting toxicity for 60 Gy was 5.3% (95% confidence interval, 1%-18.1%). Acute, nonserious AEs included grade 2 esophagitis in 7 patients (35%) and grade 2 pneumonitis in 1 patient (5%). At a median follow-up of 20.3 months for all and 44.9 months for living patients, there were no grade 4 or 5 AEs, though there were 3 (21% at 24 months) SAEs outside of the dose-escalation window. The 2-year overall survival, local, regional, and distant control rates were 48%, 84%, 77%, and 79%, respectively. Conclusions: Hypofractionated proton beam radiation therapy and chemotherapy up to 60 Gy in 15 fractions is acutely well tolerated, with high rates of locoregional control and overall survival, though late SAEs were noted.
UR - http://www.scopus.com/inward/record.url?scp=85125458600&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2022.01.012
DO - 10.1016/j.ijrobp.2022.01.012
M3 - Article
C2 - 35074432
AN - SCOPUS:85125458600
SN - 0360-3016
VL - 113
SP - 742
EP - 748
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 4
ER -