title: A Phase 2 Trial of Concurrent Chemotherapy and Proton Therapy for Stage III Non-Small Cell Lung Cancer: Results and Reflections Following Early Closure of a Single-Institution Study.
abstract: OBJECTIVE
  Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC).
  
  
  METHODS
  From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after just 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months.
  
  
  RESULTS
  Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient.
  
  
  CONCLUSIONS
  Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.
authors.affiliation: University of Florida Health Proton Therapy Institute, Jacksonville, Florida. Electronic address: bhoppe@floridaproton.org.
authors.forename: Bradford S
authors.initials: BS
authors.lastname: Hoppe
authors.affiliation: University of Florida Health Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Randal
authors.initials: R
authors.lastname: Henderson
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Dat
authors.initials: D
authors.lastname: Pham
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: James D
authors.initials: JD
authors.lastname: Cury
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Abubakr
authors.initials: A
authors.lastname: Bajwa
authors.affiliation: University of Florida Health Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Morris
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Harry
authors.initials: H
authors.lastname: D'Agostino
authors.affiliation: University of Florida Health Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Stella
authors.initials: S
authors.lastname: Flampouri
authors.affiliation: University of Florida Health Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Soon
authors.initials: S
authors.lastname: Huh
authors.affiliation: University of Florida Health Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Zuofeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Radiology, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Barry
authors.initials: B
authors.lastname: McCook
authors.affiliation: University of Florida Health Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Romaine C
authors.initials: RC
authors.lastname: Nichols
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy / Q000379:methods*; D018572:Disease-Free Survival; D057239:Early Termination of Clinical Trials; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D058958:Organs at Risk / Q000528:radiation effects; D018579:Patient Selection; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods*; D011832:Radiation Injuries / Q000517:prevention & control; D011879:Radiotherapy Dosage; D013997:Time Factors