Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial.
OBJECTIVE
Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC.


METHODS
Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy.


RESULTS
Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥ 3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥ 3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥ 3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P = .24). The median overall survival was 6 months with no significant differences between dose levels (P = .59).


CONCLUSIONS
Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long-term safety and efficacy of this therapy are warranted.
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
Kenneth D
KD
Westover
Department of Radiation Oncology, Stanford University, Stanford, California.
Billy W
BW
Loo
Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
David E
DE
Gerber
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
Puneeth
P
Iyengar
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
Hak
H
Choy
Department of Radiation Oncology, Stanford University, Stanford, California.
Maximilian
M
Diehn
Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Randy
R
Hughes
Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Joan
J
Schiller
Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Jonathan
J
Dowell
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
Zabi
Z
Wardak
Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois.
David
D
Sher
Department of Clinical Science, Southwestern Medical Center, Dallas, Texas.
Alana
A
Christie
Department of Clinical Science, Southwestern Medical Center, Dallas, Texas.
Xian-Jin
XJ
Xie
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
Irma
I
Corona
School of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Akanksha
A
Sharma
Radiation Oncology of Mississippi, Jackson, Mississippi.
Margaret E
ME
Wadsworth
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: Robert.Timmerman@utsouthwestern.edu.
Robert
R
Timmerman
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D018450:Disease Progression; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D009367:Neoplasm Staging; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D020266:Radiotherapy, Conformal / Q000379:methods*; D012720:Severity of Illness Index