Precision hypofractionated radiation therapy in poor performing patients with non-small cell lung cancer: Phase 1 dose escalation trial

Kenneth D. Westover, Billy W. Loo, David E. Gerber, Puneeth Iyengar, Hak Choy, Maximilian Diehn, Randy Hughes, Joan Schiller, Jonathan Dowell, Zabi Wardak, David Sher, Alana Christie, Xian Jin Xie, Irma Corona, Akanksha Sharma, Margaret E. Wadsworth, Robert Timmerman

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Abstract

Purpose 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 and Materials 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.

Original languageEnglish (US)
Pages (from-to)72-81
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume93
Issue number1
DOIs
StatePublished - Sep 1 2015

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Non-Small Cell Lung Carcinoma
lungs
radiation therapy
Radiotherapy
cancer
dosage
therapy
grade
Maximum Tolerated Dose
Therapeutics
dyspnea
cost effectiveness
Esophagitis
death
toxicity
Dyspnea
Cost-Benefit Analysis
Lung Neoplasms
safety
Radiation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

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Precision hypofractionated radiation therapy in poor performing patients with non-small cell lung cancer : Phase 1 dose escalation trial. / Westover, Kenneth D.; Loo, Billy W.; Gerber, David E.; Iyengar, Puneeth; Choy, Hak; Diehn, Maximilian; Hughes, Randy; Schiller, Joan; Dowell, Jonathan; Wardak, Zabi; Sher, David; Christie, Alana; Xie, Xian Jin; Corona, Irma; Sharma, Akanksha; Wadsworth, Margaret E.; Timmerman, Robert.

In: International Journal of Radiation Oncology Biology Physics, Vol. 93, No. 1, 01.09.2015, p. 72-81.

Research output: Contribution to journalArticle

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abstract = "Purpose 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 and Materials 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.",
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T2 - Phase 1 dose escalation trial

AU - Westover, Kenneth D.

AU - Loo, Billy W.

AU - Gerber, David E.

AU - Iyengar, Puneeth

AU - Choy, Hak

AU - Diehn, Maximilian

AU - Hughes, Randy

AU - Schiller, Joan

AU - Dowell, Jonathan

AU - Wardak, Zabi

AU - Sher, David

AU - Christie, Alana

AU - Xie, Xian Jin

AU - Corona, Irma

AU - Sharma, Akanksha

AU - Wadsworth, Margaret E.

AU - Timmerman, Robert

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N2 - Purpose 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 and Materials 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.

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