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Original Investigation
October 2017

Effect of Midtreatment PET/CT-Adapted Radiation Therapy With Concurrent Chemotherapy in Patients With Locally Advanced Non–Small-Cell Lung CancerA Phase 2 Clinical Trial

Author Affiliations
  • 1Department of Radiation Oncology, University of Michigan, Ann Arbor
  • 2IU Simon Cancer Center, Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana
  • 3Department of Biostatistics, University of Michigan, Ann Arbor
  • 4Division of Nuclear Medicine and Molecular Imaging, University of Michigan, Ann Arbor
  • 5VA Ann Arbor Healthcare System, Ann Arbor, Michigan
  • 6Department of Internal Medicine, University of Michigan, Ann Arbor
  • 7Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor
JAMA Oncol. 2017;3(10):1358-1365. doi:10.1001/jamaoncol.2017.0982
Key Points

Question  Can adaptive treatment target high-dose radiation to the residual tumor to improve local tumor control in locally advanced non–small-cell lung cancer (NSCLC)?

Findings  This phase 2 clinical trial, involving patients with stage II/III NSCLC from 2008 to 2012, demonstrated that adaptive radiotherapy-escalated radiation dose to the 18F-fludeoxyglucose (FDG)-avid region detected by midtreatment positron emission tomography (PET) achieved 82% local tumor control at 2 years, with a reasonable rate of radiotherapy-induced toxicity.

Meaning  This innovative adaptive radiotherapy can deliver personalized dose-escalated treatment to the resistant active tumor detected by midtreatment FDG-PET to improve local tumor control in patients with locally advanced NSCLC.


Importance  Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival.

Objective  To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non–small-cell lung cancer (NSCLC).

Design, Setting, and Participants  A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT.

Intervention  Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation.

Main Outcomes and Measures  The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population.

Results  The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45-83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63-86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82% (95% CI, 62%-92%) and 62% (95% CI, 43%-77%), respectively. Median overall survival was 25 months (95% CI, 12-32 months). The 2-year and 5-year overall survival rates were 52% (95% CI, 36%-66%) and 30% (95% CI, 16%-45%), respectively.

Conclusions and Relevance  Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion.

Trial Registration  clinicaltrials.gov Identifier: NCT01190527