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Abstract

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 pro-cedures 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.​ 

Author information

Kong FM1,2, Ten Haken RK1, Schipper M1,3, Frey KA4, Hayman J1, Gross M4,5, Ramnath N5,6, Hassan KA6, Matuszak M1, Ritter T1,5, Bi N1, Wang W1,2, Orringer M7, Cease KB5,6, Lawrence TS1, Kalemkerian GP6.

1 Department of Radiation Oncology, University of Michigan, Ann Arbor.

2 IU Simon Cancer Center, Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana.

3 Department of Biostatistics, University of Michigan, Ann Arbor.

4 Division of Nuclear Medicine and Molecular Imaging, University of Michigan, Ann Arbor.

5 VA Ann Arbor Healthcare System, Ann Arbor, Michigan.

6 Department of Internal Medicine, University of Michigan, Ann Arbor.

7 Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor.