Elsevier

Clinical Lung Cancer

Volume 16, Issue 6, November 2015, Pages 475-485
Clinical Lung Cancer

Original Study
Outcomes of Modestly Hypofractionated Radiation for Lung Tumors: Pre- and Mid-Treatment Positron Emission Tomography-Computed Tomography Metrics as Prognostic Factors

https://doi.org/10.1016/j.cllc.2015.01.007Get rights and content

Abstract

Introduction

Modestly hypofractionated radiation therapy (HypoRT; 60-66 Gy in 3-Gy fractions) allows patients with locally advanced thoracic tumors and poor performance status to complete treatment within a shorter period without concurrent chemotherapy. We evaluated the outcomes and imaging prognostic factors of HypoRT.

Materials and Methods

We retrospectively reviewed the data from all patients with primary and metastatic intrathoracic tumors treated with HypoRT from 2006 to 2012. We analyzed the survival and toxicity outcomes, including overall survival (OS), progression-free survival (PFS), local recurrence (LR), and distant metastasis. We also evaluated the following tumor metrics in an exploratory analysis: gross tumor volume (GTV), maximum standardized uptake value (SUVMax), and metabolic tumor volume using a threshold of ≥ 50% of the SUVMax (MTV50%) or the maximum gradient of fluorine-18 fluorodeoxyglucose uptake (MTVEdge). We assessed the association of these metrics and their changes from before to mid-RT using positron emission tomography-computed tomography (PET-CT) with OS and PFS.

Results

We identified 29 patients, all with pre-RT and 20 with mid-RT PET-CT scans. The median follow-up period was 15 months. The 2-year overall and non–small-cell lung cancer-only rate for OS, PFS, and LR, was 59% and 59%, 52% and 41%, and 27% and 32%, respectively. No grade ≥ 3 toxicities developed. The median decrease in GTV, SUVMax, and MTVEdge was 11%, 24%, and 18%, respectively. Inferior OS was associated with a larger pre-RT MTVEdge (P = .005) and pre-RT MTV50% (P = .007). Inferior PFS was associated with a larger mid-RT SUVMax (P = .003).

Conclusion

These findings add to the growing body of data demonstrating promising outcomes and limited toxicity with HypoRT. The pre- and mid-RT PET-CT metrics could be useful for prognostic stratification in future clinical trials.

Introduction

Modestly hypofractionated radiation therapy (HypoRT) allows for treatment completion within a shorter period and could be advantageous for patients with locally advanced lung tumors and a poor performance status or an inability to tolerate concurrent chemotherapy. HypoRT results in fewer daily treatments and a reduced cost compared with conventionally fractionated RT (CFRT) or combined chemotherapy and RT (chemoRT). Although small tumors can be treated effectively and safely with stereotactic ablative radiotherapy (SABR), a more fractionated approach is generally considered necessary for safe treatment of more advanced disease. Studies have shown effective treatment is attained with HypoRT for both early-stage non–small-cell lung cancer (NSCLC) and late-stage NSCLC and, with more accelerated courses, for oligometastatic lung cancer.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 One concern is the potential for increased toxicity from HypoRT. However, the reported toxicities have generally been found to be acceptable compared with CFRT with appropriate patient selection and conformal radiation techniques. Although HypoRT can be effective, currently, limited prognostic factors are available to guide treatment and predict the outcomes.

Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography (PET-CT) is an important tool for staging primary lung cancer and could potentially be used as a prognostic indicator of disease control and patient survival. Determining the metrics for tumor response could be used to tailor and potentially adjust treatment. Previous studies have demonstrated the usefulness of the CT-determined gross tumor volume (GTV) and metabolic tumor volume (MTV) for predicting the outcomes for NSCLC after both CFRT and SABR.11, 12, 13, 14, 15, 16 Additionally, analysis of the mid-RT PET-CT findings of different radiation fractionations and doses for lung tumors has shown that a decrease in FDG uptake is associated with improved outcomes.17, 18, 19, 20 To our knowledge, no other studies have been conducted that examined the benefit of mid-RT PET-CT with regard to MTV or as a prognosticator for patients undergoing HypoRT.

We sought to demonstrate the prognostic usefulness of pre- and mid-RT PET-CT metrics and to share our institutional experience of patients with lung cancer treated with a modestly hypofractionated course (60-66 Gy in 3-Gy fractions) of RT.

Section snippets

Patient Population

After approval by our institutional review board, we reviewed the medical records of all patients with an intrathoracic tumor treated with a modestly hypofractionated course of RT (60-66 Gy in 3-Gy fractions) using either 3-dimensional conformal (3D-CRT) or intensity-modulated RT (IMRT) at the Stanford Cancer Institute from January 2006 to January 2012. Intrathoracic tumors were those located in the lung cavity or thoracic lymph nodes. The patients included those with both primary or metastatic

Patient and Treatment Outcomes

Our review identified 29 patients who met the inclusion criteria. One patient died before the 3-month follow-up examination, and the rest were evaluated during the follow-up period. The patient characteristics are summarized in Table 1.

The median follow-up period for all patients was 15 months (range, 4-50 months) and for the surviving patients was 10 months (range, 4-50 months). Of the 29 patients, 12 (41%) developed local progression after RT, with a median interval of 10 months (range, 5-32

Discussion

We sought to share our institutional experience of patients with lung tumors treated with HypoRT and to demonstrate the prognostic usefulness of pre- and mid-RT PET-CT. The pre-RT PET-CT metrics and the change in SUV measured from the mid-RT PET scan have been shown to be useful tools for predicting the outcomes after RT for patients with lung cancer.11, 12, 13, 14, 15, 16, 17, 18, 19, 20 We focused our study on a cohort of patients with primary and metastatic lung tumors who had undergone

Conclusion

We have shared our institutional experience that HypoRT is a safe and effective method for treating primary and metastatic lung tumors in selected patients. We also performed a hypothesis-generating study that demonstrated the usefulness of pre- and mid-RT PET-CT. The PET metrics (MTVEdge, MTV50%, and SUVMax) predicted OS and PFS better than did the CT metrics (pre- and mid-RT GTV). If validated in future randomized studies, these imaging techniques could help risk stratify patients and modify

Disclosure

B.W.L., M.D., P.G.M., and E.E.G. have received research support from Varian Medical Systems. B.W.L. and P.G.M. have received research support from RaySearch Laboratories and speaking honoraria from Varian Medical Systems.

Acknowledgments

J.P.H. and C.N.C. were supported by the Stanford Medical Scholars Fellowship Program.

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    J.P.H. and C.C.-H. contributed equally to this work as first authors.

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