Elsevier

Clinical Lung Cancer

Volume 18, Issue 2, March 2017, Pages 105-121.e5
Clinical Lung Cancer

Review
Radiotherapy With Curative Intent in Patients With Early-stage, Medically Inoperable, Non–Small-cell Lung Cancer: A Systematic Review

https://doi.org/10.1016/j.cllc.2016.10.008Get rights and content

Abstract

Patients with early-stage non–small-cell lung cancer (NSCLC) who are unable to undergo surgery can be offered radiation therapy (RT). Previously, conventional RT was offered; however, newer techniques such as stereotactic body RT (SBRT) have become available. The objective of the present systematic review was to investigate the effectiveness of RT with curative intent in patients with early-stage medically inoperable NSCLC. MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing stereotactic RT with curative intent compared with observation or other types of RT for early-stage, medically inoperable, NSCLC. Comparisons of radiation dosing or fractionation schedules for SBRT were included. We include 4 systematic reviews and 52 observational studies. The evidence suggests that SBRT compared with observation or other forms of RT, such as accelerated hypofractionated RT, 3-dimensional conformal RT, conventional fractionated RT, external beam RT, proton beam therapy, and carbon ion therapy, could have similar or improved results in survival or local control, with similar or fewer adverse effects. Evidence also suggests that local tumor control and survival were associated with the biologically effective dose (BED) for SBRT. Several studies suggested a cutoff of approximately 100 BED correlated significantly with patient outcomes. The presented evidence suggests that SBRT compared with other forms of RT is a reasonable treatment option for patients with medically inoperable early-stage NSCLC.

Introduction

Non–small-cell lung cancer (NSCLC) is the most prevalent type of lung cancer.1 Surgical resection of early-stage (stage I, II) NCSLC is the standard against which other treatments are measured. A subset of these patients will be unable to tolerate surgery because of their age or medical comorbidities.2 The latter include abnormal underlying cardiovascular and/or pulmonary function. Such patients were previously offered conventional radiotherapy (RT; 60-66 Gy in 1.8-2.0 Gy fractions) or were observed without receiving specific cancer therapy. The outcomes for each of these approaches have not been ideal, with 2-year survival < 40% using either conventional RT or observation and local control of only 40% to 50% with conventional RT.3, 4

Stereotactic RT is a high-precision radiation delivery technique of a few (or even a single) high-dose fractions to small targets or volume of disease. It is characterized by a steep dose gradient beyond the target volume, and as such, the accuracy and precision of treatment planning and delivery become critical. Stereotactic body RT (SBRT) and stereotactic ablative RT were considered synonymous for the purposes of the present systematic review and referred to as SBRT from this point onward.

Because the outcomes for patients with early-stage NSCLC who were observed or were given conventional RT have not been ideal, the objective of the present review was to investigate the effectiveness of SBRT compared with other RT techniques used with curative intent in patients with early-stage NSCLC who are medically inoperable. To make recommendations as a part of a clinical practice guideline on the use of RT with curative intent,5 Cancer Care Ontario's (CCO's) Program in Evidence-Based Care, together with CCO's Lung Cancer Disease Site Group and the Radiation Treatment Program, developed this evidentiary base. Based on the objectives of the present review, we derived the research questions outlined below.

  • 1.

    What is the effectiveness of SBRT compared with other RT techniques used with curative intent in patients with early-stage NSCLC who are unable to undergo surgery?

  • 2.

    What are the most effective dose and/or fractionation schedules for curative-intent RT using SBRT?

Section snippets

Materials and Methods

CCO's Program in Evidence-Based Care produces evidence-based guidance documents using the methods of the Practice Guidelines Development Cycle, which involves development of recommendations based on evidence from this systematic review, in consultation with clinical experts, followed by internal review by content and methodology experts and external review by Ontario clinicians and other stakeholders.6 This evidentiary base was developed using a planned 2-stage method. If ≥ 1 existing

Search for Existing Systematic Reviews

Thirteen systematic reviews were considered for inclusion.9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 Two were excluded because they were abstracts only.9, 16 Although the 11 remaining reviews had different inclusion criteria, 2 reviews were included because they had performed a meta-analysis using noncomparative data.14, 21 Their results could be used to support or refute the conclusions drawn from the comparative data from the primary studies. Two other reviews were included because

Discussion

Evidence from retrospective observational studies suggest that SBRT compared with observation or other forms of RT such as accelerated hypofractionated RT, 3-dimensional conformal RT, conventional fractionated RT, external beam RT, proton beam therapy, and carbon ion therapy could have similar or improved results in patient outcomes of survival or local control, with similar or fewer adverse effects.26, 39, 44, 47, 49, 62, 69, 72, 75, 76, 77, 78, 79, 80, 81, 82, 83 In the absence of RCTs, this

Conclusion

Stereotactic RT is now emerging as the current treatment modality of choice for patients with early-stage, medically inoperable, NSCLC. The comprehensive evidentiary base compiled suggests that it is a valid treatment option that should be offered to patients with this disease. Ongoing trials will continue to review the dosages and dosing schedules for marginal gains in effectiveness. Future research should focus on establishing the most effective location-specific dose and/or fractionation

Disclosure

The authors declare that they have no competing interests.

Acknowledgments

The authors would like to thank the following individuals for their assistance in developing this report. Melissa Brouwers, Patrick Cheung, Sheila McNair, Hans Messersmith, Gunita Mitera, Gordon Okawara, Raymond Poon, Kenneth Schneider, Marko Simunovic, Cindy Walker-Dilks, Pardraig Warde, and Eric Winquist provided feedback on draft versions. Andrea Bezjak participated in the early stages of development of this systematic review. Terence Tang conducted the data audit and Sara Miller copy edited

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