patterns of failure after stereotactic body radiation ... gy, 100 gy, and 113 gy for 54 gy/3...

Download Patterns of Failure after Stereotactic Body Radiation ... Gy, 100 Gy, and 113 Gy for 54 Gy/3 fractions

Post on 10-Dec-2018

228 views

Category:

Documents

0 download

Embed Size (px)

TRANSCRIPT

192 Journal of Thoracic Oncology Volume8,Number2,February2013

Introduction: The purpose of this study was to compare patterns of failure between lobar resection (lobectomy or pneumonectomy) and stereotactic body radiation therapy (SBRT) for patients with clinical stage I nonsmall-cell lung cancer (NSCLC).Methods: From January 2004 to January 2008, 338 patients under-went definitive treatment for pathologically confirmed clinical stage I NSCLC with lobar resection (n = 260) or SBRT (n = 78). Most surgical patients underwent lobectomy (n = 237). SBRT patients received a biologically effective dose of at least 100 Gy

10. Lobar

resection patients were younger, healthier, and had superior pulmo-nary function, whereas most of the patients in the SBRT group had T1 tumors. Final pathology upstaged 32.7% of surgery patients, and 20.0% received adjuvant chemotherapy. No SBRT patients received adjuvant chemotherapy.Results: In an unmatched comparison, 4-year lobar local control (98.7% versus 93.6%, p = 0.015) was greater for lobar resection versus SBRT, respectively, though primary tumor (98.7% versus 95.3%, p = 0.088), regional (82.9% versus 78.1%, p = 0.912), and distant control (76.1% versus 54.0%, p = 0.152) were similar. Overall survival (OS, 63.5% ver-sus 29.6%, p < 0.0001) was greater for lobar resection, though cause-specific survival (CSS, 81.3% versus 75.3%, p = 0.923) was similar. In a T-stage matched comparison of 152 patients, there was no significant difference in patterns of failure or CSS, whereas OS favored surgery.Conclusion: Lobectomy/pneumonectomy or SBRT results in com-parable patterns of failure for clinical stage I NSCLC. In this retro-spective comparison, OS was superior for surgery, though CSS was similar. Randomized trials are necessary to control for fundamen-tal differences in comorbidity, which impact interpretation of both tumor control and survival.

(J Thorac Oncol. 2013;8: 192201)

For patients with medically operable clinical stage I nonsmall-cell lung cancer (NSCLC), lobectomy or pneu-monectomy results in primary tumor control approaching 100% and 5-year overall survival of 53% and 43% for tumors 2 cm or more and 2.1 to 5 cm, respectively.1,2 Patients at higher risk of surgery may be offered sublobar resection with acceptable morbidity and mortality.3 Sublobar resec-tion with a nonanatomical wedge resection results in sig-nificantly higher local failure relative to lobar resection,4 though this may be improved through the use of brachyther-apy,5 careful intraoperative margin assessment,6 or anatomi-cal segmentectomy.7 For patients with medically inoperable stage I NSCLC, stereotactic body radiotherapy (SBRT) has become a standard of care based on high rates of local control, convenience, cost, and survival relative to historic outcomes after conventional radiotherapy, with low rates of toxicity.811 As experience with SBRT has grown, improved local control and survival after SBRT has been shown to correlate with biologically effective doses (BED) of radia-tion greater than 100 Gy

10.12,13

SBRT in medically operable patients was reported first from Japan, where high 3-year rates of local control (94%) and overall survival (86%) were documented in patients refusing surgery.14 No randomized trials comparing surgery and SBRT have been completed to date. The ROSEL (Radiosurgery Or Surgery for operable Early stage non-small cell Lung cancer) trial opened in Holland and attempted to compare lobectomy versus SBRT in stage I NSCLC, though it failed to reach its accrual goal and was closed. The STARS (Randomized Study to Compare CyberKnife Stereotactic Radiotherapy With Surgical Resection in Stage I Non-small Cell Lung Cancer) trial (sponsored by Accuray, Inc., Sunnyvale, CA) exclusively compares CyberKnife SBRT with lobectomy. American College of Surgeons Oncology Group (ACOSOG) Z4099 and Radiation Therapy Oncology Group (RTOG) 1021 is a National Cancer Institute trial, which randomizes patients at high risk for surgery to either sublobar resection ( brachy-therapy) or SBRT.

Retrospective comparisons between surgery and SBRT to date have been limited and suffer from inherent imbalances in the treatment arms, with healthier patients being selected for surgery.1419 Two recent publications directly comparing surgery and SBRT have addressed this by narrowing the focus

Copyright 2012 by the International Association for the Study of Lung CancerISSN: 1556-0864/12/0802-192

PatternsofFailureafterStereotacticBodyRadiationTherapyorLobarResectionfor

ClinicalStageINonSmall-CellLungCancer

Cliff G. Robinson, MD,* Todd A. DeWees, PhD,* Issam M. El Naqa, PhD, Kimberly M. Creach, MD,* Jeffrey R. Olsen, MD,* Traves D. Crabtree, MD,* Bryan F. Meyers, MD,* Varun Puri, MD,*

Jennifer M. Bell, BSN,* Parag J. Parikh, MD,* and Jeffrey D. Bradley, MD*

*Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri; and Department of Oncology, McGill University Health Centre, Montreal, Quebec.

Portions of this article were presented at the 52nd annual ASTRO meeting in San Diego, CA (10/31-11/4/10)Abstract #32.

Disclosure:The authors declare no conflict of interest.Address for correspondence: Cliff G. Robinson, MD, Department of

Radiation Oncology, Washington University School of Medicine, 4921 Parkview Place, Campus Box 8224, St. Louis, MO 3110. E-mail: crobin-son@radonc.wustl.edu

ORIGINAL ARTICLE

mailto:crobinson@radonc.wustl.edumailto:crobinson@radonc.wustl.edu

193Copyright 2012 by the International Association for the Study of Lung Cancer

Journal of Thoracic Oncology Volume8,Number2,February2013 SBRT or Lobar Resection for Stage I NSCLC

to only high-risk patients.16,17 Such comparisons have been criticized for having different definitions for failure between surgery and SBRT.20 No publications to date have compared outcomes specifically between lobar resection and SBRT. The purpose of this study is to compare institutional outcomes between definitive standard lobar resection and optimally dosed SBRT (BED > 100 Gy

10) using a uniform definition of

failure. Given the inherent difficulty in comparing survival for groups of patients selected for therapy based on medical comorbidity, we focus primarily on patterns of failure.

MATERIALS AND METHODSFrom January 2004 to January 2008, 454 patients (336

surgery, 118 SBRT) were identified with clinical stage I lung cancer from Institutional Review Boardapproved patient registries located in the departments of Cardiothoracic Surgery and Radiation Oncology at Washington University in St. Louis, Missouri. Selection of patients with clinical stage I NSCLC was based on the American Joint Committee on Cancer (AJCC) 6th edition staging manual,21 and was ret-rospectively coded using the 7th edition for the study.22 The data set was narrowed to include only patients (1) undergoing anatomical lobar resection (lobectomy or pneumonectomy) or SBRT to a BED of 100 Gy

10 or more and (2) having patho-

logic confirmation of NSCLC. Details of inclusion or exclu-sion resulting in the final study group are described in the Figure 1.

Standard work-up for all patients included history and physical examination, computed tomography (CT) of the chest and abdomen, and [18F] fluorodeoxyglucose (FDG)positron emission tomography (PET) CT. PET or CT was performed in 100% of surgery patients and 98.7% (n = 77) SBRT patients. Patients were selected for lobar resection if they were con-sidered by the thoracic surgeon to have adequate pulmonary

function to tolerate at least a lobectomy and absence of other contraindicating medical comorbidity. Patients were selected for SBRT if they were considered to be medically inoperable by the thoracic surgeon, or if they were felt to be at high risk for surgery, and declined sublobar resection after a balanced discussion with the surgeon and radiation oncologist.

Baseline patient, tumor, and treatment variables are sum-marized in Table 1. Medical comorbidity was assessed by the Adult CoMorbidity Evaluation (ACE-27) scoring system and Charlson Comorbidity Index (CCI), both of which have been validated in patients with lung cancer.23,24 The ACE-27 score was collected prospectively during a patients registration at the Siteman Cancer Center. The CCI and an age-adjusted CCI (AA-CCI) were scored retrospectively.25

For patients treated with lobar resection, the type of resection, type of incision, and extent of lymph node dis-section were at the discretion of the treating surgeon. Most patients underwent lobectomy, with the rest undergoing bilobectomy or pneumonectomy. Surgery was through open thoracotomy in 224 patients and video-assisted thoraco-scopic surgery in 36 patients. Institutional policy dictated that patients undergo mediastinoscopy before thoracotomy (either in advance of surgery, or at the time of surgery), fol-lowed by formal lymph node dissection at the time of lobec-tomy. Pathologic upstaging occurred in 85 patients (32.7%) undergoing surgery, of which tumor stage was higher in 51 cases (19.6%), and occult nodal disease was discovered in 56 cases (21.5%). For nodal stage, 43 patients were found to have pathologic N1 disease and 13 patients had N2 dis-ease. For tumor stage, 46 patients were upstaged from T1 (36 T2, 3 T3, and 7 T4) and five patients were upstaged from T2 (4 T3, 1 T4). In addition, 10 patients (3.8%) had downstag-ing from T2 to T1 tumors. Fifty-two patients (20.0%) treated with lobar resection received adjuvant chemotherapy, and 20 (7.7%) received adjuvant radiotherapy.

Details of SBRT planning and delivery at our institution have been described previously.26 Target coverage, conformal-ity, and normal tissue constraints were followed acco

View more