Five-fraction SBRT for ultra-central NSCLC in-field recurrences following high-dose conventional radiation

Repka et al. Radiation Oncology (2017) 12:162 DOI 10.1186/s13014-017-0897-6 RESEARCH Open Access Five-fraction SBRT for ultra-central NSCLC in-field recurrences following high-dose conventional radiation Michael C. Repka1*, Nima Aghdam1, Shaan K. Kataria1, Lloyd Campbell1, Simeng Suy1, Sean P. Collins1, Eric Anderson2, Jonathan W. Lischalk1 and Brian T. Collins1 Abstract Purpose/objective: Local treatment options for patients with in-field non-small cell lung cancer (NSCLC) recurrence following conventionally fractionated external beam radiation therapy (CF-EBRT) are limited. Stereotactic body radiation therapy (SBRT) is a promising modality to achieve reasonable local control, although toxicity remains a concern. Materials/methods: Patients previously treated with high-dose CF-EBRT (≥59.4 Gy, ≤3 Gy/fraction) for non-metastatic NSCLC who underwent salvage SBRT for localized ultra-central in-field recurrence were included in this analysis. Ultracentral recurrences were defined as those abutting the trachea, mainstem bronchus, or esophagus and included both parenchymal and nodal recurrences. The Kaplan-Meier method was used to estimate local control and overall survival. Durable local control was defined as ≥12 months. Toxicity was scored per the CTC-AE v4.0. Results: Twenty patients were treated with five-fraction robotic SBRT for ultra-central in-field recurrence following CF-EBRT. Fifty percent of recurrences were adenocarcinoma, while 35% of tumors were classified as squamous cell carcinoma. The median interval between the end of CF-EBRT and SBRT was 23.3 months (range: 2.6 – 93.6 months). The median CF-EBRT dose was 63 Gy (range: 59.4 – 75 Gy), the median SBRT dose was 35 Gy (range: 25 – 45 Gy), and the median total equivalent dose in 2 Gy fractions (EQD2) was 116 Gy (range: 91.3 – 136.7 Gy). At a median follow-up of 12 months for all patients and 37.5 months in surviving patients, the majority of patients (90%) have died. High-dose SBRT was associated with improved local control (p < .01), and the one-year overall survival and local control were 77. 8% and 66.7% respectively in this sub-group. No late esophageal toxicity was noted, although a patient who received an SBRT dose of 45 Gy (total EQD2: 129.7 Gy) experienced grade 5 hemoptysis 35 months following treatment. Conclusions: Although the overall prognosis for patients with in-field ultra-central NSCLC recurrences following CFEBRT remains grim, five-fraction SBRT was well tolerated with an acceptable toxicity profile. Dose escalation above 35 Gy may offer improved local control, however caution is warranted when treating high-risk recurrences with aggressive regimens. Keywords: Sbrt, Reirradiation, Nsclc, Lung cancer, Ultra-central * Correspondence: 1 Department of Radiation Medicine, Georgetown University Hospital, 3800 Reservoir Road NW Washington, DC 2007, USA Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Repka et al. Radiation Oncology (2017) 12:162 Introduction Although the incidence of lung and bronchus cancer has been steadily decreasing in the United States, the disease is still responsible for more deaths per year than any other malignancy [1]. While patients with early stage non-small cell lung cancer (NSCLC) have seen continuous expansion and improvement in available treatment options, the prognosis for patients with locally advanced disease is poor and often presents an oncologic dilemma to the treating physician. Frequently patients are not good candidates for surgical resection due to disease extent or medical comorbidity [2], and radiation therapy plays a key role in patient management, frequently employing doses of 60 Gy or more [3, 4]. Survival rates for patients with locally advanced NSCLC reported in the literature are grim, with an estimated 5-year overall survival for stage IIIA and IIIB patients of 19% and 7% respectively according to the 2007 International Association for the Study of Lung Cancer (IASLC) database analysis [5]. As innovations in systemic therapy, surgery, and radiation techniques are implemented, the prognosis for those patients with advanced disease should improve. According to the 2016 update of the IASLC database analysis, 5-year overall survival rates have soared over the past decade to 36% and 19% in stage IIIA and IIIB patients respectively [6]. While such a drastic improvement in 5-year overall survival for locally advanced patients must be taken with a degree of caution, these data are highly encouraging. However, local recurrence is a common problem in this patient population [4], and treatment options for patients with recurrent NSCLC who have previously undergone high-dose thoracic radiation are extremely limited [7–10], particularly when disease is situated within the previously treated portal. Given increasing patient longevity, the gravity of preventing morbid local failure may grow ever more paramount. Newer modalities of radiation therapy, such as stereotactic body radiation therapy (SBRT) and proton beam therapy (PBT), may allow for safer retreatment of previously irradiated tissue by limiting radiation dose to normal tissue and organs-at-risk (OARs). Furthermore, the high dose-per-fraction typically employed with SBRT may provide a higher degree of therapeutic efficacy given the radioresistance of many lung cancers, particularly those that have already received high doses of conventionally fractionated radiation [11]. While there is considerable accumulating evidence regarding the role of SBRT for earlystage lung cancers [12, 13], there are few studies which have examined its role in the management of previously irradiated recurrent NSCLC [14–21]. However, these retrospective, single-institution studies do suggest the relative safety of SBRT reirradiation for peripheral lesions. Definitive SBRT for lesions within 2 cm of the central airway in the unirradiated chest has been associated with Page 2 of 9 higher toxicity than for peripheral treatments [22]. Furthermore, a 15% rate of fatal pulmonary hemorrhage has been reported following hypofractionated treatment of ultra-central tumors, in which the target volume overlapped with central airways [23]. One hypothesis for the enhanced morbidity of central treatment is the radiosensitivity of bronchial cartilage, which is thought to be sensitive to the high dose-per-fraction s (...truncated)