Frontiers in Oncology (Jan 2023)

High-risk patients with locally advanced non-small cell lung cancer treated with stereotactic body radiation therapy to the peripheral primary combined with conventionally fractionated volumetric arc therapy to the mediastinal lymph nodes

  • Tanja Eichkorn,
  • Tanja Eichkorn,
  • Tanja Eichkorn,
  • Jonathan W. Lischalk,
  • Cedric Stüwe,
  • Eric Tonndorf-Martini,
  • Eric Tonndorf-Martini,
  • Kai Schubert,
  • Kai Schubert,
  • Lisa-Antonia Dinges,
  • Lisa-Antonia Dinges,
  • Lisa-Antonia Dinges,
  • Sebastian Regnery,
  • Sebastian Regnery,
  • Sebastian Regnery,
  • Farastuk Bozorgmehr,
  • Farastuk Bozorgmehr,
  • Farastuk Bozorgmehr,
  • Laila König,
  • Laila König,
  • Laila König,
  • Petros Christopoulos,
  • Petros Christopoulos,
  • Petros Christopoulos,
  • Juliane Hörner-Rieber,
  • Juliane Hörner-Rieber,
  • Juliane Hörner-Rieber,
  • Sebastian Adeberg,
  • Sebastian Adeberg,
  • Sebastian Adeberg,
  • Klaus Herfarth,
  • Klaus Herfarth,
  • Klaus Herfarth,
  • Hauke Winter,
  • Hauke Winter,
  • Michael Thomas,
  • Michael Thomas,
  • Michael Thomas,
  • Stefan Rieken,
  • Jürgen Debus,
  • Jürgen Debus,
  • Jürgen Debus,
  • Jürgen Debus,
  • Jürgen Debus,
  • Rami A. El Shafie,
  • Rami A. El Shafie

DOI
https://doi.org/10.3389/fonc.2022.1035370
Journal volume & issue
Vol. 12

Abstract

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IntroductionA very narrow therapeutic window exists when delivering curative chemoradiotherapy for inoperable locally advanced non-small cell lung cancer (NSCLC), particularly when large distances exist between areas of gross disease in the thorax. In the present study, we hypothesize that a novel technique of stereotactic body radiation therapy (SBRT) to the primary tumor in combination with volumetric arc therapy (VMAT) to the mediastinal lymph nodes (MLN) is a suitable approach for high-risk patients with large volume geographically distant locally advanced NSCLC.Patients and methodsIn this single institutional review, we identified high-risk patients treated between 2014 and 2017 with SBRT to the parenchymal lung primary as well as VMAT to the involved MLN using conventional fractionation. Dosimetrically, comparative plans utilizing VMAT conventionally fractionated delivered to both the primary and MLN were analyzed. Clinically, toxicity (CTCAE version 5.0) and oncologic outcomes were analyzed in detail.ResultsA total of 21 patients were identified, 86% (n=18) of which received chemotherapy as a portion of their treatment. As treatment phase was between 2014 and 2017, none of the patients received consolidation immunotherapy. Target volume (PTV) dose coverage (99 vs. 87%) and CTV volume (307 vs. 441 ml) were significantly improved with SBRT+MLN vs. for VMAT alone (p<0.0001). Moreover, low-dose lung (median V5Gy [%]: 71 vs. 77, p<0.0001), heart (median V5Gy [%]: 41 vs. 49, p<0.0001) and esophagus (median V30Gy [%]: 54 vs. 55, p=0.03) dose exposure were all significantly reduced with SBRT+MLN. In contrast, there was no difference observed in high-dose exposure of lungs, heart, and spinal cord. Following SBRT+MLN treatment, we identified only one case of high-grade pneumonitis. As expected, we observed a higher rate of esophagitis with a total of seven patients experience grade 2+ toxicity. Overall, there were no grade 4+ toxicities identified. After a median 3 years follow up, disease progression was observed in 70% of patients irradiated using SBRT+MLN, but never in the spared ‘bridging’ tissue between pulmonary SBRT and mediastinal VMAT.ConclusionFor high risk patients, SBRT+MLN is dosimetrically feasible and can provide an alternative to dose reductions necessitated by otherwise very large target volumes.

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