title: Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study.
abstract: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD).
  
  
  
  Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients per cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated.
  
  
  
  Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively.
  
  
  
  SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.
authors.affiliation: Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts. Electronic address: jhepel@lifespan.org.
authors.forename: Jaroslaw T
authors.initials: JT
authors.lastname: Hepel
authors.affiliation: Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts.
authors.forename: Kara Lynne
authors.initials: KL
authors.lastname: Leonard
authors.affiliation: Division of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island; Division of Medical Oncology, Miriam Hospital, Brown University, Providence, Rhode Island.
authors.forename: Howard
authors.initials: H
authors.lastname: Safran
authors.affiliation: Division of Thoracic Surgery, Rhode Island Hospital, Brown University, Providence, Rhode Island.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ng
authors.affiliation: Division of Medical Oncology, Miriam Hospital, Brown University, Providence, Rhode Island.
authors.forename: Angela
authors.initials: A
authors.lastname: Taber
authors.affiliation: Division of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island.
authors.forename: Humera
authors.initials: H
authors.lastname: Khurshid
authors.affiliation: Division of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island.
authors.forename: Ariel
authors.initials: A
authors.lastname: Birnbaum
authors.affiliation: Brown University, Providence, Rhode Island.
authors.affiliation: Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts.
authors.forename: David E
authors.initials: DE
authors.lastname: Wazer
authors.affiliation: Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts.
authors.forename: Thomas
authors.initials: T
authors.lastname: DiPetrillo
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011446:Prospective Studies; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods* / Q000401:mortality