Clinical Investigation
Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

https://doi.org/10.1016/j.ijrobp.2016.08.032Get rights and content

Purpose

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).

Methods and Materials

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.

Results

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.

Conclusions

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.

Introduction

Lung cancer remains the leading cause of cancer death for both men and women in the United States (1). Although outcomes for early-stage lung cancer are encouraging, nearly half of all patients will present with stage III disease, in which the expected overall survival with standard therapy is only 15% to 30% 2, 3, 4. Patterns of failure have shown that as many as 50% of these patients will experience local (in-field) failure as a component of recurrence. Stereotactic body radiation therapy (SBRT) is a technique by which a high dose of radiation can be delivered in a highly conformal fashion in just a few treatments. We therefore postulated that using SBRT as a boost to standard chemoradiation therapy potentially can improve disease control for locally advanced lung cancer. A phase 1 dose escalation study was undertaken to evaluate the safety and define the maximum tolerated dose for this approach.

Section snippets

Methods

Between 2012 and 2014, eligible patients were accrued to this prospective phase 1 study. This study was reviewed and approved by our institutional review board (Rhode Island Hospital) and was monitored by the Brown University Oncology Research Group data safety monitoring board.

Results

The trial completed accrual with 12 patients enrolled and treated. All patients met the planning dose constraints and completed protocol treatment. Treatment was delivered between 19 and 44 days after chemoradiation. Patient demographics are shown in Table 2. The mean age was 64 years. Sixty-seven percent were men, and 50% had adenocarcinoma histology. Stage III disease accounted for 92% of patients, and all patients but 1 were medically inoperable. Two-thirds of patients received concurrent

Discussion

Standard therapy for locally advanced lung cancer remains suboptimal. Overall survival with definitive chemoradiation is expected to be 15% to 30% at 5 years 2, 3, 4. Patterns of failure show that local failure will develop in nearly half of these patients (3). The addition of surgery has potential for a modest improvement in local control and overall survival but comes at the expense of morbidity (4). Additionally, many patients are not candidates for surgery because they have underlying

Acknowledgment

The authors thank Justin Peter and Oluwademilade Osibanjo for their assistance.

References (28)

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Conflict of interest: none.

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