Title: Stereotactic Ablative Radiotherapy (SABR) can be Safe and Effective for Treatment of Central and Ultra-Central Lung Tumors.Author: Aadel Chaudhuri, MD PhD

Abstract #: 2014-A-2428-ASTROSession title: Lung 1 - Novel Prognostic Factors and SBRTDate/Time: 2014-09-14 13:15Location: Room D-1Monitor number: 7

Phase 2 trial performed by Timmerman et al. showed that stereotactic ablative radiotherapy with a dose fractionation of 60 Gy in 3 fractions was effective at controlling stage 1 T1-T2a N0M0 NSCLC (localized tumor ≤ 5 cm in diameter) with 95% local tumor control at 2y, and 32.6 months median overall survival.

Unfortunately, patients with centrally located tumors, defined as tumor location within 2cm of the proximal bronchial tree, experienced higher rates of severe toxicity (2y freedom from severe toxicity 54% for central tumor patients compared to 83% for peripheral tumor patients).

4 of 22 (18%) central lung tumor patients experienced grade 5 toxicity, where the safety monitoring board believed that SABR caused severe toxicity contributing to death.

Given these safety concerns, the followup RTOG 0236 phase 3 trial made tumor centrality one of its exclusion criteria.

Indiana University Phase 2 Trial

Timmerman et al, J of Clinical Oncology, 2006

Four retrospective studies have since followed, showing that central lung tumor patients treated with SABR experience good local tumor control and acceptable levels of toxicity (Chang et al, IJROBP, 2008; Haasbeek et al, J of Thoracic Oncology, 2011; Bral et al, IJROBP, 2011; Rowe et al, J of Thoracic Oncology, 2012).

However, none of these studies used the RTOG 0816 definition of tumor centrality, and all included examples of patients with severe toxicity, with three including patients whose death appeared treatment-related (Haasbeek et al, J of Thoracic Oncology, 2011; Bral et al, IJROBP, 2011; Rowe et al, J of Thoracic Oncology, 2012).

The NEJM also published a report of fatal hemorrhage due to central airway necrosis, deemed to be from SABR to a central tumor adjacent to the right proximal bronchial tree (Corradetti et al, NEJM, 2012).

Retrospective Studies on Central Lung Tumor SABR/SBRT

RTOG 0813 and Our Institutional StudyWith the possibility that lung SBRT might be safe and effective for central

NSCLC patients, RTOG 0813 was setup to study this issue prospectively.

RTOG 0813 Eligibility: Patients with T1-2 N0 M0 NSCLC, tumor size ≤ 5 cm, who are not candidates for complete surgical resection.

Centrality was defined as tumors within 2 cm of the proximal bronchial tree, or directly adjacent to the mediastinal or pericardial pleura.

Starting dose: 50 Gy in 5 fractions. Protocol allowed dose escalation up to 60 Gy in 5 fractions, if patients were seen to not have dose-limiting toxicity at lower doses.

We used the RTOG 0813 tumor centrality criteria, and compared its dosimetric constraints to patients treated in our institution.

We compared Peripheral and Central lung tumor patients treated with 50 Gy in 4-5 fractions. Toxicity levels were low for both groups, including for a subset of “ultra-central” tumor patients with tumors directly abutting the proximal bronchial tree.

Take Home Points

Central and Peripheral stage I-II NSCLC patients treated with SABR had similar outcomes, with local control at 2 years > 80%, and OS at 2 yrs of 70%.

Toxicity rates were low in both central and peripheral lung tumor patients, with no grade 5 toxicities and only one case of grade 4 toxicity, indicating that SABR is a safe modality for treatment of both groups.

Seven Ultra-Central tumor patients with tumors directly abutting the proximal bronchial tree, experienced no significant toxicities.

Ultra-Central tumor patients also had comparable rates of local control and survival as their less central counterparts.

Dosimetric analysis revealed that the RTOG 0813 central airway dosimetric constraints were most commonly infracted in our study, indicating they may be more conservative than necessary.

In summary, SABR appears to be a safe and effective modality for treatment of both central and peripheral lung tumors, including “ultra-central” tumors directly abutting the proximal bronchial tree.