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Mara Antonoff
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MS07 - Controversies with Stereotactic Radiation in Early Stage Lung Cancer (ID 70)
- Event: WCLC 2019
- Type: Mini Symposium
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:Laureano Molins, Salvador Villa
- Coordinates: 9/09/2019, 14:00 - 15:30, Dublin (1997)
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MS07.02 - Post SBRT Management: Surgery (Now Available) (ID 3475)
14:00 - 15:30 | Presenting Author(s): Mara Antonoff
- Abstract
- Presentation
Abstract
BACKGROUND:
For early stage NSCLC, lobectomy and mediastinal lymph node dissection has been a long-standing, established standard of care. For patients unable to tolerate surgical resection, several single-institution studies have demonstrated SBRT to be an efficacious and well-tolerated treatment strategy.1-3 The RTOG-0236 trial, subsequently published in 2010, prospectively evaluated SBRT among patients at multiple North American centers, revealing high rates of local tumor control with acceptable treatment-related morbidity, which has been corroborated by other investigators with reproducibly acceptable rates of intermediate-term local control and minimal toxicities.4-6
Given the success of using SBRT for Stage I NSCLC in medically inoperable patients, increasing interest has arisen regarding the potential application of this modality for healthier, potentially operable patients. In order to expand indications for use of this modality, important issues warranting investigation will include determination of the ideal means of following patients radiographically following SBRT as well as establishing protocols for intervention upon local failure. The outcomes for salvage lung resection following SBRT have been minimally reported. In this study, we aimed to evaluate our experience with operative lung resection in patients where SBRT has failed. Further, we review the combined outcomes in patients from our center along with those previously reported in the published literature.
METHODS:
We utilized our Departmental surgical database to identify all patients who underwent salvage pulmonary resection after prior radiation between January 2009 and September 2015. Among 716 patients who underwent pulmonary resection after previous radiotherapy, 21 met inclusion criteria, and these patients comprised the study cohort (MDACC group). Detailed patient data were retrospectively collected from our departmentally maintained, prospectively entered database and supplemented with additional chart review.
In addition, a MEDLINE search was performed to identify all previous reports of surgical resection following local failure after initial treatment with SBRT. This resulted in 56 articles, which were reviewed to specifically identify publications regarding lung resection following local recurrence after SBRT. Four studies were identified, totaling 18 patients; however, as one report7 included resection of specimens lacking any residual disease, we used only the other 3 reports for cumulative analyses.8-10 From these previous publications, data were extracted for each patient and were combined with those of the MDACC cohort, thus constituting the final aggregate cumulative group.
Student’s paired t-tests were used to compare pre-SBRT and pre-salvage surgery pulmonary function test results. Kaplan Meier analyses were performed in order to evaluate survival from the time of surgery as well as survival from completion of SBRT.
RESULTS:
At our institution, 21 individuals met inclusion criteria and comprised the MDACC group, and the cumulative group included 37 patients at 4 institutions. Baseline details regarding histology, sex, age, and medical operability are included in Figure 1. Elements of the radiation treatment received are also shown in Figure 1.
Salvage surgery was performed at a median of 16 months following completion of SBRT, with a range of 6.4 to 104 months. Extent of resection is shown in Figure 1. Three (8.1%) operations were performed via minimally invasive approaches (2 thoracoscopic and 1 robotic-assisted). Adhesions were noted intraoperatively for nearly all (36/37, 97.3%) patients. Final pathology resulted in upstaging for 9/15 (60%) of patients in the MDACC group.
Early postoperative outcomes were available for the 21 patients in the MDACC group (Figure 2). Two (9.5%) required post-operative admission to the intensive care unit (ICU), and stayed for a median of 5.5 days. Pulmonary complications were most common, occurring in 7 (33.3%) patients. Two (9.5%) patients had a prolonged air leak and 2 (9.5%) patients were discharged home on oxygen.
During follow-up of the 21 MDACC patients, 5 developed recurrence. The three-year cumulative incidence of distant recurrence was 23.8%, with all recurrences distant and median time to recurrence 36.2 months. The median disease-free survival among MDACC patients was 19.2 months. Median survival from surgery for the MDACC group was 46.9 months, with 3-year survival of 53.2%. Thirty- and 90-day mortality were both 1 (4.8%). In the cumulative group, median survival was also 46.9 months and 3-year survival was 71.8%.
CONCLUSIONS:
Our findings demonstrate that resection following local failure of SBRT in highly select individuals is feasible, safe, and has an overall acceptable morbidity and mortality, albeit higher than what is typically observed in non-irradiated patients. In considering salvage resection, we recommend careful consideration of the patient’s performance status and the likely extent of required resection, to be discussed thoughtfully both with the patient and in a multi-disciplinary tumor board setting. Further studies are clearly warranted to establish treatment algorithms for those patients who demonstrate locally persistent or recurrent disease following SBRT and to clinically characterize the most appropriate operative candidates.
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OA13 - Ideal Approach to Lung Resection and Novel Perioperative Therapy (ID 146)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:Tomasz Grodzki, Kenji Suzuki
- Coordinates: 9/10/2019, 11:30 - 13:00, Toronto (1985)
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OA13.06 - Surgical Outcomes Following Neoadjuvant Nivolumab or Nivolumab Plus Ipilimumab in Non-Small Cell Lung Cancer - NEOSTAR Study (Now Available) (ID 2041)
11:30 - 13:00 | Author(s): Mara Antonoff
- Abstract
- Presentation
Background
Surgical outcomes following neoadjuvant immune checkpoint inhibitors (ICIs) are limited. We report 90-day perioperative results of the NEOSTAR phase II trial of neoadjuvant nivolumab or nivolumab/ipilimumab in resectable non-small cell lung cancers (NSCLCs).
Method
44 pts with stage I-IIIA NSCLC (AJCC 7th) were randomized to nivolumab (3 mg/kg IV, days 1, 15, 29, n=23) or nivolumab/ipilimumab (1 mg/kg IV, day 1, n=21) with resection planned between 3-6 weeks after last dose. Surgical approach and extent of resection were at surgeons’ discretion.
Result
39 (89%) patients underwent R0 resection, of those 2 (5%) were resected off trial after additional induction chemotherapy (1 nivolumab, 1 nivolumab/ipilimumab). Among 37 patients, 21 underwent surgery following nivolumab and 16 following nivolumab/ipilimumab. Median age 66 (43-83) years, 24 (65%) male, 33 (89%) white, 22 (59%) adenocarcinoma, 22 (59%) stage I, 9 (24%) stage II, 6 (16%) stage IIIA.
5 (11%) were not resected, 1 (1/23, 4%) after nivolumab (stage II), 4 (4/21, 19%) after nivolumab/ipilimumab (1 stage I, 1 stage II, 2 stage IIIA). Reasons for unresectability were change in surgeon’s judgement (n=2), toxicity (n=1), progression (n=1), and declining pneumonectomy (n=1). Median time to surgery was 31 days (range 21-87). 8 (22%) operations were delayed beyond 42 days, 5 after nivolumab/ipilimumab (5/16, 31%) and 3 after nivolumab (3/21, 14%).
33 (89%) underwent lobectomy, 2 (5%) pneumonectomy, 1 (3%) segmentectomy and 1 (3%) wedge resection. 27 (73%) had thoracotomy, 7 (19%) thoracoscopy, 3 (8%) robotic approach. 2 (5%) were electively converted from thoracoscopy to thoracotomy. Median operative time was 147 minutes (71-315), median blood loss was 100cc (50-1000), and median length of stay was 4 days (1-18).
Perioperatively, pulmonary complications occurred in 8 (22%) patients: 8 (22%) prolonged air leak, 2 (5%) pneumonitis/pneumonias, 1 (3%) empyema, and 1 (3%) bronchopleural fistula (BPF). 1 (3%) died from complications of BPF and steroid therapy for pneumonitis. 4 (11%) developed atrial fibrillation, 1 (3%) diarrhea, 1 (3%) ileus, and 1 (3%) transient ischemic attack.
Surgeons subjectively judged 15/37 (40%) of operations to be more complex than usual with 7/37 (19%) lasting > 4 hours.
Conclusion
Following three cycles of neoadjuvant ICIs 89% of patients underwent complete R0 resection, including two patients who received additional induction chemotherapy off trial. Five marginally operable patients who didn’t proceed to resection, and one perioperative mortality highlight the importance of cautious patient selection for neoadjuvant ICIs in the management of operable NSCLC.
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