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Ellen Yorke
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FP04 - Locoregional and Oligometastatic Disease (ID 126)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Locoregional and Oligometastatic Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP04.01 - Heart Dose is a Dosimetric Predictor of Overall Survival in Patients with NSCLC Undergoing Post-Operative Radiation Therapy (ID 1369)
00:00 - 00:00 | Author(s): Ellen Yorke
- Abstract
- Presentation
Introduction
Patients undergoing PORT for locally-advanced NSCLC may be at risk for increased cardiac toxicity. There is an association between radiation dose to the heart and OS in NSCLC patients undergoing definitive radiation therapy (RT). The purpose of this analysis was to evaluate heart dose as a predictor of OS in patients with NSCLC undergoing PORT.
Methods
We reviewed 284 patients with NSCLC treated with PORT at our institution from 5/2004 to 1/2017. Complete dosimetric data and clinical records were reviewed, and OS was assessed. Patients were a median of 67 years old (range 28-87), and most had pathologic stage III NSCLC (91%) and received trimodality therapy (90%). Forty-six (16.2%) patients had pre-existing cardiac disease. Patients underwent lobectomy (81%), sublobar resection (12%) or pneumonectomy (7%). The rates of R0, R1 and R2 resections were 81%, 19%, and 0%, respectively. The median RT dose was 54 Gy (range: 45-70 Gy). Patients were treated with IMRT (71%) or 3DCRT (29%). Major adverse cardiac events (MACE, defined as myocardial infarction, coronary revascularization, cerebrovascular accident or heart failure) and all cardiac toxicities (including arrythmia, valvular or pericardial events) were identified. A systematic univariate Cox proportional hazards model analysis of OS and heart dose variables was performed, using the minimum dose to the hottest x% (Dx) and the volume receiving at least xGy (Vx) with x in increments of 5% and 2Gy respectively, together with mean, min, and max doses. Clinical variables that were univariately significant (p < 0.05), together with the most significant dosimetric variable, were entered in a step-up multivariate analysis.
Results
The median, 2-year and 5-year OS were 41.5 months, 68% and 37%, respectively. Dosimetric variables across a large range of doses to the heart were highly significant for OS, including mean (MHD), minimum and maximum heart doses. The median MHD for the population was 11.2Gy. The median OS for patients with MHD above vs. below 11.2Gy was 31.7 vs. 57.5 months (p<0.001), respectively. The volume of the heart receiving 8Gy (HV8) was the most significant dosimetric variable (p <0.0001), and the median HV8 was 35.5%. The median OS was 33.2 vs. 53.6 months (p<0.005), for patients with HV8 above or below 35.5%. On multivariable analysis, HV8 (HR:1.015/%, p<0.001), increasing age (HR:1.036/yr, p<0.001), use of anticoagulant therapy (HR:2.24, p=0.007), more extensive surgery (HR:1.49, p=0.012), and pre-operative chemotherapy (HR:1.53, p=0.019) were significant for OS. The rates of MACE and all cardiac toxicities were 7.4% and 14.8%, respectively. No heart dosimetric variables predicted for MACE or all cardiac toxicity.
Conclusion
Heart dose, as well as age, use of anticoagulants, presurgical chemotherapy, and the extent of surgery are predictive of worse OS in patients with NSCLC undergoing PORT. Heart V8 is the most significant dosimetric factor associated with OS. Despite the strong correlation between heart dose and OS, heart dose did not predict for cardiac events. This may indicate that the association between OS and heart dose cannot be explained fully by radiation-induced cardiac toxicities in NSCLC patients undergoing PORT.
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MA06 - Molecular Developments and Novel Treatments in Mesothelioma and Thymoma (ID 134)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 14:15 - 15:15, Scientific Program Auditorium
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MA06.08 - A Safety Study of Avelumab plus SBRT in Malignant Mesothelioma (ID 2301)
14:15 - 15:15 | Author(s): Ellen Yorke
- Abstract
- Presentation
Introduction
Single-agent anti-PD-L1 therapy has shown modest effects in mesothelioma. There is evidence that radiation therapy can enhance the anti-tumor effects of immunotherapy. However, the safety of combining anti-PD-L1 therapy specifically with stereotactic body radiation therapy is unknown. This is a phase I study to evaluate the safety of the anti-PD-L1 monoclonal antibody avelumab plus SBRT in malignant pleural and peritoneal mesothelioma. This is a clinical trial in progress report on the safety data of the first stage of this trial.
Methods
This is a single-arm, single-institution study in patients who have progressed after prior therapy. Baseline biopsies are obtained for histologic confirmation of progressive disease. Avelumab is delivered every other week and SBRT to one lesion is delivered over 3 to 5 fractions (minimum of 30 Gy) followed by continuation of avelumab up to 24 months or until disease progression. A second research biopsy of the radiation target lesion and a non-irradiated lesion is performed after completion of 2 doses of avelumab and SBRT. The primary endpoint of the study is the safety of this combination based on grade 3+ non-hematologic adverse events (AE) (CTCAE v4.0) within 3 months form SBRT using a Simon two-stage minimax design. If less than 3 of the first 13 patients experienced grade 3+ toxicity, the treatment would be considered safe and the trial will expand to include an additional 14 patients.
Results
Patients received a median of 7 cycles (range 2 to 26 cycles) of avelumab for a median duration of 3.5 months. With a median follow up of 4 months there were 13 grade 1, 11 grade 2 and one grade 3 AEs observed that were possibly, probably or definitely related to avelumab. There were no grade 4 or 5 toxicities related to avelumab. The most common avelumab-related toxicities were fatigue (n=4), infusion-related allergic reactions (n=3), myalgia/arthralgias (n=3), diarrhea (n=2), dyspnea (n=2) and thyroid disorders (n=2). There were 7 grade 1 and 3 grade 2 AEs observed that were possibly related to SBRT. There were no grade 3, 4 or 5 toxicities related to SBRT. The most common SBRT-related toxicities were fatigue (n=2), cough (n=2), dyspnea (n=2) and nausea/vomiting (n=2).
Conclusion
The combination of avelumab and SBRT appears safe based on the prespecified toxicity endpoints of the first stage of this Simon two-stage design phase I study. Patients continue to be monitored for long-term toxicities.
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P05 - Early Stage/Localized Disease - Radiotherapy (ID 114)
- Event: WCLC 2020
- Type: Posters
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P05.10 - Risk Factors Associated with Pulmonary Toxicities from Multiple Courses of Lung Stereotactic Body Radiation Therapy (SBRT) (ID 1957)
00:00 - 00:00 | Author(s): Ellen Yorke
- Abstract
Introduction
Although lung SBRT is generally considered safe, data are limited on toxicity from multiple courses of lung SBRT in the same patient. We, therefore, examined pulmonary toxicity from multiple courses of lung SBRT in a large, modern cohort of patients.
Methods
We reviewed all patients treated with multiple courses of definitive lung SBRT without history of other lung radiation at our institution between January 2014 and October 2019. Dosimetric data were collected from composite treatment plans with deformable registration and converted to EQD2Gy. Grade ≥2 radiation pneumonitis (Gr2+RP) and grade ≥2 pulmonary toxicities (Gr2+PT) after the last course of SBRT, including dyspnea, cough, hypoxia and RP, were assessed per CTCAE v5.0. Logistic regression analyses were performed to examine correlations between patient or treatment factors and Gr2+RP or Gr2+PT.
Results
We identified 110 eligible patients (56 female and 54 male) with a median age of 74 yrs. There were 74 patients with early stage non-small cell lung cancer, whereas 36 patients had lung metastases. The percentage of patients with smoking history, pre-existing lung disease (COPD or asthma), prior lung surgery and systemic therapy within 90 days of last SBRT course were 73.6%, 43.6%, 39.1% and 18.2%, respectively.
The majority (91.8%) of patients received 2 courses of SBRT, and 9 (8.2%) received ≥3 courses. Most common SBRT regimens were 50 Gy/5 fractions (fx) (42.9%), 48 Gy/4 fx (29.4%) and 54 Gy/3 fx (20.8%), with a median BED10 of 105.6 Gy (IQR: 100-105.6). There were a similar percentage of synchronous (51.8%) and metachronous (48.2%) courses. The median composite lung V20, lung V5 and MLD in EQD2Gy were 12.7% (IQR:9.9-16.0%), 28.3% (IQR: 22.1-34.8%) and 11.2 Gy (IQR: 8.9-13.8 Gy), respectively.
With a median follow-up of 12.1 months (IQR: 7.5-23.2), 31 (28.2%) patients experienced Gr2+PT, the most common (n=21, 19.1%) being Gr2+ RP. There were 6 (5.5%) patients that developed grade 3+PT, including 3 grade 3 RP, 3 grade 3 hypoxia, 1 grade 3 dyspnea, 1 grade 3 cough, and 1 grade 4 RP, with no grade 5 pulmonary toxicities. On univariate analysis, only female gender was found to be significantly associated with Gr2+RP, whereas female gender and composite lung V20 were found to be significantly associated with Gr2+PT. On multivariate analyses, female gender (OR=3.85, p=0.025) and age >70 (OR=4.67, p=0.03) were significant for Gr2+RP, whereas female gender (OR=2.86, p=0.038), synchronous courses (OR=2.86, p=0.037) and composite V20 (OR=1.13, p=0.02) were significant for Gr2+PT. The rates of Gr2+PT above vs. below the median lung V20 were 33.3% vs. 23.2% (p=0.238).
Conclusion
Our data suggest that incidence of pulmonary toxicities with multiple courses of lung SBRT appears to be moderate, although higher than single course lung SBRT. Female gender, age>70, synchronous courses and increasing composite lung V20 may be risk factors for Gr2+ PT or Gr2+ RP. To guide clinical decisions regarding the feasibility and risks of multiple courses of SBRT, further analyses to identify cumulative dosimetric predictors and constraints for pulmonary toxicities are planned.
