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Daniel Gomez
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FP04 - Locoregional and Oligometastatic Disease (ID 126)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Locoregional and Oligometastatic Disease
- Presentations: 2
- 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): Daniel Gomez
- 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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FP04.04 - EGFR Mutations Predict Superior Survival of NSCLC Patients with Oligometastatic Disease Treated with Local Consolidative Therapy (ID 2994)
00:00 - 00:00 | Author(s): Daniel Gomez
- Abstract
Introduction
Local consolidative therapy (LCT) following systemic therapy for selected patients with oligometastatic non-small cell lung cancer (NSCLC) is an evolving treatment strategy. We sought to identify predictive genomic markers for overall survival (OS) and progression free survival (PFS) in patients presenting with synchronous oligometastatic NSCLC at diagnosis.
Methods
Patients presenting to a single institution (2000-2017) with stage IV NSCLC and ≤3 synchronous metastatic lesions were identified. Of 194 patients who met our inclusion criteria, 121 received comprehensive local consolidative therapy (LCT) to all sites of disease with either surgery or radiation. Intrathoracic nodal disease was counted as one site. Univariable and multivariable Cox regressions were performed to identify factors associated with OS. A ninety-day landmark analysis was performed to limit survivorship bias. Mutational status was obtained via an institutional database, when available.
Results
Of 194 patients who met our inclusion criteria and had genomic data available, TP53 mutations were identified in 40 of 55 (72%), KRAS in 30 of 65 (46%), EGFR in 22 of 90 (24%), ALK in 4 of 81 (5%), ROS1 in 2 of 63 (3%), and BRAF in 1 of 32 (3%) patients. The median age was 62 years. After a median follow-up of 52.3 months, median OS and PFS for this cohort was 26.5 (CI 23.0-30.0) months and 11.1 (95%, 9.1-13.0) months, respectively. Among all patients, comprehensive LCT to all sites of disease (N=121) was associated with improved OS (HR 0.67, CI 0.47-0.96, p=0.03) consistent with our previous study. Among all patients, on univariable analysis, patients with EGFR mutations had improved median OS (95.5 vs 37.2 months, p=0.03) compared to EGFR WT patients. Conversely, TP53, and KRAS mutations did not predict for OS. Among patients who received comprehensive LCT with known EGFR mutational status (N=57), EGFR mutations continued to predict for improved median OS (97.5 vs 29.8 months, p=0.02) (Figure 1).
Conclusion
Aggressive consolidative therapy to the primary lesion and all metastatic sites was associated with improved OS in a large cohort of oligometastatic patients, supporting results of recent prospective trials. EGFR mutations, but not KRAS or TP53 mutations, predicted for improved OS among oligometastatic patients who are treated with comprehensive LCT in addition to systemic therapy. These data support ongoing prospective trials evaluating the benefit of local therapy in oligometastatic EGFR mutant NSCLC.
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P02 - Diagnostics and Interventional Pulmonology (ID 110)
- Event: WCLC 2020
- Type: Posters
- Track: Diagnostics and Interventional Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P02.14 - Radiotherapy-Associated CT Imaging as a Potential Screening Tool for COVID-19 (ID 3785)
00:00 - 00:00 | Author(s): Daniel Gomez
- Abstract
Introduction
COVID-19 is associated with characteristic lung CT findings, such as rounded ground-glass opacities in certain distributions. Diagnosing COVID-19 is a particular concern in oncology care, since cancer patients are a vulnerable population who receive treatment in close proximity to other patients and staff. Radiotherapy patients routinely undergo CT simulation before starting therapy. We hypothesized that simulation CT scans obtained on patients treated during the pandemic would reveal characteristic COVID-19 findings and represent a tool to identify patients with asymptomatic COVID-19.
Methods
We reviewed patients undergoing CT simulation during a six-week period (March 1 to April 13, 2020) at a major tertiary cancer center located in an early epicenter of the COVID-19 pandemic in the United States. Most scans were done under free-breathing conditions, with slice thickness ≤3mm and without IV contrast. All scans were reviewed according to the RSNA classification of COVID-19 lung CT findings (“typical,” “indeterminate,” “atypical,” or “negative” for COVID-19 pneumonia) by radiation oncologists who had been trained by a diagnostic radiologist. All “typical” or “indeterminate” scans were considered suspicious and re-reviewed by a board-certified diagnostic radiologist. Radiographic classifications were then compared with available COVID-19 PCR test results. A one-tailed T test was used to compare the rate of positive COVID-19 tests in the radiographically suspicious vs. non-suspicious groups.
Results
414 CT simulation scans that included the lungs were performed on 400 patients during the study period. 119 patients (corresponding to 130 scans, or 31.4%) had COVID-19 PCR test results available. The most common cancer types were breast (37%), lung/thoracic (23%), and spine (21%). On initial review by radiation oncologists, 17 scans (4.1%), were deemed “typical” for COVID-19 pneumonia, 54 (13%) were “indeterminate,” 85 (21%) were “atypical,” and 258 (62.3%) were “negative.” Of the 71 suspicious (typical or indeterminate) scans, 23 had corresponding COVID-19 test results, of which 3 (15.7%) were positive for infection. 107 non-suspicious (atypical or negative) scans had corresponding COVID-19 test results, and 9 were positive (8.4%). This difference in COVID-19 positivity between radiographically suspicious and non-suspicious groups was not statistically significant (p=0.23). Upon re-review by a diagnostic radiologist, 25 (35%) of the suspicious scans were still deemed suspicious while the majority (n=46, or 65%) were deemed “atypical.”
Conclusion
Simulation CT scans obtained for radiation treatment planning can be reviewed for signs of COVID-19 pneumonia. About 17% of patients simulated in our metropolitan pandemic epicenter demonstrated findings suspicious for COVID-19 when reviewed by radiation oncologists according to consensus criteria. However, few of these patients proved to have COVID-19 infections based on PCR testing, and there was no significant correlation between radiographically suspicious simulation CT scans and COVID-19 positivity in this study. Analysis was limited by the lack of available COVID-19 test results in many patients. The concordance between radiographic classification by radiation oncologists vs. diagnostic radiologists was also low. These results suggest that routine review of radiotherapy simulation CT scans is of limited value in identifying asymptomatic COVID-19 infection.
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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): Daniel Gomez
- 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.
