Impact of Incidental Cardiac Radiation on Cardiopulmonary Toxicity and Survival for Locally Advanced Non-Small Cell Lung Cancer: Reanalysis of NRG Oncology/RTOG 0617 With Centrally Contoured Cardiac Structures

Gore, Elizabeth; Hu, Chen; Ad, Voichita Bar; Robinson, Clifford G.; Wheatley, Matthew; Bogart, Jeffrey A.; Garces, Yolanda I.; Kavadi, Vivek S.; Narayan, Samir; Iyengar, Puneeth; Witt, Jacob S.; Welsh, James W.; Koprowski, C.D.; Larner, James M.; Bradley, J.D.

doi:10.1016/j.ijrobp.2016.06.316

Cited by 19 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent data on definitive CRT in unresectable stage III NSCLC patients indicate heart dose may be responsible to increased toxicity and poor OS. 32,33 Correlations between induction RT dose to specific cardiothoracic structures (heart, esophagus, ipsilateral, and contralateral lung) and short-term surgical outcomes has not been previously investigated, but was queried here in the 0839 cohort. Although there was a trend toward increased severe toxicity and 90day mortality with increasing ipsilateral and contralateral V 5 and lung V 10 , the number of events was small and the effect was not seen after controlling for panitumumab and extent of resection.…”

Section: Discussionmentioning

confidence: 99%

Resection following concurrent chemotherapy and high-dose radiation for stage IIIA non–small cell lung cancer

Donington

Paulus

Edelman

et al. 2020

The Journal of Thoracic and Cardiovascular Surgery

View full text Add to dashboard Cite

Objective: Concern exists regarding surgery after thoracic radiation. We aimed to assess early results of anatomic resection following induction therapy with platinum-based chemotherapy and full-dose thoracic radiation for resectable N2þ stage IIIA non-small cell lung cancer. Methods: Two prospective trials were recently conducted by NRG Oncology in patients with resectable N2þ stage IIIA non-small cell lung cancer with the primary end point of mediastinal node sterilization following concurrent full-dose chemoradiotherapy (Radiation Therapy Oncology Group trials 0229 and 0839). All surgeons demonstrated postinduction resection expertise. Induction consisted of weekly carboplatin (area under the curve, 2.0) and paclitaxel (50 mg/m 2) and concurrent thoracic radiation 60 Gy (0839)/61.2 Gy (0229) in 30 fractions. Patients in study 0839 were randomized 2:1 to weekly panitumumab þ chemoradiotherapy or chemoradiotherapy alone during induction. Primary results were similar in all treatment arms and reported previously. Short-term surgical outcomes are reported here. Results: One hundred twenty-six patients enrolled; 93 (74%) had anatomic resection, 77 underwent lobectomy, and 16 underwent extended resection. Microscopically margin-negative resections occurred in 85 (91%). Fourteen (15%) resections were attempted minimally invasively, including 2 converted without event. Grade 3 or 4 surgical adverse events were reported in 26 (28%), 30-day mortality in 4 (4%) and 90-day mortality in 5 (5%). Patients undergoing extended resection experienced similar rates of grade 3 or 4 adverse events (odds ratio, 0.95; 95% confidence interval, 0.42-3.8) but higher 30-day (1.3% vs 18.8%) (odds ratio, 17.54; 95% confidence interval, 1.75-181.8) and 90-day mortality (2.6% vs 18.8%) (odds ratio, 8.65; 95% confidence interval, 1.3-56.9). Conclusions: Lobectomy was performed safely following full-dose concurrent chemoradiotherapy in these multi-institutional prospective trials; however, increased mortality was noted with extended resections.

show abstract

Section: Discussionmentioning

confidence: 99%

Resection following concurrent chemotherapy and high-dose radiation for stage IIIA non–small cell lung cancer

Donington

Paulus

Edelman

et al. 2020

The Journal of Thoracic and Cardiovascular Surgery

View full text Add to dashboard Cite

show abstract

“…10 Importantly, recent RTOG 0617 subanalyses suggest that dose to the atrial and ventricular cardiac substructures are more strongly associated with survival than assessing dose/volume relationships to the entire heart volume. [11][12][13] In a recent study by van den Bogaard, 6 dose to the left ventricular volume receiving 5 Gy predicted major coronary events better than MHD. A study by Hoppe et al highlighted the importance of quantifying substructure dose as the MHD becomes less correlated to substructure dose with increasingly conformal delivery.…”

Section: Introductionmentioning

confidence: 99%

Incorporating sensitive cardiac substructure sparing into radiation therapy planning

Morris

Aldridge²,

Ghanem

et al. 2020

J Applied Clin Med Phys

View full text Add to dashboard Cite

Purpose: Rising evidence suggests that cardiac substructures are highly radiosensitive. However, they are not routinely considered in treatment planning as they are not readily visualized on treatment planning CTs (TPCTs). This work integrated the soft tissue contrast provided by low-field MRIs acquired on an MR-linac via image registration to further enable cardiac substructure sparing on TPCTs. Methods: Sixteen upper thoracic patients treated at various breathing states (7 end-exhalation, 7 end-inhalation, 2 free-breathing) on a 0.35T MR-linac were retrospectively evaluated. A hybrid MR/CT atlas and a deep learning three-dimensional (3D) U-Net propagated 13 substructures to TPCTs. Radiation oncologists revised contours using registered MRIs. Clinical treatment plans were re-optimized and evaluated for beam arrangement modifications to reduce substructure doses. Dosimetric assessment included mean and maximum (0.03cc) dose, left ventricular volume receiving 5Gy (LV-V5), and other clinical endpoints. As metrics of plan complexity, total MU and treatment time were evaluated between approaches. Results: Cardiac sparing plans reduced the mean heart dose (mean reduction 0.7 ± 0.6, range 0.1 to 2.5 Gy). Re-optimized plans reduced left anterior descending artery (LADA) mean and LADA 0.03cc (0.0-63.9% and 0.0-17.3 Gy, respectively). LV 0.03cc was reduced by >1.5 Gy for 10 patients while 6 cases had large reductions (>7%) in LV-V5. Left atrial mean dose was equivalent/reduced in all sparing plans (mean reduction 0.9 ± 1.2 Gy). The left main coronary artery was better spared in all cases for mean dose and D 0.03cc. One patient exhibited >10 Gy reduction in D 0.03cc to four substructures. There was no statistical difference in treatment time and MU, or clinical endpoints to the planning target volume, lung, esophagus, or spinal cord after re-optimization. Four patients benefited from new beam arrangements, leading to further dose reductions. Conclusions: By introducing 0.35T MRIs acquired on an MR-linac to verify cardiac substructure segmentations for CT-based treatment planning, an opportunity was presented for more effective sparing with limited increase in plan complexity. Validation in a larger cohort with appropriate margins offers potential to reduce radiation-related cardiotoxicities.

show abstract

“…Median OS with or without cetuximab was similar (25.0 vs 24.0 months) in this same trial that employed a 2 × 2 factorial design. An analysis of dose to cardiac structures revealed numerous cardiac dose volumes including mean pericardium dose were correlated with worse survival, and mean pericardium dose was also associated with grade 3 or higher pneumonitis ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Radiation Oncology in the 21st Century: Prospective Randomized Trials That Changed Practice… or Didn’t!

2018

View full text Add to dashboard Cite

In a two-part article published in 2009, we discussed the limitations of conventional radiation therapy, the challenges of studying new technologies in radiation oncology, and summarized the state-of-the science for various malignancies (1, 2). Here, we summarize some of the most important prospective, randomized trials that during the intervening years have attempted to improve the tumor control and/or decrease the adverse effects of radiation therapy. For consistency, we have focused here on the null and alternate hypotheses as articulated by the investigators at the onset of each trial, since the outcome of the investigational treatment should be considered clinically significant only if the null hypothesis was rejected. The readers (and patients) are of course free to make their own judgments about the clinical significance of the results when the null hypothesis was not rejected.

show abstract

Impact of Incidental Cardiac Radiation on Cardiopulmonary Toxicity and Survival for Locally Advanced Non-Small Cell Lung Cancer: Reanalysis of NRG Oncology/RTOG 0617 With Centrally Contoured Cardiac Structures

Cited by 19 publications

References 0 publications

Resection following concurrent chemotherapy and high-dose radiation for stage IIIA non–small cell lung cancer

Resection following concurrent chemotherapy and high-dose radiation for stage IIIA non–small cell lung cancer

Incorporating sensitive cardiac substructure sparing into radiation therapy planning

Radiation Oncology in the 21st Century: Prospective Randomized Trials That Changed Practice… or Didn’t!

Contact Info

Product

Resources

About