[ad_1]

Charles B. Simone II, MD, FASTRO, FACRO

Cardiotoxicity can be effectively reduced using advanced radiation techniques such as intensity-modulated radiotherapy (IMRT). IMRT is preferred over three-dimensional conformal radiation therapy (3DCRT) for patients with locally advanced lung, esophageal, and breast cancer. The ability to optimize cardiac preservation, according to Charles B. Simone II, MD, FASTRO, FACRO.1

During the presentation at 2024 ACRO Summit, Simone added: “Proton therapy can deliver even lower doses to the heart than IMRT, potentially reducing major cardiac events and improving overall survival.” [OS]” Simone is a research professor and chief medical officer at the New York Proton Center and a full member of the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center in New York.

Data published in New England Medical Journal The incidence of major coronary events was 7.4% (95% CI, 2.9-14.5; P < .001) for every 1 Gy increase in mean radiotherapy dose to the heart without threshold.2 Simone also cited data from an update published by the Danish Breast Cancer Cooperative Group, which revealed that the median mean cardiac dose for left-sided radiotherapy was 2.41 Gy compared to 0.68 Gy for the right side. did.3 “It could have a detrimental effect on the survival of these patients,” he noted.

Common prevention strategies for adverse coronary events (AEs) aim to manage modifiable cardiovascular risk factors such as smoking cessation, exercise, and healthy diet, along with lifestyle changes. However, cardioprotective interventions are required to address the major cardiac problems associated with radiation. Radiation-related AEs include pericarditis. Pericarditis is usually acute and develops within a few weeks after radiation therapy. Other toxicities that are thought to occur more than 10 years after radiation include cardiomyopathy, coronary artery disease causing ischemia, valvular heart disease, conduction abnormalities, autonomic dysfunction, and vascular changes.1

“[We’ve seen that] patient [receive] Post-operative radiation [can have] Cancer control and cancer-specific survival are improved, but mortality from cardiopulmonary complications is much higher,” Simone elaborated. “That’s been the struggle in our field: how do we optimize radiation delivery for lung cancer patients?”

A SEER analysis of 6,148 patients with pN+ non-small cell lung cancer (NSCLC) who underwent lobectomy/pneumonectomy from 1983 to 1993 regarding the incidence of toxicity associated with postoperative radiotherapy (PORT). Results revealed that PORT increased heart disease mortality by 30%. (HR, 1.30; 95% CI, 1.04-1.61; P = .0193).Four

“If you have a right upper lobe tumor, your heart won’t receive as much radiation. [but] Elsewhere, the heart is exposed to large doses of radiation. Fortunately, with advanced treatment plans, symptoms are improving over time,” Simone said.

Examining the effects of radiation dose on cardiac structures and the benefits of IMRT

“IMRT is recommended over 3DCRT for locally advanced lung, esophageal, and breast cancers to optimize heart preservation,” Simone said in his presentation.1

The phase 3 RTOG 0617 trial (NCT00533949) comparing 3DCRT and IMRT found that for a given PTV volume, IMRT was associated with lower cardiac doses (P < .05) Stage III NSCLC patients. Incidence of grade 3 or higher pneumonitis was seen with IMRT (3.5%) and 3DCRT (7.9%, adjusted). P = .046). Additionally, IMRT was associated with improved compliance to full-dose consolidation chemotherapy, but no difference in OS or progression-free survival (PFS) was observed between groups.Five

However, in the NCDB study, a survival benefit was observed in stage III NSCLC patients (n = 2543) who received at least 58 Gy and definitive chemoradiotherapy concurrently or sequentially. Median OS was 14.6 months with 3DCRT compared to 17.2 months with IMRT.6

“IMRT has similar advantages compared to 3DCRT [are observed] for [patients with] Locally advanced breast cancer, especially if it is on the left side and/or if internal breast lymph nodes are involved. Esophageal cancer, especially in mid and distal cases. [and] thymus gland [tumors]Especially large tumors and/or tumors located in the tail and definitive cases,” Simone said.

Simone is involved in research at NRG Oncology aimed at standardizing contours and cardiac substructures. These efforts evaluate the aortic valve, left atrium, left anterior descending coronary artery, left ventricle, pulmonary artery, right atrium, right coronary artery, right ventricle, and superior vena cava. Overall, the use of advanced technologies such as IMRT and proton therapy is an important area of ​​research in the field of radiology.1

“There is a huge body of literature in this field, and we are learning more and more every day about the importance of the cardiac substructures, what dosages to consider, and what is associated with what. A new publication is coming out,” Simone explained. “We don’t have enough data at this point. [create] There are informed constraints, but that’s what our field needs to do. ”

Commentary: Proton therapy in breast and lung cancer

Both the RADCOMP consortium trial in breast cancer (NCT02603341) and the phase 3 RTOG 1308 study in lung cancer (NCT01993810) are evaluating outcomes of proton and photon therapy. 1 Simone stated that the RADCOMP study requires her three patients to complete acquisition. However, the RTOG 1308 study has completed accrual.

Data from a retrospective report of NSCLC patients who received PORT (n = 136) in the form of proton beam therapy (PBT; n = 61) and IMRT (n = 75) therapy showed that adjuvant proton therapy compared with IMRT. Regarding dosimetry, which showed promising results, PBT lowered the average heart rate (P < .01; 2.0 Gy vs 7.4 Gy), cardiac V30 (P < .01; 2.6% vs 10.7%), mean lung (P = .042; 7.9 Gy vs. 10.4 Gy), lung V5 (P < .01; 23.4% vs. 42.1% in the PBT and IMRT groups, respectively).7

Cardiotoxicity occurred in 4.9% and 14.7% of patients in the PBT and IMRT groups, respectively. Grade 2 or higher esophagitis (23.0% with PBT vs. 60.0% with IMRT) and grade 2 or higher pneumonitis (4.9% vs. 17.3%) were observed. Total toxic burden was lower with PBT compared with IMRT (odds ratio, 0.35; 95% CI, 0.15-0.83; P = .017). Additionally, median OS was 46 months with IMRT compared to 76 months with PBT.

“A randomized trial in locally advanced NSCLC at the University of Texas MD Anderson Cancer Center has already been completed, and all patients benefited specifically from proton beam therapy to the heart. decrease [were observed]” added Simone.

Simone also said, “…not all protons are created equal. Currently, unfortunately, proton single-arm centers are much cheaper and we are seeing that a lot in the community. Unfortunately, most of those machines [administer] IMRT. ”

Proton therapy in the esophagus and other malignancies

PBT was associated with decreased pulmonary toxicity when protons or photons were administered after preoperative chemoradiotherapy in patients with esophageal cancer (P = .005), cardiac events (P = .047), and wound complications (P = .005) versus IMRT/3DCRT. Additionally, the mean length of stay for proton therapy was 9.3 days (95% CI, 8.2-10.3) for 3DCRT, 13.2 days (95% CI, 11.7-14.7) for 3DCRT, and 11.6 days (95% CI, 10.9) for IMRT. -12.7; P < .0001). Postoperative 90-day mortality was also lower with proton therapy, 0.9% vs. 4.2% vs. 4.3%, respectively (P = 0.264).8

“The spread of IMRT for esophageal cancer has been dramatic; [especially] Know the morbidity of these treatments [for this patient population]” said Simone.

In a randomized phase 2 trial (NCT01512589), patients with curable (n = 56) or resectable (n = 51) esophageal cancer who received PBT had fewer AEs than patients treated with IMRT. , revealed that the total toxic burden was 2.3 times higher than IMRT (39.9; 95% highest posterior density interval [HPDI], 26.2-54.9) vs. PBT (17.4; 95% HPDI, 10.5-25.0), and the postoperative complication score was IMRT (19.1; 95% HPDI, 7.3-32.3) vs. PBT (2.5; 95% CI, 0.3-) It was 7.6 times higher. 5.2). The average length of hospital stay was 13 days for IMRT compared to 8 days for PBT (P = .06), three grade 5 toxicities occurred with IMRT versus zero with PBT. Furthermore, there was no difference in PFS or OS.9

Simone said there is less data on proton therapy for lymphoma patients, but regarding thymic tumors, “…the combination of proton therapy and IMRT therapy is predicted to reduce the incidence of major coronary events by 80.7%.” said.Ten

Further consideration of advanced technology

A nonrandomized comparison of two prospective cohorts of patients with stage II-IIIB and localized stage IV (solitary brain metastases) showed that intensity-modulated proton therapy (IMPT) improved lung , heart, and esophagus were found to have lower mean doses (PSPT) and concurrent chemotherapy. Also, patients treated with IMPT (n = 53) compared with those treated with PSPT (n = 86;n = 86; P = .09).11

“Additional measures are needed to reduce the prevalence of heart disease.” [and] Current investigation using radiation protection equipment and flash [are] It’s a work in progress,” Simone said. He added that radioprotective agents may help prevent cardiotoxicity, and flash radiotherapy may also expand treatment range. “Across multiple preclinical models, FLASH can achieve protective effects on normal tissues and reduce both acute and late toxicity compared to traditional dose-rate radiotherapy,” he said.

Editor’s note: Dr. Simone disclosed his professional relationship with the National Institutes of Health. He has received grants and honoraria and serves in a consulting role for Varian Medical System.

References

  1. Simone II CB. Treatment planning techniques, dose limitations, and advanced therapies to reduce the risk of cardiotoxicity. Presentation location: Radiation Oncology Summit: ACRO 2024; March 13-16, 2024. Orlando, Florida.
  2. Darby SC, Ewarts M, McGail P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N English J Medicine. 2013;368(11):987-98. doi:10.1056/NEJMoa1209825
  3. Laugaard Lorenzen E, Christian Rehammar J, Jensen MB, Ewertz M, Brink C. Risk of radiation-induced ischemic heart disease after breast cancer radiotherapy in Denmark, 1977-2005. Radiozar Oncor. 2020;152:103-110. doi:10.1016/j.radonc.2020.08.007
  4. Lally BE, Detterbeck FC, Geiger AM, et al. Risk of cardiac death in patients with non-small cell lung cancer receiving postoperative radiation therapy: Analysis of the Surveillance, Epidemiology, and End Results database. cancer. 2007;110(4):911-7. doi:10.1002/cncr.22845
  5. Chun SG, Hu C, Choy H et al. Impact of intensity-modulated radiation therapy techniques on locally advanced non-small cell lung cancer: a secondary analysis of the NRG Oncology RTOG 0617 randomized clinical trial. J Clin Oncor. 2017;35(1):56-62. doi:10.1200/JCO.2016.69.1378
  6. Jegadeesh N, Liu Y, Gillespie T, et al Evaluation of intensity-modulated radiation therapy in locally advanced non-small cell lung cancer: Results from the National Cancer Database. Clin lung cancer. 2016;17(5):398-405. doi:10.1016/j.cllc.2016.01.007
  7. Boyce-Fapiano D, Nguyen QN, Chapman BV, et al. Single-center experience with proton- and photon-based postoperative radiotherapy for non-small cell lung cancer. Clin lung cancer. 2021;22(5):e745-e755. doi:10.1016/j.cllc.2021.02.002
  8. Lin SH, Merrell KW, Shen J et al. Multicenter analysis of radiotherapy use and postoperative outcomes of preoperative chemoradiotherapy for esophageal cancer. Radiozar Oncor. 2017;123(3):376-381. doi:10.1016/j.radonc.2017.04.013
  9. Lin SH, Hobbs BP, Verma V et al. A randomized phase IIB trial of proton therapy versus intensity-modulated radiation therapy for locally advanced esophageal cancer. J Clin Oncor. 2020;38(14):1569-1579. doi:10.1200/JCO.19.02503
  10. Vogel J, Berman AT, Lin L, Prospective study of proton radiotherapy for adjuvant and definitive treatment of other thymomas and thymic carcinomas: early response and toxicity evaluation. Radiozar Oncor. 2016;118(3):504-9. doi:10.1016/j.radonc.2016.02.003
  11. Gjyshi O, Xu T, Elhammali A, et al. Toxicity and survival after intensity-modulated proton therapy and passive scattering proton therapy for NSCLC. J Solak Oncor. 2021;16(2):269-277. doi:10.1016/j.jtho.2020.10.013

[ad_2]

Source link