Postoperative Proton Therapy in the Management of Stage III Thymoma
Authors: Nicolas Figura, Bradford S. Hoppe, Stella Flampouri, Zhong Su, Omeni Osian, Alan Monroe, Romaine C. Nichols
Journal: Journal of Thoracic Oncology (2013)

A 23-year-old woman with a Masaoka stage III type B2/B3 thymoma was referred to our institution for adjuvant proton therapy after surgical resection. The patient initially presented with chest pain, shortness of breath, and a family history notable for her brother having died from metastatic thymoma at the age of 17 years. A chest computed tomography scan demonstrated a large anterior mediastinal mass. Surgical exploration and resection demonstrated a 16.5 × 8.5 × 3.7 cm mass invading the innominate vein, requiring graft reconstruction, and extending along the right paramediastinal/cardiac border to just above the right hemidiaphragm. Pathology revealed stage III type B2/B3 thymoma with no lymph node involvement, but microscopic positive margins. Because of stage and positive margins, recommendations were made for adjuvant radiation therapy (RT). An RT plan was developed to deliver 50.4 Gy to the postoperative bed with a 10.8 Gy boost to the site that showed microscopic residual disease. Despite advanced disease at presentation, patients with stage III thymoma receiving adjuvant RT do well with a median overall survival of 127 months.1Weksler B Shende M Nason KS Gallagher A Ferson PF Pennathur A The role of adjuvant radiation therapy for resected stage III thymoma: a population-based study.Ann Thorac Surg. 2012; 93 (discussion 1828): 1822-1828Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Because this female patient was quite young, it was important to consider the long-term complications of RT to the chest. Unfortunately, even with the most conformal photon radiation technique, intensity-modulated radiotherapy (IMRT), the mean dose to the organs at risk was quite high. The patient was, therefore, referred to University of Florida Proton Therapy Institute for consideration of treatment with proton therapy. Conventional photon RT, which uses high-energy photons, deposits part of the RT dose throughout the beam's path, causing collateral damage to normal tissue ahead of and behind the actual planned target volume (PTV). Conversely, proton therapy, which uses charged particles, deposits most of the RT dose at the PTV, with a lower entrance dose (ahead of the PTV) and little to no exit dose (behind the PTV) compared with high-energy photons. Our patient underwent treatment planning with IMRT and proton therapy. Figure 1 shows the colorwash isodose plans comparing the dose distributions of both plans. Figure 2 shows dose-volume histograms of the OARs. Table 1 shows mean doses to the OARs.FIGURE 2Dose-volume histograms representing the percentage of each organ irradiated at each radiation dose level with intensity-modulated radiation therapy (dashed line) or proton therapy (solid line).View Large Image Figure ViewerDownload (PPT)TABLE 1Mean Dose to Organs with Intensity-Modulated Radiation Therapy and Proton TherapyOrganIMRT (Gy)Proton (Gy)Absolute Reduction (Gy)Relative Reduction (%)Lungs15.79.95.837Heart28.420.48.028Esophagus36.516.520.055Breasts7.69.72.1−27Nontarget thoraxaNontarget thorax refers to thorax minus planned target volume.8.73.65.159a Nontarget thorax refers to thorax minus planned target volume. Open table in a new tab RT doses as low as 4 to 5 Gy to the lung and/or breast have been associated with an increased risk of secondary lung and breast cancers,2Travis LB Gospodarowicz M Curtis RE et al.Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease.J Natl Cancer Inst. 2002; 94: 182-192Crossref PubMed Scopus (467) Google Scholar,3Travis LB Hill DA Dores GM et al.Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease.JAMA. 2003; 290: 465-475Crossref PubMed Scopus (531) Google Scholar whereas RT doses as low as 5 to 15 Gy to the heart have been shown to increase the risk of late cardiac injury, such as myocardial infarction, congestive heart failure, and valvular disease.4Mulrooney DA Yeazel MW Kawashima T et al.Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort.BMJ. 2009; 339: b4606Crossref PubMed Scopus (786) Google Scholar,5Tukenova M Guibout C Oberlin O et al.Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer.J Clin Oncol. 2010; 28: 1308-1315Crossref PubMed Scopus (335) Google Scholar Our treatment plans showed that, when compared with IMRT, proton therapy reduced the mean dose to the heart by 8 Gy, lungs by 6 Gy, and esophagus by 20 Gy, whereas it increased the dose to the breasts by 2 Gy. Because of the lower doses delivered to most of the OARs and expected lower risk of late toxicity with these lower doses, the patient was treated with proton therapy. Proton therapy should be considered in similar cases of young adults with thymoma, in whom there are concerns of the late toxicity associated with RT.