The three-dimensional dose, volume, and outcome data for lung are reviewed in detail. The rate of symptomatic pneumonitis is related to many dosimetric parameters, and there are no evident threshold "tolerance dose-volume" levels. There are strong volume and fractionation effects.

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Radiation dose-volume effects in the lung.

Summary Primary cardiac tumours are rare, with an autopsy incidence ranging from 0·001% to 0·030% Three-quarters of these tumours are benign and nearly half of the benign tumours are myxomas Metastases to the heart are far more common than primary cardiac tumours Primary cardiac tumours present with one or more of the symptoms of the classic triad of: cardiac symptoms and signs resulting from intracardiac obstruction; signs of systemic embolisation; and systemic or constitutional symptoms They are diagnosed by use of transthoracic and transoesophageal echocardiograms, MRI, and CT scan Whereas surgery is indicated in patients with benign tumours, systemic chemotherapy is indicated in those who have widespread or unresectable malignant disease, and chemotherapy and radiotherapy are usually combined in treatment of patients with primary cardiac lymphomas The prognosis after surgery is usually excellent in the case of benign tumours but is unfortunately still limited in localised malignant diseases Patients with sarcomas live for a mean of 3 months to 1 year, and those with lymphomas live up to 5 years if treated, but usually die within 1 month if untreated

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470204505700930.pdf

Cardiac tumours: diagnosis and management

Although radiotherapy improves locoregional control and survival in patients with non-small-cell lung cancer, radiation pneumonitis is a common treatment-related toxicity. Many pulmonary function tests are not significantly altered by pulmonary toxicity of irradiation, but reductions in D(L(CO)), the diffusing capacity of carbon monoxide, are more commonly associated with pneumonitis. Several patient-specific factors (e.g. age, smoking history, tumor location, performance score, gender) and treatment-specific factors (e.g. chemotherapy regimen and dose) have been proposed as potential predictors of the risk of radiation pneumonitis, but these have not been consistently demonstrated across different studies. The risk of radiation pneumonitis also seems to increase as the cumulative dose of radiation to normal lung tissue increases, as measured by dose-volume histograms. However, controversy persists about which dosimetric parameter optimally predicts the risk of radiation pneumonitis, and whether the volume of lung or the dose of radiation is more important. Radiation oncologists ought to consider these dosimetric factors when designing radiation treatment plans for all patients who receive thoracic radiotherapy. Newer radiotherapy techniques and technologies may reduce the exposure of normal lung to irradiation. Several medications have also been evaluated for their ability to reduce radiation pneumonitis in animals and humans, including corticosteroids, amifostine, ACE inhibitors or angiotensin II type 1 receptor blockers, pentoxifylline, melatonin, carvedilol, and manganese superoxide dismutase-plasmid/liposome. Additional research is warranted to determine the efficacy of these medications and identify nonpharmacologic strategies to predict and prevent radiation pneumonitis.

Radiation pneumonitis and pulmonary fibrosis in non-small-cell lung cancer: pulmonary function, prediction, and prevention.

Pulmonary fibrosis is the consequence of a variety of diseases with no satisfying treatment option. Therapy-induced fibrosis also limits the efficacy of chemotherapy and radiotherapy in numerous cancers. Here, we studied the potential of platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitors (RTKIs) to attenuate radiation-induced pulmonary fibrosis. Thoraces of C57BL/6 mice were irradiated (20 Gy), and mice were treated with three distinct PDGF RTKIs (SU9518, SU11657, or Imatinib). Irradiation was found to induce severe lung fibrosis resulting in dramatically reduced mouse survival. Treatment with PDGF RTKIs markedly attenuated the development of pulmonary fibrosis in excellent correlation with clinical, histological, and computed tomography results. Importantly, RTKIs also prolonged the life span of irradiated mice. We found that radiation up-regulated expression of PDGF (A-D) isoforms leading to phosphorylation of PDGF receptor, which was strongly inhibited by RTKIs. Our findings suggest a pivotal role of PDGF signaling in the pathogenesis of pulmonary fibrosis and indicate that inhibition of fibrogenesis, rather than inflammation, is critical to antifibrotic treatment. This study points the way to a potential new approach for treating idiopathic or therapy-related forms of lung fibrosis.

/pdf/inhibition-of-platelet-derived-growth-factor-signaling-4kmkwmbo99.pdf

Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis

Purpose: To investigate factors associated with treatment-related pneumonitis in non–small-cell lung cancer patients treated with concurrent chemoradiotherapy. Patients and Methods: We retrospectively analyzed data from 223 patients treated with definitive concurrent chemoradiotherapy. Treatment-related pneumonitis was graded according to Common Terminology Criteria for Adverse Events version 3.0. Univariate and multivariate analyses were performed to identify predictive factors. Results: Median follow-up was 10.5 months (range, 1.4–58 months). The actuarial incidence of Grade ≥3 pneumonitis was 22% at 6 months and 32% at 1 year. By univariate analyses, lung volume, gross tumor volume, mean lung dose, and relative V5 through V65, in increments of 5 Gy, were all found to be significantly associated with treatment-related pneumonitis. The mean lung dose and rV5–rV65 were highly correlated ( p 42% were 3% and 38%, respectively ( p = 0.001). Conclusions: In this study, a number of clinical and dosimetric factors were found to be significantly associated with treatment-related pneumonitis. However, rV5 was the only significant factor associated with this toxicity. Until it is better understood which dose range is most relevant, multiple clinical and dosimetric factors should be considered in treatment planning for non–small-cell lung cancer patients receiving concurrent chemoradiotherapy.

Analysis of clinical and dosimetric factors associated with treatment-related pneumonitis (TRP) in patients with non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT)

Alan H. Epstein

Papers

Pulmonary Radiation Injury

Primary Cardiac Sarcoma: A Novel Treatment Approach

Enhancing Career Paths for Tomorrow's Radiation Oncologists.