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Hypothyroidism (HT) is a frequent late side effect of Hodgkin's lymphoma (HL) therapy. The purpose of this study is to determine dose-volume constraints that correlate with functional impairment of the thyroid gland in HL patients treated with three-dimensional radiotherapy.A total of 61 consecutive patients undergoing antiblastic chemotherapy and involved field radiation treatment (median dose, 32 Gy; range, 30-36 Gy) for HL were retrospectively considered. Their median age was 28 years (range, 14-70 years). Blood levels of thyroid-stimulating hormone (TSH), free triiodo-thyronine (FT3), free thyroxine (FT4), and thyroglobulin antibody (ATG) were recorded basally and at different times after the end of therapy. For the thyroid gland, normal tissue complication probability (NTCP), dosimetric parameters, and the percentage of thyroid volume exceeding 10, 20, and 30 Gy (V10, V20, and V30) were calculated in all patients. To evaluate clinical and dosimetric factors possibly associated with HT, univariate and multivariate logistic regression analyses were performed.Eight of 61 (13.1%) patients had HT before treatment and were excluded from further evaluation. At a median follow-up of 32 months (range, 6-99 months), 41.5% (22/53) of patients developed HT after treatment. Univariate analyses showed that all dosimetric factors were associated with HT (p0.05). On multivariate analysis, the thyroid V30 value was the single independent predictor associated with HT (p = 0.001). This parameter divided the patients into low- vs. high-risk groups: if V30 was ≤ 62.5%, the risk of developing HT was 11.5%, and if V30 was62.5%, the risk was 70.8% (p0.0001). A Cox regression curve stratified by two levels of V30 value was created (odds ratio, 12.6).The thyroid V30 predicts the risk of developing HT after sequential chemo-radiotherapy and defines a useful constraint to consider for more accurate HL treatment planning.

Purpose To identify dose–heart-volume constraints that correlate with the risk of developing asymptomatic valvular defects (VD) in Hodgkin's lymphoma (HL) patients treated with three-dimensional radiotherapy (RT). Patients and methods Fifty-six patients undergoing cytotoxic chemotherapy (CHT) and involved-field radiation treatment for HL were retrospectively analyzed. Electro-echocardiography was performed before CHT, after CHT, and after RT. For the entire heart, for right and left ventricle (RV, LV), right and left atrium (RA, LA) percentage of volume exceeding 5–30Gy in increment of 5Gy ( V x ), and dosimetric parameters were calculated using 1.6Gy fraction as reference. To evaluate clinical and dosimetric factors possibly associated with VD, univariate and multivariate logistic regression analyses were performed. Results At a median follow up of 70.5months, 32.1% of patients developed VD (regurgitation and/or stenosis): 25.0% developed mitral, 5.4% developed aortic, and 14.3% tricuspid VD. In particular the percentage of LA exceeding 25Gy (LA- V 25 ) and the percentage of LV exceeding 30Gy (LV- V 30 ) correlated with mitral and aortic VD with an odds ratio (OR) of 5.7 (LA- V 25 >63.0% vs. LA- V 25 ⩽63.0%) and OR of 4.4 (LV- V 30 >25% vs. LV- V 30 ⩽25%), respectively. RV- V 30 correlated with tricuspid VD (OR=7.2, RV- V 30 >65% vs. RV- V 30 ⩽65%). Conclusion LA- V 25 , LV- and RV- V 30 prove to be predictors of asymptomatic alteration of valve functionality.