Thyroid volume changes following adjuvant radiation therapy for breast cancer.

Background and purpose: Incidental thyroid gland irradiation frequently occurs in breast cancer patients who receive regional nodal irradiation (RNI) to the supraclavicular (SCV) region. Recent studies suggest hypothyroidism (HT) is a complication of radiation therapy (RT) that includes SCV fields. We retrospectively analyzed patients who received RNI to evaluate thyroid gland evolution following RT as well as its association with the development of HT. Materials and methods: 61 breast cancer patients received SCV-directed RT between 2007 and 2019 and met inclusion criteria. Thyroid glands were retrospectively contoured on CT simulation and follow-up images. Individual dose-volume histograms were analyzed to determine thyroid volume within and outside specific isodose lines. Relative thyroid volume changes based on different radiation doses were estimated by fusing post-RT scans with CT simulation. Logistic regression was performed to assess thyroid volume changes as a factor in the development of HT. Results: Median pre-treatment thyroid volume was 11.8 cc (range: 6.3-74.1 cc) with a median of 42.2 % within the 20 Gy and 23.2 % within the 40 Gy isodose lines. A significant decrease in thyroid volume was noted by 1-year post-treatment (p < 0.0001) and thereafter. By 4 years post-treatment, average thyroid volume was decreased by 29.7 % (range: 2.3-64.4 %). Thyroid volume receiving 40 Gy or higher demonstrated a greater decrease compared to those receiving lower irradiation dosage. HT occurred in 17 patients (27.9 %). Patients who developed HT displayed a larger decrease in the thyroid volume receiving between 20 and 40 Gy at 12 months (p = 0.033). Conclusion: Our study demonstrates for the first time that a reduction in thyroid volume may be seen as early as 6 months after SCV-directed RT for breast cancer, which correlates with development of clinical and subclinical HT. Furthermore, a dose-dependent correlation exists between thyroid subvolume reduction and SCV-directed RT in breast cancer patients. As feasible, efforts should be made to reduce the dose to the thyroid in patients who undergo RNI for breast cancer.

Tumor control and cosmetic outcome of weekly iridium-192 high-dose-rate brachytherapy for nonmelanoma skin cancers in the elderly.

PURPOSE: Radiotherapy with high-dose-rate (HDR) brachytherapy is used to treat nonmelanoma skin cancers. We retrospectively analyzed a hypofractionated regimen to assess its safety and efficacy in elderly patients ≥70 years. METHODS AND MATERIALS: Forty-eight patients with 67 lesions treated since 2016 with catheter-based iridium-192 HDR brachytherapy using a custom mold or three-dimensional-printed applicator met inclusion criteria. Treatment was 36 Gy in six weekly fractions. Local and locoregional control were assessed with Kaplan-Meier curves. Acute and late toxicity were graded as per Common Terminology Criteria for Adverse Events, version 5. Cosmesis was defined as "excellent" (indistinguishable from untreated skin), "good" (minimal changes), or "poor" (extensive changes). Univariate analyses were performed. RESULTS: Median age was 85.7 years, and 21 were female. Durable local control occurred in 63 lesions (94.0%), giving estimated local control of 100% at 6 months, 95.1% at 1 year, and 88.8% at 2 years. No factors were predictive of local control on univariate analysis. All experienced acute toxicity that ultimately resolved: 28.4% Grade 2 and 4.5% Grade 3. Larger treatment volume receiving ≥36 Gy was associated with increased Grade ≥2 acute toxicity. Patients experienced late Grade 2 and late Grade 4 toxicity after 6.5% treatments each. Younger age was associated with increased Grade ≥2 late toxicity. "Good" or better cosmesis occurred in 93.2%, and "poor" cosmesis was associated with lower extremities and larger lesions. CONCLUSIONS: Hypofractionated HDR brachytherapy using 36 Gy in six weekly fractions is associated with satisfactory locoregional control and cosmesis with minimal risk of severe acute or late toxicities.

NTCP model for hypothyroidism after supraclavicular-directed radiation therapy for breast cancer.

BACKGROUND AND PURPOSE: Hypothyroidism (HT) is a well-known complication of radiation (RT) that includes supraclavicular (SCV) fields. We analyzed breast cancer patients who received SCV-directed RT to evaluate predictors of HT and developed the first normal tissue complication probability (NTCP) model for HT specific to breast cancer patients. MATERIALS AND METHODS: 192 breast cancer patients received SCV-directed RT between 2007 and 2019 and met inclusion criteria. Individual dose-volume histograms were analyzed to determine thyroid volume within and outside specific isodose lines as well as minimum, mean, and maximum doses. Multivariable logistic regression was performed to assess potential clinical and treatment factors for the development of hypothyroidism. An NTCP model was created, and model validation was performed. RESULTS: Thirty-seven patients (19.3%) developed HT following SCV-directed RT at a median 25 months (range: 2-83 months). Multivariable analysis revealed longer length of follow-up (p = 0.015) and larger thyroid volume receiving less than 20 Gy (CV20Gy[cc]; p = 0.045) were significant prognostic factors (p = 0.039). IMRT was not associated with an increased risk of hypothyroidism (p = 0.28) despite lower CV20Gy[cc] (p = 0.0002). On NTCP modeling, CV20Gy[cc] ≥ 8.5 cc was associated with a risk of HT < 15%. For smaller thyroids, mean dose and thyroid volume were found to be predictive of HT risk. Model validation demonstrated comparable performances between our model and other published models (AUC 0.69-0.72). CONCLUSION: NTCP modeling within our patient cohort suggested that greater than 8.5 cc thyroid volume receiving less than 20 Gy may be a recommended dosimetric guideline to minimize HT risk in breast cancer patients receiving SCV-directed RT.

Increased plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in lung and breast cancer are altered during chest radiotherapy.

PURPOSE: Does the release of plasma matrix metalloproteinase-9 (MMP-9) by radiation-activated airway epithelial cells and infiltrating inflammatory cells play a role in the radiation damage or repair process in the lungs? We evaluated lung damage by ionizing radiation using plasma levels of MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and MMP-3 as biologic markers of tissue damage, and also their relationship to changes in pulmonary epithelial permeability, clinical signs and symptoms, and lung structural changes. METHODS AND MATERIALS: Seven serial studies were conducted in each of 8 patients undergoing chest radiotherapy (RT) for lung or breast cancer, beginning before the first treatment (baseline) and then biweekly to approximately 100 days during and after RT. Chest radiographs were monitored for each patient. Sandwich enzyme-linked immunoassays (ELISA) were used to measure plasma MMP-3, MMP-9, and TIMP-1 levels. Lung permeability was evaluated by measuring the rate of epithelial clearance of approximately 150 microCi ( approximately 5.6 MBq) inhaled (99m)Tc diethylenetriamine pentaacetate aerosol (DTPA). RESULTS: Lung and breast cancer resulted in very high plasma levels of MMP-9 (126-893 ng/mL) and TIMP-1 (496-8985 ng/mL) in all subjects studied before initiation of RT. This compares with plasma MMP-9 and TIMP-1 values in healthy volunteers of 29 +/- 11 ng/mL and 436 +/- 86 ng/mL, respectively. RT was followed by a sharp decrease in plasma MMP-9 within the first 2 weeks, but without a corresponding change in TIMP-1. In contrast, plasma MMP-3 levels, which are generally increased with inflammation, were elevated in only 1 of 5 subjects. CONCLUSION: Lung and breast cancer are associated with high plasma levels of MMP-9 and TIMP-1. These high baseline plasma levels of MMP-9 were reduced in the first 2 weeks of RT in 7 of 8 subjects, and TIMP-1 plasma levels remained high in all subjects. The decrease in plasma MMP-9 after initiation of chest RT appears to reflect a suppressive effect on cancer-induced cellular responses rather than a primary role for MMP-9 in radiation-induced lung damage. Likewise, the lack of a rise in plasma MMP-3 levels does not support a role for MMP-3 in tissue injury or repair in the lung. It remains to be determined whether plasma MMP-9 measurements will serve as a useful parameter in predicting cancer relapse.