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PURPOSE: The purpose was to explore the role of stereotactic body radiation therapy (SBRT) in providing local control (LC) for primary breast cancer in patients unable to undergo surgery. MATERIALS/METHODS: Between 2015 and 2019, 13 non-surgical candidates with 14 lesions were treated with SBRT for primary breast cancer. In 4 cases, SBRT was used after whole breast radiation therapy (WBRT; 40-50 Gy/20-25 fractions). SBRT dose was 30-40 âGy in 5 fractions for patients treated with SBRT alone and 25-32 âGy in 4-5 fractions for those treated with SBRT â+ âWBRT. LC and overall survival (OS) were estimated using Kaplan-Meier curves. Response was also assessed using RECIST guidelines. RESULTS: Median follow-up was 32 (range: 3.4-70.4) months. Imaging at median 2.2 (0.6-8.1) months post-SBRT showed median 43.2 â% (range: 2-100 â%) decrease in the largest diameter and median 68.7 â% (range: 27.9-100 â%) SUV reduction. There were 3 cases of local progression at 8.7-10.6 months. Estimated LC was 100 â% at 6 months and 71.6 â% at 12, 24 and 36 months. Estimated median OS was 100 â% at 6 months, 76.9 â% at 12 months, and 61.5 â% at 24 and 36 months. Acute toxicity (n â= â13; 92.9 â%) included grade (G)1 (n â= â8), G2 (n â= â4), and G4 (necrosis; n â= â1). Late toxicity included G2 edema (n â= â1) and G4 necrosis (n â= â2, including 1 consequential late effect). Only patients treated with SBRT â+ âWBRT experienced acute/late G4 toxicity, managed with resection or steroids. CONCLUSIONS: SBRT to primary breast cancer resulted in good LC in non-surgical/metastatic patients. Although necrosis (n â= â2) occurred in the SBRT â+ âWBRT group, it was successfully salvaged.
Assuntos
Neoplasias da Mama , Radiocirurgia , Humanos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Radiocirurgia/métodos , Radiocirurgia/efeitos adversos , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Seguimentos , PrognósticoRESUMO
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.
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Overexpression of oncoproteins is a major cause of treatment failure using current chemotherapeutic drugs. Drug-induced degradation of oncoproteins is feasible and can improve clinical outcomes in diverse types of cancers. Mortalin-2 (mot-2) is a dominant oncoprotein in several tumors, including colorectal cancer (CRC). In addition to inactivating the p53 tumor suppressor protein, mot-2 enhances tumor cell invasion and migration. Thus, mot-2 is considered a potential therapeutic target in several cancer types. The current study investigated the biological role of a ubiquitin-like protein called UBXN2A in the regulation of mot-2 turnover. An orthogonal ubiquitin transfer technology followed by immunoprecipitation, in vitro ubiquitination, and Magnetic Beads TUBE2 pull-down experiments revealed that UBXN2A promotes carboxyl terminus of the HSP70-interacting protein (CHIP)-dependent ubiquitination of mot-2. We subsequently showed that UBXN2A increases proteasomal degradation of mot-2. A subcellular compartmentalization experiment revealed that induced UBXN2A decreases the level of mot-2 and its chaperone partner, HSP60. Pharmacological upregulation of UBXN2A using a small molecule, veratridine (VTD), decreases the level of mot-2 in cancer cells. Consistent with the in vitro results, UBXN2A+/- mice exhibited selective elevation of mot-2 in colon tissues. An in vitro Anti-K48 TUBE isolation approach showed that recombinant UBXN2A enhances proteasomal degradation of mot-2 in mouse colon tissues. Finally, we observed enhanced association of CHIP with the UBXN2A-mot-2 complex in tumors in an azoxymethane/dextran sulfate sodium-induced mouse CRC model. The existence of a multiprotein complex containing UBXN2A, CHIP, and mot-2 suggests a synergistic tumor suppressor activity of UBXN2A and CHIP in mot-2-enriched tumors. This finding validates the UBXN2A-CHIP axis as a novel and potential therapeutic target in CRC.
