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1.
Clin Imaging ; 68: 283-290, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32919154

RESUMO

OBJECTIVE: (1) Assess the feasibility of 13 N-ammonia cardiac PET (13 N-ammonia-PET) imaging in radiotherapy (RT) treatment position in locally-advanced breast cancer (LABC) patients. (2) Correlate pre-/post-RT changes in myocardial flow reserve (MFR) with the corresponding radiation heart dose. METHODS: Ten left-sided LABC patients undergoing Volumetric Modulated-Arc-Therapy (VMAT) to chest wall and regional lymph nodes underwent a rest/stress 13 N-ammonia-PET at baseline and (median) 13 months post-RT. Changes in cardiac functions and coronary artery Ca2+ scoring between baseline and follow-up were correlated with average RT dose to the myocardium,3 coronary territories, and 17 myocardial segments. RESULTS: Eight (of 10) patients successfully completed the study. The average rest (stress) global MBF (ml.g-1.min-1) for baseline (follow-up) were 0.83 ± 0.25 (2.4 ± 0.79) and 0.92 ± 0.30 (2.76 ± 0.71), respectively. Differences in MBF, heart rate, blood pressure, and rate-pressure product (RPP) between baseline and follow-up were insignificant (P > 0.1).Strong (R = 0.79; P < 0.01) and moderate (R = 0.53; P = 0.37) correlation existed between MBF Rest and MBF Stress, and RPP respectively. Four patients showed a reduction in MFR of up to ~41% in follow-up studies, increasing to ~52% in myocardial segments close to high-radiation isodose lines in 5/8 patients. Agatston Ca + 2 scoring were zero in both baseline and follow-up in six patients; two patients exhibited mild increase in Ca + 2 on follow-ups (range:10-20).Rest and stress LVEF's were normal (>50) for all patients in both studies. CONCLUSION: The feasibility of 13 N-ammonia-PET imaging in treatment position of LABC patients was demonstrated. MFR at 1-year post-irradiation of the heart decreased in 50% of the patients. MFR may be a potential index for early detection of cardiotoxicity in BC patients receiving RT to the chest wall.

2.
J Clin Oncol ; : JCO2000459, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32730184

RESUMO

PURPOSE: To independently evaluate the impact of axillary surgery type and regional lymph node radiation (RLNR) on breast cancer-related lymphedema (BCRL) rates in patients with breast cancer. PATIENTS AND METHODS: From 2005 to 2018, 1,815 patients with invasive breast cancer were enrolled in a lymphedema screening trial. Patients were divided into the following 4 groups according to axillary surgery approach: sentinel lymph node biopsy (SLNB) alone, SLNB+RLNR, axillary lymph node dissection (ALND) alone, and ALND+RLNR. A perometer was used to objectively assess limb volume. All patients received baseline preoperative and follow-up measurements after treatment. Lymphedema was defined as a ≥ 10% relative increase in arm volume arising > 3 months postoperatively. The primary end point was the BCRL rate across the groups. Secondary end points were 5-year locoregional control and disease-free-survival. RESULTS: The cohort included 1,340 patients with SLNB alone, 121 with SLNB+RLNR, 91 with ALND alone, and 263 with ALND+RLNR. The overall median follow-up time after diagnosis was 52.7 months for the entire cohort. The 5-year cumulative incidence rates of BCRL were 30.1%, 24.9%, 10.7%, and 8.0% for ALND+RLNR, ALND alone, SLNB+RLNR, and SLNB alone, respectively. Multivariable Cox models adjusted for age, body mass index, surgery, and reconstruction type showed that the ALND-alone group had a significantly higher BCRL risk (hazard ratio [HR], 2.66; P = .02) compared with the SLNB+RLNR group. There was no significant difference in BCRL risk between the ALND+RLNR and ALND-alone groups (HR, 1.20; P = .49) and between the SLNB-alone and SLNB+RLNR groups (HR, 1.33; P = .44). The 5-year locoregional control rates were similar for the ALND+RLNR, ALND-alone, SLNB+RLNR, and SLNB-alone groups (2.8%, 3.8%, 0%, and 2.3%, respectively). CONCLUSION: Although RLNR adds to the risk of lymphedema, the main risk factor is the type of axillary surgery used.

3.
Int J Radiat Oncol Biol Phys ; 108(1): 227-241, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32417409

RESUMO

Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivery, sequencing, and timing of RT with immunotherapy. Clinical trials addressing these issues are under way. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies.

4.
Cell Rep ; 30(5): 1385-1399.e7, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32023457

RESUMO

The Mre11-Rad50-Nbs1 complex is a DNA double-strand break sensor that mediates a tumor-suppressive DNA damage response (DDR) in cells undergoing oncogenic stress, yet the mechanisms underlying this effect are poorly understood. Using a genetically inducible primary mammary epithelial cell model, we demonstrate that Mre11 suppresses proliferation and DNA damage induced by diverse oncogenic drivers through a p53-independent mechanism. Breast tumorigenesis models engineered to express a hypomorphic Mre11 allele exhibit increased levels of oncogene-induced DNA damage, R-loop accumulation, and chromosomal instability with a characteristic copy number loss phenotype. Mre11 complex dysfunction is identified in a subset of human triple-negative breast cancers and is associated with increased sensitivity to DNA-damaging therapy and inhibitors of ataxia telangiectasia and Rad3 related (ATR) and poly (ADP-ribose) polymerase (PARP). Thus, deficiencies in the Mre11-dependent DDR drive proliferation and genome instability patterns in p53-deficient breast cancers and represent an opportunity for therapeutic exploitation.

5.
Int J Radiat Oncol Biol Phys ; 107(2): 233-234, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32105744
6.
Cancer ; 126(4): 850-860, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31747077

RESUMO

BACKGROUND: The current study was conducted to evaluate the efficacy and safety of pembrolizumab-mediated programmed cell death protein 1 inhibition plus radiotherapy (RT) in patients with metastatic triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. METHODS: The current study was a single-arm, Simon 2-stage, phase 2 clinical trial that enrolled a total of 17 patients with a median age of 52 years (range, 37-73 years). An RT dose of 3000 centigrays (cGy) was delivered in 5 daily fractions. Pembrolizumab was administered intravenously at a dose of 200 mg within 3 days of the first RT fraction, and then every 3 weeks ± 3 days until disease progression. The median follow-up was 34.5 weeks (range, 2.1-108.3 weeks). The primary endpoint of the current study was the overall response rate (ORR) at week 13 in patients with unirradiated lesions measured using Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Secondary endpoints included safety and progression-free survival. Exploratory objectives were to identify biomarkers predictive of ORR and progression-free survival. RESULTS: The ORR for the entire cohort was 17.6% (3 of 17 patients; 95% CI, 4.7%-44.2%), with 3 complete responses (CRs), 1 case of stable disease, and 13 cases of progressive disease. Eight patients died prior to week 13 due to disease progression. Among the 9 women assessed using RECIST version 1.1 at week 13, 3 (33%) achieved a CR, with a 100% reduction in tumor volume outside of the irradiated portal. The CRs were durable for 18 weeks, 20 weeks, and 108 weeks, respectively. The most common grade 1 to 2 toxicity (assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) was dermatitis (29%). Four grade 3 adverse events were attributed to pembrolizumab: fatigue, lymphopenia, and infection. No were no grade 4 adverse events or treatment-related deaths reported. CONCLUSIONS: The combination of pembrolizumab and RT was found to be safe and demonstrated encouraging activity in patients with poor-prognosis, metastatic, triple-negative breast cancer who were unselected for programmed death-ligand 1 expression. Larger clinical trials of checkpoint blockade plus RT with predictive biomarkers of response are needed.

7.
Adv Radiat Oncol ; 4(3): 447-452, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360798

RESUMO

Purpose: Internal mammary node recurrence after definitive breast cancer treatment is poorly characterized, with limited data to guide clinical management. The aim of this study was to analyze the outcomes of patients with recurrent breast cancer involving internal mammary nodes to understand their natural history and determine prognostic factors associated with improved overall survival. Methods and Materials: We performed a retrospective analysis of 553 patients with recurrent breast cancer and identified 161 patients with radiographic evidence of locoregional recurrence as a first event. A total of 67 patients (42%) were identified with internal mammary involvement. Median follow-up times were 76 months from date of initial diagnosis and 30 months from date of recurrence. Results: Of the 67 patients identified with internal mammary node failures, 10 (15%) presented with isolated recurrence, 14 (21%) presented with other sites of locoregional disease, and 43 (64%) presented with concomitant distant metastases. Median overall survival was 2.5 years and significantly associated with extent of disease (P < .0001). On multivariable analysis, concomitant distant metastases, inflammatory breast cancer, and triple negative histologic type were associated with worse overall survival, whereas salvage radiation therapy was associated with improved overall survival. Among the 10 patients with isolated internal mammary node failures, median progression-free survival was 6.0 years and salvage therapy with surgery, radiation, and chemotherapy were associated with the best outcomes. Conclusions: Patients with isolated internal mammary node recurrences achieved long-term survival with aggressive therapies, and salvage radiation therapy was associated with improved survival.

8.
J Appl Clin Med Phys ; 20(4): 45-50, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30945803

RESUMO

PURPOSE: Patients undergoing external beam accelerated partial breast irradiation (APBI) receive permanent tattoos to aid with daily setup alignment and verification. With the advent of three-dimensional (3D) body surface imaging and two-dimensional (2D) x-ray imaging-based matching to surgical clips, tattoos may not be necessary to ensure setup accuracy. We compared the accuracy of conventional tattoo-based setups to a patient setup without tattoos. MATERIALS/METHODS: Twenty consecutive patients receiving APBI at our institution from July 10, 2017 to February 13, 2018 were identified. All patients received tattoos per standard of care. Ten patients underwent setup using tattoos for initial positioning followed by surface imaging and 2D matching of surgical clips. The other ten patients underwent positioning using surface imaging followed by 2D matching without reference to tattoos. Overall setup time and orthogonal x-ray-based shifts after surface imaging per fraction were recorded. Shift data were used to calculate systematic and random error. RESULTS: Among ten patients in the "no tattoo" group, the average setup time per fraction was 6.83 min vs 8.03 min in the tattoo cohort (P < 0.01). Mean 3D vector shifts for patients in the "no tattoo" group were 4.6 vs 5.9 mm in the "tattoo" cohort (P = NS). Mean systematic errors in the "no tattoo" group were: 1.2 mm (1.5 mm SD) superior/inferior, 0.5 mm (1.6 mm SD) right/left, and 2.3 mm (1.9 mm SD) anterior/posterior directions. Mean systematic errors in the "tattoo" group were: 0.8 mm (2.2 mm SD) superior/inferior, 0.3 mm (2.5 mm SD) right/left, and 1.4 mm (4.4 mm SD) anterior/posterior directions. The random errors in the "no tattoo" group ranged from 0.6 to 0.7 mm vs 1.2 to 1.7 mm in the "tattoo" group. CONCLUSIONS: Using both surface imaging and 2D matching to surgical clips provides excellent accuracy in APBI patient alignment and setup verification with reduced setup time relative to the tattoo cohort. Skin-based tattoos may no longer be warranted for patients receiving external beam APBI.


Assuntos
Neoplasias da Mama/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Erros de Configuração em Radioterapia/prevenção & controle , Tatuagem , Estudos de Viabilidade , Feminino , Humanos , Dosagem Radioterapêutica
9.
J Am Soc Echocardiogr ; 32(4): 521-528, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30826225

RESUMO

BACKGROUND: Radiation therapy (RT)-induced cardiotoxicity is among the concerning sequelae of breast cancer (BCA) treatment, particularly in HER2-positive BCA patients who receive anthracyclines and trastuzumab-based therapy. The aim of this study was to assess for early RT-induced changes in echocardiographic and circulating biomarkers of left ventricular (LV) function and evaluate their association with radiation dose to the heart among patients with HER2-positive BCA treated with contemporary RT. METHODS: A total of 47 women with HER2-positive BCA who were treated with an anthracycline, trastuzumab, and RT to the breast and/or chest wall ± regional lymph nodes were included in this study. Two-dimensional echocardiography with speckle-tracking imaging was performed at baseline (prechemotherapy), prior to and after RT (pre-RT and post-RT), and 6 months post-RT. High-sensitivity troponin I (hsTnI) was measured pre-RT and post-RT. Associations between mean heart dose (MHD) and changes in LV function after RT were examined in multivariable linear regression models. RESULTS: The MHD was 1.8 ± 1.5 Gy for patients receiving left-sided RT (n = 26) and 1.1 ± 1.3 Gy for patients receiving right-sided RT (n = 21). Pre-RT, post-RT, and 6-month post-RT echocardiograms were performed at median (interquartile range) of 49 days (27, 77) before and 54 days (25, 78) and 195 days (175, 226) after RT, respectively. Compared with pre-RT, a minimal decrease in LV ejection fraction was observed post-RT (61% ± 7% vs 59% ± 8%; P = .003) without any significant change in global longitudinal, circumferential, or radial strain or diastolic indices at the post-RT timepoint. Median (interquartile range) concentrations of hsTnI decreased from 5.7 pg/mL (3.0, 8.7) pre-RT to 3.7 pg/mL (2.0, 5.9) post-RT. There was no significant change in systolic or diastolic indices of LV function at 6 months post-RT compared with pre-RT. MHD was not associated with changes in echocardiographic parameters of LV function after RT. CONCLUSIONS: Breast RT using contemporary techniques can be delivered without evidence of early subclinical LV dysfunction or injury as measured by echocardiography and hsTnI in patients treated with anthracyclines and trastuzumab. Future studies should focus on identifying alternative biomarkers to elucidate early RT-induced cardiovascular effects and further characterizing long-term cardiovascular outcomes associated with contemporary breast RT.

10.
Int J Radiat Oncol Biol Phys ; 103(5): 1100-1108, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508620

RESUMO

PURPOSE: Multibeam intensity modulated radiation therapy (IMRT) enhances the therapeutic index by increasing the dosimetric coverage of the targeted tumor tissues while minimizing volumes of adjacent organs receiving high doses of RT. The tradeoff is that a greater volume of lung is exposed to low doses of RT, raising concern about the risk of radiation pneumonitis (RP). METHODS AND MATERIALS: Between July 2010 and January 2013, patients with node-positive breast cancer received inverse-planned, multibeam IMRT to the breast or chest wall and regional nodes, including the internal mammary nodes (IMNs). The primary endpoint was feasibility, predefined by dosimetric treatment planning criteria. Secondary endpoints included the incidence of RP grade 3 or greater and changes in pulmonary function measured with the Common Terminology Criteria for Adverse Events version 3.0 scales, pulmonary function tests and community-acquired pneumonia questionnaires, obtained at baseline and 6 months after IMRT. Clinical follow-up was every 6 months for up to 5 years. RESULTS: Median follow-up was 53.4 months (range, 0-82 months). Of 113 patients enrolled, 104 completed follow-up procedures. Coverage of the breast or chest wall and IMN was comprehensive (median 48.1 Gy and 48.9 Gy, respectively). The median volume of lung receiving a high dose (V20Gy) and a low dose (V5) was 29% and 100%, respectively. The overall rate of respiratory toxicities was 10.6% (11/104), including 1 grade 3 RP event (0.96%). No differences were found in pulmonary function test or community-acquired pneumonia scores after IMRT. The 5-year rates of locoregional recurrence-free, disease-free, and overall survival were 93.2%, 63.6%, and 80.3%, respectively. CONCLUSIONS: Multibeam IMRT in patients with breast cancer receiving regional nodal irradiation was dosimetrically feasible, based on early treatment planning criteria. Despite the large volume of lung receiving low-dose RT, the incidence of grade 3 RP was remarkably low, justifying inverse-planned IMRT as a treatment modality for patients with high-risk breast cancer in whom conventional RT techniques prove inadequate.


Assuntos
Neoplasias da Mama/radioterapia , Pulmão/efeitos da radiação , Irradiação Linfática/métodos , Órgãos em Risco/efeitos da radiação , Pneumonite por Radiação/epidemiologia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Estudos de Viabilidade , Feminino , Seguimentos , Coração/efeitos da radiação , Humanos , Incidência , Linfonodos/patologia , Linfonodos/efeitos da radiação , Irradiação Linfática/efeitos adversos , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Projetos Piloto , Probabilidade , Pneumonite por Radiação/etiologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Testes de Função Respiratória , Parede Torácica/efeitos da radiação , Fatores de Tempo
11.
Med Dosim ; 44(2): 150-154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29801668

RESUMO

Locally advanced breast cancer patients with expander or implant reconstructions who require comprehensive postmastectomy radiotherapy (PMRT) can pose unique treatment planning challenges. Traditional 3D conformal radiation techniques often result in large dose inhomogeneity throughout the treatment volumes, inadequate target coverage, or excessive normal tissue doses. We have developed a volumetric modulated arc therapy (VMAT) planning technique without entering through the ipsilateral arm that produced adequate target volume coverage, excellent homogeneity throughout the target volume, and acceptable doses to the normal structures. Twenty left-sided and 10 right-sided patients with either ipsilateral or bilateral permanent implants or tissue expanders who received comprehensive PMRT between October 2014 and February 2016 were included in this study. Ten left-sided cases used deep inspiration breath hold (DIBH) technique, and others used free breathing (FB). Planning target volume (PTV) included chestwall, internal mammary nodes (IMNs), supraclavicular, and axillary lymph nodes. A VMAT plan using 4 or 5 partial arcs with 6 MV photon beam avoiding entering through the ipsilateral arm was generated for each patient. Prescription dose was 50 Gy in 25 fractions. PTV coverage, maximum depth of IMNs, dose homogeneity and dose to the heart, lungs, thyroid, contralateral intact breast or implant, liver, stomach, left anterior descending artery, ipsilateral brachial plexus, esophagus, spinal cord, and total MU were evaluated. PTV D95% (Gy) was 49.6 ± 0.9, 48.7 ± 0.9, and 49.5 ± 1.1; PTV D05% (Gy) was 55.7 ± 0.6, 55.1 ± 1.4, and 55.0 ± 0.7; maximum depth of IMNs (cm) was 4.3 ± 0.9, 4.6 ± 1.1, and 4.9 ± 2.3; ipsilateral lung, V20Gy (%) was 29.0 ± 2.1, 28.8 ± 2.5, and 27.5 ± 3.4; heart mean dose (Gy) was 4.2 ± 0.4, 7.5 ± 1.1, and 6.6 ± 0.8 for right-sided FB, left-sided FB, and left-sided DIBH cases, respectively. D95% of IMNs all received 100% prescription dose. The maximum dose (Gy) to the left anterior descending artery was 33.8 ± 11.7 for left-sided FB and 31.4 ± 7.3 for left-sided DIBH. VMAT technique avoiding ipsilateral arm can produce acceptable clinical plans for locally advanced breast cancer patients with expander or implant reconstructions receiving comprehensive PMRT.


Assuntos
Implantes de Mama , Neoplasias da Mama/radioterapia , Mamoplastia , Mastectomia , Radioterapia de Intensidade Modulada/métodos , Dispositivos para Expansão de Tecidos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Dosagem Radioterapêutica , Radioterapia Adjuvante , Estudos Retrospectivos
12.
Ann Surg Oncol ; 25(13): 3858-3866, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30298320

RESUMO

BACKGROUND: Low incidence of breast cancer in men (BCM) (< 1% of all breast cancers) has led to a paucity of outcome data. This study evaluated the impact of age on BCM outcomes. METHODS: For this study, BCM patients treated between 2000 and 2011 were stratified by age (≤ 65 or > 65 years). Kaplan-Meier methods were used to compare overall survival (OS) and breast cancer-specific survival (BCSS). Competing-risk methods analyzed time to second primary cancers (SPCs), with any-cause death treated as a competing risk. RESULTS: The study identified 152 BCM patients with a median age of 64 years (range 19-96 years). The median body mass index (BMI) was 28 kg/m2. Men age 65 years or younger (n = 78, 51%) were more overweight/obese than men older than 65 years (n = 74, 49%) (89% vs 74%, respectively; P = 0.008). Both groups had similar nodal metastases rates (P = 0.4), estrogen receptor positivity (P = 1), and human epidermal growth factor receptor 2 (HER2)neu overexpression (P = 0.6). Men 65 years of age or younger were more likely to receive chemotherapy (P = 0.002). The median follow-up period was 5.8 years (range 0.1-14.4 years). The 5-year OS was 86% (95% confidence interval [CI] 80-93%), whereas the 5-year BCSS was 95% (95% CI 91-99%). The BCM patients 65 years of age and younger had better OS (P = 0.003) but not BCSS (P = 0.8). The 5-year cumulative incidence of SPC was 8.4% (95% CI 3.4-13.4%). The prior SPC rate was higher for men older than 65 years (n = 20, 31%) than for those age 65 years or younger (n = 7, 11%) (P = 0.008). This did not account for differences in life years at risk. No difference was observed in SPC cumulative incidence stratified by age (P = 0.3). CONCLUSIONS: Men 65 years of age or younger received more chemotherapy and had improved OS, but not BCSS, compared with men older than 65 years. For all BCM, SPC is a risk, and appropriate screening may be warranted.


Assuntos
Neoplasias da Mama Masculina/terapia , Segunda Neoplasia Primária/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Índice de Massa Corporal , Neoplasias da Mama Masculina/metabolismo , Neoplasias da Mama Masculina/patologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Taxa de Sobrevida , Adulto Jovem
13.
Radiat Oncol ; 13(1): 187, 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30249274

RESUMO

BACKGROUND: Despite dosimetric benefits of volumetric modulated arc therapy (VMAT) in breast cancer patients with implant reconstruction receiving regional nodal irradiation (RNI), low dose to the thoracic structures remains a concern. Our goal was to report dosimetric effects of adding deep inspiration breath hold (DIBH) to VMAT in left-sided breast cancer patients with tissue expander (TE)/permanent implant (PI) reconstruction receiving RNI. METHODS: Ten consecutive breast cancer patients with unilateral or bilateral TE/PI reconstruction who were treated with a combination of VMAT and DIBH to the left reconstructed chest wall and regional nodes were prospectively identified. Free breathing (FB) and DIBH CT scans were acquired for each patient. VMAT plans for the same arc geometry were compared for FB versus DIBH. Prescription dose was 50 Gy in 25 fractions. Dosimetric differences were tested for statistical significance. RESULTS: For comparable coverage and target dose homogeneity, the mean dose to the heart reduced on average by 2.9 Gy (8.2 to 5.3 Gy), with the addition of DIBH (p < 0.05). The maximum dose to the left anterior descending (LAD) artery was reduced by 9.9 Gy (p < 0.05), which related closely to the reduction in the maximum heart dose (9.4 Gy). V05 Gy to the heart, ipsilateral lung, contralateral lung and total lung (p < 0.05) decreased on average by 29.6%, 5.8%, 15.4% and 10.8% respectively. No significant differences were seen in the ipsilateral lung V20 Gy or mean dose as well as in the mean contralateral breast/implant dose. However, V04 Gy and V03 Gy of the contralateral breast/implant were respectively reduced by 13.2% and 18.3% using DIBH (p < 0.05). CONCLUSION: Combination of VMAT and DIBH showed significant dosimetric gains for low dose to the heart, lungs and contralateral breast/implant. Not surprisingly, the mean and maximum dose to the heart and to the LAD were also reduced. DIBH should be considered with the use of VMAT in breast cancer patients with implant reconstructions receiving RNI.


Assuntos
Implantes de Mama , Suspensão da Respiração , Irradiação Linfática/métodos , Órgãos em Risco/efeitos da radiação , Exposição à Radiação/prevenção & controle , Radioterapia de Intensidade Modulada/métodos , Neoplasias Unilaterais da Mama/radioterapia , Mama/diagnóstico por imagem , Mama/efeitos da radiação , Vasos Coronários/efeitos da radiação , Feminino , Coração/efeitos da radiação , Humanos , Inalação , Pulmão/efeitos da radiação , Mamoplastia/instrumentação , Estudos Prospectivos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Dispositivos para Expansão de Tecidos , Neoplasias Unilaterais da Mama/diagnóstico por imagem
14.
Int J Radiat Oncol Biol Phys ; 101(2): 325-333, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29726361

RESUMO

PURPOSE: A 2-arm, double-blinded randomized trial was conducted to evaluate the efficacy of 0.1% mometasone furoate (MF) versus Eucerin Original (E) cream in preventing the development of moderate to severe acute radiation dermatitis (ARD) in breast cancer patients receiving postmastectomy radiation (PMRT). METHODS: Breast cancer patients undergoing chest wall with or without nodal radiation therapy (RT) (50 Gy) were eligible. Randomization (1:1) was to MF or E, applied twice daily from day 1 of PMRT to 14 days after PMRT. Patients were stratified by RT technique, body mass index, and reconstruction status. Daily bolus of 3 to 10 mm was applied in all patients. The primary endpoint was the development of provider-assessed grade ≥2 (Common Terminology Criteria for Adverse Events version 4.03) ARD with moist desquamation or any grade ≥3 dermatitis. Secondary endpoints were time to occurrence of maximum-grade dermatitis and patient-reported skin symptoms using a skin-related quality of life questionnaire, Skindex-16. Assessments were performed at baseline, weekly during PMRT, and 2 weeks after PMRT. RESULTS: 124 patients were enrolled between May 2013 and February 2016. Of those, 35% had pathologic stage III disease, 6% had cT4d disease, and 68% underwent reconstruction. Sixty percent received 3-dimensional conformal RT with photons only to the chest wall, 18% received electrons and photons, and 23% received inverse-planned intensity modulated RT. Groups were well balanced for age, skin type, and stage. The rate of moist desquamation was 54.8% in the entire cohort, with a significantly reduced incidence in the MF arm than in the E arm (43.8% vs 66.7%; P = .012). The MF arm had a lower incidence of maximum skin toxicities (P = .036) and longer time to development of grade 3 dermatitis (46 days vs 35.5 days, respectively; P ≤ .001). There was no difference in patient-reported skin outcomes between arms. CONCLUSIONS: Breast cancer patients receiving MF during PMRT experienced significantly reduced rates of moist desquamation in comparison with a control cream.


Assuntos
Neoplasias da Mama/radioterapia , Fármacos Dermatológicos/uso terapêutico , Furoato de Mometasona/uso terapêutico , Radiodermatite/prevenção & controle , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Fármacos Dermatológicos/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Lipídeos/administração & dosagem , Lipídeos/uso terapêutico , Mastectomia , Pessoa de Meia-Idade , Furoato de Mometasona/administração & dosagem , Bases para Pomadas/administração & dosagem , Bases para Pomadas/uso terapêutico , Cuidados Pós-Operatórios , Qualidade de Vida , Radiodermatite/patologia , Parede Torácica/efeitos da radiação , Resultado do Tratamento
15.
Cancer ; 124(3): 482-490, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29112227

RESUMO

BACKGROUND: High-level evidence is lacking to guide treatment decisions about postmastectomy radiation therapy (PMRT) in patients who have breast cancer with 1 to 3 positive lymph nodes who receive contemporary systemic therapies, leading to potential variations in PMRT delivery. The objective of this study was to examine nationwide trends in PMRT use in this group. METHODS: The National Cancer Data Base (NCDB) was used to identify 93,372 women who had T1-T2N1 breast cancer diagnosed between 2003 and 2012. Patients who received neoadjuvant chemotherapy or radiation therapy (RT) and those who had bilateral breast cancers were excluded. Time trends were evaluated using the Cochrane-Armitage test and correlated the receipt of PMRT with various patient demographic, facility, clinicopathologic, and treatment variables using multivariable logistic regression. A second analysis was performed for patients who were diagnosed during 2010 and included radiation oncologist density as an additional covariate. P values < .0001 were considered statistically significant. RESULTS: Overall, 22.5% of the study population received PMRT, representing an increase from 19.1% in 2003 to 30.3% in 2012. Factors associated with greater PMRT use included younger age, lower Charlson-Deyo comorbidity scores, shorter distance to the treating facility, treatment at a comprehensive cancer program, facility location in the New England Census division, and higher density of radiation oncologists. Increased PMRT use was associated with later year of diagnosis, receipt of chemotherapy, receipt of hormone therapy, higher grade disease, larger tumor size, greater numbers of positive lymph nodes, positive margins, and absence of immediate breast reconstruction (all P < .0001). CONCLUSIONS: The receipt of PMRT by patients with breast cancer who have 1 to 3 positive lymph nodes has increased over time, with wide variability in practice patterns in the United States. Cancer 2018;124:482-90. © 2017 American Cancer Society.


Assuntos
Neoplasias da Mama/radioterapia , Mastectomia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Terapia Combinada , Bases de Dados Factuais , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Adulto Jovem
16.
Lancet Oncol ; 18(12): e742-e753, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29208440

RESUMO

As the use of breast reconstruction and postmastectomy radiotherapy (PMRT) has increased over the past decade, the typical approach to integrating radiotherapy with breast reconstruction has provoked intense controversy in the management of breast cancer. PMRT can lead to an increased frequency of complications in the reconstructed breast. Conversely, the reconstructed breast can increase the complexity of radiotherapy delivery. How to minimise the frequency of complications without compromising oncological or cosmetic outcomes of the reconstructed breast is an important shared multidisciplinary goal for oncologists and their patients. Several questions remain, however, regarding the type of reconstruction that should be used with PMRT, when reconstruction should be done relative to PMRT and whether radiotherapy treatment should be directed towards the tissue expander or the implant for women who opt for a two-stage expander-implant reconstruction. Following advances in the planning of radiotherapy treatment, new questions about the application of these technologies in the setting of breast reconstruction have arisen. In this Review, we address these questions by reviewing contemporary evidence on the optimal integration of radiotherapy and breast reconstruction in the management of breast cancer.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Radioterapia Adjuvante/efeitos adversos , Adulto , Implante Mamário/efeitos adversos , Implante Mamário/métodos , Implantes de Mama , Feminino , Sobrevivência de Enxerto , Humanos , Mamoplastia/efeitos adversos , Mastectomia/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Prognóstico , Doses de Radiação , Medição de Risco , Fatores de Tempo , Resultado do Tratamento
17.
Int J Radiat Oncol Biol Phys ; 99(1): 153-164, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28816141

RESUMO

PURPOSE: Treatment with checkpoint inhibitors has shown durable responses in a number of solid tumors, including melanoma, lung, and renal cell carcinoma. However, most breast cancers are resistant to monotherapy with checkpoint inhibitors. Radiation therapy (RT) has been shown to have a number of immunostimulatory effects, including priming the immune system, recruiting immune cells to the tumor environment, and altering the immunosuppressive effects of the tumor microenvironment. RT therefore represents a promising adjuvant therapy to checkpoint blockade in breast cancer. METHODS AND MATERIALS: We review the data from the checkpoint blockade studies on breast cancer reported to date, the mechanisms by which RT potentiates immune responses, the preclinical and clinical data of checkpoint blockade and RT combinations, and the landscape of current clinical trials of RT and immune checkpoint inhibitor combinations in breast cancer. RESULTS: Clinical trials with checkpoint blockade therapy have demonstrated response rates of up to 19% in breast cancer, and many of the responses are durable. Preclinical data indicate that RT combined with checkpoint inhibition synergizes not only to enhance antitumor efficacy but also to induce responses outside of the radiation field. Thus multiple clinical trials are currently investigating the combination of checkpoint inhibition with RT. CONCLUSIONS: The use of combination strategies that incorporate chemotherapy and/or local strategies such as RT may be needed to augment responses to immune therapy in breast cancer. Preclinical and clinical results show that RT in combination with checkpoint blockade may be a promising therapeutic option in breast cancer.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Neoplasias da Mama/radioterapia , Neoplasias da Mama/terapia , Antígeno CTLA-4/antagonistas & inibidores , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/química , Neoplasias da Mama/imunologia , Antígeno CTLA-4/imunologia , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Feminino , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Ativação Linfocitária/imunologia , Linfócitos do Interstício Tumoral/imunologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Dosagem Radioterapêutica , Linfócitos T/imunologia
18.
Curr Breast Cancer Rep ; 9(1): 45-51, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28344743

RESUMO

The abscopal effect refers to the ability of localized radiation to trigger systemic antitumor effects. Over the past 50 years, reports on the abscopal effect arising from conventional radiation have been relatively rare. However, with the continued development and use of immunotherapy strategies incorporating radiotherapy with targeted immunomodulators and immune checkpoint blockade, the abscopal effect is becoming increasingly relevant in less immunogenic tumors such as breast cancer. Here, we review the mechanism of the abscopal effect, the current preclinical and clinical data, and the application of the abscopal effect in designing clinical trials of immunotherapy combined with radiotherapy in breast cancer.

19.
J Reconstr Microsurg ; 33(5): 312-317, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28235218

RESUMO

Background Immediate breast reconstruction (IBR) is often deferred, when postmastectomy radiotherapy (PMRT) is anticipated, due to high complication rates. Nonetheless, because of robust data supporting improved health-related quality of life associated with reconstruction, physicians and patients may be more accepting of tradeoffs. The current study explores national trends of IBR utilization rates and methods in the setting of PMRT, using the National Cancer Database (NCDB). The study hypothesis is that prosthetic techniques have become the most common method of IBR in the setting of PMRT. Methods NCDB was queried from 2004 to 2013 for women, who underwent mastectomy with or without IBR. Patients were grouped according to PMRT status. Multivariate logistic regression was used to calculate odds of IBR in the setting of PMRT. Trend analyses were done for rates and methods of IBR using Poisson regression to determine incidence rate ratios (IRRs). Results In multivariate analysis, radiated patients were 30% less likely to receive IBR (p < 0.05). The rate increase in IBR was greater in radiated compared with nonradiated patients (IRR: 1.12 vs. 1.09). Rates of reconstruction increased more so in radiated compared with nonradiated patients for both implants (IRR 1.15 vs. 1.11) and autologous techniques (IRR 1.08 vs. 1.06). Autologous reconstructions were more common in those receiving PMRT until 2005 (p < 0.05), with no predominant technique thereafter. Conclusion Although IBR remains a relative contraindication, rates of IBR are increasing to a greater extent in patients receiving PMRT. Implants have surpassed autologous techniques as the most commonly used method of breast reconstruction in this setting.


Assuntos
Implantes de Mama/estatística & dados numéricos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mamoplastia/estatística & dados numéricos , Radioterapia Adjuvante/estatística & dados numéricos , Adulto , Bases de Dados Factuais , Tomada de Decisões , Feminino , Seguimentos , Humanos , Mamoplastia/tendências , Mastectomia , Padrões de Prática Médica , Qualidade de Vida , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
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