RESUMO
PURPOSE: To evaluate the targetability of late-stage cervical cancer by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-induced hyperthermia (HT) as an adjuvant to radiation therapy (RT). METHODS: Seventy-nine cervical cancer patients (stage IIIB-IVA) who received RT with lesions visible on positron emission tomography-computed tomography (PET-CT) were retrospectively analyzed for targetability using a commercially-available HT-capable MRgHIFU system. Targetability was assessed for both primary targets and/or any metastatic lymph nodes using both posterior (supine) and anterior (prone) patient setups relative to the transducer. Thirty-four different angles of rotation along subjects' longitudinal axis were analyzed. Targetability was categorized as: (1) Targetable with/without minimal intervention; (2) Not targetable. To determine if any factors could be used for prospective screening of patients, potential associations between demographic/anatomical factors and targetability were analyzed. RESULTS: 72.15% primary tumors and 33.96% metastatic lymph nodes were targetable from at least one angle. 49.37% and 39.24% of primary tumors could be targeted with patient laying in supine and prone positions, respectively. 25°-30° rotation and 0° rotation had the highest rate of the posterior and anterior targetability, respectively. The ventral depth of the tumor and its distance to the coccyx were statistically correlated with the anterior and posterior targetability, respectively. CONCLUSION: Most late-stage cervical cancer primaries were targetable by MRgHIFU HT requiring either no/minimal intervention. A rotation of 0° or 25°-30° relative to the transducer might benefit anterior and posterior targetability, respectively. Certain demographic/anatomic parameters might be useful in screening patients for treatability.
Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Neoplasias do Colo do Útero , Feminino , Humanos , Hipertermia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapiaRESUMO
PURPOSE: To evaluate the cost-effectiveness of axillary observation versus sentinel lymph node biopsy (SLNB) after negative axillary ultrasound (AUS). In patients with clinical T1-T2 N0 breast cancer and negative AUS, SLNB is the current standard of care for axillary staging. However, SLNB is costly, invasive, decreasing in importance for medical decision-making, and is not considered therapeutic. Observation alone is currently being evaluated in randomized clinical trials, and is thought to be non-inferior to SLNB for patients with negative AUS. METHODS: We performed cost-effectiveness analyses of observation versus SLNB after negative AUS in postmenopausal women with clinical T1-T2 N0, HR+/HER2- breast cancer. Costs at the 2016 price level were evaluated from a third-party commercial payer perspective using the MarketScan® Database. We compared cost, quality-adjusted life years (QALYs), and net monetary benefit (NMB). Multiple sensitivity analyses varying baseline probabilities, costs, utilities, and willingness-to-pay thresholds were performed. RESULTS: Observation was superior to SLNB for patients with N0 and N1 disease, and for the entire patient population (NMB in US$: $655,659 for observation versus $641,778 for SLNB for the entire patient population). In the N0 and N1 groups, observation incurred lower cost and was associated with greater QALYs. SLNB was superior for patients with > 3 positive lymph nodes, representing approximately 5% of the population. Sensitivity analyses consistently demonstrated that observation is the optimal strategy for AUS-negative patients. CONCLUSION: Considering both cost and effectiveness, observation is superior to SLNB in postmenopausal women with cT1-T2 N0, HR+/HER2- breast cancer and negative AUS.
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Neoplasias da Mama/economia , Receptor alfa de Estrogênio/metabolismo , Observação/métodos , Pós-Menopausa/fisiologia , Receptores de Progesterona/metabolismo , Biópsia de Linfonodo Sentinela/métodos , Ultrassonografia Mamária/métodos , Axila , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Tomada de Decisão Clínica , Feminino , Humanos , Linfonodos/patologiaRESUMO
BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) predicts decreased distant metastasis. However, most patients do not experience pCR, and other risk factors for distant metastasis after NAC are poorly characterized. This study investigated factors predictive of distant metastasis in TNBC without pCR after NAC. METHODS: Women with TNBC treated with NAC, surgery, and radiation therapy in 2000 through 2013 were reviewed. Freedom from distant metastasis (FFDM) was compared between patients with and without pCR using the Kaplan-Meier method. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of distant metastasis. RESULTS: We identified 153 patients with median follow-up of 4.0 years (range, 0.5-14.0 years). After NAC, 108 had residual disease (pCR, 29%). Five-year FFDM was 98% and 55% in patients with and without pCR, respectively (P<.001). Factors independently predicting FFDM in patients without pCR were pathologic nodal positivity (hazard ratio, 3.08; 95% CI, 1.54-6.14; P=.001) and lymphovascular space invasion (hazard ratio, 1.91; 95% CI, 1.07-3.43; P=.030). Patients with a greater number of factors had worse FFDM; 5-year FFDM was 76.5% for patients with no factors (n=38) versus 54.9% and 27.5% for patients with 1 (n=44) and 2 factors (n=26), respectively (P<.001). CONCLUSIONS: Lack of pCR after NAC resulted in worse overall survival and FFDM, despite trimodality therapy. In patients with residual disease after NAC, pathologic lymph node positivity and lymphovascular space invasion predicted worse FFDM.
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Terapia Neoadjuvante/métodos , Neoplasias de Mama Triplo Negativas/complicações , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
PURPOSE: To characterize temperature fields and tissue damage profiles of large-volume hyperthermia (HT) induced by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) in deep and superficial targets in vivo in a porcine model. METHODS: Nineteen HT sessions were performed in vivo with a commercial MRgHIFU system (Sonalleve® V2, Profound Medical Inc., Mississauga, ON, Canada) in hind leg muscles of eight pigs with temperature fields of cross-sectional diameter of 58-mm. Temperature statistics evaluated in the target region-of-interest (tROI) included accuracy, temporal variation, and uniformity. The impact of the number and location of imaging planes for feedback-based temperature control were investigated. Temperature fields were characterized by time-in-range (TIR, the duration each voxel stays within 40-45 °C) maps. Tissue damage was characterized by contrast-enhanced MRI, and macroscopic and histopathological analysis. The performance of the Sonalleve® system was benchmarked against a commercial phantom. RESULTS: Across all HT sessions, the mean difference between the average temperature (Tavg) and the desired temperature was -0.4 ± 0.5 °C; the standard deviation of temperature 1.2 ± 0.2 °C; the temporal variation of Tavg for 30-min HT was 0.6 ± 0.2 °C, and the temperature uniformity was 1.5 ± 0.2 °C. A difference of 2.2-cm (in pig) and 1.5-cm (in phantom) in TIR dimensions was observed when applying feedback-based plane(s) at different locations. Histopathology showed 62.5% of examined HT sessions presenting myofiber degeneration/necrosis within the target volume. CONCLUSION: Large-volume MRgHIFU-mediated HT was successfully implemented and characterized in a porcine model in deep and superficial targets in vivo with heating distributions modifiable by user-definable parameters.
Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Hipertermia , Animais , Estudos Transversais , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , SuínosRESUMO
PURPOSE: To perform a comprehensive validation of plans generated on a preconfigured Halcyon 2.0 with preloaded beam model, including evaluations of new features and implementing the patient specific quality assurance (PSQA) process with multiple detectors. METHODS: A total of 56 plans were generated in Eclipse V15.6 (Varian Medical System) with a preconfigured Halcyon treatment machine. Ten plans were developed via the AAPM TG-119 test suite with both IMRT and VMAT techniques. 34 clinically treated plans using C-arm LINAC from 24 patients were replanned on Halcyon using IMRT or VMAT techniques for a variety of sites including: brain, head and neck, lung, breast, abdomen, and pelvis. Six of those plans were breast VMAT plans utilizing the extended treatment field technique available with Halcyon 2.0. The dynamically flattened beam (DFB), another new feature on Halcyon 2.0, was also used for an AP/PA spine and four field box pelvis, as well as ten 3D breast plans. All 56 plans were measured with an ion chamber (IC), film, portal dosimetry (PD), ArcCHECK, and Delta4. Tolerance and action limits were calculated and compared to the recommendations of TG-218. RESULTS: TG-119 IC and film confidence limits met those set by the task group, except for IMRT target point dose. Forty-four of 46 clinical plans were within 3% for IC measurements. Average gamma passing rates with 3% dose difference and 2mm distance-to-agreement for IMRT/VMAT plans were: Film - 96.8%, PD - 99.9%, ArcCHECK - 99.1%, and Delta4 - 99.2%. Calculated action limits were: Film - 86.3%, PD - 98.4%, ArcCHECK - 96.1%, and Delta4 - 95.7%. Extended treatment field technique was fully validated and 3D plans with DFB had similar results to IMRT/VMAT plans. CONCLUSION: Halcyon plan deliveries were verified with multiple measurement devices. New features of Halcyon 2.0 were also validated. Traditional PSQA techniques and process specific tolerance and action limits were successfully implemented.
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Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Aceleradores de Partículas , Radiometria , Dosagem RadioterapêuticaRESUMO
BACKGROUND: This study evaluated factors predictive of locoregional recurrence (LRR) in women with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy who do not experience pathologic complete response (pCR). METHODS: This is a single-institution retrospective review of women with TNBC treated with neoadjuvant chemotherapy, surgery, and radiation therapy in 2000 through 2013. LRR was estimated between patients with and without pCR using the Kaplan-Meier method. Patient-, tumor-, and treatment-specific factors in patients without pCR were analyzed using the Cox proportional hazards method to evaluate factors predictive of LRR. Log-rank statistics were then used to compare LRR among these risk factors. RESULTS: A total of 153 patients with a median follow-up of 48.6 months were included. The 4-year overall survival and LRR were 70% and 15%, respectively, and the 4-year LRR in patients with pCR was 0% versus 22.0% in those without (P<.001). In patients without pCR, lymphovascular space invasion (LVSI; hazard ratio, 3.92; 95% CI, 1.64-9.38; P=.002) and extranodal extension (ENE; hazard ratio, 3.32; 95% CI, 1.35-8.15; P=.009) were significant predictors of LRR in multivariable analysis. In these patients, the 4-year LRR with LVSI was 39.8% versus 15.0% without (P<.001). Similarly, the 4-year LRR was 48.1% with ENE versus 16.1% without (P=.002). In patients without pCR, the presence of both LVSI and ENE were associated with an even further increased risk of LRR compared with patients with either LVSI or ENE alone and those with neither LVSI nor ENE in the residual tumor (P<.001). CONCLUSIONS: In patients without pCR, the presence of LVSI and ENE increases the risk of LRR in TNBC. The risk of LRR is compounded when both LVSI and ENE are present in the same patient. Future clinical trials are warranted to lower the risk of LRR in these high-risk patients.
Assuntos
Terapia Neoadjuvante/métodos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Purpose: To evaluate the feasibility and assess safety parameters of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated hyperthermia (HT; heating to 40-45 °C) in various pelvic targets in a porcine model in vivo.Methods: Thirteen HT treatments were performed in six pigs with a commercial MRgHIFU system (Sonalleve V2, Profound Medical Inc., Mississauga, Canada) to muscle adjacent to the ventral/dorsal bladder wall and uterus to administer 42 °C (±1°) for 30 min (±5%) using an 18-mm target diameter and 100 W power. Feasibility was assessed using accuracy, uniformity, and MR-thermometry performance-based metrics. Safety parameters were assessed for tissues in the targets and beam-path by contrast-enhanced MRI, gross-pathology and histopathology.Results: Across all HT sessions, the mean difference between average temperature (Tavg) and the target temperature within the target region-of-interest (tROI, the cross-section of the heated volume at focal depth) was 0.51 ± 0.33 °C. Within the tROI, the temperature standard deviation averaged 1.55 ± 0.31 °C, the average 30-min Tavg variation was 0.80 ± 0.17 °C, and the maximum difference between Tavg and the 10th- or 90th-percentile temperature averaged 2.01 ± 0.44 °C. The average time to reach ≥41 °C and cool to ≤40 °C within the tROI at the beginning and end of treatment was 47.25 ± 27.47 s and 66.37 ± 62.68 s, respectively. Compared to unheated controls, no abnormally-perfused tissue or permanent damage was evident in the MR images, gross pathology or histological analysis.Conclusions: MRgHIFU-mediated HT is feasible and safety assessment is satisfactory for treating an array of clinically-mimicking pelvic geometries in a porcine model in vivo, implying the technique may have utility in treating pelvic targets in human patients.
Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Imageamento por Ressonância Magnética/métodos , Pelve/patologia , Animais , Estudos de Viabilidade , Febre , Humanos , SuínosRESUMO
BACKGROUND: Triple negative breast cancer (TNBC) has worse prognosis than other subtypes of breast cancer, and many patients develop brain metastasis (BM). We developed a simple predictive model to stratify the risk of BM in TNBC patients receiving neo-adjuvant chemotherapy (NAC), surgery, and radiation therapy (RT). METHODS: Patients with TNBC who received NAC, surgery, and RT were included. Cox proportional hazards method was used to evaluate factors associated with BM. Significant factors predictive for BM on multivariate analysis (MVA) were used to develop a risk score. Patients were divided into three risk groups: low, intermediate, and high. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of the risk group in predicting BM. This predictive model was externally validated. RESULTS: A total of 160 patients were included. The median follow-up was 47.4 months. The median age at diagnosis was 49.9 years. The 2-year freedom from BM was 90.5%. Persistent lymph node positivity, HR 8.75 (1.76-43.52, P = 0.01), and lack of downstaging, HR 3.46 (1.03-11.62, P = 0.04), were significant predictors for BM. The 2-year rate of BM was 0%, 10.7%, and 30.3% (P < 0.001) in patients belonging to low-, intermediate-, and high-risk groups, respectively. Area under the ROC curve was 0.81 (P < 0.001). This model was externally validated (C-index = 0.79). CONCLUSIONS: Lack of downstaging and persistent lymph node positivity after NAC are associated with development of BM in TNBC. This model can be used by the clinicians to stratify patients into the three risk groups to identify those at increased risk of developing BM and potentially impact surveillance strategies.
Assuntos
Neoplasias da Mama/secundário , Modelos Biológicos , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Biópsia de Linfonodo SentinelaRESUMO
BACKGROUND: This study intends to develop an efficient field-in-field (FiF) planning technique with the Eclipse treatment planning system (TPS) to determine the feasibility of using the Halcyon treatment delivery system for 3D treatment of breast cancer. METHODS: Ten treatment plans were prepared on the Halcyon treatment planning system and compared to the same patients' clinically delivered TrueBeam plans which used flattened 6 MV and 10 MV beams. Patients selected for this study were treated via simple, tangential breast irradiation and did not receive radiotherapy of the supraclavicular or internal mammary lymph nodes. Planning target volumes (PTV) volumes ranged from 519 cc to 1211 cc with a mean target volume of 877 cc. Several planning techniques involving collimator, gantry rotation, and number of FiF segments were investigated as well as the use of the dynamically flattened beam (DFB) - a predefined MLC pattern that is designed to provide a flattened beam profile at 10 cm depth on a standard water phantom. For comparison, the clinically delivered TrueBeam plans remained unaltered except for normalization of the target coverage to more readily compare the two treatment delivery techniques. RESULTS: Using the physician defined PTV, normalized such that 98% of the volume was covered by 95% of the prescribed dose, the Halcyon plans were deemed clinically acceptable and comparable to the TrueBeam plans by the radiation oncologist. Resulting average global maximum doses in the test patients were identical between the TrueBeam and Halcyon plans (108% of Rx) and a mean PTV dose of 102.5% vs 101.6%, respectively. CONCLUSIONS: From this study a practical and efficient planning method for delivering 3D conformal breast radiotherapy using the Halcyon linear accelerator has been developed. When normalized to the clinically desired coverage, hot spots were maintained to acceptable levels and overall plan quality was comparable to plans delivered on conventional C-arm LINACs.
Assuntos
Neoplasias da Mama/radioterapia , Órgãos em Risco/efeitos da radiação , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/instrumentação , Feminino , Humanos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodosRESUMO
PURPOSE: Since mild hyperthermia therapy (MHT) requires maintaining the temperature within a narrow window (e.g. 40-43 °C) for an extended duration (up to 1 h), accurate and precise temperature measurements are essential for ensuring safe and effective treatment. This study evaluated the precision and accuracy of MR thermometry in healthy volunteers at different anatomical sites for long scan times. METHODS: A proton resonance frequency shift method was used for MR thermometry. Eight volunteers were subjected to a 5-min scanning protocol, targeting chest wall, bladder wall, and leg muscles. Six volunteers were subjected to a 30-min scanning protocol and three volunteers were subjected to a 60-min scanning protocol, both targeting the leg muscles. The precision and accuracy of the MR thermometry were quantified. Both the mean precision and accuracy <1 °C were used as criteria for acceptable thermometry. RESULTS: Drift-corrected MR thermometry measurements based on 5-min scans of the chest wall, bladder wall, and leg muscles had accuracies of 1.41 ± 0.65, 1.86 ± 1.20, and 0.34 ± 0.44 °C, and precisions of 2.30 ± 1.21, 1.64 ± 0.56, and 0.48 ± 0.05 °C, respectively. Measurements based on 30-min scans of the leg muscles had accuracy and precision of 0.56 ± 0.05 °C and 0.42 ± 0.50 °C, respectively, while the 60-min scans had accuracy and precision of 0.49 ± 0.03 °C and 0.56 ± 0.05 °C, respectively. CONCLUSIONS: Respiration, cardiac, and digestive-related motion pose challenges to MR thermometry of the chest wall and bladder wall. The leg muscles had satisfactory temperature accuracy and precision per the chosen criteria. These results indicate that extremity locations may be preferable targets for MR-guided MHT using the existing MR thermometry technique.
Assuntos
Hipertermia Induzida , Imageamento por Ressonância Magnética , Músculo Esquelético , Termometria/métodos , Parede Torácica , Bexiga Urinária , Adulto , Feminino , Voluntários Saudáveis , Humanos , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Background To evaluate whether the timing of surgery after radiation in autologous breast reconstruction affects major complications. Methods We performed a retrospective review of 454 free flaps (331 patients) for breast reconstruction at a single institution from 2003 to 2014. Charts were reviewed for age, BMI, laterality, flap type (TRAM, msTRAM, DIEP), surgeon, donor vessels (IMA, TD), chemotherapy, smoking, diabetes, hypertension, DVT, venous anastomoses, vein size, and time from radiation (none, < 12 months, or ≥ 12 months). The primary outcome of major complications was defined as partial/total flap loss, thrombosis, ischemia, or hematoma requiring return to the operating room. To identify independent predictors of major complications, a multivariate logistic regression was constructed. Alpha = 0.05 indicated significance in all tests. Results Average age was 47.4 ± 8.4. Free flaps consisted of msTRAM (41.1%), TRAM (29.6%), or DIEP (29.3%). The donor vessel was IMA in 66.9% of flaps or TD in 33.0% of patients with 90.7% using only one vein and 9.3% with two veins. The average IMA/TDV size was 2.5 cm ± 0.5. Preoperative radiation occurred in 31.2% of flaps. There were 54 flaps with at least one major complication (11.7%). On multivariate regression, only flap type (OR =4.04, p < .01) and vein size (OR = 0.13, p = 0.02) independently predicted major complications. Conclusion There was no significant difference in major complications between flaps who had reconstruction within 12 months and greater than 12 months after radiation. Only having a more muscle sparing technique or smaller vein size were independent risk factors for major complications.
Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Complicações Pós-Operatórias/prevenção & controle , Feminino , Retalhos de Tecido Biológico , Guias como Assunto , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Reto do Abdome/transplante , Estudos Retrospectivos , Fatores de Risco , Retalhos Cirúrgicos/irrigação sanguínea , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Delayed wound healing or infection leads to premature tissue expander (TE) explantation after immediate postmastectomy breast reconstruction. A large study with sufficient duration of follow-up focusing on the impact of chemotherapy (CT) on premature TE removal after immediate breast reconstruction is lacking. METHODS: A retrospective review of patients undergoing immediate TE reconstruction was conducted. Multivariate analyses identified factors contributing to premature removal of TEs including neoadjuvant and adjuvant CT, specific chemotherapeutic regimens, and other factors like cancer stage, body mass index, smoking, radiation, and age. Kaplan-Meier curves were plotted to study the timing of premature TE removal. RESULTS: Of 899 patients with TEs, 256 received no, 295 neoadjuvant, and 348 adjuvant CT. Premature removal occurred more frequently in the neoadjuvant (17.3 %) and adjuvant (19.9 %) cohorts than the no-CT (12.5 %) cohort (p = 0.056). Premature TE removal occurred earlier (p = 0.005) in patients who received no CT than those with adjuvant CT. Radiation in patients receiving neoadjuvant CT prolonged the mean time to premature removal (p = 0.003). In the absence of radiation, premature removal occurred significantly sooner with neoadjuvant than adjuvant CT (p = 0.035). DISCUSSION: Premature removal of a TE occurs more commonly in patients treated with neoadjuvant or adjuvant CT and is most commonly observed 2-3 months after placement-well after the follow-up period recorded by the American College of Surgeons National Surgery Quality Improvement Program (NSQIP) database. These findings can be used to aid preoperative counseling and guide the timing of follow-up for these patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/cirurgia , Mamoplastia/efeitos adversos , Mastectomia/efeitos adversos , Terapia Neoadjuvante , Complicações Pós-Operatórias/tratamento farmacológico , Dispositivos para Expansão de Tecidos , Adulto , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos RetrospectivosRESUMO
Accelerated partial breast irradiation (APBI) is an excellent treatment option for many women with early stage breast cancer. Patient selection criteria include age over 40, status post lumpectomy, breast cancer (invasive or in situ disease) measuring <3 cm, negative margins (at least 2 mm), negative lymph nodes, and no lymphovascular space invasion. APBI is effective, well tolerated, and convenient. Women with early stage breast cancer and theii caregivers should be aware of this potential treatment option.
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Neoplasias da Mama/radioterapia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Radioterapia/efeitos adversos , Radioterapia/instrumentação , Radioterapia/métodos , Radioterapia/normasRESUMO
PURPOSE: Lapatinib plus whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) was hypothesized to improve the 12-week intracranial complete response (CR) rate compared with either option of radiation therapy (RT) alone for patients with brain metastases (BM) from human epidermal growth factor receptor 2-positive (HER2+) breast cancer. METHODS AND MATERIALS: This study included patients with HER2+ breast cancer with ≥1 measurable, unirradiated BM. Patients were randomized to WBRT (37.5 Gy/3 wk)/SRS (size-based dosing) ± concurrent lapatinib (1000 mg daily for 6 weeks). Secondary endpoints included objective response rate (ORR), lesion-specific response, central nervous system progression-free survival, and overall survival. RESULTS: From July 2012 to September 2019, 143 patients were randomized, with 116 analyzable for the primary endpoint. RT + lapatinib did not improve 12-week CR (0% vs 6% for RT alone, 1-sided P = .97), or ORR at 12 weeks. At 4 weeks, RT + lapatinib showed higher ORR (55% vs 42%). Higher graded prognostic assessment and ≤10 lesions were associated with higher 12-week ORR. Grade 3 and 4 adverse event rates were 8% and 0% for RT and 28% and 6% for RT + lapatinib. CONCLUSIONS: The addition of 6 weeks of concomitant lapatinib to WBRT/SRS did not improve the primary endpoint of 12-week CR rate or 12-week ORR. Adding lapatinib to WBRT/SRS showed improvement of 4-week ORR, suggesting a short-term benefit from concomitant therapy.
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Neoplasias Encefálicas , Neoplasias da Mama , Radiocirurgia , Humanos , Feminino , Lapatinib , Neoplasias da Mama/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Radiocirurgia/métodos , Encéfalo/patologiaRESUMO
INTRODUCTION: A kV imager coupled to a novel, ring-gantry radiotherapy system offers improved on-board kV-cone-beam computed tomography (CBCT) acquisition time (17-40 seconds) and image quality, which may improve CT radiotherapy image-guidance and enable online adaptive radiotherapy. We evaluated whether inter-observer contour variability over various anatomic structures was non-inferior using a novel ring gantry kV-CBCT (RG-CBCT) imager as compared to diagnostic-quality simulation CT (simCT). MATERIALS/METHODS: Seven patients undergoing radiotherapy were imaged with the RG-CBCT system at breath hold (BH) and/or free breathing (FB) for various disease sites on a prospective imaging study. Anatomy was independently contoured by seven radiation oncologists on: 1. SimCT 2. Standard C-arm kV-CBCT (CA-CBCT), and 3. Novel RG-CBCT at FB and BH. Inter-observer contour variability was evaluated by computing simultaneous truth and performance level estimation (STAPLE) consensus contours, then computing average symmetric surface distance (ASSD) and Dice similarity coefficient (DSC) between individual raters and consensus contours for comparison across image types. RESULTS: Across 7 patients, 18 organs-at-risk (OARs) were evaluated on 27 image sets. Both BH and FB RG-CBCT were non-inferior to simCT for inter-observer delineation variability across all OARs and patients by ASSD analysis (p < 0.001), whereas CA-CBCT was not (p = 0.923). RG-CBCT (FB and BH) also remained non-inferior for abdomen and breast subsites compared to simCT on ASSD analysis (p < 0.025). On DSC comparison, neither RG-CBCT nor CA-CBCT were non-inferior to simCT for all sites (p > 0.025). CONCLUSIONS: Inter-observer ability to delineate OARs using novel RG-CBCT images was non-inferior to simCT by the ASSD criterion but not DSC criterion.
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Tomografia Computadorizada de Feixe Cônico , Radioterapia Guiada por Imagem , Humanos , Estudos Prospectivos , Tomografia Computadorizada de Feixe Cônico/métodos , Radioterapia Guiada por Imagem/métodos , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
PURPOSE: In vitro data demonstrate that heat-induced radiosensitisation is maximised if hyperthermia and radiotherapy are given simultaneously, with the radiation fraction delivered midway through a hyperthermia session, rather than sequentially. The long-term normal tissue toxicity of full-dose simultaneous thermoradiotherapy is unknown. MATERIALS AND METHODS: Patients with locally advanced breast cancer (T3, T4 or more than three involved nodes or local recurrence), no prior radiotherapy, received between four and eight sessions of simultaneous thermoradiotherapy. Hyperthermia always included the primary tumour site. In addition an electively heated sector (EHS) was included. The EHS was randomised to either medial or lateral to the tumour site, with the other side an irradiated but unheated control. As per our usual practice, patients received surgery and/or chemotherapy prior to radiotherapy. Radiation doses were 46-50 Gy followed by a boost of ≤16 Gy at 1.8-2 Gy per fraction. EHS and control sectors received the same dose. RESULTS: A total of 57 evaluable cases with average follow-up of 79 months experienced two local and two nodal recurrences. There was no significant difference in ≥grade 2 toxicity for heated versus control sectors (LR χ(2 )= 0.78, p = 0.38) with no relationship between number of hyperthermia sessions and toxicity (LR χ(2 )= 2.90, p = 0.09). CONCLUSIONS: Simultaneous full-dose thermoradiotherapy for breast cancer is feasible and well tolerated, with no significant difference in late toxicity between electively heated and unheated control sectors. All patients had hyperthermia to the primary tumour site with excellent local control.
Assuntos
Neoplasias da Mama/terapia , Hipertermia Induzida , Pele/efeitos da radiação , Adulto , Neoplasias da Mama/radioterapia , Terapia Combinada/efeitos adversos , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Pessoa de Meia-Idade , Parede TorácicaAssuntos
Neoplasias da Mama/radioterapia , Mama/efeitos da radiação , Mamoplastia/métodos , Artéria Torácica Interna/efeitos da radiação , Microcirurgia , Actinas/efeitos da radiação , Adulto , Mama/irrigação sanguínea , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Tomada de Decisão Clínica , Colágeno/efeitos da radiação , Elastina/efeitos da radiação , Feminino , Humanos , Macrófagos/efeitos da radiação , Artéria Torácica Interna/cirurgia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: This study explored the feasibility of cetuximab with chemoradiation in women with cervical carcinoma and evaluated fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) to assess early response to cetuximab (NCT00292955). PATIENTS AND METHODS: Eligible patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IVB invasive carcinoma of the uterine cervix were treated on 1 of 3 dose levels (DL). DL1 consisted of neoadjuvant cetuximab, then concurrent radiotherapy with cetuximab 250 mg/m2/cisplatin 40 mg/m2, followed by weekly cetuximab. DL2 consisted of radiotherapy with cetuximab 200 mg/m2 and cisplatin 30 mg/m2. DL3 consisted of radiotherapy with cetuximab 250 mg/m2 and cisplatin 30 mg/m2. Patients underwent 18F-FDG-PET/CT before treatment, after neoadjuvant cetuximab, and at the end of treatment. RESULTS: Of the 21 patients enrolled, 9, 3, and 9 were treated in DL1, DL2, and DL3, respectively. DL1 required dose reductions due to gastrointestinal toxicities. DL2 and 3 were tolerated with 1 dose-limiting toxicity (grade 4 renal failure) at DL3. Following 3 weekly treatments of neoadjuvant cetuximab in DL1, 7 patients had maximum standardized uptake value changes on 18F-FDG-PET/CT consistent with response to cetuximab. Of the 12 patients with locally advanced disease, eleven evaluable patients had no evidence of disease on 18F-FDG-PET/CT at treatment end. Five-year progression-free survival and overall survival rates for all patients were 57.5% and 58.5%, respectively. CONCLUSIONS: Cetuximab with cisplatin 30 mg/m2 and radiotherapy was tolerated. 18F-FDG-PET/CT demonstrated early evidence of response to neoadjuvant cetuximab. With advances in precision oncology and the recent approval of pembrolizumab in metastatic cervical cancer, dual-target inhibition with an epidermal growth factor receptor inhibitor may be a promising treatment in the future.
Assuntos
Neoplasias do Colo do Útero , Cetuximab , Quimiorradioterapia/métodos , Cisplatino , Feminino , Fluordesoxiglucose F18 , Humanos , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Medicina de Precisão , Compostos Radiofarmacêuticos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapiaRESUMO
BACKGROUND: Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in patients with breast cancer. The aim of our study was to assess the effect of zoledronic acid on clearance of disseminated tumour cells (DTCs) from the bone marrow in women undergoing neoadjuvant chemotherapy for breast cancer. METHODS: Patients were recruited for this open-label, phase 2 randomised trial between March 17, 2003, and May 19, 2006, at a single centre. Eligible patients had clinical stage II-III (> or = T2 and/or > or = N1) newly diagnosed breast cancer, Eastern Cooperative Oncology Group performance status of 0 or 1, and normal cardiac, renal, and liver function. 120 women were randomly assigned, using allocation concealment, to receive 4 mg zoledronic acid intravenously every 3 weeks (n=60), or no zoledronic acid (n=60), for 1 year concomitant with four cycles of neoadjuvant epirubicin (75 mg/m(2)) plus docetaxel (75 mg/m(2)) and two cycles of adjuvant epirubicin plus docetaxel. The primary endpoint was the number of patients with detectable DTCs at 3 months. Final analysis was done 1 year after the last patient was enrolled. Analyses were done for all patients with available data at 3 months. This study is registered with ClinicalTrials.gov, number NCT00242203. FINDINGS: Of the 120 patients initially enrolled, one withdrew after signing consent and one patient's baseline bone marrow was not available. Both of these patients were in the control group. At 3 months, 109 bone-marrow samples were available for analysis. In the zoledronic acid group, bone marrow was not collected from one patient because of disease progression, one patient was taken off study because of severe diarrhoea, and two patients had not consented at the time of surgery. In the control group, bone marrow was not collected from two patients because of disease progression, one patient withdrew consent, and three patients were not consented at the time of surgery. At baseline, DTCs were detected in 26 of 60 patients in the zoledronic acid group and 28 of 58 patients in the control group. At 3 months, 17 of 56 patients receiving zoledronic acid versus 25 of 53 patients who did not receive zoledronic acid had detectable DTCs (p=0.054). The most common grade 3-4 toxicities were infection (five of 60 patients in the zoledronic acid group and six of 59 in the control group) and thrombosis (five of 60 in the zoledronic acid and two of 59 in the control group). There was one documented case of osteonecrosis in the zoledronic acid group. INTERPRETATION: Zoledronic acid administered with chemotherapy resulted in a decreased proportion of patients with DTCs detected in the bone marrow at the time of surgery. Our study supports the hypothesis that the antimetastatic effects of zoledronic acid may be through effects on DTCs. FUNDING: Novartis Pharmaceuticals and Pfizer Inc.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Difosfonatos/farmacologia , Imidazóis/farmacologia , Células Neoplásicas Circulantes/efeitos dos fármacos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Medula Óssea/patologia , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/uso terapêutico , Feminino , Humanos , Imidazóis/uso terapêutico , Pessoa de Meia-Idade , Terapia Neoadjuvante , Ácido ZoledrônicoRESUMO
INTRODUCTION: Accelerated partial breast irradiation (APBI) seeks to reduce irradiated volumes and radiation exposure for patients while maintaining acceptable clinical outcomes. Magnetic resonance image-guided radiotherapy (MRgRT) provides excellent soft-tissue contrast for treatment localization, which can reduce setup uncertainty, thus reducing margins in the external beam setting. Additionally, stereotactic body radiotherapy (SBRT)-style regimens with high gradients can also be executed. This MR-guided stereotactic APBI (MRgS-APBI) approach can be utilized for a lower number of fractions and spare a greater volume of healthy tissues compared to conventional 3D external beam APBI. METHODS: Our MRgS-APBI program was developed for two prospective non-randomized phase I/II clinical trials (20Gyx1 and 8.5Gyx3). Both breast SBRT treatment planning and MRgRT delivery techniques were described in this study. Simulation included both CT and MRI with specialized immobilization to accommodate MR-guided setup and cine-MRI treatment gating. Dosimetry data from 48 single-fraction and 19 three-fraction patients were collected and evaluated. This included planning objectives and SBRT-specific indices. During treatment, setup errors were calculated to evaluate setup reproducibility and duty cycle was calculated using cine-MRI data during gated delivery. RESULTS: In both the single- and three- fraction trials combined, 88.5% of the possible dosimetric objectives across all patients were met during planning. The majority of the planning objectives were easily achievable indicating the potential for stricter objectives for subsequent S-APBI treatments. The average magnitude of setup uncertainties was 1.0â¯cm⯱â¯0.6â¯cm across all treatments. In the three-fraction trial, the average beam-on duty-cycle for the MRI-gated delivery was 83.0⯱â¯13.0%. There were no technical MRgS-APBI related issues that resulted in discontinuation of treatment across all patients. CONCLUSION: SBRT-style dosimetry and delivery for APBI is feasible using MR-guidance. The program development and dosimetric outcomes reported here can serve as a guide for other institutions considering the clinical implementation of MR-guided stereotactic APBI.