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1.
Breast Cancer Res Treat ; 204(3): 485-495, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38183516

RESUMO

PURPOSE: Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS: We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS: 442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS: Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.


Assuntos
Braquiterapia , Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/etiologia , Braquiterapia/efeitos adversos , Mastectomia Segmentar , Mama/cirurgia , Fibrose , Resultado do Tratamento
2.
Front Oncol ; 12: 1049704, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439449

RESUMO

Accelerated partial breast irradiation (APBI) is increasingly used to treat select patients with early stage breast cancer. However, radiation technique, dose and fractionation as well as eligibility criteria differ between studies. This has led to controversy surrounding appropriate patients for APBI and an assessment of the toxicity and cosmetic outcomes of APBI as compared to whole breast irradiation (WBI). This paper reviews existing data for APBI, APBI delivery at our institution, and ongoing research to better define patient selection, treatment delivery, dosimetric considerations and toxicity outcomes.

3.
Pract Radiat Oncol ; 12(2): 106-112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34474168

RESUMO

PURPOSE: Randomized data support accelerated partial breast irradiation (APBI) for early-stage breast cancer with variable techniques and cosmesis outcomes. We have treated patients with 5-fraction prone external beam APBI for over a decade and herein report acute and late outcomes. METHODS AND MATERIALS: Patients receiving APBI 600 cGy × 5 between 2010 and 2019 were included. APBI was primarily delivered prone, with opposed tangents targeting the tumor bed expanded by 1.5 cm (cropped 6 mm from skin). Ipsilateral breast was constrained to V50% < 60% and V100% < 35%. Survival was estimated with Kaplan-Meier. Late toxicities and clinician- and patient-rated cosmesis were evaluated for patients with >6 months follow-up (FU). RESULTS: Of 345 patients meeting criteria, 14 were excluded due to APBI given for ipsilateral breast tumor recurrence (IBTR; n = 3), palliation (n = 9), and incomplete radiation therapy course (n = 2). Of the 331 remaining, median age was 70, 7.2% had ductal carcinoma in situ, and 94.3% were treated prone, with 32% treated every other day and 68% on consecutive days. Mean heart dose was 23.8 cGy for left-sided and 12.7 cGy for right-sided cancers. Ipsilateral lung V30% was 0.4%. At 5-year median FU, there were 7 (2.1%) IBTR, 9 (2.7%) contralateral recurrences, and 1 (0.3%) distant metastasis. Five-year local recurrence-free, disease-free, and overall survival was 99.5%, 96.7%, and 98.1%, respectively. When comparing patients with IBTR versus without, a higher proportion did not receive hormone therapy (71.4% vs. 26.2%, P = .018). Rates of acute grade 1 to 2 dermatitis, fatigue, and pain were 35.4%, 21.8%, and 9.4%, respectively, with no grade 3 toxicity. The rate of good-excellent physician- and patient-rated cosmesis (n = 199, median FU 2.8 years) was 92.5% and 89.4%, respectively. Patients experienced low rates of telangiectasia, fibrosis, and retraction/atrophy. CONCLUSIONS: We report excellent dosimetric, oncologic, cosmetic, and late toxicity outcomes for patients treated with 5-fraction APBI. To our knowledge this is the largest series of women treated with prone APBI.


Assuntos
Braquiterapia , Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Braquiterapia/métodos , Mama/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/radioterapia , Feminino , Humanos , Mastectomia Segmentar , Recidiva Local de Neoplasia/etiologia , Dosagem Radioterapêutica , Resultado do Tratamento
4.
Clin Lymphoma Myeloma Leuk ; 20(12): 820-829, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32800712

RESUMO

INTRODUCTION: Treatment for early-stage Hodgkin lymphoma (HL) involves radiotherapy (RT), chemotherapy, or combined modality therapy (CMT). We analyzed reduction of RT dose in CMT, particularly in the context of German Hodgkin Study Group (GHSG) HD10 randomized trial results of 2010. PATIENTS AND METHODS: The National Cancer Data Base was queried for patients with stage I-II HL receiving CMT. RT dose and associated characteristics were analyzed. Stage I and absence of B symptoms were used as a surrogate for early-stage favorable disease. RESULTS: Of 31,301 patients with stage I-II HL, 11,457 received CMT between 2004 and 2015. Using the surrogate defined above, 1955 patients (17.1%) were classified as having favorable disease. The majority (61.6%) received 30-36 Gy, while 7.0% received 20 Gy. The provision of 20 Gy was more common in stage I patients (12.3% vs. 5.4% in stage II) and at academic facilities (10.8% vs. 6.3%-8.9% at other facilities). Use of 20 Gy (vs. 30-36 Gy) was less likely with thorax site (odds ratio [OR] 0.43 vs. head and neck), stage II disease (OR 0.41), and B symptoms (OR 0.33). Notably, the use of 20 Gy increased dramatically after 2010 (the year of publication of GHSG HD10 trial results), with rates of 12.3% in 2010-2015 versus 0.1% in 2004-2009 (OR 6.3, P < .001). This was even more pronounced in cases of favorable early-stage disease, with 25.5% after 2010 versus 2.8% before 2010 (OR 13.2, P < .001). The use of doses > 36 Gy decreased over a corresponding time period (OR 0.44, P < .001). CONCLUSION: Analysis of CMT for patients with early-stage HL demonstrates variability in RT dose, including increasing use of 20 Gy and decreasing use of high doses > 36 Gy.


Assuntos
Doença de Hodgkin/radioterapia , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Adulto Jovem
5.
J Contemp Brachytherapy ; 10(6): 503-509, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30662472

RESUMO

PURPOSE: While Ir-192 remains the mainstay isotope for gynecologic high-dose-rate (HDR) brachytherapy in the U.S., Co-60 is used abroad. Co-60 has a longer half-life than Ir-192, which may lead to long-term cost savings; however, its higher energy requires greater shielding. This study analyzes Co-60 acceptability based on a one-time expense of additional shielding and reports the financial experience of Co-60 in Peru's National Cancer Institute, which uses both isotopes. MATERIAL AND METHODS: A nationwide survey was undertaken assessing physician knowledge of Co-60 and willingness-to-pay (WTP) for additional shielding, assuming a source more cost-effective than Ir-192 was available. With 440 respondents, 280 clinicians were decision-makers and provided WTPs, with results previously reported. After completing a shielding report, we estimated costs for shielding expansion, noting acceptability to decision makers' WTP. Using activity-based costing, we note the Peruvian fiscal experience. RESULTS: Shielding estimates ranged from $173,000 to $418,000. The percentage of respondents accepting high-density modular or lead shielding (for union and non-union settings) were 17.5%, 11.4%, 3.9%, and 3.2%, respectively. Shielding acceptance was associated with greater number of radiation oncologists in a respondent's department but not time in practice or the American Brachytherapy Society membership. Peru's experience noted cost savings with Co-60 of $52,400 annually. CONCLUSIONS: By comparing the cost of additional shielding for a sample institution's HDR suite with radiation oncologists' WTP, this multi-institutional collaboration noted < 20% of clinicians would accept additional shielding. Despite low acceptability in the US, Co-60 demonstrates cost-favorability in Peru and may similarly in other locations.

6.
J Cancer Educ ; 33(6): 1176-1180, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-28488259

RESUMO

Medical students at our institution all take a pre-clinical oncology course as well as a clinical radiation oncology didactic session during their clinical curriculum. The objective of this analysis is to demonstrate the impact of the radiation oncology didactic on medical student knowledge of core oncology concepts. All students received a standardized didactic lecture introducing students to core concepts of general oncology and radiation. We administered an 18-question pretest and a posttest examining student knowledge between 2012 and 2015. Changes in student responses between pre-test and post-tests were analyzed to evaluate the effectiveness of the didactic session. Over the course of three years, 319 (64.4%) of 495 students who completed the Radiology block completed both the pre-test and post-test. The average student test grade improved from 62.0% on the pretest to 69.6% on the posttest (p < 0.001). By category, students increased their score from 81.4% to 89.8% (p < 0.001) in general oncology, from 59.9% to 69.9% (p < 0.001) in breast oncology, from 43.0% to 51.0% (p < 0.001) in prostate oncology, and from 71.3% to 75.7% (p = 0.003) in radiation oncology. Students showed increases in knowledge across general oncology, prostate oncology, breast oncology, and radiation oncology.


Assuntos
Competência Clínica , Avaliação Educacional , Radioterapia (Especialidade)/educação , Estudantes de Medicina , Currículo , Feminino , Humanos , Masculino , Radio-Oncologistas
7.
Laryngoscope ; 128(4): 831-840, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28833217

RESUMO

OBJECTIVES/HYPOTHESIS: Randomized trials have demonstrated that adjuvant chemoradiotherapy (CRT) confers an overall survival (OS) benefit over adjuvant radiation therapy (RT) alone in patients with resected head and neck squamous cell carcinoma (HNSCC) with adverse pathologic features (positive surgical margins [SM+] and/or extracapsular extension [ECE]). Whether this OS benefit exists in an elderly population remains unknown. STUDY DESIGN: Retrospective database study. METHODS: Using the National Cancer Database, we identified 1,686 elderly patients (age ≥70 years) with resected HNSCC with SM+ and/or ECE, who received adjuvant CRT (491 patients, 29%) or adjuvant RT alone (1,195 patients, 71%) between 1998 and 2011. Three-year survival rates were estimated using the Kaplan-Meier method both before and after propensity score matching (PSM). Crude and adjusted hazard ratios (HR) with 95% confidence intervals (CI) were computed using Cox regression modeling. RESULTS: Median follow-up was 23.5 and 42.8 months for all and surviving patients, respectively. Three-year OS was 50.7% and 44.4% among patients receiving adjuvant CRT and RT alone, respectively (P = .002). On multivariate analysis, there was no significant improvement in OS with adjuvant CRT relative to adjuvant RT alone (HR: 0.88, 95% CI: 0.73-1.06). Similarly, a PSM cohort showed no significant difference in the 3-year OS for patients receiving adjuvant CRT versus adjuvant RT alone (48.8% and 50.9%, respectively; P = .839). CONCLUSIONS: Although the addition of chemotherapy to adjuvant RT has been proven effective in randomized trials of patients with resected HNSCC with SM+ or ECE, it may be less efficacious in an elderly patient population treated outside of a controlled trial setting. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:831-840, 2018.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia Adjuvante/mortalidade , Neoplasias Laríngeas/mortalidade , Laringectomia/mortalidade , Terapia de Salvação/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/terapia , Laringectomia/métodos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Terapia de Salvação/métodos , Taxa de Sobrevida , Resultado do Tratamento
8.
Am J Otolaryngol ; 38(4): 456-461, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28427799

RESUMO

BACKGROUND: To compare cumulative acute toxicity in head and neck cancer patients treated with concurrent chemoradiotherapy alone (CCRT) versus induction chemotherapy (IC) followed by CCRT (I/CCRT). METHODS: 77 patients underwent definitive CCRT (30 I/CCRT and 47 CCRT). Toxicity was graded using the Common Terminology Criteria for Adverse Events version 4.0. Using the TAME adverse event reporting system, short-term toxicity (T) scores were generated for IC (TIC), CCRT (TCCRT), total treatment duration (TRx), post-treatment period (TPT) and an overall score (Toverall) from treatment start to post treatment period. RESULTS: Acute toxicity other than dysphagia, odynophagia, or dermatitis was reported in 90.0% and 66.0% of I/CCRT and CCRT patients, respectively (P=0.02). Compared to CCRT group, I/CCRT patients reported greater mean TRx (TRx: 2.11 vs. 2.87, P=0.01) and Toverall (Toverall: 2.60 vs. 3.70, P=0.003). CONCLUSION: I/CCRT patients reported more cumulative acute toxicity during treatment compared to CCRT patients using the TAME reporting system.


Assuntos
Carcinoma/terapia , Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Quimioterapia de Indução/efeitos adversos , Idoso , Carcinoma/mortalidade , Carcinoma/patologia , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
9.
Pract Radiat Oncol ; 6(4): 248-254, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26777060

RESUMO

PURPOSE: To evaluate incorporation of National Cancer Comprehensive Network (NCCN) guidelines in decision making at a head and neck cancer (HNC) multidisciplinary tumor board (MDT) at an urban academic medical center. METHODS AND MATERIALS: A retrospective study of 176 HNC patients was performed. The extent to which MDT decisions and subsequent patient care incorporate NCCN guidelines was evaluated. RESULTS: A total of 173 (98.3%) HNC patients received MDT recommendations according to NCCN guidelines. Of the 159 patients treated, 153 (96.2%) received treatment according to NCCN guidelines. The MDT recommended the highest available evidence-based NCCN category guideline in 78.0%. Subsequent treatment using the same or higher category MDT recommendation occurred in 87.0% of patients. CONCLUSIONS: Evaluation of patients at an MDT using NCCN guidelines incorporates the highest level of evidence in approximately 80% of patients and translates well into subsequent care. Incorporation of the highest available NCCN guideline may be improved, although management should be individualized.


Assuntos
Tomada de Decisões/ética , Fidelidade a Diretrizes , Neoplasias de Cabeça e Pescoço/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Int J Radiat Oncol Biol Phys ; 92(4): 735-9, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-26104929

RESUMO

PURPOSE: There is a recognized need for more robust training in oncology for medical students. At our institution, we have offered a core dedicated oncology block, led by a radiation oncologist course director, during the second year of the medical school curriculum since the 2008-2009 academic year. Herein, we report the outcomes of the oncology block over the past 5 years through an analysis of student perceptions of the course, both immediately after completion of the block and in the third year. METHODS AND MATERIALS: We analyzed 2 separate surveys. The first assessed student impressions of how well the course met each of the course's learning objectives through a survey that was administered to students immediately after the oncology block in 2012. The second was administered after students completed the oncology block during the required radiology clerkship in the third year. All questions used a 5-level Likert scale and were analyzed by use of a Wilcoxon signed-rank test. RESULTS: Of the 169 students who took the oncology course in 2012, 127 (75.1%) completed the course feedback survey. Over 73% of students agreed or strongly agreed that the course met its 3 learning objectives. Of the 699 medical students who took the required radiology clerkship between 2010 and 2013, 538 participated in the second survey, for a total response rate of 77%. Of these students, 368 (68.4%) agreed or strongly agreed that the course was effective in contributing to their overall medical education. CONCLUSION: Student perceptions of the oncology block are favorable and have improved across multiple categories since the inception of the course. Students self-reported that a dedicated preclinical oncology block was effective in helping identify the basics of cancer therapy and laying the foundation for clinical electives in oncology, including radiation oncology.


Assuntos
Estágio Clínico , Neoplasias/radioterapia , Avaliação de Programas e Projetos de Saúde , Radioterapia (Especialidade)/educação , Estudantes de Medicina , Atitude , Coleta de Dados , Humanos , Desenvolvimento de Programas , Estatísticas não Paramétricas
11.
AJR Am J Roentgenol ; 202(2): 406-12, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24450684

RESUMO

OBJECTIVE: The purpose of this article is to evaluate the interreader agreement and variability of two (18)F-FDG PET parameters, metabolic tumor volume and total lesion glycolysis, in human solid tumors. MATERIALS AND METHODS: One hundred eleven patients (mean [± SD] age, 61.9 ± 12.5 years) with baseline staging FDG PET/CT scans were included. Two readers independently read the scans and segmented metabolic tumor volume and total lesion glycolysis using two fixed thresholds, 40% and 50% of the lesion's maximum standardized uptake value (SUVmax). The impact of the lesion's FDG avidity and location on reader agreement and variability was established. Intraclass correlation coefficient (ICC), precision, and Bland-Altman analysis were used to evaluate agreement and variability. RESULTS: The ICCs for 40% and 50% SUVmax segmentations of metabolic tumor volume between the readers were 0.987 and 0.995, and the corresponding values for 40% and 50% SUVmax segmentations of total lesion glycolysis were 0.987 and 0.986, respectively (p = 0.0001). The corresponding precisions were 0.5%, 0.2%, 0.5%, and 0.5%, respectively. The mean biases between the readers for 40% and 50% SUVmax segmentations of metabolic tumor volume were -1.78 ± 8.42 mL and -0.46 ± 2.1 mL and for 40% and 50% SUVmax segmentations of total lesion glycolysis were -7.3 ± 31.6 g and -2.97 ± 12.86 g, respectively. Subgroup analysis showed better precision and lesser variability for 50% SUVmax segmentations of metabolic tumor volume and total lesion glycolysis in patients with the highest and lowest FDG-avid primary tumors. The precision was highest and variability was lowest for lung tumors. CONCLUSION: There is excellent interreader agreement for measurement of metabolic tumor volume and total lesion glycolysis with 40% and 50% SUVmax threshold segmentations in human solid tumors.


Assuntos
Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Idoso , Feminino , Fluordesoxiglucose F18 , Glicólise , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Compostos Radiofarmacêuticos , Carga Tumoral
12.
AJR Am J Roentgenol ; 200(4): 884-90, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23521465

RESUMO

OBJECTIVE: Multiple myeloma is the most common cause of primary malignancy in bones. Radiography has been the imaging reference standard for decades. However, the growing use of CT, MRI, and PET technology has led to earlier diagnosis of multiple myeloma, more accurate therapy assessment, and better prediction of patient outcome. This article is focused on the evolving role of (18)F-FDG PET/CT in multiple myeloma diagnosis, therapy assessment, and prognosis. CONCLUSION: FDG PET/CT is a valuable imaging modality in diagnosis, therapy assessment, and prognosis of multiple myeloma.


Assuntos
Imagem Multimodal , Mieloma Múltiplo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Fluordesoxiglucose F18 , Humanos , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Estadiamento de Neoplasias , Compostos Radiofarmacêuticos
13.
Ann Nucl Med ; 26(7): 527-34, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22610386

RESUMO

OBJECTIVE: To compare the prognostic utility of the 2-[(18)F] fluoro-2-deoxy-D: -glucose (FDG) maximum standardized uptake value (SUV(max)), primary gross tumor volume (GTV), and FDG metabolic tumor volume (MTV) for disease control and survival in patients with head and neck squamous cell carcinoma (HNSCC) undergoing intensity-modulated radiotherapy (IMRT). METHODS: Between 2007 and 2011, 41 HNSCC patients who underwent a staging positron emission tomography with computed tomography and definitive IMRT were identified. Local (LC), nodal (NC), distant (DC), and overall (OC) control, overall survival (OS), and disease-free survival (DFS) were assessed using the Kaplan-Meier product-limit method. RESULTS: With a median follow-up of 24.2 months (range 2.7-56.3 months) local, nodal, and distant recurrences were recorded in 10, 5, and 7 patients, respectively. The median SUV(max), GTV, and MTV were 15.8, 22.2 cc, and 7.2 cc, respectively. SUV(max) did not correlate with LC (p = 0.229) and OS (p = 0.661) when analyzed by median threshold. Patients with smaller GTVs (<22.2 cc) demonstrated improved 2-year actuarial LC rates of 100 versus 56.4 % (p = 0.001) and OS rates of 94.4 versus 65.9 % (p = 0.045). Similarly, a smaller MTV (<7.2 cc) correlated with improved 2-year actuarial LC rates of 100 versus 54.2 % (p < 0.001) and OS rates of 94.7 versus 64.2 % (p = 0.04). Smaller GTV and MTV correlated with improved NC, DC, OC, and DFS, as well. CONCLUSION: GTV and MTV demonstrate superior prognostic utility as compared to SUV(max), with larger tumor volumes correlating with inferior local control and overall survival in HNSCC patients treated with definitive IMRT.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Radioterapia de Intensidade Modulada , Tomografia Computadorizada por Raios X , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Falha de Tratamento
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