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1.
Anticancer Res ; 40(9): 5291-5294, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878819

RESUMO

BACKGROUND/AIM: Palbociclib is an FDA-approved cyclin-dependent kinase inhibitor for the treatment of advanced breast cancer. Limited information is available regarding the toxicity of palbociclib and concurrent radiation therapy. CASE REPORT: Herein, we report a case of esophageal toxicity in a patient treated with palbociclib and radiation therapy. A 63-year-old woman was treated with palbociclib followed by palliative radiation therapy. The patient presented three days after completing radiation therapy with severe odynophagia, and dysphagia and was found to have grade 2-3 esophageal ulcers. Palbociclib and radiation therapy was held on admission, and a resolution of her symptoms and improvement in her oral intake was noted at which time she was restarted on palbociclib with no further radiation treatment. CONCLUSION: Caution is advised when patients are undergoing concurrent palbociclib and even low-dose palliative radiation treatment. In these patients, providers should maintain a high index of suspicion for toxicities such as dermatitis or mucositis.


Assuntos
Antineoplásicos/efeitos adversos , Mucosite/diagnóstico , Mucosite/etiologia , Piperazinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Endoscopia Gastrointestinal , Feminino , Humanos , Cuidados Paliativos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Dosagem Radioterapêutica , Radioterapia Adjuvante/métodos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
2.
Zhonghua Zhong Liu Za Zhi ; 42(8): 682-686, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867462

RESUMO

Objective: To analyze the safety and short-term efficacy of breast-conserving surgery combined with intraoperative radiotherapy for early-stage breast cancer. Methods: A total of 101 consecutive patients who received breast-conserving surgery plus intraoperative radiotherapy were recruited to summarize the recent follow-up results and clinicopathological data. Univariate analysis and Logistic regression model were used to evaluate the factors affecting the postoperative adverse reactions and cosmetic effects. Results: Among 101 patients, 4 patients had recurrence or metastasis. The 3-years disease free survival rate was 94.9%, and the 3-years cumulative recurrence rate was 5.1%. Univariate analysis showed that the menstrual status and postoperative whole breast radiotherapy were associated with the postoperative adverse reactions (P<0.05). The T stage and applicator diameter were associated with the cosmetic effect (P<0.05). Multivariate analysis indicated that the diameter of the applicator (OR=3.701, P=0.026) and postoperative whole breast radiotherapy (OR=5.962, P=0.005) were independent factors for the postoperative adverse reactions, and the diameter of the applicator (OR=2.522, P=0.037) was an independent factor for the cosmetic effect. Conclusion: Breast-conserving surgery combined with intraoperative radiotherapy shows safety and good short-term efficacy in low-risk early-stage breast cancer.


Assuntos
Neoplasias da Mama/terapia , Mastectomia Segmentar , Radioterapia Adjuvante/métodos , Neoplasias da Mama/patologia , Terapia Combinada , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Resultado do Tratamento
3.
Am J Clin Oncol ; 43(9): 648-653, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889835

RESUMO

OBJECTIVES: Optimal radiation target volumes for neoadjuvant therapy in patients with borderline resectable pancreatic cancer (BRPCa) are undefined. Most local recurrences are near the celiac axis and superior mesenteric artery. Methods for generating radiation target volumes include symmetric expansion around the tumor or a customized vascular based approach. We investigated 3 current prospective trials' coverage of vascular regions at increased risk of recurrence by comparing them to 2 reference standards. MATERIALS AND METHODS: Fourteen computed tomography simulation scans from an institutional prospective trial on BRPCa were used to replicate distinct volumes corresponding to each of 3 contemporary BRPCa trials. Trial volumes were compared with 2 reference volumes (vascular planning target volume and Hopkins planning target volume), which were both based on vascular regions at increased risk of recurrence. Boolean operators and DICE analyses were performed to evaluate trial volume coverage of reference standards. RESULTS: A total of 42 target volumes and 28 reference volumes were created using the 14-patient data set. DICE coefficients were highly variable ranging from 0.11 to 0.99. Mean % coverage of reference volumes ranged from 5.8% to 98.6%. CONCLUSIONS: The wide range of DICE coefficients and coverage indicate heterogeneity in high risk vascular target coverage using symmetric Boolean expansions from the primary tumor. This approach may inadequately cover regions at high risk of local recurrence in BRPCa. A customized clinical target volume that specifically includes the superior mesenteric artery and celiac axis will improve coverage to this region and will account for individual and tumor variability.


Assuntos
Artéria Celíaca , Artéria Mesentérica Superior , Neoplasias Pancreáticas/radioterapia , Ensaios Clínicos como Assunto , Simulação por Computador , Humanos , Terapia Neoadjuvante , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Adjuvante/métodos , Tomografia Computadorizada por Raios X , Carga Tumoral
4.
Medicine (Baltimore) ; 99(27): e20964, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629705

RESUMO

Intraoperative radiotherapy (IORT) has been used to treat different residual solid tumors after tumor removal and has shown many advantages over other treatment methods. However, the use of IORT for invasive thymoma has not been reported. Therefore, in this study, we tried to determine the safety and efficacy of INTRABEAM IORT for the treatment of invasive thymoma.Among the patients admitted to our hospital from September to December 2016 who were diagnosed with invasive thymoma, 14 were selected as study subjects. With medical histories taken beforehand, 8 of these patients were diagnosed with Masaoka stage IIA and 6 with Masaoka stage IIB; furthermore, 5 of the patients were diagnosed with myasthenia gravis (MG). INTRABEAM radiation (8-10 Gy, low energy) was delivered to the postoperative tumor bed of each patient during surgery. The intra- and postoperative complications were observed and evaluated, and the improvement in symptoms was assessed. An additional 23 patients with stage II thymoma undergoing radical surgery from April to August 2016 were chosen as the control group.One month after the operation, only 1 patient in the IORT group had cough, increased levels of leucocytes and neutrophils, and pulmonary inflammation on chest computed tomography. Reactive inflammation and pleural effusion in the 2 groups were similar (P > .05). There was no significant difference between the 2 groups in the improvement of myasthenia gravis (P > .05). Postoperative chest computed tomography and routine blood examination at 3 and 12 months showed that all the patients recovered, with normal hemogram levels and no pulmonary fibrosis around the radiation field. In addition, ultrasonic cardiography and electrocardiography demonstrated no significant difference before or after surgery within the IORT group. At the end of the follow-up, all the patients were alive, no relapse or remote metastasis was observed in the IORT group, and 2 inpatients in the control group had experienced relapse at 24 and 26 months. There was a significant difference in disease-free survival between the 2 groups (P = .00).It is safe to administer low-energy INTRABEAM IORT at a dose of approximately 10 Gy in patients with stage II invasive thymoma. INTRABEAM IORT does not significantly increase operation- or radiation-related complications and has no significant effect on vital organs such as the lungs and heart. Its long-term efficacy is worth expecting.


Assuntos
Timoma/radioterapia , Neoplasias do Timo/radioterapia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/complicações , Dosagem Radioterapêutica , Radioterapia Adjuvante/instrumentação , Radioterapia Adjuvante/métodos , Cirurgia Torácica Vídeoassistida/métodos , Timoma/complicações , Timoma/patologia , Timoma/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia
5.
Lancet ; 395(10237): 1613-1626, 2020 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-32580883

RESUMO

BACKGROUND: We aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial. METHODS: FAST-Forward is a multicentre, phase 3, randomised, non-inferiority trial done at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK. Patients aged at least 18 years with invasive carcinoma of the breast (pT1-3, pN0-1, M0) after breast conservation surgery or mastectomy were eligible. We randomly allocated patients to either 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall. Allocation was not masked because of the nature of the intervention. The primary endpoint was ipsilateral breast tumour relapse; assuming a 2% 5-year incidence for 40 Gy, non-inferiority was predefined as ≤1·6% excess for five-fraction schedules (critical hazard ratio [HR] of 1·81). Normal tissue effects were assessed by clinicians, patients, and from photographs. This trial is registered at isrctn.com, ISRCTN19906132. FINDINGS: Between Nov 24, 2011, and June 19, 2014, we recruited and obtained consent from 4096 patients from 97 UK centres, of whom 1361 were assigned to the 40 Gy schedule, 1367 to the 27 Gy schedule, and 1368 to the 26 Gy schedule. At a median follow-up of 71·5 months (IQR 71·3 to 71·7), the primary endpoint event occurred in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); HRs versus 40 Gy in 15 fractions were 0·86 (95% CI 0·51 to 1·44) for 27 Gy in five fractions and 0·67 (0·38 to 1·16) for 26 Gy in five fractions. 5-year incidence of ipsilateral breast tumour relapse after 40 Gy was 2·1% (1·4 to 3·1); estimated absolute differences versus 40 Gy in 15 fractions were -0·3% (-1·0 to 0·9) for 27 Gy in five fractions (probability of incorrectly accepting an inferior five-fraction schedule: p=0·0022 vs 40 Gy in 15 fractions) and -0·7% (-1·3 to 0·3) for 26 Gy in five fractions (p=0·00019 vs 40 Gy in 15 fractions). At 5 years, any moderate or marked clinician-assessed normal tissue effects in the breast or chest wall was reported for 98 of 986 (9·9%) 40 Gy patients, 155 (15·4%) of 1005 27 Gy patients, and 121 of 1020 (11·9%) 26 Gy patients. Across all clinician assessments from 1-5 years, odds ratios versus 40 Gy in 15 fractions were 1·55 (95% CI 1·32 to 1·83, p<0·0001) for 27 Gy in five fractions and 1·12 (0·94 to 1·34, p=0·20) for 26 Gy in five fractions. Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy versus 40 Gy but not for 26 Gy versus 40 Gy. INTERPRETATION: 26 Gy in five fractions over 1 week is non-inferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumour control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer. FUNDING: National Institute for Health Research Health Technology Assessment Programme.


Assuntos
Neoplasias da Mama/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Mastectomia/métodos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Hipofracionamento da Dose de Radiação , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Medição de Risco/métodos , Resultado do Tratamento , Reino Unido/epidemiologia
6.
Medicine (Baltimore) ; 99(18): e19916, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358358

RESUMO

We compared the cumulative incidence of ipsilateral breast tumor recurrence (IBTR) between 2 whole breast irradiation (WBI) dose range with conventional fractionation.We retrospectively reviewed 1122 patients who received WBI at 2 institutions between 2004 and 2012. One institution delivered WBI 41.4 to 45 Gy followed by boost 14 to 18 Gy (adjusted group), while the other delivered WBI 50 to 50.4 Gy followed by boost 10 Gy (standard group).The median follow-up period was 85 months. The 10-year cumulative incidence in all patients was 6.1% (95% confidence interval [CI]: 4.3%-8.4%) for IBTR and 3.0% (95% CI: 1.7%-4.8%) for regional recurrence. The 10-year cumulative incidence of IBTR was not significantly influenced by WBI dose (6.3% in the adjusted group vs 5.2% in the standard group, P = .136). Comparable IBTR rates between the 2 groups were observed regardless of clinical and pathological factors. The WBI dose was not significantly associated with the 10-year cumulative incidence of regional recurrence in these groups (3.5% in the adjusted group vs 0.5% in the standard group, P = .214).De-escalated WBI doses while intensifying tumor bed boost did not compromise local and regional outcomes compared to standard group.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Fracionamento da Dose de Radiação , Recidiva Local de Neoplasia/patologia , Radioterapia Adjuvante/métodos , Adulto , Fatores Etários , Antineoplásicos/uso terapêutico , Feminino , Humanos , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos
7.
Pediatr Blood Cancer ; 67(7): e28407, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32426927

RESUMO

Little is known about pseudoprogression in brain tumours other than gliomas. A 9-year-old male child with a pineal teratoma/germinoma underwent surgical resection followed by adjuvant chemo-radiotherapy. The magnetic resonance imaging scan 4 months post-radiotherapy showed a contrast-enhancing lesion within the surgical cavity suspicious of recurrence. These radiological findings subsequently resolved without any specific intervention. The child continues in remission 2 years post-treatment. This case illustrates the occurrence of pseudoprogression post-radiotherapy in intracranial GCT and highlights an unmet need for greater implementation of functional imaging techniques in paediatric neuro-oncology to avoid undue discontinuation of effective treatments or inappropriate enrolment in clinical trials.


Assuntos
Imagem por Ressonância Magnética/métodos , Imagem Molecular/métodos , Neoplasias Embrionárias de Células Germinativas/patologia , Pinealoma/patologia , Radioterapia Adjuvante/métodos , Teratoma/patologia , Criança , Progressão da Doença , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/radioterapia , Pinealoma/diagnóstico por imagem , Pinealoma/radioterapia , Prognóstico , Teratoma/diagnóstico por imagem , Teratoma/radioterapia
8.
Zhonghua Zhong Liu Za Zhi ; 42(4): 336-339, 2020 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-32375451

RESUMO

Objective: To investigate the outcomes of limited stage small cell lung cancer (L-SCLC) undergoing surgical therapy and to explore the value of adjuvant therapy for those patients. Methods: A retrospective analysis was initialed for the L-SCLC patients who underwent the surgical treatment in the Zhongnan Hospital of Wuhan University from January 2012 to December 2018. The median disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method. Cox regression was used to explore the prognostic factors. Results: A total of 44 patients were included in our study. The median DFS was 25 months, 1- and 2-year DFS rate were 70.2% and 51.9%, respectively. The median OS was 41 months, 1- and 2- year OS rate were 88.4% and 69.9%, respectively. Multivariate analysis showed male (RR=6.56, P=0.03), T3-4 (RR=6.23, P=0.01), pathological lymph node metastasis (RR=6.52, P=0.03) and adjuvant radiotherapy (RR=0.13, P=0.002) were associated with disease relapse significantly. Moreover, pathological lymph node metastasis (RR=3.62, P=0.01) coupled with sufficient adjuvant chemotherapy (≥4 cycles) (RR=0.12, P=0.01) were independent prognostic factors of OS. Conclusions: Surgical therapy may be an alternative primary treatment for L-SCLC. Additional adjuvant radiotherapy can reduce the risk of recurrence. Giving sufficient course of adjuvant chemotherapy can improve OS.


Assuntos
Quimioterapia Adjuvante/métodos , Neoplasias Pulmonares/terapia , Pneumonectomia/métodos , Radioterapia Adjuvante/métodos , Carcinoma de Pequenas Células do Pulmão/terapia , Adulto , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
9.
Anticancer Res ; 40(5): 3003-3009, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366455

RESUMO

Backround/Aim: Adjuvant radiotherapy in patients with cancer of the left breast may lead to impaired cardiac function. The aim of our prospective study is to evaluate (i) doses to the irradiated volume of the heart and its substructures and (ii) determine whether their correlation with changes in strain echo measurements contribute to the prediction of subclinical heart morbidity. PATIENTS AND METHODS: Twenty-five patients were enrolled in our study. We retrospectively assessed the radiation doses to the whole heart, left anterior descending artery (LAD) and left ventricle (LV). RESULTS: The mean heart dose (MHD) was 152 cGy (SD=50.56 cGy) and the range was 74-279 cGy. The LAD was the most exposed structure, with a mean dose of 448.91 cGy (SD=490.53 cGy) and range of 120-2,057cGy. Finally, the mean LV dose was 149.12 cGy (SD=69.57) with a range of 63-317 cGy. CONCLUSION: The early results of our study showed low radiation exposure of the whole heart and left ventricle, and higher exposure of the LAD. The data that will emerge from the evaluation of strain echo parameters should show whether these associations might be useful in clinical practice for the prediction of early subclinical cardiac changes.


Assuntos
Neoplasias da Mama/radioterapia , Coração/anatomia & histologia , Radioterapia Adjuvante/efeitos adversos , Feminino , Coração/fisiopatologia , Humanos , Pessoa de Meia-Idade , Radioterapia Adjuvante/métodos
10.
Radiol Med ; 125(10): 990-998, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32277332

RESUMO

PURPOSE: The potential role of neoadjuvant radiation dose intensification in locally advanced rectal cancer (LARC) is still largely debated. In the present study, a comparative analysis between radiation dose intensification and conventional fractionation was performed. MATERIALS AND METHODS: In the current prospective observational study (protocol ID RT-03/2011), 56 patients diagnosed with LARC were enrolled between January 2013 and December 2016. More specifically, 25 patients underwent preoperative conventional radiation dose [i.e., 50.4 Gy in 28 fractions here defined as standard dose radiotherapy (SDR)-group 1], whereas 31 patients were candidate for radiation dose intensification (RDI) (i.e., 60 Gy in 30 fractions-group 2). The primary endpoint was the complete pathological response (pCR) rate. Secondary endpoints were postoperative complications and ChT-RT-related toxicity. RESULTS: No statistical significance was observed in pCR rate (20.8% and 22.6% in SDR and RDI group, respectively, p = 0.342). Of contrast, the RDI group showed a significantly higher primary tumor downstaging in case of T3 tumor compared to SDR group (p = 0.049). Sphincter-preserving surgery was 84% and 93.5% in SDR and RDI groups, respectively (p = 0.25). All patients had R0 margins. No surgical-related death was recorded. No statistically significant difference was observed regarding surgical complications and incomplete mesorectal excision. Acute genitourinary toxicity was significantly higher in RDI group (p = 0.015). CONCLUSIONS: The intensification of the neoadjuvant radiotherapy for LARC seems to produce a major pathological response in T3 tumors. The radiation dose intensification appears probably associated with a higher rate of genitourinary toxicity.


Assuntos
Quimiorradioterapia/métodos , Neoplasias Retais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal , Quimiorradioterapia/efeitos adversos , Fracionamento da Dose de Radiação , Feminino , Cabeça do Fêmur/efeitos da radiação , Hospitalização , Humanos , Intestinos/efeitos da radiação , Laparoscopia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/efeitos da radiação , Tomografia por Emissão de Pósitrons/métodos , Complicações Pós-Operatórias , Estudos Prospectivos , Doses de Radiação , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Radioterapia de Intensidade Modulada , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Bexiga Urinária/efeitos da radiação
11.
Plast Reconstr Surg ; 145(5): 917e-926e, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32332528

RESUMO

BACKGROUND: Whether to irradiate the tissue expander before implant exchange or to defer irradiation until after exchange in immediate, two-stage expander/implant reconstruction remains uncertain. The authors evaluated the effects of irradiation timing on complication rates and patient-reported outcomes in patients undergoing immediate expander/implant reconstruction. METHODS: Immediate expander/implant reconstruction patients undergoing postmastectomy radiation therapy at 11 Mastectomy Reconstruction Outcomes Consortium sites with demographic, clinical, and complication data were analyzed. Patient-reported outcomes were assessed with BREAST-Q, Patient-Reported Outcomes Measurement Information System, and European Organisation for Research and Treatment of Cancer Breast Cancer-Specific Quality-of-Life Questionnaire surveys preoperatively and 2 years postoperatively. Survey scores and complication rates were analyzed using bivariate comparison and multivariable regressions. RESULTS: Of 317 patients who met inclusion criteria, 237 underwent postmastectomy radiation therapy before expander/implant exchange (before-exchange cohort), and 80 did so after exchange (after-exchange cohort). Timing of radiation had no significant effect on risks of overall complications (OR, 1.25; p = 0.46), major complications (OR, 1.18; p = 0.62), or reconstructive failure (OR, 0.72; p = 0.49). Similarly, radiation timing had no significant effect on 2-year patient-reported outcomes measured by the BREAST-Q or the European Organisation for Research and Treatment of Cancer survey. Outcomes measured by the Patient-Reported Outcomes Measurement Information System showed less anxiety, fatigue, and depression in the after-exchange group. Compared with preoperative assessments, 2-year patient-reported outcomes significantly declined in both cohorts for Satisfaction with Breasts, Physical Well-Being, and Sexual Well-Being, but improved for anxiety and depression. CONCLUSIONS: Radiation timing (before or after exchange) had no significant effect on complication risks or on most patient-reported outcomes in immediate expander/implant reconstruction. Although lower levels of anxiety, depression, and fatigue were observed in the after-exchange group, these differences may not be clinically significant. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.


Assuntos
Implante Mamário/efeitos adversos , Implantes de Mama/efeitos adversos , Neoplasias da Mama/terapia , Complicações Pós-Operatórias/epidemiologia , Dispositivos para Expansão de Tecidos/efeitos adversos , Expansão de Tecido/efeitos adversos , Adulto , Ansiedade/epidemiologia , Ansiedade/etiologia , Ansiedade/psicologia , Implante Mamário/instrumentação , Implante Mamário/métodos , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Humanos , Mastectomia/efeitos adversos , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/psicologia , Estudos Prospectivos , Qualidade de Vida , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Fatores de Tempo , Tempo para o Tratamento , Expansão de Tecido/instrumentação
12.
Am J Clin Oncol ; 43(7): 491-495, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32217853

RESUMO

OBJECTIVES: A total of 30% to 40% of soft tissue sarcoma (STS) patients develop major wound complications (MWCs) after preoperative radiation (preRT). The optimal preRT-surgery interval and its association with MWCs is unknown. This study investigated whether a longer preRT-surgery interval is associated with fewer MWCs compared with historical controls. METHODS: All patients treated by a single surgeon after preRT with limb-sparing wide resection for extremity and trunk STS were retrospectively reviewed from 2004 to 2014. The primary outcome was MWCs defined as a secondary operation, invasive procedure, wound packing, or readmission for wound care. Secondary outcomes of local recurrence and survival were followed and independent variables were analyzed for an association with MWCs. RESULTS: Fifty-four patients were included with a median follow-up of 32 months and age of 61 years. The majority of tumors were deep (91%), large (median size of 11 cm), high grade (78%) and within the lower extremity (78%). The median preRT-surgery interval was 43 days and 80% of patients received surgery 35 to 49 days after radiation. MWCs were observed in 15% of patients and 88% occurred within 40 days. Predictors for MWCs on multivariate analysis were peripheral vascular disease (P=0.03), location in the medial compartment of the thigh (P=0.03), and neurovascular involvement (P=0.03). CONCLUSIONS: This study presents a cohort of STS patients with an extended preRT-surgery interval of ~6 weeks. MWCs in this population occurred at a lower rate than historical controls. Overall these findings support the exploration of a longer interval to reduce MWCs and their associated morbidity.


Assuntos
Terapia Neoadjuvante/métodos , Complicações Pós-Operatórias/etiologia , Radioterapia Adjuvante/métodos , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Cicatrização , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
13.
Lancet Oncol ; 21(5): 685-698, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32203696

RESUMO

BACKGROUND: BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-low-risk ductal carcinoma in situ following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years. METHODS: The BIG 3-07/TROG 07.01 trial is ongoing at 118 hospitals in 11 countries. Women aged 18 years or older with completely excised non-low-risk ductal carcinoma in situ were randomly assigned, by use of a minimisation algorithm, to tumour bed boost or no tumour bed boost, following conventional whole breast radiotherapy or hypofractionated whole breast radiotherapy using one of three randomisation categories. Category A was a 4-arm randomisation of tumour bed boost versus no boost following conventional whole breast radiotherapy (50 Gy in 25 fractions over 5 weeks) versus hypofractionated whole breast radiotherapy (42·5 Gy in 16 fractions over 3·5 weeks). Category B was a 2-arm randomisation between tumour bed boost versus no boost following conventional whole breast radiotherapy, and category C was a 2-arm randomisation between tumour bed boost versus no boost following hypofractionated whole breast radiotherapy. Stratification factors were age at diagnosis, planned endocrine therapy, and treating centre. The primary endpoint, time to local recurrence, will be reported when participants have completed 5 years of follow-up. The HRQOL statistical analysis plan prespecified eight aspects of HRQOL, assessed by four questionnaires at baseline, end of treatment, and at 6, 12, and 24 months after radiotherapy: fatigue and physical functioning (EORTC QLQ-C30); cosmetic status, breast-specific symptoms, arm and shoulder functional status (Breast Cancer Treatment Outcome Scale); body image and sexuality (Body Image Scale); and perceived risk of invasive breast cancer (Cancer Worry Scale and a study-specific question). For each of these measures, tumour bed boost was compared with no boost, and conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy, by use of generalised estimating equation models. Analyses were by intention to treat, with Hochberg adjustment for multiple testing. This trial is registered with ClinicalTrials.gov, NCT00470236. FINDINGS: Between June 1, 2007, and Aug 14, 2013, 1208 women were enrolled and randomly assigned to receive no tumour bed boost (n=605) or tumour bed boost (n=603). 396 of 1208 women were assigned to category A: conventional whole breast radiotherapy with tumour bed boost (n=100) or no boost (n=98), or to hypofractionated whole breast radiotherapy with tumour bed boost (n=98) or no boost (n=100). 447 were assigned to category B: conventional whole breast radiotherapy with tumour bed boost (n=223) or no boost (n=224). 365 were assigned to category C: hypofractionated whole breast radiotherapy with tumour bed boost (n=182) or no boost (n=183). All patients were followed up at 2 years for the HRQOL analysis. 1098 (91%) of 1208 patients received their allocated treatment, and most completed their scheduled HRQOL assessments (1147 [95%] of 1208 at baseline; 988 [87%] of 1141 at 2 years). Cosmetic status was worse with tumour bed boost than with no boost across all timepoints (difference 0·10 [95% CI 0·05-0·15], global p=0·00014, Hochberg-adjusted p=0·0016); at the end of treatment, the estimated difference between tumour bed boost and no boost was 0·13 (95% CI 0·06-0·20; p=0·00021), persisting at 24 months (0·13 [0·06-0·20]; p=0·00021). Arm and shoulder function was also adversely affected by tumour bed boost across all timepoints (0·08 [95% CI 0·03-0·13], global p=0·0033, Hochberg adjusted p=0·045); the difference between tumour bed boost and no boost at the end of treatment was 0·08 (0·01 to 0·15, p=0·021), and did not persist at 24 months (0·04 [-0·03 to 0·11], p=0·29). None of the other six prespecified aspects of HRQOL differed significantly after adjustment for multiple testing. Conventional whole breast radiotherapy was associated with worse body image than hypofractionated whole breast radiotherapy at the end of treatment (difference -1·10 [95% CI -1·79 to -0·42], p=0·0016). No significant differences were reported in the other PROs between conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy. INTERPRETATION: Tumour bed boost was associated with persistent adverse effects on cosmetic status and arm and shoulder functional status, which might inform shared decision making while local recurrence analysis is pending. FUNDING: National Health and Medical Research Council, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Mastectomia Segmentar , Recidiva Local de Neoplasia/cirurgia , Braquiterapia , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/radioterapia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Estadiamento de Neoplasias , Qualidade de Vida , Radioterapia Adjuvante/métodos , Resultado do Tratamento
14.
Br J Radiol ; 93(1110): 20200047, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32187503

RESUMO

OBJECTIVE: To analyze the effect of intra- and interfractional motion during breast intensity modulated radiation therapy (IMRT) by calculating dose distribution based on four-dimensional computed tomography (4DCT). METHODS: 20 patients diagnosed with left breast cancer were enrolled. Three-dimensional CT (3DCT) along with 10 phases of 4DCT were collected for each patient, with target volumes independently delineated on both 3DCT and all phases of 4DCT. IMRT plans were generated based on 3DCT (43.2 Gy in 16 fractions). The plan parameters for each segment were split into phases based on time duration estimates for each respiratory phase, with phase-specific dose distributions calculated and summated (4D-calculated dose). The procedure is repeated for 16 fractionations by randomly allocating starting phase using random-number generation to simulate interfractional discrepancy caused by different starting phase. Comparisons of plan quality between the original and 4D-calculated doses were analyzed. RESULTS: There was a significant distortion in 4D-calculated dose induced by respiratory motion in terms of conformity and homogeneity index compared to those of the original 3D plan. Mean doses of the heart and the ipsilateral lung were significantly higher in the 4D-calculated doses compared to those of the original 3D plan (0.34 Gy, p = 0.010 and 0.59 Gy, p < 0.001), respectively). The mean internal mammary lymph node (IMN) dose was significantly greater in the 4D-calculated plan, compared to the original 3D plan (1.42 Gy, p < 0.001). CONCLUSIONS: IMN doses should be optimized during the dose-calculation for the free-breathing left breast IMRT. ADVANCES IN KNOWLEDGE: The interplay effect between respiratory motion and multileaf collimator modulation caused discrepancies in dose distribution, particularly in IMN.


Assuntos
Tomografia Computadorizada Quadridimensional , Imageamento Tridimensional/métodos , Radioterapia de Intensidade Modulada , Neoplasias Unilaterais da Mama/diagnóstico por imagem , Neoplasias Unilaterais da Mama/radioterapia , Fracionamento da Dose de Radiação , Feminino , Coração , Humanos , Pulmão , Irradiação Linfática/métodos , Movimentos dos Órgãos , Planejamento da Radioterapia Assistida por Computador , Radioterapia Adjuvante/métodos , Respiração , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Unilaterais da Mama/cirurgia
15.
BMC Cancer ; 20(1): 125, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059705

RESUMO

BACKGROUND: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. METHODS: This is a multicenter phase II study randomizing one hundred and forty patients with T1-2 N0-2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50-60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity. DISCUSSION: This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.


Assuntos
Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/terapia , Protocolos Clínicos , Procedimentos Cirúrgicos Bucais , Neoplasias Orofaríngeas/etiologia , Neoplasias Orofaríngeas/terapia , Infecções por Papillomavirus/complicações , Radioterapia Adjuvante , Carcinoma de Células Escamosas/diagnóstico , Terapia Combinada , Feminino , Humanos , Masculino , Procedimentos Cirúrgicos Bucais/métodos , Neoplasias Orofaríngeas/diagnóstico , Infecções por Papillomavirus/virologia , Radioterapia Adjuvante/métodos , Projetos de Pesquisa
16.
BMC Cancer ; 20(1): 153, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093638

RESUMO

BACKGROUND: There is a discrepancy about the metastatic rate of internal mammary lymph nodes (IMNs) between clinical and pathologic findings. We aimed to investigate the metastatic rate of IMNs and to provide recommendations on target volume delineation of IMNs for adjuvant radiotherapy in breast cancer patients. METHODS: We retrospectively analyzed data from 114 breast cancer patients treated with surgery without adjuvant radiotherapy who developed local and/or regional lymph node recurrence/metastasis at our institute from January 2015 to January 2019. Patients with widely lung or pleural metastases were excluded. We first analyzed the recurrence rate with the chest wall, the metastatic rate of internal mammary/anterior mediastinal, ipsilateral axillary and supraclavicular lymph nodes, and then investigated the distribution of the IMNs. RESULTS: Among the 114 included patients, the recurrence rate with the chest wall, metastatic rate of IMNs, IMNs/anterior mediastinal lymph nodes, ipsilateral axillary lymph nodes, and the ipsilateral supraclavicular lymph nodes was 43, 37.7, 59.6, 12.3, and 22.8%, respectively. The metastatic IMNs were mainly located from the first to the second intercostal space. However, metastatic lymph nodes could also be observed above the upper edge of the first rib. CONCLUSIONS: The metastatic rate is high in the IMNs and irradiation of the internal mammary lymphatic chain is required. It is suggested that the upper bound of the internal mammary lymphatic chain should be up to the subclavian vein with a 5-mm margin, thus connecting to the caudal border of supraclavicular clinical target volume in breast cancer patients at high risk of recurrence.


Assuntos
Neoplasias da Mama/patologia , Linfonodos/patologia , Irradiação Linfática/normas , Recidiva Local de Neoplasia/patologia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Adjuvante/métodos , Adulto , Idoso , Axila , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Incidência , Metástase Linfática , Mastectomia/métodos , Mediastino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Estudos Retrospectivos
17.
Neurocirugía (Soc. Luso-Esp. Neurocir.) ; 31(1): 47-51, ene.-feb. 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-190372

RESUMO

Los sarcomas granulocíticos son neoplasias sólidas compuestas de células mieloides inmaduras, de localización extramedular, asociadas a síndromes mieloproliferativos. La afectación del sistema nervioso central es muy infrecuente y puede desarrollarse tras un periodo de remisión completa, coexistir con o preceder a la enfermedad sistémica, siendo esta el elemento fundamental que orienta el diagnóstico radiológico y marca el pronóstico. En este trabajo, presentamos 2 casos de sarcoma granulocítico intracraneal, verificados desde el punto de vista patológico tras ser tratados mediante cirugía, y discutimos sus características clínicas, diagnósticas, terapéuticas y pronósticas tras realizar una revisión bibliográfica de la literatura científica destacada publicada hasta la fecha


Granulocytic sarcomas are solid, extramedullary-located neoplasms composed of immature myeloid cells, associated with myeloproliferative syndromes. Central nervous system involvement is very rare and may develop either after complete remission, coexist with or precede the systemic disease, being the last one that guides the radiological diagnosis and marks the prognosis. In this work, we report 2 pathologically-verified cases of intracranial granulocytic sarcoma treated by surgical means. Their clinical, diagnostic, therapeutic and prognostic features are discussed in the light of the most relevant scientific literature published to date


Assuntos
Humanos , Masculino , Adulto , Idoso , Sarcoma Mieloide/cirurgia , Sistema Nervoso Central/patologia , Sarcoma Mieloide/patologia , Sarcoma Mieloide/diagnóstico por imagem , Crânio/diagnóstico por imagem , Crânio/patologia , Hemorragia Subaracnóidea/complicações , Craniotomia/métodos , Radioterapia Adjuvante/métodos , Meningite/complicações , Progressão da Doença , Imuno-Histoquímica , Diagnóstico Diferencial
18.
World Neurosurg ; 137: e176-e182, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32001392

RESUMO

BACKGROUND: Central neurocytomas (CNCs) are rare intraventricular lesions comprising <1% of primary brain tumors. Their surgical and adjuvant management is unclear. OBJECTIVE: Our goal was to update Rades et al.'s 2006 systematic review to assess the outcome differences among 3 fundamental therapies for CNC: gross total resection with and without radiation therapy (RT) versus maximal safe resection with adjuvant RT. METHODS: Articles indexed on PubMed and Google Scholar and published between January 1, 2006 and December 31, 2019 were selected using the PRISMA criteria. Studies were excluded if they had fewer than 3 cases, did not categorize extent of resection, or were duplicate studies, technical reports, case reports, or studies without follow-up. Complication rates, recurrence rates, overall survival and progression-free survival were extracted where possible. χ2 proportionality tests were used for comparison (P values >0.05 suggested significance). RESULTS: On aggregation, 615 patients from 13 studies including ours were assessed. Although overall survival was not significantly different (χ2 = 1.56; P = 0.46), the recurrence rate differed significantly between GTR + RT (6.9%, 92.11 months), GTR-RT (23.9%, 96.8 months), and MSR + RT (16.8%, 85 months) (χ2 = 10.94; P = 0.004). Pooled complication rates for GTR and MSR + RT were 31.2% and 24% (P = 0.049), respectively. CONCLUSIONS: RT remains an important adjuvant treatment that can improve patient survival in the presence of MSR to levels comparable to those of GTR or GTR + RT. Where total resection carries too much risk, MSR + RT can be considered as the next best alternative for tumor control.


Assuntos
Neoplasias Encefálicas/terapia , Recidiva Local de Neoplasia/epidemiologia , Neurocitoma/terapia , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/epidemiologia , Radioterapia Adjuvante/métodos , Terapia Combinada , Humanos , Resultado do Tratamento
19.
Am J Clin Oncol ; 43(5): 334-339, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32000167

RESUMO

BACKGROUND: Preoperative chemotherapy is important in the management of women with breast cancer, with the ability to downstage the breast primary tumor and axillary lymph nodes. Long-term studies are needed to identify late toxicities, recurrence patterns, and equivalency with postoperative chemotherapy for recurrence-free survival (RFS) and overall survival (OS). PATIENTS AND METHODS: We conducted a single-institution prospective randomized control trial comparing preoperative or postoperative fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamides/granulocyte colony-stimulating factor chemotherapy for women with untreated clinical stage II (T1N1, T2N0, and T2N1) breast cancer. Long-term follow-up was conducted to define toxicities, recurrence patterns and RFS and OS. RESULTS: Fifty-three women with clinical stage II breast cancer were randomized, 26 patients to receive preoperative chemotherapy and 27 to receive postoperative chemotherapy. Long-term follow-up, with a median of 25.3 years, was obtained. Local or systemic recurrence occurred in 8 women in the preoperative group and in 10 women in the postoperative group, and recurrences were predominantly within 10 years of treatment. Late toxicities included local upper extremity paresthesia's, upper extremity edema and congestive heart failure in 1 patient each. Analysis revealed no difference in RFS (20-year RFS probabilities; preoperative: 61.3%, postoperative: 54.7%, P=0.42), or in OS between the 2 treatment groups (20-year probabilities, preoperative: 64.6%, postoperative: 62.2%, P=0.44). Twenty-five of 53 patients (47%) were alive and without disease at this follow-up. CONCLUSION: Twenty-five-year follow-up for this prospective randomized trial confirms the equivalency of preoperative versus postoperative chemotherapy with fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamides/granulocyte colony-stimulating factor for stage II breast cancer for both RFS and OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Seguimentos , Humanos , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Pessoa de Meia-Idade , Radioterapia Adjuvante/métodos , Resultado do Tratamento
20.
J Clin Neurosci ; 73: 144-149, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31956087

RESUMO

New Zealand has one of the highest rates of melanoma in the world. In up to 10% of cases, the disease is metastatic at diagnosis. Cerebral metastatic involvement carries a particularly poor prognosis. 110 patients were included in the analysis. A retrospective consecutive series of patients treated surgically at Auckland City Hospital were studied, with parameters of demographics, tumour characteristics, surgery, pathology, systemic therapy and survival analysed. Mean age was 59.9 years (range 22-81 years). Median survival from date of surgery was 8.1 months (95% CI 6.9-9.4 months). Of the 58 patients tested for BRAF mutation, 28 were positive, similar to previously published data. This conferred a better prognosis with median overall survival of 12.3 months (95% CI 7.2-17.3 months) compared to 7.8 months (95% CI 5.6-10 months) for those who were negative (p < 0.05). Survival correlated positively with extent of surgical resection. Both BRAF positive status and targeted and/or immunotherapy were significant predictors of improved survival. In this cohort, radiation therapy did not show a statistically significant improvement in overall survival. Survival from resection of cerebral metastases from melanoma is improving. Survival benefit is conferred by BRAF mutation, solitary metastasis and gross total resection of lesion.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Melanoma/patologia , Melanoma/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Encefálicas/mortalidade , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/mortalidade , Terapia Combinada/métodos , Feminino , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/mortalidade , Nova Zelândia , Prognóstico , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/mortalidade , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Adulto Jovem
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