RESUMO
Background Overall survival (OS) for patients with uveal melanoma (UM) hepatic metastases is extremely poor. Therefore, stabilization of hepatic metastases is essential to prolonging OS. Purpose To assess the safety and effectiveness of radioembolization (RE) for treatment of UM hepatic metastases. Materials and Methods Enrollment for this prospective phase II trial began November 2011 and concluded January 2017. Treatment-naïve participants (group A) and participants who progressed after immunoembolization (group B) with hepatic tumor burden less than 50% underwent RE. Participants were followed for 1 month and every 3 months for acute and delayed toxicities, respectively. MRI, CT, and PET were performed every 3 months to evaluate for tumor response and extrahepatic disease. Participants were followed for at least 2 years or until death. Kaplan-Meier method and multivariable Cox proportional hazard models were used for data analysis. Results In group A, 24 participants (mean age ± standard deviation, 59 years ± 13; 13 men and 11 women) underwent unilobar (n = 7), fractionated whole-liver (n = 1), or sequential lobar (n = 16) RE. One participant was excluded from the trial. Complete response (n = 0), partial response (n = 9), or stable disease (n = 11) was achieved in 20 of 23 (87.0%; 95% confidence interval [CI]: 66.4%, 97.2%) participants. Median progression-free survival from liver metastasis was 8.1 months (95% CI: 6.4, 11.8; range, 3.3-33.7 months). Median OS was 18.5 months (95% CI: 11.3, 23.5; range, 6.5-73.7 months). In group B, 24 participants (mean age, 58 years ± 10; nine men and 15 women) underwent unilobar (n = 5) or sequential lobar (n = 19) RE. Complete response (n = 0), partial response (n = 8), or stable disease (n = 6) was achieved in 14 of 24 (58.3%; 95% CI: 36.3%, 77.9%) participants. Median progression-free survival from liver metastasis was 5.2 months (95% CI: 3.7, 9.8; range, 2.9-22.0 months). Median OS was 19.2 months (95% CI: 11.5, 24.0; range, 4.8-76.6 months). Grade 3 treatment-related toxicities included transient lymphopenia (group A, n = 1; group B, n = 1), pain (group A, n = 2) and nausea or vomiting (group A, n = 1). Conclusion Radioembolization is a promising treatment for patients with uveal melanoma hepatic metastases. © RSNA, 2019 Online supplemental material is available for this article.
Assuntos
Embolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Melanoma/patologia , Segunda Neoplasia Primária/radioterapia , Neoplasias Uveais/patologia , Radioisótopos de Ítrio/uso terapêutico , Diagnóstico por Imagem/métodos , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/efeitos da radiação , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico por imagem , Estudos Prospectivos , Resultado do TratamentoRESUMO
PURPOSE: To report the incidence of liver function test (LFT) toxicities after radioembolization with yttrium-90 ((90)Y) SIR-Spheres and review potential risk factors. MATERIALS AND METHODS: Patients receiving (90)Y for radioembolization of primary or metastatic liver tumors had follow-up LFTs 29-571 days after treatment. The incidence and duration of bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) toxicities were documented using common terminology criteria. Factors that were assessed included previous intra-arterial (IA) therapy, systemic chemotherapy, low tumor-to-normal liver tissue ratio at mapping angiography, vascular stasis, and higher prescribed (90)Y doses. RESULTS: There were 81 patients who underwent 122 infusions and had follow-up LFTs. Of 122 infusions, 71 (58%) were associated with toxicity. One patient died with radiation-induced liver disease. Grade 3 or greater toxicities occurred in seven (7%) patients after nine procedures. The median durations of laboratory elevations for bilirubin, AST, and ALT were 29 days, 29 days, and 20 days. Toxicity developed after 51 (71%) of 72 infusions with previous IA therapy versus 20 (40%) of 50 infusions in treatment-naïve areas (P = .0006). Absence of previous systemic therapy was associated with greater risk of toxicity versus previous chemotherapy (47% vs 66%, P = .03). Other factors were not associated with increased toxicity. CONCLUSIONS: Mild hepatotoxicity developed frequently after infusion of SIR-Spheres using the body surface area method, with normalization of LFTs in most patients. Grade 3 or greater toxicities were seen in < 10% of infusions. Toxicity was strongly associated with previous IA therapy.
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Embolização Terapêutica/efeitos adversos , Hepatopatias/etiologia , Neoplasias Hepáticas/radioterapia , Lesões por Radiação/etiologia , Compostos Radiofarmacêuticos/efeitos adversos , Radioisótopos de Ítrio/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Embolização Terapêutica/mortalidade , Feminino , Humanos , Incidência , Hepatopatias/diagnóstico , Hepatopatias/mortalidade , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Philadelphia/epidemiologia , Lesões por Radiação/diagnóstico , Lesões por Radiação/mortalidade , Compostos Radiofarmacêuticos/administração & dosagem , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem , Radioisótopos de Ítrio/administração & dosagemRESUMO
OBJECTIVE: The purpose of this study was to assess the safety and efficacy of radioembolization in the management of hepatic metastasis of uveal melanoma after failure of immunoembolization or chemoembolization. MATERIALS AND METHODS: From January 2007 through April 2009, 32 patients underwent radioembolization therapy for hepatic metastasis of uveal melanoma. Pretreatment tumor burdens were divided into three categories: less than 25% (n = 25), 25-50% (n = 5), and greater than 50% (n = 2). Toxicity, extrahepatic disease, and hepatic tumor response were assessed 1 month and then every 3 months after treatment. Best radiographic response of hepatic metastasis was determined with the Response Evaluation Criteria in Solid Tumors criteria. Overall survival and progression-free survival of hepatic metastasis were estimated by Kaplan-Meier analysis. Differences in survival between subgroups were evaluated by log-rank test in univariate analysis. RESULTS: The clinical follow-up period ranged from 1.0 to 29.0 months (median, 10.0 months). The median overall survival was 10.0 months, and the progression-free survival of hepatic metastasis, 4.7 months. Twenty-two patients died 1.0-29.0 months (median, 5.8 months) after treatment owing to progression of liver disease (n = 13), extrahepatic disease (n = 4), or both (n = 5). Patients who had a pretreatment tumor burden less than 25% had longer median overall survival (10.5 vs 3.9 months, p = 0.0003) and progression-free survival (6.4 vs 3.0 months, p = 0.03) than patients who had a pretreatment tumor burden of 25% or greater. Patients who had a complete response (n = 1), partial response (n = 1), or stable disease (n = 18) had longer median overall survival (14.7 vs 4.9 months, p = 0.0006) and progression-free survival of hepatic metastasis (7.9 vs 3.1 months, p < 0.0001) than patients with tumor progression (n = 12). Self-limiting grade 1-2 systemic toxicity included tiredness (n = 9), indigestion (n = 2), and abdominal discomfort (n = 5). Grade 3-4 hepatic toxicity was attributed to tumor progression. CONCLUSION: Radioembolization is safe and effective salvage therapy for limited metastasis of uveal melanoma.
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Embolização Terapêutica/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Melanoma/secundário , Melanoma/terapia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Terapia por Radiofrequência , Terapia de Salvação , Taxa de Sobrevida , Carga Tumoral , Neoplasias Uveais/mortalidadeRESUMO
OBJECTIVE: The purpose of this study was to assess the rate of recanalization and collateral vessel formation after side-branch embolization during mapping angiography for planned (90)Y radioembolization. MATERIALS AND METHODS: Patients who underwent side-branch embolization at mapping angiography before (90)Y administration were included. Embolized vessels included the gastroduodenal artery, right gastric artery, and accessory arteries. Four interventional radiologists reviewed follow-up angiograms to assess recanalization and new collateral formation of embolized vessels. The time to recanalization or new collateral formation was tracked within 60 days and after the final arteriographic study. Differences in outcome among patients who had and those who had not undergone previous arterial directed therapy were reviewed. RESULTS: Fifty-six patients underwent side-branch embolization and follow-up arteriography; 124 treatments were performed after side-branch embolization (median, 2; range, 1-7), and the median follow-up period was 134 days (range, 7-684 days). Recanalization or new collateral vessel formation was found in 6 of 56 patients (10.7%) and in 8 of 56 patients (14.3%) 60 days after treatment or at final angiography, respectively. Embolization of 110 arteries was accomplished (42 gastroduodenal arteries, 46 right gastric arteries, and 22 accessory arteries). Two of 110 arteries (1.8%) recanalized, and four of 110 (3.6%) had new collateral vessels within 60 days. At final evaluation, 2 of 110 arteries (1.8%) had recanalized and 7 of 110 (6.4%) had new collaterals. Previous liver-directed therapy did not affect outcome (p > 0.05). No patient had symptomatic gastrointestinal ulceration. CONCLUSION: In more than 89% of patients, side-branch embolization provides durable occlusion for (90)Y radioembolization without collateral development or recanalization for a bilobar cycle of therapy. Further recanalization and collateral development at longer-term follow-up are minimal.
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Embolização Terapêutica/estatística & dados numéricos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/prevenção & controle , Neovascularização Patológica/diagnóstico por imagem , Adulto , Idoso , Embolização Terapêutica/métodos , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/radioterapia , Radiografia , Compostos Radiofarmacêuticos/uso terapêutico , Resultado do Tratamento , Radioisótopos de Ítrio/uso terapêuticoRESUMO
BACKGROUND: Esophageal carcinoma is an aggressive disease that is often treated with neoadjuvant therapy followed by surgical resection. Diabetes mellitus (DM) has been associated with reduced efficacy of chemoradiation (CRT) in other gastrointestinal cancers. The goal of this study was to determine if DM affects response to neoadjuvant CRT in the management of gastroesophageal carcinoma. METHODS: We retrospectively reviewed the esophageal cancer patient databases and subsequently analyzed those patients who received neoadjuvant CRT followed by surgical resection at two institutions, Thomas Jefferson University (TJUH) and Fox Chase Cancer Center (FCCC). Comparative analyses of rates of pathologic complete response rate (pCR) and pathologic downstaging in DM patients versus non-DM patients was performed. RESULTS: Two hundred sixty patients were included in the study; 36 patients had DM and 224 were non-diabetics. The average age of the patients was 61 years (range 24-84 years). The overall pCR was 26%. The pCR rate was 19% and 27% for patients with DM and without DM, respectively (P = 0.31). Pathologic downstaging occurred in 39% of study patients, including of 33% of DM patients and 40% of non-DM patients (P = 0.42). CONCLUSIONS: Although the current analysis does not demonstrate a significant reduction in pCR rates or pathologic downstaging in patients with DM, the observed trend suggests that a potential difference may be observed with a larger patient population. Further studies are warranted to evaluate the influence of DM on the effectiveness of neoadjuvant CRT in esophageal cancer.
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Diabetes Mellitus/patologia , Neoplasias Esofágicas/terapia , Junção Esofagogástrica , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
PURPOSE: This study evaluated the strategy of performing neck dissection (ND) without primary tumor resection prior to definitive chemoradiotherapy (CRT) for N2+ oropharynx cancer. METHODS: We analyzed records of 25 patients who underwent ND before concurrent CRT with weekly low-dose concurrent paclitaxel and a platinum compound. The extent of ND was highly customized (1 to 39 nodes) and median radiotherapy dose was 70 Gy. RESULTS: Median follow-up was 36 months. Two-year and 3-year actuarial locoregional control rates were 95% and 88%. No patient had regional neck nodal failure. Two-year rate of freedom from distant metastases was 91%. The 2- and 3-year event-free survival rates were 88% and 75%. Fifteen percent had Grade 3+ late toxicity; none had permanent gastrostomy tube dependence. CONCLUSIONS: Neck dissection without primary tumor resection before definitive chemoradiotherapy for oropharynx cancer is a safe and effective management program and warrants further exploration.
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Carcinoma de Células Escamosas/terapia , Esvaziamento Cervical/métodos , Neoplasias Orofaríngeas/terapia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Neoplasias Orofaríngeas/patologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Few medical students are given proper clinical training in oncology, much less radiation oncology. We attempted to assess the value of adding a radiation oncology clinical rotation to the medical school curriculum. METHODS AND MATERIALS: In July 2010, Jefferson Medical College began to offer a 3-week radiation oncology rotation as an elective course for third-year medical students during the core surgical clerkship. During 2010 to 2012, 52 medical students chose to enroll in this rotation. The rotation included outpatient clinics, inpatient consults, didactic sessions, and case-based presentations by the students. Tests of students' knowledge of radiation oncology were administered anonymously before and after the rotation to evaluate the educational effectiveness of the rotation. Students and radiation oncology faculty were given surveys to assess feedback about the rotation. RESULTS: The students' prerotation test scores had an average of 64% (95% confidence interval [CI], 61-66%). The postrotation test scores improved to an average of 82% (95% CI, 80-83%; 18% absolute improvement). In examination question analysis, scores improved in clinical oncology from 63% to 79%, in radiobiology from 70% to 77%, and in medical physics from 62% to 88%. Improvements in all sections but radiobiology were statistically significant. Students rated the usefulness of the rotation as 8.1 (scale 1-9; 95% CI, 7.3-9.0), their understanding of radiation oncology as a result of the rotation as 8.8 (95% CI, 8.5-9.1), and their recommendation of the rotation to a classmate as 8.2 (95% CI, 7.6-9.0). CONCLUSIONS: Integrating a radiation oncology clinical rotation into the medical school curriculum improves student knowledge of radiation oncology, including aspects of clinical oncology, radiobiology, and medical physics. The rotation is appreciated by both students and faculty.
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Estágio Clínico , Radioterapia (Especialidade)/educação , Avaliação Educacional/métodos , Avaliação Educacional/normas , Humanos , Philadelphia , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Faculdades de MedicinaRESUMO
INTRODUCTION: The prognosis after pancreaticoduodenectomy (PD) for ampullary carcinoma (AC) is superior to that of pancreatic cancer. Decisions regarding adjuvant therapy are influenced by factors such as nodal status, stage, and grade, but the influence of these individual variables on survival is unclear. METHODS: A prospective tumor registry database was queried to identify patients who underwent PD for AC at Thomas Jefferson University between Jan 1997 and Apr 2009. The study was conducted with the approval of the institutional review board. Data were collected through review of hospital and departmental charts. Overall survival (OS) was analyzed using univariate and multivariate Cox proportional hazard models. The proportional hazard assumption was verified for the overall model and individual covariates. RESULTS: A total of 61 patients underwent PD for AC at our institution. There were five perioperative deaths (8.2%). Mean age was 70 years (62% male). Median survival time (MST) was 50 months for all patients. Only primary tumor stage, T1/T2 versus T3/T4 (American Joint Committee on Cancer Staging, version 6), was associated with OS in univariate analyses (p = 0.003). The association of nodal status with OS was borderline-significant (p = 0.08), with the MST being 84 months for node-negative and 17 months for node-positive patients. The remaining covariates were not predictors of OS. In the multivariate analysis, only primary tumor stage (HR, 5.1; p < 0.001) and age (HR, 1.04; p = 0.06), but not nodal status or adjuvant therapy, were associated with overall survival. CONCLUSIONS: Advanced primary tumor stage and age were associated with inferior OS after PD for AC. Adjuvant therapy did not impact survival. Patients with advanced tumor stage should be considered for clinical trials of adjuvant therapy after PD with novel compounds and optimized radiation therapy strategies.
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Ampola Hepatopancreática/patologia , Carcinoma/patologia , Carcinoma/terapia , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/terapia , Recidiva Local de Neoplasia , Fatores Etários , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Capecitabina , Quimioterapia Adjuvante , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pancreaticoduodenectomia , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Tempo , GencitabinaRESUMO
PURPOSE: Delivering adequate dose to tracheal mucosa recurrence after multiple prior courses of surgery and radiation presented a challenge for radiation delivery. Tumor bed location and size, combined with previous doses to surrounding areas, complicated the use of external beam therapy with either photons or electrons. High-dose-rate (HDR) brachytherapy was explored to provide sufficient dose coverage. METHODS AND MATERIALS: A 45-year-old gentleman presented with recurrent head and neck cancer. After undergoing additional excision of gross tumor in the tracheal region, radiation was recommended to improve local control. The region of residual tumor was confined to a small superficial lesion at the posterior-superior aspect of the trachea, involving mucosa located along the bend of the trachea, immediately deep to the stoma. External beam treatment was discussed but was not recommended based on recurrence location in the prior radiation field and patient's flexed chin position. HDR technique with a custom applicator was preferred. RESULTS: A three-dimensional HDR plan based on computed tomography used a single catheter optimized to cover gross tumor volume as delineated by physician. Prescribed dose was 5 Gy/fraction for six fractions (two fractions/wk). The applicator position was verified daily with computed tomography and physician setup approval before treatment. The patient was positioned on a wing board to allow access to the stoma. HDR brachytherapy was well tolerated. CONCLUSIONS: Intraluminal HDR brachytherapy is a viable option for providing dose to region inside tracheal stoma. Advantages over photon and electron beam therapy include reduced dose to surrounding tissues previously irradiated, skin dose, and reproducibility of treatment delivery.
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Braquiterapia/métodos , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Mucosa Respiratória/efeitos da radiação , Neoplasias da Traqueia/radioterapia , Neoplasias da Traqueia/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Resultado do TratamentoRESUMO
BACKGROUND: We studied the potential prognostic significance of pretreatment 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) standardized uptake value (SUV) in squamous cell carcinoma of the head and neck (SCCHN). METHODS: A retrospective review of the pretreatment FDG-PET scans of 60 patients with SCCHN was performed. All patients received radiotherapy and 37 also received concurrent chemotherapy. SUV was calculated by 2 nuclear-medicine physicians who were blinded to the clinical data. Disease-free survival (DFS) was analyzed with respect to SUV (and other potential prognostic factors). RESULTS: The median SUV was 7.2 (range, 1-24.7); 34 patients (57%) had SUV < 9.0 compared with 26 patients (43%) with an SUV > or = 9.0. The group with low SUV had significantly better 2-year DFS compared with the high SUV group (72% vs 37%), p = .007. On multivariate analysis, stage and age were also associated with DFS, but SUV remained an independent predictor of DFS (hazard ratio: 1.08; p = .016). CONCLUSION: SUV was significantly associated with outcome after modern definitive therapy of SCCHN.
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Carcinoma de Células Escamosas/diagnóstico , Fluordesoxiglucose F18/farmacocinética , Neoplasias de Cabeça e Pescoço/diagnóstico , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Preoperative therapy for localized gastric cancer has considerable appeal. We hypothesized that, in a cooperative group setting, preoperative chemoradiotherapy would induce a 20% pathologic complete response (pathCR) rate. Combined-modality therapy quality, survival, and safety were secondary end points. PATIENTS AND METHODS: Patients with localized gastric adenocarcinoma were eligible. A negative laparoscopic evaluation was required. Patients received two cycles of induction fluorouracil, leucovorin, and cisplatin followed by concurrent radiation and chemotherapy (infusional fluorouracil and weekly paclitaxel). Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed. Quality of therapy was assessed with other end points. RESULTS: Twenty institutions participated. Forty-nine patients were entered and 43 were assessable (12% stage IB; 37% stage II; and 52% stage III). The pathCR and R0 resection rates were 26% and 77%, respectively. At 1 year, more patients with pathCR (82%) are living than those with less than pathCR (69%). Grade 4 toxicity occurred in 21% of patients. Chemotherapy, radiotherapy, and surgery per protocol (including acceptable variations) occurred in 98%, 44%, and 63% of patients, respectively. A D2 dissection was performed in 50% of patients. Of 18 major radiotherapy variations, 17 were due to the lack of inclusion of the L3-4 vertebral interphase as prespecified. CONCLUSION: For localized gastric cancer, preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20% in a cooperative group setting. The quality of surgery improved (50% with D2 dissection) possibly because surgery was part of this trial. With some refinements, this preoperative chemoradiotherapy strategy is poised for a randomized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer.