RESUMO
PURPOSE: To determine the maximum tolerated dose of upper abdominal low-dose fractionated radiotherapy (<1.0 Gy per fraction) given in combination with, and as a chemopotentiator for, gemcitabine. METHODS AND MATERIALS: Gemcitabine was given at 1,250 mg/m(2) at 10 mg/m(2)/min on Days 1 and 8 of a 3-week cycle. Low-dose fractionated radiotherapy was tested at two dose levels: 60 cGy per fraction and 70 cGy per fraction. Radiotherapy was given b.i.d. on Days 1, 2, 8, and 9. Four cycles were planned. RESULTS: Twenty-seven patients have been put on study. Ten patients have been entered in Phase I: 6 with metastatic/recurrent pancreatic carcinoma and 4 with unresectable pancreatic/small bowel carcinoma. Two of four patients at Dose Level 2 experienced dose-limiting toxicity. The overall radiographic response was 30%, and median survival was 11 months (range, 4-37 months). CONCLUSION: Low-dose fractionated radiotherapy to the upper abdomen is well tolerated at 60 cGy per fraction when combined with gemcitabine. Phase II evaluation is ongoing.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/radioterapia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Fracionamento da Dose de Radiação , Esquema de Medicação , Feminino , Humanos , Neoplasias Intestinais/mortalidade , Intestino Delgado , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Radiossensibilizantes/efeitos adversos , Radiossensibilizantes/uso terapêutico , GencitabinaRESUMO
We review our recent experience with intensity-modulated radiation therapy (IMRT) and conventional three-dimensional radiation therapy (C3DRT) in advanced head and neck cancer. Sixty-nine patients with Stage IV head and neck cancer (and stage III base of tongue and hypopharynx) enrolled in a Phase II study of definitive chemoradiation; 20 received all or part of their radiation with IMRT. Image-guided set-up, using video subtraction techniques, was used in all patients. Six weekly doses of induction carboplatin (AUC=2) and paclitaxel (135 mg/m2) were followed by alternating weekly chemoradiation to 75 Gy with 1.5 Gy BID fractions, concurrent with paclitaxel (100 mg/m2/week), 5-fluorouracil (600 mg/m2/d) and hydroxyurea (500 mg PO BID). Two consecutive cohorts enrolled, differing in radiation scheme: 75 Gy to gross disease in both, 60 or 54 Gy to first echelon lymphatics and 45 or 39 Gy to second echelon lymphatics. With a median follow-up of 47 months, 3-year overall survival is 68.5% and 3-year locoregional control is 94.0%, with no significant differences between those treated with C3DRT versus IMRT, nor between the two radiation dosing schemes. Actuarial overall survival without tracheostomy or laryngectomy, or without a gastrostomy tube was also similar. Acute mucositis, dermatitis and pain were similar with C3DRT and IMRT. Preliminary data suggests IMRT is well tolerated, and does not compromise locoregional control, indicating that IMRT adequately covers the clinical volume at risk. Building on the present clinical experience, future directions include more directed efforts at reducing toxicity, with better planning software and planning techniques.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Biópsia , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Terapia Combinada/efeitos adversos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Radioterapia/efeitos adversos , Dosagem Radioterapêutica , Análise de SobrevidaRESUMO
PURPOSE: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. METHODS AND MATERIALS: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). RESULTS: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥ 2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. CONCLUSION: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.
Assuntos
Quimiorradioterapia Adjuvante/métodos , Radioterapia de Intensidade Modulada , Neoplasias Retais/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina , Quimiorradioterapia Adjuvante/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Diarreia/etiologia , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Cuidados Pré-Operatórios , Qualidade de Vida , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Taxa de SobrevidaRESUMO
The management of locoregionally recurrent or second primary tumors in a previously irradiated head and neck volume presents a challenging clinical problem. Only a small subset of patients are candidates for potentially curative surgery. Chemotherapy alone provides only limited palliation with no long term survivors. Reirradiation, particularly with aggressive concomitant chemotherapy, results in prolonged median survival and long term survival for some patients. The toxicity of reirradiation, while greater than chemotherapy alone or primary irradiation, is lower than expected for the high cumulative radiation doses. The results of reirradiation in recurrent head and neck cancer and the prognostic factors predicting outcome in this patient population are reviewed.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Recidiva Local de Neoplasia/radioterapia , Segunda Neoplasia Primária/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Prognóstico , SobrevidaRESUMO
PURPOSE: To assess the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) in pancreatic and bile duct (cholangiocarcinoma) malignancies. METHODS AND MATERIALS: Twenty-five patients with pancreatic and bile duct cancer were treated with IMRT. Twenty-three received concurrent 5-fluoruracil. One patient with a pancreatic primitive neuroectodermal tumor received concurrent etoposide and ifosfamide. Eight patients had resected tumors, and 17 had unresectable primary (n = 14) or recurrent (n = 3) tumors. Six patients underwent treatment planning with conventional three-dimensional four-field techniques for dosimetric comparison with IMRT. RESULTS: Compared with conventional RT, IMRT reduced the mean dose to the liver, kidneys, stomach, and small bowel. IMRT was well tolerated, with 80% experiencing Grade 2 or less acute upper GI toxicity. At a median follow-up of 10.2 months, no resected patients had local failure, and only 1 of 10 assessable patients with unresectable cancer had local progression. The median survival and distant metastasis-free survival of the 24 patients with adenocarcinoma was 13.4 and 7.3 months, respectively. Grade 4 late liver toxicity occurred in 1 patient surviving >5 years. The remainder of the assessable patients experienced no (n = 9) or Grade 1 (n = 4) late toxicity. CONCLUSION: In this hypothesis-generating analysis, the acute and chronic toxicity profile with IMRT in the treatment of pancreatic and bile duct cancer was encouraging. Local control was not compromised, despite efforts to increase conformality and avoid doses to normal structures. Distant failure remains a major obstacle in pancreatic cancer.
Assuntos
Adenocarcinoma/radioterapia , Neoplasias dos Ductos Biliares/radioterapia , Neoplasias Pancreáticas/radioterapia , Radioterapia Conformacional/efeitos adversos , Radioterapia Conformacional/métodos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/mortalidade , Fluoruracila/uso terapêutico , Humanos , Imageamento Tridimensional/métodos , Pessoa de Meia-Idade , Tumores Neuroectodérmicos/tratamento farmacológico , Tumores Neuroectodérmicos/radioterapia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
The benefit of postoperative adjuvant chemoradiation in the treatment of resected pancreatic cancers was first established by a randomized trial conducted by the Gastrointestinal Tumor Study Group in 1974. During the past 3 decades, treatment has evolved toward more dose-intensive regimens of chemoradiation. Historical split-course conventional radiation therapy has been replaced by continuous-course radiotherapy to higher doses, and gemcitabine is being actively investigated as a potentially more effective agent than 5-fluorouracil. This article critically examines the results of important randomized multi-institutional trials and reviews the evolution toward dose-intensive adjuvant treatment regimens. Implications of the recently completed intergroup study are discussed, modern radiation therapy delivery techniques are reviewed, and suggestions for future trials are made.
Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/radioterapia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/radioterapia , Adenocarcinoma/cirurgia , Adulto , Idoso , Ensaios Clínicos Fase III como Assunto , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Cuidados Pós-Operatórios/métodos , Prognóstico , Dosagem Radioterapêutica , Radioterapia Adjuvante , Medição de Risco , Resultado do Tratamento , Estados UnidosRESUMO
The objective of this pilot study was to explore whether administration of a catalytic antioxidant, AEOL 10150 (C48H56C15MnN12), could reduce radiation-induced lung injury and improve overall survival when administered after 11.5 Gy of whole thorax lung irradiation in a non-human primate model. Thirteen animals were irradiated with a single exposure of 11.5 Gy, prescribed to midplane, and delivered with 6 MV photons at a dose rate of 0.8 Gy min. Beginning at 24 h post irradiation, the AEOL 10150 cohort (n = 7) received daily subcutaneous injections of the catalytic antioxidant at a concentration of 5 mg kg for a total of 4 wk. All animals received medical management, including dexamethasone, based on clinical signs during the planned 180-d in-life phase of the study. All decedent study animals were euthanized for failure to maintain saturation of peripheral oxygen > 88% on room air. Exposure of the whole thorax to 11.5 Gy resulted in radiation-induced lung injury in all animals. AEOL 10150, as administered in this pilot study, demonstrated potential efficacy as a mitigator against fatal radiation-induced lung injury. Treatment with the drug resulted in 28.6% survival following exposure to a radiation dose that proved to be 100% fatal in the control cohort (n = 6). Computed tomography scans demonstrated less quantitative radiographic injury (pneumonitis, fibrosis, effusions) in the AEOL 10150-treated cohort at day 60 post-exposure, and AEOL 10150-treated animals required less dexamethasone support during the in-life phase of the study. Analysis of serial plasma samples suggested that AEOL 10150 treatment led to lower relative transforming growth factor-Beta-1 levels when compared with the control animals. The results of this pilot study demonstrate that treatment with AEOL 10150 results in reduced clinical, radiographic, anatomic, and molecular evidence of radiation-induced lung injury and merits further study as a medical countermeasure against radiation-induced pulmonary injury.
Assuntos
Antioxidantes/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/efeitos da radiação , Metaloporfirinas/farmacologia , Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/uso terapêutico , Catálise , Dexametasona/farmacologia , Pulmão/patologia , Pulmão/fisiopatologia , Macaca mulatta , Masculino , Metaloporfirinas/administração & dosagem , Metaloporfirinas/química , Metaloporfirinas/uso terapêutico , Peso Molecular , Oxigênio/metabolismo , Projetos Piloto , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/fisiopatologia , Pneumonite por Radiação/sangue , Pneumonite por Radiação/tratamento farmacológico , Pneumonite por Radiação/patologia , Pneumonite por Radiação/fisiopatologia , Protetores contra Radiação/administração & dosagem , Protetores contra Radiação/química , Protetores contra Radiação/uso terapêutico , Respiração/efeitos dos fármacos , Respiração/efeitos da radiação , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Fator de Crescimento Transformador beta1/sangueRESUMO
Liposarcomas are uncommon in the pediatric population. We present the case of a boy who had experienced multiple recurrences of liposarcoma in the buccal space before he reached the age of 13 years. We also provide a review of the literature and a discussion of adjuvant therapy, which are important to understanding the nature of this disease.
Assuntos
Lipossarcoma Mixoide/diagnóstico , Mucosa Bucal , Neoplasias Bucais/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Criança , Humanos , Lipossarcoma Mixoide/terapia , Masculino , Neoplasias Bucais/terapia , Recidiva Local de Neoplasia/terapiaRESUMO
PURPOSE: To develop a Radiation Therapy Oncology Group (RTOG) atlas of the elective clinical target volume (CTV) definitions to be used for planning pelvic intensity-modulated radiotherapy (IMRT) for anal and rectal cancers. METHODS AND MATERIALS: The Gastrointestinal Committee of the RTOG established a task group (the nine physician co-authors) to develop this atlas. They responded to a questionnaire concerning three elective CTVs (CTVA: internal iliac, presacral, and perirectal nodal regions for both anal and rectal case planning; CTVB: external iliac nodal region for anal case planning and for selected rectal cases; CTVC: inguinal nodal region for anal case planning and for select rectal cases), and to outline these areas on individual computed tomographic images. The imaging files were shared via the Advanced Technology Consortium. A program developed by one of the co-authors (I.E.N.) used binomial maximum-likelihood estimates to generate a 95% group consensus contour. The computer-estimated consensus contours were then reviewed by the group and modified to provide a final contouring consensus atlas. RESULTS: The panel achieved consensus CTV definitions to be used as guidelines for the adjuvant therapy of rectal cancer and definitive therapy for anal cancer. The most important difference from similar atlases for gynecologic or genitourinary cancer is mesorectal coverage. Detailed target volume contouring guidelines and images are discussed. CONCLUSION: This report serves as a template for the definition of the elective CTVs to be used in IMRT planning for anal and rectal cancers, as part of prospective RTOG trials.
Assuntos
Linfonodos/diagnóstico por imagem , Ilustração Médica , Radioterapia (Especialidade)/normas , Radioterapia de Intensidade Modulada/normas , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/radioterapia , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/radioterapia , Humanos , Ílio , Canal Inguinal/diagnóstico por imagem , Funções Verossimilhança , Pelve , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Reto/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Primary lymphomas of mucosa associated lymphoid tissue (MALT) are exceedingly rare. We report the case of a 51 year old female diagnosed with primary MALT lymphoma of the gallbladder after cholecystectomy. Further staging workup was negative for metastatic disease. When the disease is localized to the gallbladder, primary MALT lymphomas of the gallbladder carry an excellent prognosis, and surgical resection is curative in the majority of cases.
Assuntos
Neoplasias da Vesícula Biliar/diagnóstico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Biópsia , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Despite recent research and advances in the understanding of the molecular and genetic basis of pancreatic cancer, the poor outcomes experienced by pancreatic cancer patients have changed little during the past 30 years. Adenocarcinoma of the pancreas is the fourth leading cause of cancer-related death in the United States, with only a small fraction of patients achieving long-term survival. According to data from the American Cancer Society, 5-year survival for pancreatic cancer patients is 5%; an estimated 33,730 newly diagnosed cases of pancreatic cancer will be nearly equaled by an estimated 32,300 pancreatic cancer deaths in the United States. This underscores the continued need to develop novel multimodality treatment approaches for this disease. Surgery has proved vital to a curative-intent treatment approach for these patients. However, only 10% to 20% of newly diagnosed patients present with potentially resectable nonmetastatic disease. In light of the minority of patients with resectable disease, there has been considerable debate over the potential advantages of adjuvant chemotherapy and radiotherapy. In recent decades, cooperative groups both in the United States and abroad have conducted randomized clinical trials seeking to define the potential benefit of adjuvant chemotherapy or adjuvant chemoradiotherapy vs. surgery alone for patients with resectable disease. Unfortunately, the results of these trials have been conflicting and no definitive consensus has yet been reached regarding optimal adjuvant therapy. This article reviews cooperative group data pertinent to this debate. It is suggested that (1) patients do benefit from adjuvant therapy, and (2) optimal adjuvant therapy should include gemcitabine-based chemoradiotherapy for select patient subgroups.
RESUMO
The treatment options for patients with recurrent head and neck malignancies arising in a previously irradiated field are limited. Surgical salvage is feasible in a minority of patients. The majority are referred for palliative chemotherapy with no realistic chance for cure. Data are accumulating to support reirradiation as a potentially curative approach for patients with locally or regionally recurrent head and neck cancer. This article provides a rationale for management and reviews recent results of reirradiation.