RESUMO
OBJECTIVES: Adjuvant gemcitabine with or without chemoradiation is a standard therapeutic option for patients with resected pancreatic cancer. The feasibility and toxicity of gemcitabine with docetaxel before and after 5-fluorouracil (5FU)-based chemoradiation in the adjuvant pancreatic and biliary cancer setting were investigated. METHODS: After a curative-intent resection, eligible patients with pancreaticobiliary cancers were treated with two cycles of gemcitabine and docetaxel followed by 5FU-based chemoradiation. Four weeks after completing chemoradiation, two cycles of gemcitabine and docetaxel were administered. The primary endpoint was the incidence of severe toxicities. Secondary endpoints included disease-free survival (DFS) and overall survival (OS). RESULTS: Fifty patients with pancreaticobiliary cancers were enrolled. Twenty-nine patients had pancreatic cancer whereas 21 patients had biliary tract or ampullary cancers. There was one death as a result of pneumonia, and 15% of patients experienced grade 3 or greater non-haematological toxicities. The median DFS and OS for patients with pancreatic cancer were 9.6 and 17 months, respectively, and for those with resected biliary tract cancer were 12 and 23 months, respectively. CONCLUSIONS: This combination of gemcitabine and docetaxel with chemoradiation is feasible and tolerable in the adjuvant setting. Future studies utilizing a different gemcitabine/taxane combination and schedule may be appropriate in the adjuvant treatment of both pancreatic cancer and biliary tumours.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Biliar/terapia , Procedimentos Cirúrgicos do Sistema Biliar , Carcinoma/terapia , Quimiorradioterapia Adjuvante , Desoxicitidina/análogos & derivados , Pancreatectomia , Neoplasias Pancreáticas/terapia , Taxoides/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/mortalidade , Carcinoma/mortalidade , Carcinoma/patologia , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Docetaxel , Estudos de Viabilidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Fatores de Risco , Taxoides/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , GencitabinaRESUMO
Like other technically sophisticated medical endeavours, a hyperthermia clinic relies on skilled staffing. Physicians, physicists and technologists perform multiple tasks to ensure properly functioning equipment, appropriate patient selection, and to plan and administer this treatment. This paper reviews the competencies and tasks that are used in a hyperthermia clinic.
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Instituições de Assistência Ambulatorial , Hipertermia Induzida , Humanos , Hipertermia Induzida/instrumentação , Corpo Clínico , Monitorização Fisiológica , Médicos , Termometria/instrumentação , Recursos HumanosRESUMO
PURPOSE: Unresectable chest wall recurrences of breast cancer (CWR) in heavily pretreated patients are especially difficult to treat. We hypothesised that thermally enhanced drug delivery using low temperature liposomal doxorubicin (LTLD), given with mild local hyperthermia (MLHT), will be safe and effective in this population. PATIENTS AND METHODS: This paper combines the results of two similarly designed phase I trials. Eligible CWR patients had progressed on the chest wall after prior hormone therapy, chemotherapy, and radiotherapy. Patients were to get six cycles of LTLD every 21-35 days, followed immediately by chest wall MLHT for 1 hour at 40-42 °C. In the first trial 18 subjects received LTLD at 20, 30, or 40 mg/m2; in the second trial, 11 subjects received LTLD at 40 or 50 mg/m2. RESULTS: The median age of all 29 patients enrolled was 57 years. Thirteen patients (45%) had distant metastases on enrolment. Patients had received a median dose of 256 mg/m2 of prior anthracyclines and a median dose of 61 Gy of prior radiation. The median number of study treatments that subjects completed was four. The maximum tolerated dose was 50 mg/m2, with seven subjects (24%) developing reversible grade 3-4 neutropenia and four (14%) reversible grade 3-4 leucopenia. The rate of overall local response was 48% (14/29, 95% CI: 30-66%), with. five patients (17%) achieving complete local responses and nine patients (31%) having partial local responses. CONCLUSION: LTLD at 50 mg/m2 and MLHT is safe. This combined therapy produces objective responses in heavily pretreated CWR patients. Future work should test thermally enhanced LTLD delivery in a less advanced patient population.
Assuntos
Adenocarcinoma/terapia , Antibióticos Antineoplásicos , Neoplasias da Mama/terapia , Doxorrubicina/análogos & derivados , Hipertermia Induzida , Recidiva Local de Neoplasia/terapia , Adenocarcinoma/sangue , Adulto , Idoso , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/sangue , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/sangue , Terapia Combinada , Doxorrubicina/efeitos adversos , Doxorrubicina/sangue , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapêutico , Feminino , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/uso terapêutico , Temperatura , Resultado do TratamentoRESUMO
PURPOSE: To present design aspects and acceptance tests performed for clinical implementation of electronic brachytherapy treatment of early stage rectal adenocarcinoma. A dosimetric comparison is made between the historically used Philips RT-50 unit and the newly developed Axxent(®) Model S700 electronic brachytherapy source manufactured by Xoft (iCad, Inc.). METHODS: Two proctoscope cones were manufactured by ElectroSurgical Instruments (ESI). Two custom surface applicators were manufactured by Xoft and were designed to fit and interlock with the proctoscope cones from ESI. Dose rates, half value layers (HVL), and percentage depth dose (PDD) measurements were made with the Xoft system and compared to historical RT-50 data. A description of the patient treatment approach and exposure rates during the procedure is also provided. RESULTS: The electronic brachytherapy system has a lower surface dose rate than the RT-50. The dose rate to water on the surface from the Xoft system is approximately 2.1 Gy∕min while the RT-50 is 10-12 Gy∕min. However, treatment times with Xoft are still reasonable. The HVLs and PDDs between the two systems were comparable resulting in similar doses to the target and to regions beyond the target. The exposure rate levels around a patient treatment were acceptable. The standard uncertainty in the dose rate to water on the surface is approximately ±5.2%. CONCLUSIONS: The Philips RT-50 unit is an out-of-date radiotherapy machine that is no longer manufactured with limited replacement parts. The use of a custom-designed proctoscope and Xoft surface applicators allows delivery of a well-established treatment with the ease of a modern radiotherapy device. While the dose rate is lower with the use of Xoft, the treatment times are still reasonable. Additionally, personnel may stand farther away from the Xoft radiation source, thus potentially reducing radiation exposure to the operator and other personnel.
Assuntos
Braquiterapia/instrumentação , Desenho de Equipamento , Humanos , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
PURPOSE: In vitro data demonstrate that heat-induced radiosensitisation is maximised if hyperthermia and radiotherapy are given simultaneously, with the radiation fraction delivered midway through a hyperthermia session, rather than sequentially. The long-term normal tissue toxicity of full-dose simultaneous thermoradiotherapy is unknown. MATERIALS AND METHODS: Patients with locally advanced breast cancer (T3, T4 or more than three involved nodes or local recurrence), no prior radiotherapy, received between four and eight sessions of simultaneous thermoradiotherapy. Hyperthermia always included the primary tumour site. In addition an electively heated sector (EHS) was included. The EHS was randomised to either medial or lateral to the tumour site, with the other side an irradiated but unheated control. As per our usual practice, patients received surgery and/or chemotherapy prior to radiotherapy. Radiation doses were 46-50 Gy followed by a boost of ≤16 Gy at 1.8-2 Gy per fraction. EHS and control sectors received the same dose. RESULTS: A total of 57 evaluable cases with average follow-up of 79 months experienced two local and two nodal recurrences. There was no significant difference in ≥grade 2 toxicity for heated versus control sectors (LR χ(2 )= 0.78, p = 0.38) with no relationship between number of hyperthermia sessions and toxicity (LR χ(2 )= 2.90, p = 0.09). CONCLUSIONS: Simultaneous full-dose thermoradiotherapy for breast cancer is feasible and well tolerated, with no significant difference in late toxicity between electively heated and unheated control sectors. All patients had hyperthermia to the primary tumour site with excellent local control.
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Neoplasias da Mama/terapia , Hipertermia Induzida , Pele/efeitos da radiação , Adulto , Neoplasias da Mama/radioterapia , Terapia Combinada/efeitos adversos , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Pessoa de Meia-Idade , Parede TorácicaRESUMO
PURPOSE: A multi-institutional phase 2 trial assessed long-term outcomes of dose-painted intensity modulated radiation therapy (IMRT) with 5-fluorouracil (5FU) and mitomycin-C (MMC) for anal canal cancer. METHODS AND MATERIALS: T2-4N0-3M0 anal cancers received 5FU (1000 mg/m2/d, 96-hour infusion) and MMC (10 mg/m2 bolus) on days 1 and 29 of dose-painted IMRT prescribed as follows: T2N0 = 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes, 28 fractions; T3-4N0-3 = 45Gy elective nodal, 50.4 Gy ≤3 cm and 54 Gy >3cm metastatic nodal and 54 Gy anal tumor planning target volumes, 30 fractions. Local-regional failures, distant metastases, and colostomy failures were assessed using the cumulative incidence method, and disease-free survival, overall survival, and colostomy-free survival were assessed using the Kaplan-Meier method. Late effects were scored using National Cancer Institute-Common Terminology Criteria for Adverse Events v3. RESULTS: Of 52 patients, 54% were stage II, 25% were stage IIIA, and 21% were stage IIIB. Median follow-up was 7.9 years (min-max, 0.02-9.2 years). Local-regional failure, colostomy failures, distant metastases, overall survival, disease-free survival, and colostomy-free survival at 5 years are 16% (95% confidence interval [CI], 7%-27%), 10% (95% CI, 4%-20%), 16% (95% CI, 7%-27%), 76% (95% CI, 61%-86%), 70% (95% CI, 56%-81%), and 74% (95% CI, 59%-84%); and at 8 years they are 16% (95% CI, 7%-27%), 12% (95% CI, 5%-23%), 22% (95% CI, 12%-34%), 68% (95% CI, 53%-79%), 62% (95% CI, 47%-74%) and 66% (95% CI, 51%-77%), respectively. Eight patients experienced local-regional failure, with 5 patients having persistent disease at 12 weeks. No isolated nodal failures occurred in the microscopic elective nodal volumes. Six patients required colostomy-5 for local-regional salvage and 1 for a temporary ostomy for anorectal dysfunction. Rates of late adverse events included: 28 patients (55%) with grade 2, 8 patients (16%) with grade 3, 0 patients with grade 4, and 2 patients (4%) with grade 5 events (sinus bradycardia and myelodysplasia, possibly owing to chemotherapy). Only 11 patients reported grade 1 to 3 sexual dysfunction. CONCLUSIONS: Dose-painted IMRT with 5FU/MMC for the treatment of anal canal cancer yields comparable long-term efficacy as conventional radiation cohorts. Enhanced normal tissue protection lowered rates of grade 3 and higher late effects without compromising pelvic tumor control.
Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Radioterapia de Intensidade Modulada , Canal Anal , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Fluoruracila/efeitos adversos , Humanos , Mitomicina/efeitos adversos , Morbidade , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodosRESUMO
PURPOSE: To determine conditions under which hypofractionation could be favorable for a normal tissue--even if tumor [alpha/beta] exceeds the normal tissue's [alpha/beta]. METHODS: The hypofractionation sufficiency condition (HSC) for an organ is defined as a dose conformality constraint such that, if satisfied, a family of tumor control probability isoeffective fractionation schemes will show decreasing normal tissue complication probability with decreasing number of fractions. RESULTS: In the extended equivalent uniform dose (EUD) model [obtained by replacing dose with linear quadratic (LQ) 2 Gy equivalent dose], the HSC for a normal organ is proven to be satisfied if a suitably weighted average of the relative dose [hypofractionation sufficiency index (HSI)] is less than the ratio of normal tissue to tumor [alpha/beta]. The HSI is determined solely by dose distribution and the normal tissue volume factor, "a." If the HSC is satisfied for every normal tissue of concern, then there is a therapeutic gain with hypofractionation. The corresponding multifractionation sufficiency condition (therapeutic gain with increasing number of fractions) and multifractionation sufficiency index (MSI) are also derived. A sample clinical case is presented. CONCLUSIONS: Within the context of the LQ/EUD models, conformality measures (HSI and MSI) can be used to inform fractionation decisions.
Assuntos
Fracionamento da Dose de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Órgãos em Risco/efeitos da radiaçãoRESUMO
This paper reviews systems and techniques to deliver simultaneous thermoradiotherapy of breast cancer. It first covers the clinical implementation of simultaneous delivery of superficial (microwave or ultrasound) hyperthermia and external photon beam radiotherapy, first using a Cobalt-60 teletherapy unit and later medical linear accelerators. The parallel development and related studies of the Scanning Ultrasound Reflector Linear Arrays System (SURLAS), an advanced system specifically designed and developed for simultaneous thermoradiotherapy, follows. The performance characteristics of the SURLAS are reviewed and power limitation problems at high acoustic frequencies (>3 MHz) are discussed along with potential solutions. Next, the feasibility of simultaneous SURLAS hyperthermia and intensity modulated radiation therapy/image-guided radiotherapy (IMRT/IGRT) is established based on published and newly presented studies. Finally, based on the encouraging clinical results thus far, it is concluded that new trials employing the latest technologies are warranted along with further developments in treatment planning.
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Neoplasias da Mama/terapia , Hipertermia Induzida , Neoplasias da Mama/radioterapia , Terapia Combinada , Feminino , Humanos , GravidezRESUMO
PURPOSE: This is a phase II, single-center, single-arm study of patients with resectable adenocarcinoma of the pancreas who were treated with adjuvant interferon-based chemoradiation followed by gemcitabine. The primary end point was 2-year overall survival, with secondary endpoints being 2-year disease-free survival, and the frequency of grade 3 or 4 toxicity. PATIENTS AND METHODS: From April 2002 to September 2005, 53 patients with adenocarcinoma of the pancreas underwent curative resection at a single institution, and subsequently received interferon- and gemcitabine-based adjuvant therapy consisting of external-beam irradiation at a dose of 5040 cGy (25 fractions per 5 weeks) and simultaneous 3-drug chemotherapy consisting of (1) continuous infusion 5-fluorouracil (175 mg/m2); (2) weekly intravenous bolus cisplatin (25 mg/m2); and (3) interferon-alpha (3 million units subcutaneously 3 times per week) during the 6 weeks of radiation. This was followed by two 4-week courses of weekly intravenous infusion of gemcitabine (1000 mg/m2, 3 of 4 weeks). RESULTS: Median follow-up is 38 months. Seventy-seven percent of patients had node-positive disease. Sixteen patients (30%) failed to complete adjuvant therapy, due to disease progression (7 patients), toxicity (7 patients), and consent withdrawal (2 patients). No patients completed planned therapy without dose modification. Median overall survival was 25 months (confidence interval [CI] = 21.5-48.5 months). Actuarial overall survival for the 1-, 2- and 3-year periods were 75% (CI = 61-85%), 56% (CI = 41-69%), and 41% (26-55%), respectively. CONCLUSIONS: This phase II trial demonstrated increased patient survival compared with historical controls, and equivalent survival compared with the regimen combining interferon-alpha with 5-fluorouracil-based chemoradiation. Despite these encouraging results, significant concerns regarding dose- and treatment-limiting toxicities remain.
Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Terapia Combinada , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Pancreatectomia/métodos , Neoplasias Pancreáticas/patologia , Probabilidade , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Medição de Risco , Análise de Sobrevida , Fatores de Tempo , GencitabinaRESUMO
PURPOSE: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. PATIENTS AND METHODS: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. RESULTS: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDG uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). CONCLUSIONS: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer.
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Neoplasias do Ânus/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/metabolismo , Neoplasias do Ânus/terapia , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Compostos Radiofarmacêuticos/farmacocinética , Taxa de SobrevidaRESUMO
PURPOSE: Radiation Therapy Oncology Group (RTOG) 92-08 began as a single arm, Phase II trial for patients with anal cancer consisting of radiation (RT) + 5-flourouracil + mitomycin-C with a mandatory 2-week break and was amended after completion to evaluate the same treatment regimen without a treatment break. Long-term efficacy and late toxicity reporting are the specific aims of this study. METHODS AND MATERIALS: Survivals were estimated with the Kaplan-Meier method. Overall survival (OS) was compared with RTOG 87-04 with the log-rank test. Time to local failure, regional failure, locoregional failure (LRF), distant metastases, second primary, and colostomy failure were estimated by the cumulative incidence method. LRF was compared with RTOG 87-04 using the Gray's test. RESULTS: Forty-seven patients entered in the mandatory treatment break cohort. The study was reopened in 1995 to the no mandatory treatment break cohort completing accrual with 20 patients in 1996. Of 67 total patients, 1 patient in the mandatory treatment break portion of the study did not receive any protocol treatment and is excluded from analyses. After adjusting for tumor size, neither cohort showed a statistically significant difference in OS or LRF compared with the RTOG 87-04 mitomycin-C arm. No patient in either cohort experienced a Grade 3 or higher late toxicity. CONCLUSIONS: No statistically significant differences were seen in OS or LRF when compared to the mitomycin-C arm of RTOG 87-04, but the sample sizes for the mandatory break cohort and the no mandatory break cohort are small. Late toxicity was low and similar for the treatment cohorts.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapia , Lesões por Radiação/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/patologia , Colostomia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/efeitos adversosRESUMO
PURPOSE: The response of rectal cancers to neoadjuvant chemoradiotherapy is variable. Tumor hypoxia reduces the effectiveness of both radiation therapy and chemotherapy and is a well-known risk factor for tumor radioresistence. We hypothesized that imaging with the novel hypoxia-detecting agent, (60)Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) ((60)Cu-ATSM), previously validated in cervical and lung cancers, would predict the response of rectal cancers to neoadjuvant chemoradiotherapy and prognosis. METHODS: Patients with locally invasive (T2-4) primary or node-positive rectal cancer located <12 cm from the anal verge were recruited for this pilot study. Pretreatment tumor size and stage were determined by endorectal ultrasonography, CT, and magnetic resonance imaging. Eleven patients also underwent clinical positron emission tomography with (18)F-fluorodeoxyglucose at the discretion of the treating clinician. The primary tumor was imaged by positron emission tomography with (60)Cu-ATSM, and accumulation of the tracer was measured semiquantitatively by determining the tumor-to-muscle activity ratio. Neoadjuvant chemoradiotherapy was then administered (within 2 weeks of (60)Cu-ATSM-positron emission tomography) and consisted of 45 Gy given in 25 fractions to the pelvis with continuous intravenous infusion of 5-fluorouracil (225 mg/m(2)/day). Proctectomy was performed six to eight weeks after neoadjuvant chemoradiotherapy and the tumor submitted to pathology for size measurement and staging. Tumor-to-muscle activity ratios were compared with tumor (18)F-fluorodeoxyglucose uptake, tumor response to neoadjuvant chemoradiotherapy, and with patient survival. RESULTS: Nineteen patients were enrolled in the study, two of whom were excluded from final analysis (1 death during neoadjuvant chemoradiotherapy and 1 tumor perforation during neoadjuvant chemoradiotherapy requiring emergent surgery). Of the 17 remaining patients, 14 had a reduction in tumor size and 13 were downstaged. The median tumor-to-muscle activity ratio of 2.6 discriminated those with worse prognosis from those with better prognosis. Both overall and progression-free survivals were worse with hypoxic tumors (tumor-to-muscle activity ratio >2.6) than with nonhypoxic tumors (tumor-to-muscle activity ratio
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Carcinoma/diagnóstico , Carcinoma/terapia , Compostos Organometálicos , Tomografia por Emissão de Pósitrons , Neoplasias Retais/diagnóstico , Neoplasias Retais/terapia , Tiossemicarbazonas , Adulto , Idoso , Carcinoma/mortalidade , Hipóxia Celular , Estudos de Coortes , Complexos de Coordenação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Neoplasias Retais/mortalidadeRESUMO
PURPOSE: The use of radioembolization of hepatic metastases with yttrium-90 ((90)Y) microspheres is increasing. The present report describes the outcomes in a cohort of patients with metastatic liver tumors treated with a resin-based microsphere agent. MATERIALS AND METHODS: Thirty patients with colon (n = 13), breast (n = 7), and other primary cancers (n = 10) were treated after the failure of first- and second-line therapy. Overall survival (OS), time to progression (TTP), and time to treatment failure (TTTF) were calculated from the first treatment. Response was measured according to Response Evaluation Criteria In Solid Tumors at interval follow-up imaging. RESULTS: Thirty patients underwent 56 infusions of (90)Y, and 18 remained alive at the end of the study. Fourteen patients (47%) had a partial response or stable disease. OS (604 vs 251 days), TTP (223 vs 87 days), and TTTF (363 vs 87 days) were all significantly longer for patients who had a partial response or stable disease (P < .05). Median OS, TTP, and TTTF for patients with colorectal carcinoma were 357, 112, and 107 days, respectively, versus 638, 118, and 363 days in patients with other metastatic sources. Median survival was not reached for patients with breast carcinoma, and the TTP and TTTF were each 282 days. One patient (3%) experienced grade 3 toxicity (gastrointestinal ulceration). CONCLUSIONS: (90)Y microsphere therapy produced promising survival rates compared with systemic salvage options, with minimal toxicity.
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Neoplasias da Mama/radioterapia , Neoplasias da Mama/secundário , Neoplasias do Colo/radioterapia , Neoplasias do Colo/secundário , Neoplasias Hepáticas/radioterapia , Terapia de Salvação/métodos , Radioisótopos de Ítrio/uso terapêutico , Resinas Acrílicas/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias do Colo/diagnóstico por imagem , Portadores de Fármacos/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Radiografia , Compostos Radiofarmacêuticos/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
It is common belief that patients failing chemoradiation therapy (CRT) for squamous cell cancer of the anus (SCCA) can be salvaged with subsequent surgery. The aim of this study was to examine our experience with abdominoperineal resection (APR) in cases of persistent or recurrent SCCA with an emphasis on survival and morbidity. All patients between 1985 and 2001 undergoing salvage APR were reviewed. Details of CRT, surgery, tumor characteristics, postoperative complications, and survival were obtained from medical records. There were 22 patients (13 women, 9 men) with a mean age of 62 years (range=42-87). Initial tumors were AJCC stage 2 (16 cases), 3A (3 cases), and 4 (1 case). Mean radiation dose was 47.6 Gy (30-60) and most received concomitant 5-FU. In 20 patients, APR was felt to be "curative" but only 13 (65%) had negative margins on final pathology. Thirteen (59%) perineal wounds broke down with a median time to healing of 7 months. Tumor differentiation (p=0.02) and positive resection margins (p=0.004) were significantly associated with DFS (5-year DFS of 37%). Salvage APR in patients with poorly differentiated tumors or positive resection margins has a high morbidity and poor survival and may warrant a planned APR after CRT instead.
Assuntos
Neoplasias do Ânus/cirurgia , Carcinoma de Células Escamosas/cirurgia , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Análise de Sobrevida , Falha de TratamentoRESUMO
PURPOSE: To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. METHODS AND MATERIALS: Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. RESULTS: Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). CONCLUSIONS: Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution.
Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/mortalidade , Neoplasias Retais/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Cuidados Pré-Operatórios , Radioterapia/métodos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologiaRESUMO
PURPOSE: Preoperative short-course radiation therapy (SCRT) has rarely been used for rectal cancer in the United States, although 2 randomized phase 3 trials demonstrate equivalence to conventional chemoradiation (CRT), and recent updates to national guidelines include this regimen as a treatment option. We sought to evaluate the efficacy and safety of preoperative SCRT followed by immediate surgery within 1 week to treat rectal cancer in the US setting. METHODS AND MATERIALS: All patients treated with preoperative SCRT (4 Gy × 5 fractions for total 20 Gy) followed by planned surgery within 1 week at our institution were retrospectively evaluated. Censored cases with ≥2 years of follow-up were included along with any disease failure or death. Patients with cM1 disease were excluded. Patients with yp stage II/III disease typically received adjuvant chemotherapy from the 1990s onwards. The primary outcomes were actuarial (Kaplan-Meier) 5-year locoregional control (LC), disease-free survival (DFS), and overall survival (OS) as well as late severe (greater than or equal to grade 3) toxicity. RESULTS: Our analysis included 202 consecutive patients with clinical stage I-III disease treated from 1977 through 2011. Median follow-up was 6.5 years (range, 2-29.2). Five-year disease outcomes were 95.9% ± 1.5% for LC, 76.4% ± 3.1% for DFS, and 84.6% ± 2.6% for OS. For patients with locally advanced rectal cancer (cT3-4 and/or cN+), 5-year LC, DFS, and OS were 95.1% ± 2.1%, 73.3% ± 4.3%, and 80.6% ± 3.7%, respectively. The late severe toxicity rate was 11.4%. CONCLUSIONS: SCRT followed by immediate surgery is a safe and effective treatment for patients with rectal cancer in the United States. Though SCRT has not been widely adopted, recent updates to the national guidelines for rectal cancer as well as financial pressures to reduce healthcare costs may lead to increased utilization of this treatment regimen in the future.
Assuntos
Neoplasias Retais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/mortalidade , Neoplasias Retais/cirurgia , Estudos RetrospectivosRESUMO
PURPOSE: NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). METHODS AND MATERIALS: NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structure receiving doses ≥5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ≥2 acute and late GI AEs, and grade ≥3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). RESULTS: Among 52 evaluable patients, grade ≥2 acute, grade ≥2 late, and grade ≥3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P<.05) toward statistically significant associations were observed between grade ≥2 acute GI AEs and small bowel dose (V20-V40), grade ≥2 late GI AEs and APC dose (V60), grade ≥3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size >4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. CONCLUSIONS: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/efeitos adversos , Intestino Delgado/efeitos da radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Doença Aguda , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/métodos , Colo/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Intestino Delgado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/efeitos adversos , Órgãos em Risco/diagnóstico por imagem , Órgãos em Risco/patologia , Órgãos em Risco/efeitos da radiação , Pelve/diagnóstico por imagem , Modelos de Riscos Proporcionais , Curva ROC , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Análise de Regressão , Carga TumoralRESUMO
PURPOSE: Surgical staging and treatment of anal carcinoma has been replaced by noninvasive staging studies and combined modality therapy. In this study, we compare computed tomography (CT) and physical examination to [(18)F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the staging of carcinoma of the anal canal, with special emphasis on determination of spread to inguinal lymph nodes. METHODS AND MATERIALS: Between July 2003 and July 2005, 41 consecutive patients with biopsy-proved anal carcinoma underwent a complete staging evaluation including physical examination, CT, and 2-FDG-PET/CT. Patients ranged in age from 30 to 89 years. Nine men were HIV-positive. Treatment was with standard Nigro regimen. RESULTS: [(18)F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) detected 91% of nonexcised primary tumors, whereas CT visualized 59%. FDG-PET/CT detected abnormal uptake in pelvic nodes of 5 patients with normal pelvic CT scans. FDG-PET/CT detected abnormal nodes in 20% of groins that were normal by CT, and in 23% without abnormality on physical examination. Furthermore, 17% of groins negative by both CT and physical examination showed abnormal uptake on FDG-PET/CT. HIV-positive patients had an increased frequency of PET-positive lymph nodes. CONCLUSION: [(18)F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography detects the primary tumor more often than CT. FDG-PET/CT detects substantially more abnormal inguinal lymph nodes than are identified by standard clinical staging with CT and physical examination.
Assuntos
Neoplasias do Ânus/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Soropositividade para HIV/diagnóstico por imagem , Humanos , Canal Inguinal , Linfonodos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pelve , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND AND PURPOSE: To report outcomes and toxicities of a single-institution phase I/II study of stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular cancer (HCC) and intrahepatic cholangiocarcinoma (IHC). MATERIALS AND METHODS: Patients with Child-Pugh score less than 8 were eligible. A total of 32 lesions in 26 patients were treated with SBRT. Kaplan-Meier survival analysis was performed. Toxicities were graded by CTCAEv4 criteria and response was scored by EASL guidelines. RESULTS: Median prescribed dose was 55Gy (range 40-55Gy) delivered in 5 fractions. Mean tumor diameter was 5.0cm and mean GTV was 107cc. Median follow-up was 8.8months with a median survival of 11.1months, and one-year overall survival was 45%. Overall response rate was 42% and one-year local control was 91%. Nine patients experienced a decline in Child-Pugh class following treatment, and two grade 5 hepatic failure toxicities occurred during study follow-up. CONCLUSIONS: Primary hepatic malignancies not amenable to surgical resection portend a poor prognosis, despite available treatment options. Though radiation-induced liver disease (RILD) is rare following SBRT, this study demonstrates a risk of hepatic failure despite adherence to protocol constraints.