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OBJECTIVES: Clinical concerns about hematologic toxicities in human immunodeficiency virus (HIV)+ patients with squamous cell anal cancer (SCAC) may lead to de-escalation of treatment intensity. The objective of this study is to evaluate clinical outcomes including toxicity following standard concurrent curative-intent chemoradiation for HIV+ and HIV- patients with SCAC. MATERIALS AND METHODS: Among 97 evaluable patients treated between 2009 and 2016 (median age 52.2 y), 43 (44.3%) were HIV+ and 54 (55.7%) HIV-. The majority of the radiation was delivered using intensity-modulated radiation therapy and chemotherapy consisting primarily (93%) of 5-fluorouracil and mitomycin C. Clinical outcomes assessed included toxicity, locoregional control (LRC), distant metastasis (DM), progression-free survival (PFS), colostomy-free survival (CFS), overall survival (OS), and cause-specific survival (CSS). RESULTS: With a median follow-up of 45 months, HIV+ patients exhibited a trend toward reduced OS compared with HIV- patients (4 y OS 61.2% vs. 78.3%; HR 2.09; 95% CI, 0.97-4.52; P=0.055) on univariable analysis, but HIV status was not significant after adjusting for additional parameters on multivariable analysis. Toxicity rates, LRC, CFS, PFS, freedom from DM, and CSS were similar between the 2 cohorts. On multivariable analysis, tumor size >5 cm impacted all clinical outcomes (trend for LRC) except CFS. Radiation treatment extension beyond 7 days was found to negatively impact LRC and CSS. Male sex was associated with worse CFS. CONCLUSIONS: Radiation therapy with concurrent 5-fluorouracil and mitomycin C chemotherapy is reasonably well-tolerated as curative treatment for HIV+ patients with SCAC, and no significant difference in outcomes was noted relative to HIV- patients.
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Neoplasias del Ano/terapia , Carcinoma de Células Escamosas/terapia , Quimioradioterapia/métodos , Infecciones por VIH/complicaciones , Huésped Inmunocomprometido , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Ano/etiología , Neoplasias del Ano/inmunología , Neoplasias del Ano/mortalidad , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/mortalidad , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Fluorouracilo/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Mitomicina/uso terapéutico , Radioterapia de Intensidad Modulada/métodos , Resultado del TratamientoRESUMEN
PURPOSE: ASCO introduced the Quality Training Program (QTP) in 2013 with the aim to train oncology professionals to design, implement, and lead successful quality improvement (QI) activities and assume leadership positions to champion culture change in their practices. METHODS: The QTP is a formal 6-month program taught by QI faculty and mentored by QI coaches over 5 days of in-person learning across 3 sessions and hands-on learning at the participants' practices. Sessions include seminars, case examples, and small-group exercises. Participants attend in multidisciplinary teams and focus on a problem they wish to solve in their practice. Scheduled conference calls with QI coaches are held between sessions. Participants complete pre- and post-QTP surveys (10-point Likert scale, with 1 = no knowledge/competence and 10 = complete knowledge/competence) and provide direct written feedback. RESULTS: Since its inception, QTP has had 15 courses (10 domestic and 5 international) with 120 teams and 544 total participants. QTP is led by an 8-member steering group with 16 faculty and coaches. All postsurvey items showed an increase in knowledge and competence. Each item's score was calculated as the mean difference between before and after scores. Participants stated an increase of 46%-84% (overall mean increase: knowledge, 38%; competence, 37%). The greatest increases were in methodology and practical tools to make changes in practice (writing an aim statement, implementing rapid improvement, using process analysis tools, flowcharting the process). The most common suggestion for improvement was allowing more time for the project. Participants are encouraged to write articles and present work in poster and plenary sessions. QTP courses have led to 7 manuscripts and 21 abstract presentations to national meetings. Six QTP alumni are now QI coaches and faculty. CONCLUSION: The QTP is a successful QI course for oncology professionals who need to measure performance, investigate quality and safety issues, and implement change. It is the only oncology-focused QI training, as all faculty and coaches are providers and QI specialists with oncology experience, which makes this a unique opportunity. The success will provide further momentum to offer QTP domestically and around the world.
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Internado y Residencia , Mejoramiento de la Calidad , Competencia Clínica , Humanos , Liderazgo , Oncología MédicaAsunto(s)
Biomarcadores/sangre , Ayuno/sangre , Glucagón/sangre , Glucosa/administración & dosificación , Neoplasias Pancreáticas/diagnóstico , Anciano , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/complicaciones , Pioglitazona/uso terapéuticoRESUMEN
OBJECTIVES: There is interest in improving the tumoricidal effects of preoperative radiotherapy for rectal carcinoma by studying new radiosensitizers. The safety and toxicity profile of these combination regimens needs rigorous clinical evaluation. The primary objective of this study was to evaluate the toxicity of combining bavituximab, an antibody that targets exposed phosphatidylserine, with capecitabine and radiation therapy. MATERIALS AND METHODS: Patients with stage II or III rectal adenocarcinoma were enrolled on a phase I study combining radiation therapy, capecitabine, and bavituximab. A standard 3+3 trial designed was used. RESULTS: In general, bavituximab was safe and well tolerated in combination with radiation therapy and capecitabine in the treatment of rectal adenocarcinoma. One patient at the highest dose level experienced a grade III infusion reaction related to the bavituximab. One tumor demonstrated a complete pathologic response to the combination treatment. CONCLUSIONS: Bavituximab is safe in combination with capecitabine and radiation therapy at the doses selected for the study. Further clinical investigation would be necessary to better define the efficacy of this combination.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Recurrencia Local de Neoplasia/terapia , Neoplasias del Recto/terapia , Adenocarcinoma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Capecitabina/administración & dosificación , Estudios de Cohortes , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Neoplasias del Recto/patología , Tasa de Supervivencia , Adulto JovenRESUMEN
Peripheral nerve sheath tumors (PNSTs) are neoplasms derived from neoplastic Schwann cells or their precursors. Whereas benign PNSTs are relatively common and considered curable lesions, their malignant counterparts are rare but highly aggressive and require early diagnosis and treatment. MR imaging has been the modality of choice for noninvasive evaluation of PNSTs. This article discusses the features of PNSTs in conventional and advanced MR imaging, and it emphasizes the features that help differentiate benign and malignant variants.
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Imagen por Resonancia Magnética/métodos , Neoplasias de la Vaina del Nervio/diagnóstico , Neoplasias del Sistema Nervioso Periférico/diagnóstico , Diagnóstico Diferencial , Imagen de Difusión por Resonancia Magnética , Humanos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Neoplasias de la Vaina del Nervio/patología , Neoplasias del Sistema Nervioso Periférico/patologíaRESUMEN
BACKGROUND: Capecitabine and irinotecan have demonstrated in vitro synergistic anti-cancer activity, and both are substrates for carboxyl esterases (CES). We conducted a study to identify a safe dose and potential drug-drug interactions of this combination. METHODS: This was an open-label phase I dose escalation trial. Irinotecan was given as a 30 min infusion on days 1 and 8, and capecitabine on days 1-14 of a 21-day cycle. Plasma for pharmacokinetic analyses was drawn on days 1 and 8. RESULTS: Forty-seven patients with advanced solid tumors received 202 cycles of chemotherapy in 6 dose cohorts. At the highest dose tested, 1 of 3 patients developed fatal neutropenia and gram-negative sepsis. At dose level 5 (100/2000), 2 of 28 patients developed cycle 1 DLT-grade 3 diarrhea/vomiting, and grade 3 diarrhea. Responses were observed in 9 of 35 (5 of 9 ovarian cancer) evaluable patients. The AUC((0-last)) of irinotecan, SN-38G, and APC were similar on days 1 and 8. However, SN-38 T(max) was longer on Day 8 (0.88 h vs. 1.23 h, p = 0.012). While SN-38 AUC((0-last)) was lower on day 8 by 35%, this was not statistically significant (p = 0.123). CONCLUSIONS: Capecitabine results in a significantly delayed conversion of irinotecan to SN-38, suggesting drug-drug interaction at the level of CES. This suggests caution should be used when irinotecan is combined with substrates of CES, and warrants further study. The combination of irinotecan and capecitabine is safe and well tolerated at 100/2000, and warrants further evaluation in ovarian and breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/sangre , Área Bajo la Curva , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Camptotecina/sangre , Capecitabina , Carboxilesterasa/metabolismo , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Interacciones Farmacológicas , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Infusiones Intravenosas , Irinotecán , Masculino , Persona de Mediana Edad , Neoplasias/metabolismo , Neoplasias/patología , Neutropenia/inducido químicamente , Resultado del TratamientoRESUMEN
The objective of this research is to develop arrays of tuned chemical sensors wherein each sensor element responds to a particular target analyte in a unique manner. By creating sol-gel-derived xerogels that are co-doped with two luminophores at a range of molar ratios, we can form suites of sensor elements that can exhibit a continuum of response profiles. We trained an artificial neural network (ANN) to "learn" to identify the optical outputs from these xerogel-based sensor arrays. By using the ANN in concert with our tailored sensor arrays we obtained a 5-10 fold improvement in accuracy and precision for quantifying O2 in unknown samples. We also explored the response characteristics of these types of sensor elements after they had been contacted with rat plasma/blood. Contact with plasma/blood caused approximately 15% of the luminophore molecules within the xerogels to become non-responsive to O2. This behavior is consistent with rat albumin blocking certain pore sub-populations within the mesoporous xerogel matrix thereby limiting O2 access to the luminophores.
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Advanced-stage or relapsed/refractory Hodgkin's disease (HD) has a poor prognosis despite aggressive chemotherapy regimens and the use of high-dose therapy with autologous stem cell support. Mitoxantrone, vinblastine and CCNU (lomustine) (MVC) combines the most effective chemotherapeutic agents of previous regimens for poor prognosis HD, and eliminates marginally active agents with unnecessary toxicities, such as bleomycin and dacarbazine. Sixty-eight patients with HD (23 newly diagnosed and 45 with relapsed/refractory disease, one patient treated both de novo and years later in relapse) were treated with the MVC regimen (mitoxantrone 8 mg/m(2)/day i.v. days 1 - 3; vinblastine 8 m/m(2)/day days 1 and 22; and CCNU (lomustine) 100 mg/m(2) on day 1, repeated at 6 - 8 weeks) in a single-arm Phase II study. All patients responded to treatment in the newly diagnosed group (overall response = 100%). The median response duration was not reached, but was in the range 7.6 - 180 + months, and median survival was 94 months. Eleven complete responses are ongoing at 39 - 180 + months. In the previously-treated patients, 41 responded to MVC (OR = 91%). The median response duration for this group was 11 months, and the median survival was 34 months after initiating MVC. Four secondary myeloid leukemias occurred, three in de novo, and one in the relapsed/refractory group, at a median follow-up of 14 years. MVC regimen for HD is highly active, for both de novo and relapsed/refractory disease, with high response rates and survival that compare favourably with the results obtained by high-dose therapy with stem-cell transplantation. Although significant, the toxicities associated with this regimen were manageable.