RESUMEN
Excision repair cross-complementation group 1 (ERCC1) expression by non-small cell lung cancer (NSCLC) has been reported to predict resistance to platinum-based therapies. On this basis, several commercial laboratories have offered ERCC1 testing to facilitate clinical decision making, but the reliability of such assays has recently been called into question. Methods. First, three large commercial laboratories were queried for their cumulative ERCC1 test results in NSCLC patients to compare their independent rates of ERCC1 expression. Second, identical tumor blocks from individual NSCLC patients underwent round-robin analysis to evaluate interlaboratory concordance for ERCC1 expression. Third, a retrospective review of medical records from NSCLC patients identified those who were both highly responsive and resistant to platinum-based chemotherapies. Tumor blocks from these patients were then used in a gold standard analysis to determine individual laboratory sensitivity and specificity for ERCC1 results. Results. Significant differences were observed in independent laboratory ERRC1 expression rates (Clarient 70% vs. Genzyme 60% vs. Third Laboratory 44%, p < .0001 for all two-way comparisons). Only 4 of 18 tumors examined in round-robin analysis were fully concordant (κ ≤ 0.222 for all two-way comparisons). In preselected platinum responsive and resistant specimens, none of these three commercially marketed laboratory assays achieved a specificity of greater than 50%. Conclusion. The results of commercial laboratory testing for ERCC1 are inconsistent and unreliable. Better validation and postmarketing surveillance should be mandated before tumor biomarker assays are allowed to enter the clinical arena.
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Biomarcadores de Tumor/genética , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/uso terapéutico , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Pruebas Genéticas/métodos , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteínas de Unión al ADN/biosíntesis , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/genética , Endonucleasas/biosíntesis , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/genética , Estudios RetrospectivosRESUMEN
The Oncotype DX recurrence score (RS) reduces breast cancer adjuvant treatment utilization, but the reasons for this effect are not straightforward. We performed a retrospective chart review of 89 consecutive node-negative breast cancer patients for whom RS was ordered to facilitate adjuvant treatment decisions. By subtracting the relapse rate predicted by RS from that calculated using the Adjuvant! Online (AOL) web-based instrument, a "prognostic delta" (P∆) was determined, reflecting the difference between prognoses predicted by these two indices. Clinician interviews were conducted to evaluate the actual effect of RS on treatment decisions and its relation to P∆. Adjuvant chemotherapy use decreased from 61 to 26 % as a consequence of RS results (p < 0.0001). In multivariate analysis, RS was the only factor significantly associated with the final adjuvant treatment choice. Surprisingly, RS caused chemotherapy to be withheld even when P∆ was negative (i.e., cases in which RS predicted a less favorable outcome than AOL). The prognostic and chemotherapy predictive utilities of the RS do not fully account for its effect in reducing adjuvant chemotherapy use. Further studies are required to more fully elucidate other factors that may be responsible for this effect, including the possibility of unintended influence.
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Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Perfilación de la Expresión Génica/métodos , Adulto , Anciano , Neoplasias de la Mama/patología , Toma de Decisiones , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Recurrencia , Estudios RetrospectivosRESUMEN
INTRODUCTION: For patients with recurrent SCLC, topotecan remains the only approved second-line treatment, and the outcomes are poor. CheckMate 032 is a phase 1/2, multicenter, open-label study of nivolumab or nivolumab plus ipilimumab in SCLC or other advanced/metastatic solid tumors previously treated with one or more platinum-based chemotherapies. We report results of third- or later-line nivolumab monotherapy treatment in SCLC. METHODS: In this analysis, patients with limited-stage or extensive-stage SCLC and disease progression after two or more chemotherapy regimens received nivolumab monotherapy, 3 mg/kg every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. RESULTS: Between December 4, 2013, and November 30, 2016, 109 patients began receiving third- or later-line nivolumab monotherapy. At a median follow-up of 28.3 months (from first dose to database lock), the objective response rate was 11.9% (95% confidence interval: 6.5-19.5) with a median duration of response of 17.9 months (range 3.0-42.1). At 6 months, 17.2% of patients were progression-free. The 12-month and 18-month overall survival rates were 28.3% and 20.0%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 11.9% of patients. Three patients (2.8%) discontinued because of treatment-related adverse events. CONCLUSIONS: Nivolumab monotherapy provided durable responses and was well tolerated as a third- or later-line treatment for recurrent SCLC. These results suggest that nivolumab monotherapy is an effective third- or later-line treatment for this patient population.
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Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/uso terapéutico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Supervivencia sin Progresión , Retratamiento , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Carcinoma Pulmonar de Células Pequeñas/secundario , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The adrenal gland is a common site of cancer metastasis. Surgery remains a mainstay of treatment for solitary adrenal metastasis. For patients who cannot undergo surgery, radiation is an alternative option. Stereotactic body radiotherapy (SBRT) is an ablative treatment option allowing larger doses to be delivered over a shorter period of time. In this study, we report on our experience with the use of SBRT to treat adrenal metastases using CyberKnife technology. We retrospectively reviewed the Winthrop University radiation oncology data base to identify 14 patients for whom SBRT was administered to treat malignant adrenal disease. Of the factors examined, the biological equivalent dose (BED) of radiation delivered was found to be the most important predictor of local adrenal tumor control. We conclude that CyberKnife-based SBRT is a safe, non-invasive modality that has broadened the therapeutic options for the treatment of isolated adrenal metastases.
RESUMEN
PURPOSE/OBJECTIVE(S): Stereotactic body radiation therapy (SBRT) has been shown to have increased local control and overall survival relative to conventional external beam radiation therapy in patients with medically inoperable stage I non-small cell lung cancer (NSCLC). Excellent rates of local control have been demonstrated both in clinical trials and in single-center studies at large academic institutions. However, there is limited data on the experiences of small academic hospitals with SBRT for stage I NSCLC. The purpose of this study is to report the local control and overall survival rates in patients treated with SBRT for stage I NSCLC at Winthrop-University Hospital (WUH), a small academic hospital. MATERIALS/METHODS: This is a retrospective review of 78 stage I central and peripheral NSCLC tumors treated between December 2006 and July 2012 with SBRT at WUH. Treatment was given utilizing fiducials and a respiratory tracking system. If the fiducials were not trackable, a spine tracking system was used for tumor localization. CT-based planning was performed using the ray trace algorithm. Treatment was delivered over consecutive days to a median dose of 4800 cGy delivered in four fractions. The Kaplan-Meier method was used to calculate local control and overall survival. RESULTS: The median age was 78.5 years. Fifty-four percent of the patient population was female. Sixty seven percent of the tumors were stage IA, and 33% of the tumors were stage IB. Fifty-three percent of the tumors were adenocarcinomas and 29% were squamous cell carcinomas, with the remainder being of unknown histology or NSCLC, not otherwise specified The 2-year local control rate was 87%, and the 2-year overall survival was 68%. CONCLUSION: Our findings support that local control and overall survival at a small academic hospital are comparable to that of larger academic institutions' published experiences with SBRT for stage I NSCLC.