RESUMEN
BACKGROUND: Epstein-Barr virus positivity (EBV+) and microsatellite instability (MSI-high) are positive prognostic factors for survival in resectable gastric cancer (GC). However, benefit of perioperative treatment in patients with MSI-high tumors remains topic of discussion. Here, we present the clinicopathological outcomes of patients with EBV+, MSI-high, and EBV-/MSS GCs who received either surgery only or perioperative treatment. METHODS: EBV and MSI status were determined on tumor samples collected from 447 patients treated with surgery only in the D1/D2 trial, and from 451 patients treated perioperatively in the CRITICS trial. Results were correlated to histopathological response, morphological tumor characteristics, and survival. RESULTS: In the D1/D2 trial, 5-year cancer-related survival was 65.2% in 47 patients with EBV+, 56.7% in 47 patients with MSI-high, and 47.6% in 353 patients with EBV-/MSS tumors. In the CRITICS trial, 5-year cancer-related survival was 69.8% in 25 patients with EBV+, 51.7% in 27 patients with MSI-high, and 38.6% in 402 patients with EBV-/MSS tumors. Interestingly, all three MSI-high tumors with moderate to complete histopathological response (3/27, 11.1%) had substantial mucinous differentiation. No EBV+ tumors had a mucinous phenotype. 115/402 (28.6%) of EBV-/MSS tumors had moderate to complete histopathological response, of which 23/115 (20.0%) had a mucinous phenotype. CONCLUSIONS: In resectable GC, MSI-high had favorable outcome compared to EBV-/MSS, both in patients treated with surgery only, and in those treated with perioperative chemo(radio)therapy. Substantial histopathological response was restricted to mucinous MSI-high tumors. The mucinous phenotype might be a relevant parameter in future clinical trials for MSI-high patients.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Neoplasias Gástricas , Ensayos Clínicos como Asunto , Herpesvirus Humano 4/genética , Humanos , Inestabilidad de Microsatélites , Terapia Neoadyuvante , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirugíaRESUMEN
PURPOSE: We report the recruitment rate, reasons for and factors influencing non-participation, and descriptive results of a randomized controlled trial of two different exercise programs for patients with colon cancer undergoing adjuvant chemotherapy. METHODS: Participants were randomized to a low-intensity, home-based program (Onco-Move), a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack), or Usual Care. Non-participants provided reasons for non-participation and were asked to complete a questionnaire assessing behavioral and attitudinal variables. Trial participants completed performance-based and self-reported outcome measures prior to randomization, at the end of chemotherapy, and at the 6-month follow-up. RESULTS: Twenty-three of 63 referred patients agreed to participate in the trial. All 40 non-participants provided reasons for non-participation. Forty-five percent of the non-participants completed the questionnaire. Those who did not want to exercise had higher fatigue scores at baseline and a more negative attitude toward exercise. Compliance to both programs was high and no adverse events occurred. On average, the colon cancer participants were able to maintain or improve their physical fitness levels and maintain or decrease their fatigue levels during chemotherapy and follow-up. CONCLUSIONS: Recruitment of patients with colon cancer to a physical exercise trial during adjuvant chemotherapy proved to be difficult, underscoring the need to develop more effective strategies to increase participation rates. Both home-based and supervised programs are safe and feasible in patients with colon cancer undergoing chemotherapy. Effectiveness needs to be established in a larger trial. TRIAL REGISTRATION: Netherlands Trial Register - NTR2159.
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Neoplasias del Colon/terapia , Ejercicio Físico , Quimioterapia Adyuvante , Neoplasias del Colon/complicaciones , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/fisiopatología , Demografía , Fatiga/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular , Cooperación del Paciente , Aptitud Física , Proyectos Piloto , Calidad de Vida , Autoinforme , Resultado del TratamientoRESUMEN
BACKGROUND: Cross resistance between androgen-receptor targeting therapies (ARTs) (abiraterone acetate plus prednisone [ABI+P] or enzalutamide [ENZ]) for treatment of metastatic castration-resistant prostate cancer (mCRPC) may affect responses to second ART (ART2). OBJECTIVE: To establish treatment duration and prostate-specific antigen (PSA) response of ART2 in real-world mCRPC patients treated with or without other life-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) between ART1 and ART2. DESIGN, SETTING, AND PARTICIPANTS: Castration-resistant prostate cancer patients, diagnosed between 2010 and 2016 were retrospectively registered in Castration-resistant Prostate Cancer Registry (CAPRI). Patients treated with both ARTs were clustered into two subgroups: ART1>ART2 or ART1>LPD>ART2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were ≥50% PSA response and treatment duration of ART2. Descriptive statistics and binary logistic regression after multiple imputations were performed. RESULTS AND LIMITATIONS: A total of 273 patients were included with a median follow-up of 8.4 mo from ART2. Patients with ART1>ART2 were older and had favourable prognostic characteristics at ART2 baseline compared with patients with ART1>LPD>ART2. No differences between ART1>ART2 and ART1>LPD>ART2 were found in PSA response and treatment duration. Multivariate analysis suggested that PSA response of ART2 was less likely in patients with visceral metastases (odds ratio [OR] 0.143, p=0.04) and more likely in patients with a relatively longer duration of androgen-deprivation treatment (OR 1.028, p=0.01) and with ABI + P before ENZ (OR 3.192, p=0.02). A major limitation of this study was missing data, a common problem in retrospective observational research. CONCLUSIONS: The effect of ART2 seems to be low, with a low PSA response rate and a short treatment duration irrespective of interposed chemotherapy or radium-223, especially in patients with short time on castration, visceral disease, and ENZ before ABI+P. PATIENT SUMMARY: We observed no differences in outcomes of patients treated with sequential abiraterone acetate plus prednisone (ABI+P) and enzalutamide (ENZ) with or without interposed chemotherapy or radium-223. In general, outcomes were lower than those in randomised trials, questioning the additional effect of second treatment with ABI+P or ENZ in daily practice.
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Preparaciones Farmacéuticas , Neoplasias de la Próstata Resistentes a la Castración , Antagonistas de Andrógenos , Andrógenos , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Sistema de Registros , Estudios RetrospectivosRESUMEN
BACKGROUND: The purpose of this study was to determine generic, cancer-specific, and prostate cancer-specific health-related quality of life (HRQoL), pain and changes over time in patients with metastatic castration-resistant prostate cancer (mCRPC) in daily practice. PATIENTS AND METHODS: PRO-CAPRI is an observational, prospective study in 10 hospitals in the Netherlands. Patients with mCRPC completed the EQ-5D, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Brief Pain Inventory-Short Form (BPI-SF) every 3 months and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Prostate Cancer Module (EORTC QLQ-PR25) every 6 months for a maximum of 2 years. Subgroups were identified based on chemotherapy pretreatment. Outcomes were generic, cancer-specific, and prostate cancer-specific HRQoL and self-reported pain. Descriptive statistics were performed including changes over time and minimal important differences (MID) between subgroups. RESULTS: In total, 151 included patients answered 873 questionnaires. The median follow-up from the start of the study was 19.5 months, and 84% were treated with at least 1 life-prolonging agent. Overall, patients were in good clinical condition (Eatern Cooperative Oncology Group performance status 0-1 in 78%) with normal baseline hemoglobin, lactate dehydrogenase, and alkaline phosphatase. At inclusion, generic HRQoL was high with a mean EQ visual analog score of 73.2 out of 100. The lowest scores were reported on role and physical functioning (mean scores of 69 and 76 of 100, respectively), and fatigue, pain, and insomnia were the most impaired domains. These domains deteriorated in > 50% of patients. CONCLUSION: Although most patients were treated with new treatments during follow-up, mCRPC has a negative impact on HRQoL with deterioration in all domains over time, especially role and physical functioning. These domains need specific attention during follow-up to maintain HRQoL as long as possible by timely start of adequate supportive care management.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dolor en Cáncer/epidemiología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Calidad de Vida , Anciano , Anciano de 80 o más Años , Dolor en Cáncer/inducido químicamente , Dolor en Cáncer/patología , Dolor en Cáncer/psicología , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Pronóstico , Estudios Prospectivos , Neoplasias de la Próstata Resistentes a la Castración/psicología , Encuestas y Cuestionarios , Tasa de SupervivenciaRESUMEN
Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.
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Ácidos Nucleicos Libres de Células/química , ADN de Neoplasias/análisis , Leucocitos/química , Recurrencia Local de Neoplasia/diagnóstico , Análisis de Secuencia de ADN , Neoplasias Gástricas/diagnóstico , ADN de Neoplasias/química , Hematopoyesis , Humanos , Pronóstico , Prueba de Estudio Conceptual , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Gástricas/genética , Análisis de SupervivenciaRESUMEN
BACKGROUND: Trials in castration-resistant prostate cancer (CRPC) treatment have shown improved outcomes, including survival. However, as trial populations are selected, results may not be representative for the real-world population. The aim of this study was to assess the differences between patients treated in a clinical trial versus standard care during the course of CRPC in a real-world CRPC population. DESIGN, SETTING, AND PARTICIPANTS: Castration-resistant Prostate Cancer Registry is a population-based, observational, retrospective registry. CRPC patients from 20 hospitals in the Netherlands have been included from 2010 to 2013. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline characteristics, systemic treatment, and overall survival were the main outcomes. Descriptive statistics, multivariate Cox regression, and multiple imputations with the Monte Carlo Markov Chain method were used. RESULTS AND LIMITATIONS: In total, 1524 patients were enrolled of which 203 patients had participated in trials at any time. The median follow-up period was 23 mo. Patients in the trial group were significantly younger and had less comorbidities. Docetaxel treatment was more frequently used in trial patients (85% vs 40%). Despite an observed unadjusted median overall survival difference of 35 mo versus 24 mo between the trial and standard care group, this difference was not retained after adjustment for baseline characteristics and treatment effect. CONCLUSIONS: At CRPC diagnosis, the baseline characteristics of the patients who had been enrolled in trials notably differed from patients who received standard treatment options only. The survival difference between the trial and standard care group could be explained by baseline differences and treatment effects. These results indicate that trial results cannot easily be translated to real-world practice. PATIENT SUMMARY: We observed that patients treated in clinical trials differed from patients who were not. We concluded that this may lead to differential treatment and survival. Caution is warranted when real-world outcomes are compared with trial results.
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Ensayos Clínicos Pragmáticos como Asunto/métodos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/epidemiología , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Docetaxel/administración & dosificación , Docetaxel/uso terapéutico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Países Bajos/epidemiología , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/secundario , Sistema de Registros , Estudios Retrospectivos , Resultado del Tratamiento , Moduladores de Tubulina/uso terapéuticoRESUMEN
CONTEXT: Improved survival of children with cancer has been accompanied by multiple treatment-related complications. However, most studies in survivors of childhood cancer focused on only 1 late effect. OBJECTIVE: To assess the total burden of adverse health outcomes (clinical or subclinical disorders ["adverse events"]) following childhood cancer in a large cohort of childhood cancer survivors with long-term and complete medical follow-up. DESIGN, SETTING, AND POPULATION: Retrospective cohort study of 1362 five-year survivors of childhood cancer treated in a single institution in the Netherlands between 1966 and 1996. All survivors were invited to a late-effects clinic for medical assessment of adverse events. Adverse events occurring before January 2004 were graded for severity in a standardized manner. MAIN OUTCOME MEASURES: Treatment-specific prevalence of adverse events (according to severity) at end of follow-up and relative risk of high or severe burden of disease (> or =2 severe or > or =1 life-threatening or disabling adverse events) associated with various treatments. RESULTS: Medical follow-up was complete for 94.3% of survivors (median follow-up, 17.0 years). The median attained age at end of follow-up was 24.4 years. Almost 75% of survivors had 1 or more adverse events, and 24.6% had 5 or more adverse events. Furthermore, 40% of survivors had at least 1 severe or life-threatening or disabling adverse event. A high or severe burden of adverse events was observed in 55% of survivors who received radiotherapy only and 15% of survivors treated with chemotherapy only, compared with 25% of survivors who had surgery only (adjusted relative risks, 2.18 [95% confidence interval, 1.62-2.95] and 0.65 [95% confidence interval, 0.46-0.90], respectively). A high or severe burden of adverse events was most often observed in survivors of bone tumors (64%) and least often in survivors of leukemia or Wilms tumor (12% each). CONCLUSIONS: In young adulthood, a substantial proportion of childhood cancer survivors already has a high or severe burden of disease, particularly after radiotherapy. This underscores the need for lifelong risk-stratified medical surveillance of childhood cancer survivors.
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Costo de Enfermedad , Estado de Salud , Neoplasias/terapia , Sobrevivientes , Adulto , Niño , Femenino , Humanos , Masculino , Morbilidad , Estudios RetrospectivosRESUMEN
PURPOSE: We evaluated the effectiveness of a low-intensity, home-based physical activity program (Onco-Move) and a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack) versus usual care (UC) in maintaining or enhancing physical fitness, minimizing fatigue, enhancing health-related quality of life, and optimizing chemotherapy completion rates in patients undergoing adjuvant chemotherapy for breast cancer. PATIENTS AND METHODS: We randomly assigned patients who were scheduled to undergo adjuvant chemotherapy (N = 230) to Onco-Move, OnTrack, or UC. Performance-based and self-reported outcomes were assessed before random assignment, at the end of chemotherapy, and at the 6-month follow-up. We used generalized estimating equations to compare the groups over time. RESULTS: Onco-Move and OnTrack resulted in less decline in cardiorespiratory fitness (P < .001), better physical functioning (P ≤ .001), less nausea and vomiting (P = .029 and .031, respectively) and less pain (P = .003 and .011, respectively) compared with UC. OnTrack also resulted in better outcomes for muscle strength (P = .002) and physical fatigue (P < .001). At the 6-month follow-up, most outcomes returned to baseline levels for all three groups. A smaller percentage of participants in OnTrack required chemotherapy dose adjustments than those in the UC or Onco-Move groups (P = .002). Both intervention groups returned earlier (P = .012), as well as for more hours per week (P = .014), to work than the control group. CONCLUSION: A supervised, moderate- to high-intensity, combined resistance and aerobic exercise program is most effective for patients with breast cancer undergoing adjuvant chemotherapy. A home-based, low-intensity physical activity program represents a viable alternative for women who are unable or unwilling to follow the higher intensity program.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia por Ejercicio , Ejercicio Físico , Fatiga , Actividad Motora , Aptitud Física , Actividades Cotidianas , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Esquema de Medicación , Fatiga/prevención & control , Femenino , Estudios de Seguimiento , Estado de Salud , Humanos , Persona de Mediana Edad , Fuerza Muscular , Náusea/inducido químicamente , Náusea/prevención & control , Dolor/etiología , Dolor/prevención & control , Calidad de Vida , Autoinforme , Trastuzumab , Resultado del Tratamiento , Vómitos/inducido químicamente , Vómitos/prevención & controlRESUMEN
Late effects of treatment for childhood cancer on the thyroid axis are ascribed predominantly to radiotherapy. Whether chemotherapy has an additional detrimental effect is still unclear. Our aim was to evaluate this effect in young adult survivors of a broad spectrum of childhood cancers. The thyroid axis in 205 childhood cancer survivors was evaluated in relation to former use of chemotherapy and radiotherapy (cranial, cranio-spinal, cervical, mediastinal, or thoracic). The mean follow-up time was 17.5 yr. Damage to the thyroid axis was found in 55 patients (26.8%). Thirty-seven patients (18%) had thyroidal disease. Diagnoses varied from TSH elevation to papillary carcinoma. After multivariate analysis, high risk radiation field, irradiation dose, and the diagnosis of non-Hodgkin lymphoma/Hodgkin's disease were found to be significant risk factors for developing thyroid disease. Treatment with chemotherapy did not have an additional negative effect on the thyroid axis. For the development of central (pituitary or hypothalamic) thyroid dysfunction, patients with a brain tumor were at increased risk. Chemotherapy for childhood cancer does not contribute to the damage on the thyroid axis inflicted by radiotherapy during young adulthood.
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Antineoplásicos/efectos adversos , Neoplasias/terapia , Radioterapia/efectos adversos , Glándula Tiroides/fisiología , Adolescente , Adulto , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Hipotiroidismo/epidemiología , Hipotiroidismo/etiología , Lactante , Masculino , Análisis Multivariante , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Factores de Riesgo , Sobrevivientes , Enfermedades de la Tiroides/epidemiología , Enfermedades de la Tiroides/etiología , Pruebas de Función de la Tiroides , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/efectos de la radiación , Hormonas Tiroideas/sangreRESUMEN
PURPOSE: The purpose of our study was to evaluate the effect of cognitive behavioral therapy (CBT), physical exercise (PE), and of these two interventions combined (CBT/PE) on menopausal symptoms (primary outcome), body image, sexual functioning, psychological well-being, and health-related quality of life (secondary outcomes) in patients with breast cancer experiencing treatment-induced menopause. PATIENTS AND METHODS: Patients with breast cancer reporting treatment-induced menopausal symptoms (N=422) were randomly assigned to CBT (n=109), PE (n=104), CBT/PE (n=106), or to a waiting list control group (n=103). Self-report questionnaires were completed at baseline, 12 weeks, and 6 months. Multilevel procedures were used to compare the intervention groups with the control group over time. RESULTS: Compared with the control group, the intervention groups had a significant decrease in levels of endocrine symptoms (Functional Assessment of Cancer Therapy-Endocrine Symptoms; P<.001; effect size, 0.31-0.52) and urinary symptoms (Bristol Female Lower Urinary Tract Symptoms Questionnaire; P=.002; effect size, 0.29-0.33), and they showed an improvement in physical functioning (36-Item Short Form Health Survey physical functioning subscale; P=.002; effect size, 0.37-0.46). The groups that included CBT also showed a significant decrease in the perceived burden of hot flashes and night sweats (problem rating scale of the Hot Flush Rating Scale; P<.001; effect size, 0.39-0.56) and an increase in sexual activity (Sexual Activity Questionnaire habit subscale; P=.027; effect size, 0.65). Most of these effects were observed at both the 12-week and 6-month follow-ups. CONCLUSION: CBT and PE can have salutary effects on endocrine symptoms and, to a lesser degree, on sexuality and physical functioning of patients with breast cancer experiencing treatment-induced menopause. Future work is needed to improve the design and the planning of these interventions to improve program adherence.
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Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Terapia Cognitivo-Conductual/métodos , Ejercicio Físico/psicología , Menopausia/fisiología , Menopausia/psicología , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Sofocos/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the prevalence and severity of adverse events (AEs) and treatment-related risk factors in long-term Wilms' tumor (WT) survivors, with special attention to radiotherapy. METHODS AND MATERIALS: The single-center study cohort consisted of 185 WT survivors treated between 1966 and 1996, who survived at least 5 years after diagnosis. All survivors were invited to a late-effects clinic for medical assessment of AEs. AEs were graded for severity in a standardized manner. Detailed radiotherapy data enabled us to calculate the equivalent dose in 2 Gy fractions (EQD(2)) to compare radiation doses in a uniform way. Risk factors were evaluated with multivariate logistic regression analysis. RESULTS: Medical follow-up was complete for 98% of survivors (median follow-up, 18.9 years; median attained age, 22.9 years); 123 survivors had 462 AEs, of which 392 had Grade 1 or 2 events. Radiotherapy to flank/abdomen increased the risk of any AE (OR, 1.08 Gy(-1) [CI, 1.04-1.13]). Furthermore, radiotherapy to flank/abdomen was associated with orthopedic events (OR, 1.09 Gy(-1) [CI, 1.05-1.13]) and second tumors (OR, 1.11 Gy(-1) [CI, 1.03-1.19]). Chest irradiation increased the risk of pulmonary events (OR, 1.14 Gy(-1) [CI, 1.06-1.21]). Both flank/abdominal and chest irradiation were associated with cardiovascular events (OR, 1.05 Gy(-1) [CI, 1.00-1.10], OR, 1.06 Gy(-1) [CI, 1.01-1.12]) and tissue hypoplasia (OR, 1.17 Gy(-1) [CI, 1.10-1.24], OR 1.10 Gy(-1) [CI, 1.03-1.18]). CONCLUSION: The majority of AEs, overall as well as in irradiated survivors, were mild to moderate. Nevertheless, the large amount of AEs emphasizes the importance of follow-up programs for WT survivors.