Risk of late effects of treatment in children newly diagnosed with standard-risk acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study cohort

BACKGROUND Treatment of patients with paediatric acute lymphoblastic leukaemia has evolved such that the risk of late effects in survivors treated in accordance with contemporary protocols could be different from that noted in those treated decades ago. We aimed to estimate the risk of late effects in children with standard-risk acute lymphoblastic leukaemia treated with contemporary protocols. METHODS We used data from similarly treated members of the Childhood Cancer Survivor Study cohort. The Childhood Cancer Survivor Study is a multicentre, North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. We included cohort members if they were aged 1·0-9·9 years at the time of diagnosis of acute lymphoblastic leukaemia and had received treatment consistent with contemporary standard-risk protocols for acute lymphoblastic leukaemia. We calculated mortality rates and standardised mortality ratios, stratified by sex and survival time, after diagnosis of acute lymphoblastic leukaemia. We calculated standardised incidence ratios and absolute excess risk for subsequent neoplasms with age-specific, sex-specific, and calendar-year-specific rates from the Surveillance, Epidemiology and End Results Program. Outcomes were compared with a sibling cohort and the general US population. FINDINGS We included 556 (13%) of 4329 cohort members treated for acute lymphoblastic leukaemia. Median follow-up of the survivors from 5 years after diagnosis was 18·4 years (range 0·0-33·0). 28 (5%) of 556 participants had died (standardised mortality ratio 3·5, 95% CI 2·3-5·0). 16 (57%) deaths were due to causes other than recurrence of acute lymphoblastic leukaemia. Six (1%) survivors developed a subsequent malignant neoplasm (standardised incidence ratio 2·6, 95% CI 1·0-5·7). 107 participants (95% CI 81-193) in each group would need to be followed-up for 1 year to observe one extra chronic health disorder in the survivor group compared with the sibling group. 415 participants (376-939) in each group would need to be followed-up for 1 year to observe one extra severe, life-threatening, or fatal disorder in the group of survivors. Survivors did not differ from siblings in their educational attainment, rate of marriage, or independent living. INTERPRETATION The prevalence of adverse long-term outcomes in children treated for standard risk acute lymphoblastic leukaemia according to contemporary protocols is low, but regular care from a knowledgeable primary-care practitioner is warranted. FUNDING National Cancer Institute, American Lebanese-Syrian Associated Charities, Swiss Cancer Research.

Late toxicity and five year outcomes after high-dose-rate brachytherapy as a monotherapy for localized prostate cancer

BACKGROUND To determine the 5-year outcome after high-dose-rate brachytherapy (HDR-BT) as a monotherapy. METHODS Between 10/2003 and 06/2006, 36 patients with low (28) and intermediate (8) risk prostate cancer were treated by HDR-BT monotherapy. All patients received one implant and 4 fractions of 9.5 Gy within 48 hours for a total prescribed dose (PD) of 38 Gy. Five patients received concomitant androgen deprivation therapy (ADT). Toxicity was scored according to the common terminology criteria for adverse events from the National Cancer Institute (CTCAE) version 3.0. Biochemical recurrence was defined according to the Phoenix criteria and analyzed using the Kaplan Meier method. Predictors for late grade 3 GU toxicity were analyzed using univariate and multivariate Cox regression analyses. RESULTS The median follow-up was 6.9 years (range, 1.5-8.0 years). Late grade 2 and 3 genitourinary (GU) toxicity was observed in 10 (28%) and 7 (19%) patients, respectively. The actuarial proportion of patients with late grade 3 GU toxicity at 5 years was 17.7%. Late grade 2 and 3 gastrointestinal (GI) toxicities were not observed. The crude erectile function preservation rate in patients without ADT was 75%. The 5 year biochemical recurrence-free survival (bRFS) rate was 97%. Late grade 3 GU toxicity was associated with the urethral volume (p = 0.001) and the urethral V120 (urethral volume receiving ≥120% of the PD; p = 0.0005) after multivariate Cox regression. CONCLUSIONS After HDR-BT monotherapy late grade 3 GU was observed relatively frequently and was associated with the urethral V120. GI toxicity was negligible, the erectile function preservation rate and the bRFS rate was excellent.

Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10

PURPOSE Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification. PATIENTS AND METHODS Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25. RESULTS Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02). CONCLUSION Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.

Outcomes of Active Surveillance for Ductal Carcinoma in Situ: A Computational Risk Analysis.

BACKGROUND Ductal carcinoma in situ (DCIS) is a noninvasive breast lesion with uncertain risk for invasive progression. Usual care (UC) for DCIS consists of treatment upon diagnosis, thus potentially overtreating patients with low propensity for progression. One strategy to reduce overtreatment is active surveillance (AS), whereby DCIS is treated only upon detection of invasive disease. Our goal was to perform a quantitative evaluation of outcomes following an AS strategy for DCIS. METHODS Age-stratified, 10-year disease-specific cumulative mortality (DSCM) for AS was calculated using a computational risk projection model based upon published estimates for natural history parameters, and Surveillance, Epidemiology, and End Results data for outcomes. AS projections were compared with the DSCM for patients who received UC. To quantify the propagation of parameter uncertainty, a 95% projection range (PR) was computed, and sensitivity analyses were performed. RESULTS Under the assumption that AS cannot outperform UC, the projected median differences in 10-year DSCM between AS and UC when diagnosed at ages 40, 55, and 70 years were 2.6% (PR = 1.4%-5.1%), 1.5% (PR = 0.5%-3.5%), and 0.6% (PR = 0.0%-2.4), respectively. Corresponding median numbers of patients needed to treat to avert one breast cancer death were 38.3 (PR = 19.7-69.9), 67.3 (PR = 28.7-211.4), and 157.2 (PR = 41.1-3872.8), respectively. Sensitivity analyses showed that the parameter with greatest impact on DSCM was the probability of understaging invasive cancer at diagnosis. CONCLUSION AS could be a viable management strategy for carefully selected DCIS patients, particularly among older age groups and those with substantial competing mortality risks. The effectiveness of AS could be markedly improved by reducing the rate of understaging.

Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In Situ

BACKGROUND Impact of contemporary treatment of pre-invasive breast cancer (ductal carcinoma in situ [DCIS]) on long-term outcomes remains poorly defined. We aimed to evaluate national treatment trends for DCIS and to determine their impact on disease-specific (DSS) and overall survival (OS). METHODS The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients diagnosed with DCIS from 1991 to 2010. Treatment pattern trends were analyzed using Cochran-Armitage trend test. Survival analyses were performed using inverse probability weights (IPW)-adjusted competing risk analyses for DSS and Cox proportional hazard regression for OS. All tests performed were two-sided. RESULTS One hundred twenty-one thousand and eighty DCIS patients were identified. The greatest proportion of patients was treated with lumpectomy and radiation therapy (43.0%), followed by lumpectomy alone (26.5%) and unilateral (23.8%) or bilateral mastectomy (4.5%) with significant shifts over time. The rate of sentinel lymph node biopsy increased from 9.7% to 67.1% for mastectomy and from 1.4% to 17.8% for lumpectomy. Compared with mastectomy, OS was higher for lumpectomy with radiation (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.76 to 0.83, P < .001) and lower for lumpectomy alone (HR = 1.17, 95% CI = 1.13 to 1.23, P < .001). IPW-adjusted ten-year DSS was highest in lumpectomy with XRT (98.9%), followed by mastectomy (98.5%), and lumpectomy alone (98.4%). CONCLUSIONS We identified substantial shifts in treatment patterns for DCIS from 1991 to 2010. When outcomes between locoregional treatment options were compared, we observed greater differences in OS than DSS, likely reflecting both a prevailing patient selection bias as well as clinically negligible differences in breast cancer outcomes between groups.

Cutaneous malignant melanoma: A study of skin cancer in the United States from 1973--1997

Cutaneous malignant melanoma (CMM) is the cancer of the melanocytes, the cells that produce the pigment melanin, and is an aggressive skin cancer that is most prevalent in the white population. Although most cases of malignant melanoma are white, black and other non-white populations also develop this disease. However, the etiologic factors involved in the development of melanoma in these lower-risk populations are not well known. Generally, survival rates of malignant melanoma have been found to be lower in blacks than for whites with similar stage of disease at diagnosis. ^ This study presents an analysis of the differences in survival between black and white cases with malignant melanoma of the skin as the only or first primary cancer, found in the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) cancer registry from 1973 to 1997. A total of 54,193 cases of CMM were diagnosed in black and white patients between 1973 and 1997. Black patients tended to be older, with a mean age of 64.46 years, compared to 53.14 years for white patients. Eighty-nine percent of patients were diagnosed with CMM as the only cancer. (Abstract shortened by UMI.)^

Seasonal aspects of leukemia

An investigation of (a) month/season-of-birth as a risk factor and (b) month/season-of-treatment initation as a prognostic factor in acute lymphoblastic leukemia (ALL) in children, 0-15 years of age, was conducted. The study population used was that of the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and included children diagnosed and treated for ALL from 1973-1986. Two separate sets of analyses using different exclusion criteria led to similar results. Specifically, the inability to reject the null hypothesis of no significant difference in the variation of monthly/seasonal incidence rates among children residing within the 10 SEER sites using either cosinor analysis or one-way analysis of variance. No association was established between month/season of treatment initiation and survival in ALL among children using either Kaplan-Meier or cosinor analysis. In separate Kaplan-Meier analyses, age, gender, and treatment type were each found to be significant univariate prognostic factors for survival, however. ^

An evaluation of a behavioral change intervention for smokeless tobacco use

During the last three decades considerable attention has been placed on the reduction of tobacco use due to cigarette smoking. During this time, studies have been funded and programs have been developed that focus on both prevention and cessation of cigarette smoking. This intense focus has led to a significant decline in cigarette smoking. But now, use of another form of tobacco--smokeless tobacco--is gaining in popularity.^ In 1989, the National Cancer Institute funded a research study at The University of Texas M. D. Anderson Cancer Center, called Working Well, to develop, implement, and evaluate worksite health promotion programs aimed at reducing cancer risks. As part of this program, a behavioral intervention for smokeless tobacco use was developed. This dissertation evaluates the impact of that behavioral change intervention for smokeless tobacco use.^ Data collected during the Working Well program were analyzed to determine the effect of the intervention. The primary outcomes analyzed were smokeless tobacco cessation, stages of change movement, and prevalence. The secondary outcomes analyzed included the prediction of smokeless tobacco use, stage movement, and cessation. Primary outcome analyses were conducted using the worksite as the unit of analysis, while the secondary analyses were conducted using the individual as the unit of analysis.^ Approximately 20% of the male population used smokeless tobacco. Results of intervention analyses indicate that the Working Well program produced no intervention effect on any of the primary outcomes. At the final observation, the experimental worksites achieved a quit rate of 27%, while the control worksites achieved a quit rate of 26% (P = 0.78). Stage movement for the experimental worksites was 49%, while the control worksites experienced stage movement of 43% (P = 0.20). The results of the analyses on smokeless tobacco prevalence followed the same pattern. Predictors of smokeless tobacco use, cessation, and stage movement were also identified.^ Based on the results found in this study, smokeless tobacco should remain a research priority. Future research should focus on smokeless tobacco use, including the identification of the determinants of smokeless tobacco use and the development of measures and effective intervention strategies. ^

Using spatial linear models with SAR and CAR structure to examine Texas lung cancer incidence rates

Scholars have found that socioeconomic status was one of the key factors that influenced early-stage lung cancer incidence rates in a variety of regions. This thesis examined the association between median household income and lung cancer incidence rates in Texas counties. A total of 254 individual counties in Texas with corresponding lung cancer incidence rates from 2004 to 2008 and median household incomes in 2006 were collected from the National Cancer Institute Surveillance System. A simple linear model and spatial linear models with two structures, Simultaneous Autoregressive Structure (SAR) and Conditional Autoregressive Structure (CAR), were used to link median household income and lung cancer incidence rates in Texas. The residuals of the spatial linear models were analyzed with Moran's I and Geary's C statistics, and the statistical results were used to detect similar lung cancer incidence rate clusters and disease patterns in Texas.^

Construcción de normas locales para la técnica Rorschach : Sistema Comprehensivo

Se describe el camino recorrido por los temas de investigación abordados por el equipo desde 1995 hasta 2008, camino en el cual se sitúa el Proyecto de construcción de normas para la técnica Rorschach, Sistema Comprehensivo(1999-2004) El Objetivo se origina en la actual gran difusión internacional y en nuestro país, del Sistema Comprehensivo de Exner (1974) para la Técnica Rorschach, lo que planteó la necesidad de contar con normas de nuestro contexto cultural para analizar e interpretar los resultados. Luego de destinar un año completo a la capacitación del equipo en el Sistema Comprehensivo y de obtener mediante información del INDEC (Instituto Nacional de Estadísticas y Censos) la distribución de los rangos de género y edad demográficamente representativos de la población, se obtuvo la muestra de 506 casos, estratificados según rangos de edad de 18-25 años; 26-35 años; 36-45 años; 46 a 55 años y 56 a 65 años, En la muestra normativa se excluyeron todos los casos que estuvieran o hubieran estado en tratamiento psicoterapéutico o psiquiátrico. Se describe el proyecto y comentan resultados

Turismo y trabajo : Una aproximación desde el mercado hotelero

El presente trabajo tiene por objetivo profundizar en el comportamiento del mercado de trabajo en regiones donde la principal actividad económica es el turismo mediante el análisis de la información que desde el año 2004 se obtiene a través de la Encuesta de Ocupación Hotelera (EOH) que releva el INDEC. La posibilidad de contar con la EOH, especialmente en aquellas localidades que, por su dimensión no poseen información proveniente de las Encuestas Permanente de Hogares (EPH), abre la posibilidad de que, a través del comportamiento hotelero y para-hotelero, se acceda a una aproximación de la situación ocupacional en esas localidades, donde se presentan serias dificultades durante algunos períodos del año. Aunque la serie de que se dispone es aún breve 'en el mejor de los casos de hasta cinco años', se la analiza mediante técnicas estadísticas para determinación de estacionalidad, como punto de partida para un posterior seguimiento y puesta en discusión de otras alternativas de abordaje. Se trabaja con localidades de manera desagregada, pudiendo advertirse nítidamente las especificidades según la modalidad turística de cada una de ellas y concentrando el comportamiento de las mismas en dos grupos diferentes: a) Localidades con economías de perfiles más diversificadas; b) Localidades con base económica preponderantemente turística. Mediante este análisis se pretende alcanzar algunos resultados que, eventualmente complementados con información de carácter primaria tanto cuantitativa como de carácter más cualitativo, aporten al conocimiento de un mercado de trabajo cuyas especificidades lo tornan complejo y cuyas consecuencias preocupan tanto al sector público como al privado

Construcción de normas locales para la técnica Rorschach : Sistema Comprehensivo

Se describe el camino recorrido por los temas de investigación abordados por el equipo desde 1995 hasta 2008, camino en el cual se sitúa el Proyecto de construcción de normas para la técnica Rorschach, Sistema Comprehensivo(1999-2004) El Objetivo se origina en la actual gran difusión internacional y en nuestro país, del Sistema Comprehensivo de Exner (1974) para la Técnica Rorschach, lo que planteó la necesidad de contar con normas de nuestro contexto cultural para analizar e interpretar los resultados. Luego de destinar un año completo a la capacitación del equipo en el Sistema Comprehensivo y de obtener mediante información del INDEC (Instituto Nacional de Estadísticas y Censos) la distribución de los rangos de género y edad demográficamente representativos de la población, se obtuvo la muestra de 506 casos, estratificados según rangos de edad de 18-25 años; 26-35 años; 36-45 años; 46 a 55 años y 56 a 65 años, En la muestra normativa se excluyeron todos los casos que estuvieran o hubieran estado en tratamiento psicoterapéutico o psiquiátrico. Se describe el proyecto y comentan resultados

Turismo y trabajo : Una aproximación desde el mercado hotelero

El presente trabajo tiene por objetivo profundizar en el comportamiento del mercado de trabajo en regiones donde la principal actividad económica es el turismo mediante el análisis de la información que desde el año 2004 se obtiene a través de la Encuesta de Ocupación Hotelera (EOH) que releva el INDEC. La posibilidad de contar con la EOH, especialmente en aquellas localidades que, por su dimensión no poseen información proveniente de las Encuestas Permanente de Hogares (EPH), abre la posibilidad de que, a través del comportamiento hotelero y para-hotelero, se acceda a una aproximación de la situación ocupacional en esas localidades, donde se presentan serias dificultades durante algunos períodos del año. Aunque la serie de que se dispone es aún breve 'en el mejor de los casos de hasta cinco años', se la analiza mediante técnicas estadísticas para determinación de estacionalidad, como punto de partida para un posterior seguimiento y puesta en discusión de otras alternativas de abordaje. Se trabaja con localidades de manera desagregada, pudiendo advertirse nítidamente las especificidades según la modalidad turística de cada una de ellas y concentrando el comportamiento de las mismas en dos grupos diferentes: a) Localidades con economías de perfiles más diversificadas; b) Localidades con base económica preponderantemente turística. Mediante este análisis se pretende alcanzar algunos resultados que, eventualmente complementados con información de carácter primaria tanto cuantitativa como de carácter más cualitativo, aporten al conocimiento de un mercado de trabajo cuyas especificidades lo tornan complejo y cuyas consecuencias preocupan tanto al sector público como al privado

Turismo y trabajo : Una aproximación desde el mercado hotelero

El presente trabajo tiene por objetivo profundizar en el comportamiento del mercado de trabajo en regiones donde la principal actividad económica es el turismo mediante el análisis de la información que desde el año 2004 se obtiene a través de la Encuesta de Ocupación Hotelera (EOH) que releva el INDEC. La posibilidad de contar con la EOH, especialmente en aquellas localidades que, por su dimensión no poseen información proveniente de las Encuestas Permanente de Hogares (EPH), abre la posibilidad de que, a través del comportamiento hotelero y para-hotelero, se acceda a una aproximación de la situación ocupacional en esas localidades, donde se presentan serias dificultades durante algunos períodos del año. Aunque la serie de que se dispone es aún breve 'en el mejor de los casos de hasta cinco años', se la analiza mediante técnicas estadísticas para determinación de estacionalidad, como punto de partida para un posterior seguimiento y puesta en discusión de otras alternativas de abordaje. Se trabaja con localidades de manera desagregada, pudiendo advertirse nítidamente las especificidades según la modalidad turística de cada una de ellas y concentrando el comportamiento de las mismas en dos grupos diferentes: a) Localidades con economías de perfiles más diversificadas; b) Localidades con base económica preponderantemente turística. Mediante este análisis se pretende alcanzar algunos resultados que, eventualmente complementados con información de carácter primaria tanto cuantitativa como de carácter más cualitativo, aporten al conocimiento de un mercado de trabajo cuyas especificidades lo tornan complejo y cuyas consecuencias preocupan tanto al sector público como al privado