Feasibility and potential effectiveness of nurse-led video-coaching interventions for childhood, adolescent, and young adult cancer survivors: the REVIVER study.

BACKGROUND: Childhood, adolescent, and young adult (CAYA) cancer survivors, at risk for late effects, including cancer-related fatigue, cardiovascular issues, and psychosocial challenges, may benefit from interventions stimulating behaviour adjustments. Three nurse-led eHealth interventions (REVIVER) delivered via video calls and elaborating on person-centred care, cognitive behaviour therapy and/or motivational interviewing were developed. These interventions target: 1) fatigue management, 2) healthier lifestyle behaviours, and 3) self-efficacy and self-management. This study aimed to assess the feasibility and potential effectiveness of the REVIVER interventions for CAYA cancer survivors and healthcare professionals. METHODS: In a single-group mixed methods design, CAYA cancer survivors aged 16-54, more than five years post-treatment, were enrolled. Feasibility, assessed via Bowen's outcomes for feasibility studies, included acceptability, practicality, integration and implementation, demand and adherence. Qualitative data from semi-structured interviews and a focus group interview with survivors and healthcare professionals supplemented the evaluation. Paired sample t-tests assessed changes in self-reported quality of life, fatigue, lifestyle, self-management, and self-efficacy at baseline (T0), post-intervention (T1), and 6-month follow-up (T2). RESULTS: The interventions and video consults were generally acceptable, practical, and successfully integrated and implemented. Success factors included the nurse consultant (i.e., communication, approach, and attitude) and the personalised approach. Barriers included sustainability concerns, technical issues, and short intervention duration. Regarding demand, 71.4%, 65.4%, and 100% of eligible CAYA cancer survivors engaged in the fatigue (N = 15), lifestyle (N = 17) and empowerment (N = 3) intervention, respectively, with 5, 5 and 2 participants interviewed, correspondingly. Low interest (demand) in the empowerment intervention (N = 3) and dropout rates of one-third for both fatigue and empowerment interventions were noted (adherence). Improvements in quality of life, fatigue (fatigue intervention), lifestyle (lifestyle intervention), self-efficacy, and self-management were evident among survivors who completed the fatigue and lifestyle interventions, with medium and large effect sizes observed immediately after the intervention and six months post-intervention. CONCLUSIONS: Our study demonstrates the feasibility of nurse-led video coaching (REVIVER interventions) despite lower demand for the empowerment intervention and lower adherence to the fatigue and empowerment interventions. The medium and high effect sizes found for those who completed the interventions hold potential clinical significance for future studies investigating the effectiveness of the REVIVER interventions.

Development and Validation of Risk Prediction Models for Coronary Heart Disease and Heart Failure After Treatment for Hodgkin Lymphoma.

PURPOSE: Previous efforts to predict absolute risk of treatment-related cardiovascular diseases (CVDs) have mostly focused on childhood cancer survivors. We aimed to develop prediction models for risk of coronary heart disease (CHD) and heart failure (HF) for survivors of adolescent/adult Hodgkin lymphoma (HL). METHODS: For model development, we used a multicenter cohort including 1,433 5-year HL survivors treated between 1965 and 2000 and age 18-50 years at HL diagnosis, with complete data on administered chemotherapy regimens, radiotherapy volumes and doses, and cardiovascular follow-up. Using cause-specific hazard models, covariate-adjusted cumulative incidences for CHD and HF were estimated in the presence of competing risks of death because of other causes than CHD and HF. Age at HL diagnosis, sex, smoking status, radiotherapy, and anthracycline treatment were included as predictors. External validation for the CHD model was performed using a Canadian cohort of 708 HL survivors treated between 1988 and 2004 and age 18-50 years at HL diagnosis. RESULTS: After a median follow-up of 24 years, 341 survivors had developed CHD and 102 had HF. We were able to predict CHD and HF risk at 20 and 30 years after treatment with moderate to good overall calibration and moderate discrimination (areas under the curve: 0.68-0.74), which was confirmed by external validation for the CHD model (areas under the curve: 0.73-0.74). On the basis of our model including prescribed mediastinal radiation dose, 30-year risks ranged from 4% to 78% for CHD and 3% to 46% for HF, depending on risk factors. CONCLUSION: We developed and validated prediction models for CHD and HF with good overall calibration and moderate discrimination. These models can be used to identify HL survivors who might benefit from targeted screening for CVD and early treatment for CVD risk factors.

Future steps in cardio-oncology-a national multidisciplinary survey among healthcare professionals in the Netherlands.

BACKGROUND: The awareness of cancer therapy-related adverse cardiac effects is fueled by recent literature on cardiotoxicity incidence and detection strategies. Although this influences the sense of urgency, in current practice, cardiotoxicity monitoring and treatment is not structurally performed. With this study, we aimed to evaluate current perspectives on cardio-oncology and to assess needs, ultimately to determine an agenda for improvements in current practice. MATERIAL AND METHODS: A national multidisciplinary 36-question survey was conducted. The survey was developed by a multidisciplinary team, theoretically based on an implementation checklist and distributed by email, through cardiology and oncology societies as well as social media. RESULTS: One hundred ninety professionals completed the survey, of which 66 were cardiologists, 66 radiation oncologists, and 58 medical oncologists and hematologists. Many professionals were unaware of their specialisms' cardio-oncology guidelines: 62.1% of cardiologists and 29.3% of the hematologists and medical oncologists respectively. Many cardiologists (N = 46; 69.7%), radiation oncologists (N = 45; 68.2%), and hematologists and medical oncologists (N = 38; 65.5%) expressed that they did not have sufficient knowledge to treat cardio-oncology patients and would either refer a patient or aspire to gain more knowledge on the topic. CONCLUSION: The field of cardio-oncology is advancing rapidly, with progress in stratification and detection strategies leading to the development of new guidelines and consensus statements. However, the application of these guidelines in current practice appears to be lagging. Professionals express a need for additional training and a practical guideline including risk stratification, monitoring, and treatment strategies. Multidisciplinary discussion and consensus on cardio-oncology care is vital to improve implementation of cardio-oncology guidelines, ultimately to improve cardiac care for oncology patients.

IRF8 is a transcriptional activator of CD37 expression in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) represents the most common form of non-Hodgkin lymphoma (NHL) that is still incurable in a large fraction of patients. Tetraspanin CD37 is highly expressed on mature B lymphocytes, and multiple CD37-targeting therapies are under clinical development for NHL. However, CD37 expression is nondetectable in ∼50% of DLBCL patients, which correlates with inferior treatment outcome, but the underlying mechanisms for differential CD37 expression in DLBCL are still unknown. Here, we investigated the regulation of the CD37 gene in human DLBCL at the (epi-)genetic and transcriptional level. No differences were observed in DNA methylation within the CD37 promoter region between CD37-positive and CD37-negative primary DLBCL patient samples. On the contrary, CD37-negative DLBCL cells specifically lacked CD37 promoter activity, suggesting differential regulation of CD37 gene expression. Using an unbiased quantitative proteomic approach, we identified transcription factor IRF8 to be significantly higher expressed in nuclear extracts of CD37-positive as compared with CD37-negative DLBCL. Direct binding of IRF8 to the CD37 promoter region was confirmed by DNA pulldown assay combined with mass spectrometry and targeted chromatin immunoprecipitation (ChIP). Functional analysis indicated that IRF8 overexpression enhanced CD37 protein expression, while CRISPR/Cas9 knockout of IRF8 decreased CD37 levels in DLBCL cell lines. Immunohistochemical analysis in a large cohort of primary DLBCL (n = 206) revealed a significant correlation of IRF8 expression with detectable CD37 levels. Together, this study provides new insight into the molecular mechanisms underlying differential CD37 expression in human DLBCL and reveals IRF8 as a transcriptional regulator of CD37 in B-cell lymphoma.

Light Therapy for Cancer-Related Fatigue in (Non-)Hodgkin Lymphoma Survivors: Results of a Randomized Controlled Trial.

PURPOSE: To evaluate the short- and long-term effects of light therapy on fatigue (primary outcome) and sleep quality, depression, anxiety, quality of life, and circadian rhythms (secondary outcomes) in survivors of (non-)Hodgkin lymphoma presenting with chronic cancer-related fatigue. METHODS: We randomly assigned 166 survivors (mean survival 13 years) to a bright white light intervention (BWL) or dim white light comparison (DWL) group. Measurements were completed at baseline (T0), post-intervention (T1), at three (T2), and nine (T3) months follow-up. A mixed-effect modeling approach was used to compare linear and non-linear effects of time between groups. RESULTS: There were no significant differences between BWL and DWL in the reduction in fatigue over time. Both BWL and DWL significantly (p < 0.001) improved fatigue levels during the intervention followed by a slight reduction in this effect during follow-up (EST0-T1 = -0.71; EST1-T3 = 0.15). Similar results were found for depression, sleep quality, and some aspects of quality of life. Light therapy had no effect on circadian rhythms. CONCLUSIONS: BWL was not superior in reducing fatigue compared to DWL in HL and DLBCL survivors. Remarkably, the total sample showed clinically relevant and persistent improvements on fatigue not commonly seen in longitudinal observational studies in these survivors.

Oncology professionals' perspectives towards cardiac surveillance in breast cancer patients with high cardiotoxicity risk: A qualitative study.

Breast cancer (BC) patients have an increased risk of developing cancer therapy-related cardiac dysfunction (CTRCD) and cardiovascular morbidity, which seems to have a substantial prognostic impact. Oncologists, in collaboration with dedicated cardiologists, have the opportunity to perform cardiovascular risk stratification. Despite guideline recommendations, strategies to detect cardiac damage at an early stage are not structurally implemented in clinical practice. The perspectives of oncology professionals regarding cardiac surveillance in BC patients have not been qualitatively evaluated. We aim to explore the perceptions of oncology professionals regarding cardiac surveillance in BC patients and, more specifically, the influencing factors of delivering cardiac surveillance. A qualitative study with semi-structured interviews was conducted and thematically analyzed. Twelve oncology professionals participated in this study. Four themes were selected to answer the study objectives: (1) sense of urgency, (2) multidisciplinary collaboration, (3) patient burden, and (4) practical tools for cardiac surveillance. Most professionals did not feel the need to deliver cardiac surveillance as they considered the incidence of CTRCD as rare. Multidisciplinary collaboration was also perceived as unnecessary, and cardiac surveillance was considered disproportionately burdensome with respect to its benefits. Nevertheless, professionals affirmed the need for practical tools to deliver cardiac surveillance. Most professionals are currently unaware of CTRCD incidence and cardiac surveillance benefits. Encouraging multidisciplinary collaboration and improving their knowledge of cardiotoxic effects of treatments and possibility of early detection can lead to structured cardiac surveillance for breast cancer patients.

Long-Term Cause-Specific Mortality in Hodgkin Lymphoma Patients.

BACKGROUND: Few studies have examined the impact of treatment-related morbidity on long-term, cause-specific mortality in Hodgkin lymphoma (HL) patients. METHODS: This multicenter cohort included 4919 HL patients, treated before age 51 years between 1965 and 2000, with a median follow-up of 20.2 years. Standardized mortality ratios, absolute excess mortality (AEM) per 10 000 person-years, and cause-specific cumulative mortality by stage and primary treatment, accounting for competing risks, were calculated. RESULTS: HL patients experienced a 5.1-fold (AEM = 123 excess deaths per 10 000 person-years) higher risk of death due to causes other than HL. This risk remained increased in 40-year survivors (standardized mortality ratio = 5.2, 95% confidence interval [CI] = 4.2 to 6.5, AEM = 619). At age 54 years, HL survivors experienced similar cumulative mortality (20.0%) from causes other than HL to 71-year-old individuals from the general population. Whereas HL mortality statistically significantly decreased over the calendar period (P < .001), solid tumor mortality did not change in the most recent treatment era. Patients treated in 1989-2000 had lower 25-year cardiovascular disease mortality than patients treated in 1965-1976 (4.3% vs 5.7%; subdistribution hazard ratio = 0.65, 95% CI = 0.46 to 0.93). Infectious disease mortality was not only increased after splenectomy but also after spleen irradiation (hazard ratio = 2.81, 95% CI = 1.55 to 5.07). For stage I-II, primary treatment with chemotherapy (CT) alone was associated with statistically significantly higher HL mortality (P < .001 for CT vs radiotherapy [RT]; P = .04 for CT vs RT+CT) but lower 30-year mortality from causes other than HL (15.8%, 95% CI = 9.7% to 23.3%) compared with RT alone (36.9%, 95% CI = 34.0% to 39.8%, P = .001) and RT and CT combined (29.8%, 95% CI = 26.8% to 32.9%, P = .02). CONCLUSIONS: Compared with the general population, HL survivors have a substantially reduced life expectancy. Optimal selection of patients for primary CT is crucial, weighing risks of HL relapse and long-term toxicity.

White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer.

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.

Effective Information Provision About the Side Effects of Treatment for Malignant Lymphoma: Protocol of a Randomized Controlled Trial Using Video Vignettes.

BACKGROUND: Informing patients with cancer about the possible implications of prospective treatment is a crucial yet challenging task. Unfortunately, patients' recall of medical information is generally poor and their information needs are not met. Effective information giving entails that oncologists help patients understand and recall the implications of their treatment, meanwhile fostering a trusting physician-patient relationship. Communication strategies that are often suggested to be effective are structuring and tailoring (cognition-oriented) but also are oncologists' expressions of caring or empathy (affect-oriented). OBJECTIVE: The aim of this study is to provide evidence concerning the pathways linking physician communication to (improved) consultation outcomes for patients. More specifically, the aim is to determine the effects of information structuring and information tailoring, combined with physician caring, on information recall, satisfaction with information, and trust in the physician (primary objective) and on symptom distress (secondary objective). METHODS: A randomized controlled trial, systematically testing the effects of information structuring and information tailoring, each combined with caring, in 2 video-vignette experiments (2×2 and 2×2×2 design). Using an online survey platform, participants will be randomly allocated (blinded) to 1 of 12 conditions in which they are asked to view a video vignette (intervention) in which an oncologist discusses a treatment plan for malignant lymphoma with a patient. The independent variables of interest are systematically varied across conditions. The outcome measures are assessed in a survey, using validated instruments. Study participants are (former) patients with cancer and their relatives recruited via online panels and patient organizations. This protocol discusses the trial design, including the video-vignette design, intervention pretesting, and a pilot study. RESULTS: Data collection has now been completed, and preliminary analyses will be available in Spring 2019. A total of 470 participants completed the first part of the survey and were randomized to receive the intervention. CONCLUSIONS: The results of the proposed trial will provide evidence concerning the pathways linking physician information, giving skills to (improved) consultation outcomes for patients. TRIAL REGISTRATION: Netherlands Trial Register NTR6153; https://www.trialregister.nl/trial/6022 (Archived by Webcite at http://www.webcitation.org/76xVV9xC8). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12453.

Towards an evidence-based model of fear of cancer recurrence for breast cancer survivors.

PURPOSE: In order to understand the multidimensional mechanism of fear of cancer recurrence (FCR) and to identify potential targets for interventions, it is important to empirically test the theoretical model of FCR. This study aims at assessing the validity of Lee-Jones et al.'s FCR model. METHODS: A total of 1205 breast cancer survivors were invited to participate in this study. Participants received a questionnaire booklet including questionnaires on demographics and psychosocial variables including FCR. Data analysis consisted of the estimation of direct and indirect effects in mediator models. RESULTS: A total of 460 women (38 %) participated in the study. Median age was 55.8 years (range 32-87). Indirect effects of external and internal cues via FCR were found for all mediation models with limited planning for the future (R 2 = .28) and body checking (R 2 = .11-.15) as behavioral response variables, with the largest effects for limited planning for the future. A direct relation was found between feeling sick and seeking professional advice, not mediated by FCR. CONCLUSIONS: In the first tested models of FCR, all internal and external cues were associated with higher FCR. In the models with limited planning for the future and body checking as behavioral response, an indirect effect of cues via FCR was found supporting the theoretical model of Lee-Jones et al. IMPLICATIONS FOR CANCER SURVIVORS: An evidence-based model of FCR may facilitate the development of appropriate interventions to manage FCR in breast cancer survivors.

Phase 1/2 study of lenalidomide combined with low-dose cyclophosphamide and prednisone in lenalidomide-refractory multiple myeloma.

The prognosis of multiple myeloma (MM) patients who become refractory to lenalidomide and bortezomib is very poor, indicating the need for new therapeutic strategies for these patients. Next to the development of new drugs, the strategy of combining agents with synergistic activity may also result in clinical benefit for patients with advanced myeloma. We have previously shown in a retrospective analysis that lenalidomide combined with continuous low-dose cyclophosphamide and prednisone (REP) had remarkable activity in heavily pretreated, lenalidomide-refractory MM patients. To evaluate this combination prospectively, we initiated a phase 1/2 study to determine the optimal dose and to assess its efficacy and safety in lenalidomide-refractory MM patients. The maximum tolerated dose (MTD) was defined as 25 mg lenalidomide (days 1-21/28 days), combined with continuous cyclophosphamide (50 mg/d) and prednisone (20 mg/d). At the MTD (n = 67 patients), the overall response rate was 67%, and at least minimal response was achieved in 83% of the patients. Median progression-free survival and overall survival were 12.1 and 29.0 months, respectively. Similar results were achieved in the subset of patients with lenalidomide- and bortezomib-refractory disease as well as in patients with high-risk cytogenetic abnormalities, defined as t(4;14), t(14;16), del(17p), and/or ampl(1q) as assessed by fluorescence in situ hybridization. Neutropenia (22%) and thrombocytopenia (22%) were the most common grade 3-4 hematologic adverse events. Infections (21%) were the most common grade 3-5 nonhematologic adverse events. In conclusion, the addition of continuous low-dose oral cyclophosphamide to lenalidomide and prednisone offers a new therapeutic perspective for multidrug refractory MM patients. This trial was registered at www.clinicaltrials.gov as #NCT01352338.

Ultrasound is at least as good as magnetic resonance imaging in predicting tumour size post-neoadjuvant chemotherapy in breast cancer.

BACKGROUND: The aim of this study was to evaluate the accuracy of clinical imaging of the primary breast tumour post-neoadjuvant chemotherapy (NAC) related to the post-neoadjuvant histological tumour size (gold standard) and whether this varies with breast cancer subtype. In this study, results of both magnetic resonance imaging (MRI) and ultrasound (US) were reported. METHODS: Patients with invasive breast cancer were enrolled in the INTENS study between 2006 and 2009. We included 182 patients, of whom data were available for post-NAC MRI (n=155), US (n=123), and histopathological tumour size. RESULTS: MRI estimated residual tumour size with <10-mm discordance in 54% of patients, overestimated size in 28% and underestimated size in 18% of patients. With US, this was 63%, 20% and 17%, respectively. The negative predictive value in hormone receptor-positive tumours for both MRI and US was low, 26% and 33%, respectively. The median deviation in clinical tumour size as percentage of pathological tumour was 63% (P25=26, P75=100) and 49% (P25=22, P75=100) for MRI and US, respectively (P=0.06). CONCLUSIONS: In this study, US was at least as good as breast MRI in providing information on residual tumour size post-neoadjuvant chemotherapy. However, both modalities suffered from a substantial percentage of over- and underestimation of tumour size and in addition both showed a low negative predictive value of pathologic complete remission (Gov nr: NCT00314977).

Multimodality imaging to predict response to systemic treatment in patients with advanced colorectal cancer.

AIM: Aim of this study was to investigate the potential of 18F-FDG PET, diffusion weighted imaging (DWI) and susceptibility-weighted (T2*) MRI to predict response to systemic treatment in patients with colorectal liver metastases. The predictive values of pretreatment measurements and of early changes one week after start of therapy, were evaluated. METHODS: Imaging was performed prior to and one week after start of first line chemotherapy in 39 patients with colorectal liver metastases. 18F-FDG PET scans were performed on a PET/CT scanner and DWI and T2* were performed on a 1.5T MR scanner. The maximum standardized uptake values (SUV), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC) and T2* value were assessed in the same lesions. Up to 5 liver metastases per patient were analyzed. Outcome measures were progression free survival (PFS), overall survival (OS) and size response. RESULTS: Pretreatment, high SUVmax, high TLG, low ADC and high T2* were associated with a shorter OS. Low pretreatment ADC value was associated with shorter PFS. After 1 week a significant drop in SUVmax and rise in ADC were observed. The drop in SUV was correlated with the rise in ADC (r=-0.58, p=0.002). Neither change in ADC nor in SUV was predictive of PFS or OS. T2* did not significantly change after start of treatment. CONCLUSION: Pretreatment SUVmax, TLG, ADC, and T2* values in colorectal liver metastases are predictive of patient outcome. Despite sensitivity of DWI and 18F-FDG PET for early treatment effects, change in these parameters was not predictive of long term outcome.

Impairment of cognitive functioning during Sunitinib or Sorafenib treatment in cancer patients: a cross sectional study.

BACKGROUND: Impairment of cognitive functioning has been reported in several studies in patients treated with chemotherapy. So far, no studies have been published on the effects of the vascular endothelial growth factor receptor (VEGFR) inhibitors on cognitive functioning. We investigated the objective and subjective cognitive function of patients during treatment with VEGFR tyrosine kinase inhibitors (VEGFR TKI). METHODS: Three groups of participants, matched on age, sex and education, were enrolled; 1. metastatic renal cell cancer (mRCC) or GIST patients treated with sunitinib or sorafenib (VEGFR TKI patients n = 30); 2. patients with mRCC not receiving systemic treatment (patient controls n = 20); 3. healthy controls (n = 30). Sixteen neuropsychological tests examining the main cognitive domains (intelligence, memory, attention and concentration, executive functions and abstract reasoning) were administered by a neuropsychologist. Four questionnaires were used to assess subjective cognitive complaints, mood, fatigue and psychological wellbeing. RESULTS: No significant differences in mean age, sex distribution, education level or IQ were found between the three groups. Both patient groups performed significantly worse on the cognitive domains Learning & Memory and Executive Functions (Response Generation and Problem Solving) compared to healthy controls. However only the VEGFR TKI patients showed impairments on the Executive subdomain Response Generation. Effect sizes of cognitive dysfunction in patients using VEGFR TKI were larger on the domains Learning & Memory and Executive Functions, compared to patient controls. Both patients groups performed on the domain Attention & Concentration the same as the healthy controls. Longer duration of treatment on VEGFR TKI was associated with a worse score on Working Memory tasks. CONCLUSIONS: Our data suggest that treatment with VEGFR TKI has a negative impact on cognitive functioning, specifically on Learning & Memory, and Executive Functioning. We propose that patients who are treated with VEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01246843.

Actual prognosis during follow-up of survivors of B-cell non-Hodgkin lymphoma in the Netherlands.

Survival rates determined at diagnosis are often too negative for cancer survivors. Conditional relative survival reflects actual prognosis during follow-up better. Data from all 54,015 patients newly diagnosed in the Netherlands with B-cell non-Hodgkin lymphoma during 1989-2008, aged 15-89 years (Netherlands Cancer Registry), were used. Five-year conditional relative survival was computed for every additional year of survival up to 16 years after diagnosis, according to entity, grade, gender, age, and Ann Arbor stage. The prognosis for survivors of indolent B-cell non-Hodgkin lymphoma improved slightly with each additional year survived up to 91%. For patients with aggressive non-Hodgkin lymphoma conditional relative survival improved strongly during the first year after diagnosis (from 48% to 68%) and gradually thereafter to 93% after 16 years. There were differences between morphological entities. Initial differences in conditional relative survival at diagnosis between groups with different disease stages became smaller with increasing number of years survived. Age remained a prognostic indicator, also after prolonged follow-up. These results help caregivers to plan optimal surveillance and inform patients about their actual prognosis during follow-up. Long-lasting excess mortality among patients with B-cell non-Hodgkin lymphoma indicates the need for additional care long after their diagnosis.

Successful centralisation of patients with vulvar carcinoma: a population-based study in The Netherlands.

INTRODUCTION: In general, centralisation of care for patients with rare malignancies is advised in order to improve outcome with respect to prognosis and treatment related morbidity. Therefore, centralisation of women with vulvar squamous cell carcinoma (SCC), which is an extremely rare tumour, has been advocated by the national guidelines of the Dutch Society of Obstetrics and Gynaecology in 2000. The objective of this study was to determine whether this advice has been adapted and has led to improved survival. METHODS: All patients diagnosed with vulvar malignancies between 1989 and 2008 in the Eastern part of the Netherlands were retrieved from the population-based cancer registry held by the Comprehensive Cancer Centre, The Netherlands. Patient- and tumour characteristics and vital status until January 2011 were retrieved. Data of patients diagnosed in two periods (before and after release of the guideline; 1989-1999 and 2000-2008) were compared. Relative survival rates were calculated as a good approximation of cause-specific survival. RESULTS: A total number of 382 patients with vulvar SCC with invasion > 1mm, who had an indication for groin surgery, were included in the analysis. In the first decade 62% (123 of 198 patients) were treated in a specialised oncology centre, which increased to 93% (172 of 184 patients) in the more recent period. Overall, the 5 year relative survival improved slightly from 69% (95% confidence interval (CI) 60-77%) to 75% (95% CI 65-83%). After adjustment for age and stage, being treated in a specialised oncology centre was an independent prognostic factor for survival. CONCLUSION: Centralisation of care for vulvar SCC patients has been well adopted in the Eastern part of the Netherlands. Being treated in a specialised oncology centre was associated with a better survival after adjustment for age and stage.

A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.

To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).

Declined guideline adherence in older breast cancer patients: a population-based study in the Netherlands.

Older women with primary operable breast cancer might receive suboptimal care due to their advanced age. Although several studies reported age as an independent determinant for receiving none or less treatment according to accepted standards, prospective data are lacking. This study evaluates the adherence to a consensus protocol in unselected women aged 80 years and older in the Netherlands. Data were derived from the Dutch population-based Cancer Registry held by the Comprehensive Cancer Centre East. In this study all female patients, 60 years and older, diagnosed with breast cancer TNM stage I-IIIa in the period 2001 until 2006 were selected. Applied treatment according to the Dutch guideline was compared for different age groups. Differences between age groups were evaluated using a chi-square test. In total, 2336 breast cancer patients were studied. Treatment adherence was significantly lower for surgery, radiation therapy and systemic therapy in women aged 80 years and older, and all modalities were applied much less frequently, except for endocrine therapy which was more frequently applied in the oldest old. This study shows a sharp decline in guideline adherence for unselected women aged 80 years and older with primary operable breast cancer, with an observed shift from appropriate locoregional treatment toward endocrine therapy. Whether this approach is justified or not should preferably be tested prospectively.

Excess of autoimmune and chronic inflammatory disorders in patients with lymphoma compared with all cancer patients: a cancer registry-based analysis in the south of the Netherlands.

OBJECTIVE: We investigated the association between autoimmune and chronic inflammatory disorders and several cancer types including lymphomas. METHODS: All cancer patients diagnosed between 1995 and 2007, aged 15 to 90 years, and registered in the Eindhoven Cancer Registry were included in this study. Co-morbidity at diagnosis was recorded by qualified registry personnel who obtained the information from the clinical record. We determined the prevalence of rheumatoid arthritis (RA), chronic inflammatory bowel diseases, connective and vascular tissue diseases, ulcers of the stomach and duodenum, hepatitis, human immunodeficiency virus (HIV), and tuberculosis (TBC) among newly diagnosed patients with lymphoma and compared this with the prevalence among patients with all other cancers. RESULTS: The prevalence of most of these co-morbidities was higher in patients with lymphomas than those with other malignancies. RA was more often present in newly diagnosed patients with most lymphomas, ulcers of stomach and duodenum in patients with marginal zone lymphoma, hepatitis in case of diffuse large B-cell lymphoma, HIV with aggressive B-cell lymphoma, and TBC with mantle cell lymphoma. CONCLUSION: This study confirms the positive association between autoimmune and chronic inflammatory disorders and the various lymphoproliferative malignancies, suggesting either a shared etiology or pathogenesis or a direct causal relation. This is a fairly new method to study aetiological questions about cancers in a population-based cancer registry.

Improving relative survival, but large remaining differences in survival for non-Hodgkin's lymphoma across Europe and the United States from 1990 to 2004.

PURPOSE: Non-Hodgkin's lymphoma (NHL) is the most common hematologic malignant neoplasm in adults. Monitoring differential changes in population-based survival is across Europe and the United States (US) could point to progress attained and impact of application of novel treatments. PATIENTS AND METHODS: We examined trends in age-specific 5-year relative survival among patients with NHL age 15 years or older between 1990 and 1994 and 2000 and 2004, on the basis of follow-up data from 12 population-based cancer registries across Europe, using period analysis techniques and compared the results with similar trends of patients with NHL in the US, as recorded in the Surveillance, Epidemiology, and End Results database. RESULTS: By 2000 to 2004, overall 5-year relative survival of patients with NHL across Europe was between 37% and 62%, achieved by overall increases in 5-year relative survival ranging from 4% to 12% units between 1990 and 1994 and 2000 and 2004. Changes in age-specific survival ranged from -1% to 43% units during the same time interval. For patients with NHL older than age 55 years, relative survival in individual European registries for the whole period was between 8% and 36% units lower than in the US, theoretically representing a lag of 4 to 10 years of progress. CONCLUSION: Our analyses disclosed a strong and ongoing increase in long-term survival for patients with NHL in European populations. The geographic differences potentially indicate that further improvements could be possible, especially for patients age 55 years or older. The presumptive delay in improvement in survival among elderly patients with NHL in Europe remains to be clarified.