Lonneke V. van de Poll-Franse

Less aggressive treatment and worse overall survival in cancer patients with diabetes: A large population based analysis

The purpose of this study was to document the prevalence of diabetes among newly diagnosed cancer patients and to evaluate the influence of diabetes on stage at diagnosis, treatment and overall survival. We performed a population‐based analyses of all 58,498 cancer patients newly diagnosed between 1995 and 2002 in the registration area of the Eindhoven Cancer Registry. Stage of cancer, cancer treatment and comorbidities were actively collected by hospital medical records review. Follow‐up of all patients was completed until January 1, 2005. Nine percent of all cancer patients had diabetes at the time of cancer diagnosis. The prevalence of diabetes was highest among patients with cancer of the pancreas (19%), uterus (14%) and among young men with kidney cancer (8%). Colon, breast and ovarian cancer patients with diabetes were more often diagnosed with a higher tumour stage (p < 0.05). Patients with diabetes and cancer of the oesophagus, colon, breast and ovary were treated less aggressively compared to those without diabetes (p < 0.05). During the follow‐up period 3,902 of 5,555 cancer patients with diabetes died and 29,909 of 52,943 cancer patients without diabetes died. For all cancers combined, in a multivariate cox‐regression model, adjusting for age, gender, stage, treatment and cardiovascular disease, patients with diabetes experienced a significant increase in overall mortality (HR = 1.44, 95% CI 1.40–1.49), ranging however from 0 to 40% for different types of cancer, compared to those without diabetes. In conclusion, diabetic cancer patients frequently were treated less aggressively and had a worse prognosis compared to those without diabetes.

Chemotherapy-Induced Neuropathy and Its Association With Quality of Life Among 2- to 11-Year Colorectal Cancer Survivors: Results From the Population-Based PROFILES Registry

PURPOSE To gain insight into the prevalence and severity of chemotherapy-induced neuropathy and its influence on health-related quality of life (HRQOL) in a population-based sample of colorectal cancer (CRC) survivors 2 to 11 years after diagnosis. METHODS All alive individuals diagnosed with CRC between 2000 and 2009 as registered by the Dutch population-based Eindhoven Cancer Registry were eligible for participation. Eighty-three percent (n = 1,643) of patients filled out the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the EORTC QLQ Chemotherapy-Induced Peripheral Neuropathy 20. RESULTS The five neuropathy subscale-related symptoms that bothered patients with CRC the most during the past week were erectile problems (42% of men), trouble hearing (11%), trouble opening jars or bottles (11%), tingling toes/feet (10%), and trouble walking stairs or standing up (9%). Additionally, patients who received oxaliplatin more often reported tingling (29% v 8%; P = .001), numbness (17% v 5%; P = .005), and aching or burning pain (13% v 6%; P = .03) in toes/feet compared with those not treated with chemotherapy. They also more often reported tingling toes/feet (29% v 14%; P = .0127) compared with those treated with chemotherapy without oxaliplatin. Those with many neuropathy symptoms (eg, upper 10%) reported statistically significant and clinically relevant worse HRQOL scores on all EORTC QLQ-C30 subscales (all P < .01). CONCLUSION Two to 11 years after diagnosis of CRC, neuropathy-related symptoms are still reported, especially sensory symptoms in the lower extremities among those treated with oxaliplatin. Because neuropathy symptoms have a negative influence on HRQOL, these should be screened for and alleviated. Future studies should focus on prevention and relief of chemotherapy-induced neuropathy.

Well-being, posttraumatic growth and benefit finding in long-term breast cancer survivors.

This study evaluates posttraumatic growth, benefit finding and well-being, and their mutual association in a random sample of disease-free 10-year breast cancer survivors. The population-based Eindhoven Cancer Registry (ECR) was used to select all women diagnosed with breast cancer in 1993 in six hospitals. Of the 254 breast cancer survivors, 183 (72%) returned a completed questionnaire. Measures included the Posttraumatic Growth Inventory (posttraumatic growth), the Perceived Disease Impact Scale (benefit finding) and the CentERdata Health monitor (life satisfaction, health status and psychological well-being). Self-reported health status and psychological well-being were similar in survivors compared to general population norms, whereas life satisfaction was significantly higher among survivors. In addition, posttraumatic growth was seen in the following domains: relationships with others, personal strength and appreciation of life. The number of patients reporting benefit finding was high (79%, N = 145). Benefit finding showed a moderately positive correlation with posttraumatic growth. In addition, women who stated that their satisfaction with life was high reported higher levels of posttraumatic growth in comparison to women who did not. Radiotherapy was negatively associated with posttraumatic growth. Women with a higher tumour stage at diagnosis experienced less benefit finding in comparison to women with a lower tumour stage at diagnosis. The above results can help to identify those patients who will probably experience posttraumatic growth and benefit finding after cancer. However, it is important to be aware that the positive effects of cancer on a patients life do not occur in all cancer patients and all phases of the disease trajectory.

Fifteen-year radiotherapy outcomes of the randomized PORTEC-1 trial for Endometrial Carcinoma

PURPOSE To evaluate the very long-term results of the randomized Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 trial for patients with Stage I endometrial carcinoma (EC), focusing on the role of prognostic factors for treatment selection and the long-term risk of second cancers. PATIENTS AND METHODS The PORTEC trial (1990-1997) included 714 patients with Stage IC Grade 1-2 or Stage IB Grade 2-3 EC. After surgery, patients were randomly allocated to external-beam pelvic radiotherapy (EBRT) or no additional treatment (NAT). Analysis was by intention to treat. RESULTS 426 patients were alive at the date of analysis. The median follow-up time was 13.3 years. The 15-year actuarial locoregional recurrence (LRR) rates were 6% for EBRT vs. 15.5% for NAT (p < 0.0001). The 15-year overall survival was 52% vs. 60% (p = 0.14), and the failure-free survival was 50% vs. 54% (p = 0.94). For patients with high-intermediate risk criteria, the 15-year overall survival was 41% vs. 48% (p = 0.51), and the 15-year EC-related death was 14% vs. 13%. Most LRR in the NAT group were vaginal recurrences (11.0% of 15.5%). The 15-year rates of distant metastases were 9% vs. 7% (p = 0.25). Second primary cancers had been diagnosed over 15 years in 19% of all patients, 22% vs. 16% for EBRT vs. NAT (p = 0.10), with observed vs. expected ratios of 1.6 (EBRT) and 1.2 (NAT) compared with a matched population (p = NS). Multivariate analysis confirmed the prognostic significance of Grade 3 for LRR (hazard ratio [HR] 3.4, p = 0.0003) and for EC death (HR 7.3, p < 0.0001), of age >60 (HR 3.9, p = 0.002 for LRR and 2.7, p = 0.01 for EC death) and myometrial invasion >50% (HR 1.9, p = 0.03 and HR 1.9, p = 0.02). CONCLUSIONS The 15-year outcomes of PORTEC-1 confirm the relevance of HIR criteria for treatment selection, and a trend for long-term risk of second cancers. EBRT should be avoided in patients with low- and intermediate-risk EC.

Health-Related Quality of Life in Cervical Cancer Survivors: A Population-Based Survey

PURPOSE In a population-based sample of cervical cancer survivors, health-related quality of life (HRQoL) was assessed 2-10 years postdiagnosis. METHODS AND MATERIALS All patients given a diagnosis of cervical cancer in 1995-2003 in the Eindhoven region, The Netherlands, and alive after Jan 2006 were identified through the cancer registry. Generic HRQoL (36-Item Short-Form Health Survey, EQ-5D), cervical cancer-specific HRQoL (European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire cervical cancer module), and anxiety (6-item State Trait Anxiety Inventory) were assessed and compared with a reference population (n = 349). Data for tumor characteristics at diagnosis and disease progression were available. RESULTS A total of 291 women responded (69%), with a mean age of 53 +/- 13 (SD) years (range, 31-88 years). Treatment had consisted of surgery (n = 195) or a combination of therapies (n = 75); one woman had not been treated. Of all women, 85% were clinically disease free, 2% had a recurrence/metastasis, and in 13%, this was unknown. After controlling for background characteristics (age, education, job and marital status, having children, and country of birth), generic HRQoL scale scores were similar to the reference population, except for worse mental health in survivors. The most frequent symptoms were crampy pain in the abdomen or belly (17%), urinary leakage (15%), menopausal symptoms (18%), and problems with sexual activity. Compared with the 6-10-year survivors, more sexual worry and worse body image were reported by the 2-5-year survivors. Compared with surgery only, especially primary radiotherapy was associated with an increased frequency of treatment-related side effects, also after controlling for age and disease stage at diagnosis and follow-up. CONCLUSIONS Most cervical cancer survivors were coping well, although their mental health was worse than in the reference population. Even after 2-10 years, radiotherapy was associated with an increased frequency of treatment-related side effects.

Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review

BackgroundThe objective of this study was to systematically review all available literature concerning chemotherapy-induced peripheral neuropathy (CIPN) and quality of life (QOL) among cancer patients.MethodsA computerized search of the literature was performed in December 2013. Articles were included if they investigated CIPN and QOL among cancer patients. Twenty-five articles were selected and were subjected to a 13-item quality checklist independently by two investigators.ResultsThe methodological quality of the majority of the selected studies was adequate to high. The included studies differed tremendously with respect to study design (19 prospective studies, 5 cross-sectional, 1 both cross-sectional and prospective), patient population (lung, colorectal, ovarian, endometrial, cervical or breast cancer, lymphoma, acute lymphoblastic leukemia, or a mixed population), number of included patients (ranging from 14 to 1643), and ways to assess CIPN (objectively, subjectively, or both). Of the 25 included studies, 11 assessed the association of CIPN on patients’ QOL. While three of these studies did not find an association between CIPN and QOL, the others concluded that more CIPN was associated with a lower QOL.Implications for cancer survivorsAlthough the included studies in this systematic review were very diverse, which impedes drawing firm conclusions on this topic, CIPN is likely to have a negative association with QOL. The variety of the studied patient populations and chemotherapeutic agents in the existing studies calls for further studies on this topic. These studies are preferably prospective in nature, include a large number of patients, and assess QOL and CIPN with validated questionnaires.

Five-year quality of life of endometrial cancer patients treated in the randomised Post Operative Radiation Therapy in Endometrial Cancer (PORTEC-2) trial and comparison with norm data.

BACKGROUND The PORTEC-2 trial showed efficacy and reduced side-effects of vaginal brachytherapy (VBT) compared with external beam pelvic radiotherapy (EBRT) for patients with high-intermediate risk endometrial cancer. The current analysis was done to evaluate long-term health related quality of life (HRQL), and compare HRQL of patients to an age-matched norm population. METHODS Patients were randomly allocated to EBRT (n=214) or VBT (n=213). HRQL was assessed using EORTC QLQ-C30 and subscales from PR25 and OV28 (bladder, bowel, sexual symptoms); and compared to norm data. FINDINGS Median follow-up was 65 months; 348 (81%) patients were evaluable for HRQL (EBRT n=166, VBT n=182). At baseline, patient functioning was at lowest level, increasing during and after radiotherapy to reach a plateau after 12 months, within range of scores of the norm population. VBT patients reported better social functioning (p=0.005) and lower symptom scores for diarrhoea, faecal leakage, need to stay close to a toilet and limitation in daily activities due to bowel symptoms (p⩽0.001), compared to EBRT. There were no differences in sexual functioning or symptoms between the treatment groups; however, sexual functioning was lower and sexual symptoms more frequent in both treatment groups compared to the norm population. INTERPRETATION Patients who received EBRT reported clinically relevant higher levels of bowel symptoms and related limitations in daily activities with lower social functioning, 5 years after treatment. VBT provides a better HRQL, which remained similar to that of an age-matched norm population, except for sexual symptoms which were more frequent in both treatment groups.

New opportunities for drug outcomes research in cancer patients: The linkage of the Eindhoven Cancer Registry and the PHARMO Record Linkage System

BACKGROUND Insight into co-morbidity and treatment effects is pivotal to improve quality of care for cancer patients. OBJECTIVES To determine whether linkage of the Eindhoven Cancer Registry (ECR) and the PHARMO Record Linkage System (RLS) was technically feasible and to assess which patient-centric data would result from this linkage. METHODS The ECR records data on tumour stage and primary treatment of all newly diagnosed cancer patients in the southeastern Netherlands including co-morbidity at diagnosis, whereas the PHARMO RLS includes data from multiple linked observational databases such as data on drug utilisation (for both in- and out-patients, including chemotherapy), hospitalisations and clinical laboratory measurements. All patients who lived or had been living in the overlapping area served by the ECR and the PHARMO RLS during 1998-2006 were selected for linkage which was performed with probabilistic medical record linkage. RESULTS The linkage resulted in an ECR-PHARMO cohort of 40,004 cancer patients with a total of 42,767 primary tumours. The cancer patients in the linked ECR-PHARMO cohort were representatives for the cancer patients included in the total ECR during 1998-2006. Cancer patients included in the cohorts had a mean history of 5 years and a mean follow-up ranging from 2 to more than 4 years (dependent on the survival rate of the specific cancer type). CONCLUSIONS Linkage of ECR and the PHARMO RLS creates the possibility to study patient-centric drug utilisation, health resources utilisation and their costs, in addition to the effectiveness and safety of pharmaceuticals in routine daily practice in cancer patients.

Adrenocortical carcinoma: A population-based study on incidence and survival in the Netherlands since 1993

BACKGROUND The reported annual incidence of adrenocortical carcinoma (ACC) is 0.5-2.0 cases per million individuals. Updated population-based studies on incidence are lacking. The aim of this nationwide survey was to describe the incidence and survival rates of ACC in the Netherlands. Secondary objectives were to evaluate changes in both survival rates and the number of patients undergoing surgery. METHODS All ACC patients registered in the Netherlands Cancer Registry (NCR) between 1993 and 2010 were included. Data on demographics, stage of disease, primary treatment modality and survival were evaluated. RESULTS Included were 359 patients, 196 of whom were female (55%). Median age at diagnosis was 56 years (range 1-91). The 5-year age-standardised incidence rate decreased from 1.3 to 1.0 per one million person-years. Median survival for patients with stage I-II, stage III and stage IV disease was 159 months (95% confidence interval (CI) 93-225 months), 26 months (95% CI: 4-48 months) and 5 months (95% CI: 2-7 months), respectively (P<0.001). Improvement in survival was not observed, as reflected by the lack of association between survival and time of diagnosis. The percentage of patients receiving treatment within 6 months after diagnosis increased significantly from 76% in 1993-1998 to 88% in 2005-2010 (P=0.047), mainly due to an increase in surgery for stage III-IV patients. CONCLUSION These nationwide data provide an up-to-date survey of the epidemiology of ACC in the Netherlands. A trend towards a decreasing overall incidence rate was observed. Survival rates did not change during this period despite an increased number of surgical procedures.

Improved overall survival for patients with rectal cancer since 1990: the effects of TME surgery and pre-operative radiotherapy.

AIM The aim was to study the effects of the introduction of TME surgery and pre-operative radiotherapy on overall survival (OS) by comparing patients treated in the period before (1990-1995), during (1996-1999) and after (2000-2002) the TME trial. PATIENTS AND METHODS Patients diagnosed with rectal carcinoma in the region of Comprehensive Cancer Centres South and West were used (n=3179). RESULTS Five-year OS was, respectively, 56%, 62% and 65% in the pre-trial, trial and post-trial periods (p<0.001). Pre-operative RT was increasingly used over time and significantly related to OS in the post-trial period (p=0.002), but not in the pre-trial and trial periods. CONCLUSIONS Population-based OS improved markedly since the introduction of TME surgery. With standardised TME surgery, pre-operative RT improved OS, whereas withholding pre-operative RT was associated with a poorer prognosis. The present study supports that pre-operative RT was correctly introduced as a standard treatment before TME surgery in our national guideline.