The MELFO-Study:Prospective, Randomized, Clinical Trial for the Evaluation of a Stage-adjusted Reduced Follow-up Schedule in Cutaneous Melanoma Patients-Results after 1 Year

Guidelines for evidence-based follow-up in melanoma patients are not available. This study examined whether a reduced follow-up schedule affects: patient-reported outcome measures, detection of recurrences, and follow-up costs.This multicenter trial included 180 patients treated for AJCC stage IB-II cutaneous melanoma, who were randomized in a conventional follow-up schedule group (CSG, 4 visits first year, n = 93) or experimental follow-up schedule group (ESG, 1-3 visits first year, n = 87). Patients completed the State-Trait Anxiety Inventory, cancer worry scale, impact of events scale, and a health-related quality of life questionnaire (HRQoL, RAND-36). Physicians registered clinicopathologic features and the number of outpatient clinic visits.Sociodemographic and illness-related characteristics were equal in both groups. After 1-year follow-up, the ESG reported significantly less cancer-related stress response symptoms than the CSG (p = 0.01), and comparable anxiety, mental HRQoL, and cancer-related worry. Mean cancer-related worry and stress response symptoms decreased over time (p &lt;0.001), whereas mental HRQoL increased over time (p &lt;0.001) in all melanoma patients. Recurrence rate was 9 % in both groups, mostly patient-detected and not physician-detected (CSG 63 %, ESG 43 %, p = 0.45). Hospital costs of 1-year follow-up were reduced by 45 % in the ESG compared to the CSG.This study shows that the stage-adjusted, reduced follow-up schedule did not negatively affect melanoma patients' mental well-being and the detection of recurrences compared with conventional follow-up as dictated by the Dutch guideline, at 1 year after diagnosis. Additionally, reduced follow-up was associated with significant hospital cost reduction.</p

The MELFO Study:A Multicenter, Prospective, Randomized Clinical Trial on the Effects of a Reduced Stage-Adjusted Follow-Up Schedule on Cutaneous Melanoma IB-IIC Patients-Results After 3 Years

Background This study compares well-being, recurrences, and deaths of early-stage cutaneous melanoma patients in follow-up, as recommended in the Dutch guideline, with that of patients in a stage-adjusted reduced follow-up schedule, 3 years after diagnosis, as well as costs. Methods Overall, 180 eligible pathological American Joint Committee on Cancer (AJCC) stage IB-IIC, sentinel node staged, melanoma patients (response rate = 87%, 48% male, median age 57 years), randomized into a conventional (CSG, n = 93) or experimental (ESG, n = 87) follow-up schedule group, completed patient-reported outcome measures (PROMs) at diagnosis (T1): State-Trait Anxiety Inventory-State version (STAI-S), Cancer Worry Scale (CWS), Impact of Event Scale (IES), and RAND-36 (Mental and Physical Component scales [PCS/MCS]). Three years later (T3), 110 patients (CSG, n = 56; ESG, n = 54) completed PROMs, while 42 declined (23%). Results Repeated measures analyses of variance (ANOVAs) showed a significant group effect on the IES (p = 0.001) in favor of the ESG, and on the RAND-36 PCS (p = 0.02) favoring the CSG. Mean IES and CWS scores decreased significantly over time, while those on the RAND-36 MCS and PCS increased. Effect sizes were small. Twenty-five patients developed a recurrence or second primary melanoma, of whom 13 patients died within 3 years. Cox proportional hazards models showed no differences between groups in recurrence-free survival (hazard ratio [HR] 0.71 [0.32-1.58]; p = 0.400) and disease-free survival (HR 1.24 [0.42-3.71]; p = 0.690). Costs per patient after 3 years (computed for 77.3% of patients) were 39% lower in the ESG. Conclusion These results seemingly support the notion that a stage-adjusted reduced follow-up schedule forms an appropriate, safe, and cost-effective alternative for pathological AJCC stage IB-IIC melanoma patients to the follow-up regimen as advised in the current melanoma guideline

Surgical treatment for non-parasitic liver cysts improves quality of life

BACKGROUND&PURPOSE: Liver cysts occur frequently. Most are harmless, however some carry a significant patient burden. Optimizing treatment strategy is complicated as needs differ between patients. The current study assesses the effect of surgery on quality of life (QoL) of patients with non-parasitic liver cysts. METHODS: A retrospective cohort study of all patients who underwent surgery for non-parasitic liver cysts in three major Dutch medical centers from 1993 to 2017. Patient characteristics and surgery related variables were collected from the electronic patient file. QoL was measured before and after surgery using the EORTC QLQ-C30. Summary scores (SumSc) were calculated and compared to reference values of the general population. Multivariate analysis using logistic regression was performed for identifying outcome related factors. Increase of ≥ 10% in SumSc was defined as clinically relevant. MAIN FINDINGS: Eighty-eight of 132 eligible patients (67%) completed two QoL assessments. Respondents demonstrated significant improvement in the global health status, on all 5 functional scales (all p ≤ 0.005), on all 9 symptom scales after surgery (all p < 0.05), and on SumSc (p < 0.001) to levels similar or better than the general population. Patients with complications demonstrated a significant QoL gain (p < 0.05), and reported a similar postoperative status compared to patients without complications (p = 0.74). QoL gain for patients who underwent open and laparoscopic cyst fenestration were similar (p = 0.08). Multivariate analysis of SumSc found mechanical complaints as significant factor for ≥ 10% SumSc increase (OR 0.11, 95% CI (0.02-0.55). CONCLUSIONS: Surgery is a safe and effective strategy to significantly improve QoL in patients with symptomatic liver cysts

Small but significant socioeconomic inequalities in axillary staging and treatment of breast cancer in the Netherlands

Background: The use of sentinel node biopsy (SNB), lymph node dissection, breast-conserving surgery, radiotherapy, chemotherapy and hormonal treatment for breast cancer was evaluated in relation to socioeconomic status (SES) in the Netherlands, where access to care was assumed to be equal. Methods: Female breast cancer patients diagnosed between 1994 and 2008 were selected from the nationwide population-based Netherlands Cancer Registry (N=176 505). Socioeconomic status was assessed based on income, employment and education at postal code level. Multivariable models included age, year of diagnosis and stage. Results: Sentinal node biopsy was less often applied in high-SES patients (multivariable analyses, ≤49 years: odds ratio (OR) 0.70 (95% CI: 0.56-0.89); 50-75 years: 0.85 (0.73-0.99)). Additionally, lymph node dissection was less common in low-SES patients aged ≥76 years (OR 1.34 (0.95-1.89)). Socioeconomic status-related differences in treatment were only significant in the age group 50-75 years. High-SES women with stage T1-2 were more likely to undergo breast-conserving surgery (radiotherapy) (OR 1.15 (1.09-1.22) and OR 1.16 (1.09-1.22), respectively). Chemotherapy use among node-positive patients was higher in the high-SES group, but was not significant in multivariable analysis. Hormonal therapy was not related to SES. Conclusion: Small but significant differences were observed in the use of SNB, lymph node dissection and breast-conserving surgery according to SES in Dutch breast cancer patients despite assumed equal access to health care

The MelFo Study UK: Effects of a reduced-frequency, stage-adjusted follow-up schedule for cutaneous melanoma 1B to 2C patients after 3-years

Background: Evidence-based guidelines for follow-up treatment of American Joint Committee on Cancer (AJCC) stages 1B to 2C melanoma patients are lacking. The MELanoma FOllow-up study is an international phase 3 randomized trial, and the 3-year interim data were recently reported from the Netherlands. The study was undertaken concurrently with a British cohort for comparison and validation of the Dutch study.  Methods: The study enrolled and stratified 207 patients by AJCC stage. The conventional schedule group (CSG; n = 103) cohort was reviewed as per UK guidelines. The experimental schedule group (ESG; n = 104) cohort was reviewed in a reduced-frequency nurse-led, consultant-supervised clinic. Quality of life (QoL) was measured at baseline (T1), a 1 year (T2), and at 3 years (T3) using the State-Trait Anxiety Inventory, the Cancer Worry Scale, the Impact-of-Event Scale, and the Mental and Physical Component scales (PCS/MCS) of the RAND-36.  Results: Of the 207 QoL questionnaires, 170 (82.1%) were completed at T3. Both cohorts expressed high satisfaction (' 93%) with their regimens. At T3, no significant group effect was found on any patient-reported outcome measures scores, indicating no QoL difference between the follow-up protocols. Recurrence had developed in 33 patients Conventional follow-up (CFU), 16 [15.5%]; Experimental follow-up (EFU), 17 [16.3%]. Self-examination was the method of detection for 12 ESG patients (70.6%) and 11 CSG patients (68.8%). The melanoma-specific survival was identical.  Conclusion: The UK 3-year data were consistent with the previous Dutch report. The reduced follow-up strategy was shown to be safe, with significant resource usage benefits for national cancer services. Patient anxiety levels were not increased by a less-intensive follow-up regimen, and acceptance was high. The study data indicate that patient self-examination is very effective for recurrence detection

The effect of aspirin and nonsteroidal anti-inflammatory drug use after diagnosis on survival of oesophageal cancer patients

Background:Aspirin use has been shown to lower incidence and mortality in cancer patients. The aim of this population-based study was to determine the effect of postdiagnosis low-dose aspirin use on survival of patients with oesophageal cancer.Methods:Patients with oesophageal cancer (1998-2010) were selected from the Eindhoven Cancer Registry and linked with outpatient pharmacy data regarding aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Users were subdivided into both prediagnosis and postdiagnosis or only postdiagnosis users. Parametric survival models with an exponential (Poisson) distribution were used with non-specific death as endpoint.Results:In this study 560 patients were included. Overall, 157 patients (28.0%) were non-users, 293 patients (52.3%) pre-and postdiagnosis (89 aspirin and 204 NSAID users) and 110 patients (19.6%) only postdiagnosis users (16 aspirin and 94 NSAID users). Postdiagnosis aspirin use was associated with overall survival (RR 0.45 (95% CI 0.34-0.60; P<0.001); adjusted rat

Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare the expression and the prognostic effect of the breast cancer stem cell marker aldehyde dehydrogenase-1 (ALDH1) in young and elderly breast cancer patients.</p> <p>Methods</p> <p>The study population (N = 574) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Median follow-up was 17.9 years (range: 0.1 to 23.5). Tissue microarray slides were immunohistochemically stained for ALDH1 expression and quantified by two independent observers who were blinded to clinical outcome. Assessment of the prognostic effect of ALDH1 expression was stratified according to age and systemic treatment.</p> <p>Results</p> <p>Complete lack of expression of ALDH1 was found in 40% of tumors. With increasing age more tumors showed complete absence of ALDH1 expression (<it>P </it>< .001). In patients aged > 65 years, ALDH1 status was not associated with any clinical outcome. Conversely, in patients aged < 65 years, ALDH1 positivity was an independent risk factor of worse outcome for relapse free period (hazard ratio = 1.71 (95% CI, 1.09 to 2.68); <it>P </it>= .021) and relative survival (relative excess risks of death = 2.36 (95% CI, 1.22 to 3.68); <it>P </it>= .016). Ten-year relative survival risk was 57% in ALDH1-positive patients compared to 83% in ALDH1-negative patients.</p> <p>Conclusion</p> <p>ALDH1 expression and its prognostic effect are age-dependent. Our results support the hypothesis that breast cancer biology is different in elderly patients compared to their younger counterparts and emphasizes the importance of taking into consideration age-specific interactions in breast cancer research.</p

Treatment and Survival of Elderly Patients with Stage I–II Pancreatic Cancer: A Report of the EURECCA Pancreas Consortium

Background: Elderly patients with pancreatic cancer are underrepresented in clinical trials, resulting in a lack of evidence. Objective: The aim of this study was to compare treatment and overall survival (OS) of patients aged ≥ 70 years with stage I–II pancreatic cancer in the EURECCA Pancreas Consortium. Methods: This was an observational cohort study of the Belgian (BE), Dutch (NL), and Norwegian (NOR) cancer registries. The primary outcome was OS, while secondary outcomes were resection, 90-day mortality after resection, and (neo)adjuvant and palliative chemotherapy. Results: In total, 3624 patients were included. Resection (BE: 50.2%; NL: 36.2%; NOR: 41.3%; p < 0.001), use of (neo)adjuvant chemotherapy (BE: 55.9%; NL: 41.9%; NOR: 13.8%; p < 0.001), palliative chemotherapy (BE: 39.5%; NL: 6.0%; NOR: 15.7%; p < 0.001), and 90-day mortality differed (BE: 11.7%; NL: 8.0%; NOR: 5.2%; p < 0.001). Furthermore, median OS in patients with (BE: 17.4; NL: 15.9; NOR: 25.4 months; p < 0.001) and without resection (BE: 7.0; NL: 3.9; NOR: 6.5 months; p < 0.001) also differed. Conclusions: Differences were observed in treatment and OS in patients aged ≥ 70 years with stage I–II pancreatic cancer, between the population-based cancer registries. Future studies should focus on selection criteria for (non)surgical treatment in older patients so that clinicians can tailor treatment

The influence of BRAF and KRAS mutation status on the association between aspirin use and survival after colon cancer diagnosis

Background: Use of aspirin after diagnosis of colon cancer has been associated with improved survival. Identification of cancer subtypes that respond to aspirin treatment may help develop personalized treatment regimens. The aim of this study was to investigate the influence of BRAF and KRAS mutation status on the association between aspirin use and overall survival after colon cancer diagnosis. Methods: A random selection of 599 patients with colon cancer were analyzed, selected from the Eindhoven Cancer Registry, and BRAF and KRAS mutation status was determined. Data on aspirin use (80 mg) were obtained from the PHARMO Database Network. Parametric survival models with exponential (Poisson) distribution were used. Results: Aspirin use after colon cancer diagnosis was associated with improved overall survival in wild-type BRAF tumors, adjusted rate ratio (RR) of 0.60 (95% CI 0.44-0.83). In contrast, aspirin use in BRAF mutated tumors was not associated with an improved survival (RR 1.11, 95% CI 0.57-2.16). P-value for interaction was non-significant. KRAS mutational status did not differentiate in the association between aspirin use and survival. Conclusion: Low-dose aspirin use after colon cancer diagnosis was associated with improved survival in BRAF wild-type tumors only. However, the large confidence interval of the rate ratio for the use of aspirin in patients with BRAF mutation does not rule out a possible benefit. These results preclude BRAF and KRAS mutation status to be used as a marker for individualized treatment with aspirin, if aspirin becomes regular adjuvant treatment for colon cancer patients in the future

The intra-tumoral stroma in patients with breast cancer increases with age

Purpose The tumor microenvironment in older patients is subject to changes. The tumor-stroma ratio (TSR) was evaluated in order to estimate the amount of intra-tumoral stroma and to evaluate the prognostic value of the TSR in older patients with breast cancer (≥70 years). Methods Two retrospective cohorts, the FOCUS study (N = 619) and the Nottingham Breast Cancer series (N = 1793), were used for assessment of the TSR on hematoxylin and eosin stained tissue slides. Results The intra-tumoral stroma increases with age in the FOCUS study and the Nottingham Breast Cancer series (B 0.031, 95% CI 0.006-0.057, P = 0.016 and B 0.034, 95% CI 0.015-0.054, P ≤ 0.001, respectively). Fifty-one percent of the patients from the Nottingham Breast Cancer series ≤40 years had a stroma-high tumor compared to 73% of the patients of ≥90 years from the FOCUS study. The TSR did not validate as an independent prognostic parameter in patients ≥70 years. Conclusions The intra-tumoral stroma increases with age. This might be the result of an activated tumor microenvironment. The TSR did not validate as an independent prognostic parameter in patients ≥70 years in contrast to young women with breast cancer as published previously