The impact of geriatric characteristics and comorbidities on distant metastases and other cause mortality in older women with non-metastatic breast cancer treated with primary endocrine therapy.

INTRODUCTION: In recent years, primary surgical treatment of older women with non-metastatic breast cancer has decreased in favor of primary endocrine therapy (PET). PET can be considered in women with a remaining life expectancy of less than five years. The aim of this study was to (1) assess the risk of distant metastases and other cause mortality over ten years in women aged 65 and older with stage I-III breast cancer treated with PET, (2) whether this was associated with geriatric characteristics and comorbidities and to (3) describe the reasons on which the choice for PET was made. METHODS: Women were included from the retrospective FOCUS cohort, which comprises all incident women diagnosed with breast cancer aged 65 or older between January 1997 and December 2004 in the Comprehensive Cancer Center Region West in the Netherlands. We selected women (N = 257) with stage I-III breast cancer and treated with PET from this cohort. Patient characteristics (including comorbidity, polypharmacy, walking, cognitive and sensory impairment), treatment and tumor characteristics were retrospectively extracted from charts. Outcomes were distant metastasis and other cause mortality. Cumulative incidences were calculated using the Cumulative Incidence for Competing Risks method (CICR); and subdistribution hazard ratios (SHR) were tested between groups based on age, geriatric characteristics and comorbidity with the Fine and Gray model. RESULTS: Women treated with PET were on average 84 years old and 41% had one or more geriatric characteristics. Other cause mortality exceeded the cumulative incidence of distant metastasis over ten years (83 versus 5.6%). The risk of dying from another cause further increased in women with geriatric characteristics (SHR 2.06, p < 0.001) or two or more comorbidities (SHR 1.72, p < 0.001). Often the reason for omitting surgery was not recorded (52.9%), but if recorded surgery was omitted mainly at the patient's request (18.7%). DISCUSSION: This study shows that the cumulative incidence of distant metastasis is much lower than other cause mortality in older women with breast cancer treated with PET, especially in the presence of geriatric characteristics or comorbidities. This confirms the importance of assessment of geriatric characteristics to aid counseling of older women.

Clinical characteristics of phenotypes of fecal incontinence.

PURPOSE: Fecal incontinence (FI) is common, but its etiology is complex with large knowledge gaps. Several phenotypes of FI are known, but the phenotype is often not decisive in the chosen therapy. In this study we aimed to assess the association of the clinical characteristics of patients with FI and the various phenotypes, in order to establish a targeted clinical treatment decision tree. METHODS: We retrospectively studied the charts of patients with FI, who visited our institute from January 2018 until December 2020. Patients were divided into the following groups: passive fecal loss, urge incontinence, combined fecal incontinence with predominantly passive fecal loss, and combined fecal incontinence with predominantly urge incontinence. We compared the characteristics between the passive and urge incontinence groups, the passive  and combined mainly passive groups, and the urge and combined mainly urge groups. RESULTS: Patients with passive incintinence were older, more often had a flaccid anus with presence of a mucosal prolapse, and had a lower resting pressure on anorectal manometry. Patients with urge incontinence were younger and more often had a history of birth trauma. The combined groups showed characteristics of both of the main types of FI. CONCLUSION: Differentiating into phenotypes of FI can be clinically meaningful. The patient history and clinical judgement of the consulting specialist, rather than the physical characteristics, seem to be decisive in the categorization. Additional diagnostic testing can be helpful in complicated cases, but should not be used routinely.

Predictive value of selected geriatric parameters for postoperative outcomes in older patients with rectal cancer - A multicenter cohort study.

INTRODUCTION: Older patients have a higher risk for complications after rectal cancer surgery. Although screening for geriatric impairments may improve risk prediction in this group, it has not been studied previously. METHODS: We retrospectively investigated patients ≥70 years with elective surgery for non-metastatic rectal cancer between 2014 and 2018 in nine Dutch hospitals. The predictive value of six geriatric parameters in combination with standard preoperative predictors was studied for postoperative complications, delirium, and length of stay (LOS) using logistic regression analyses. The geriatric parameters included the four VMS-questionnaire items pertaining to functional impairment, fall risk, delirium risk, and malnutrition, as well as mobility problems and polypharmacy. Standard predictors included age, sex, body mass index, American Society of Anesthesiologists (ASA)-classification, comorbidities, tumor stage, and neoadjuvant therapy. Changes in model performance were evaluated by comparing Area Under the Curve (AUC) of the regression models with and without geriatric parameters. RESULTS: We included 575 patients (median age 75 years; 32% female). None of the geriatric parameters improved risk prediction for complications or LOS. The addition of delirium risk to the standard preoperative prediction model improved model performance for predicting postoperative delirium (AUC 0.75 vs 0.65, p = 0.03). CONCLUSIONS: Geriatric parameters did not improve risk prediction for postoperative complications or LOS in older patients with rectal cancer. Delirium risk screening using the VMS-questionnaire improved risk prediction for delirium. Older patients undergoing rectal cancer surgery are a pre-selected group with few impairments. Geriatric screening may have additional value earlier in the care pathway before treatment decisions are made.

Predicting postoperative complications and their impact on quality of life and functional status in older patients with breast cancer.

BACKGROUND: The percentage of older patients undergoing surgery for early-stage breast cancer has decreased over the past decade. This study aimed to develop a prediction model for postoperative complications to better inform patients about the benefits and risks of surgery, and to investigate the association between complications and functional status and quality of life (QoL). METHODS: Women aged at least 70 years who underwent surgery for Tis-3 N0 breast cancer were included between 2013 and 2018. The primary outcome was any postoperative complication within 30 days after surgery. Secondary outcomes included functional status and QoL during the first year after surgery, as assessed by the Groningen Activity Restriction Scale and the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 questionnaires. A prediction model was developed using multivariable logistic regression and validated externally using data from the British Bridging the Age Gap Study. Linear mixed models were used to assess QoL and functional status over time. RESULTS: The development and validation cohorts included 547 and 2727 women respectively. The prediction model consisted of five predictors (age, polypharmacy, BMI, and type of breast and axillary surgery) and performed well in internal (area under curve (AUC) 0.76, 95 per cent c.i. 0.72 to 0.80) and external (AUC 0.70, 0.68 to 0.72) validations. Functional status and QoL were not affected by postoperative complication after adjustment for confounders. CONCLUSION: This validated prediction model can be used to counsel older patients with breast cancer about the postoperative phase. Postoperative complications did not affect functional status nor QoL within the first year after surgery even after adjustment for predefined confounders.

Surgery remains the standard of care for the majority of older patients with breast cancer. The percentage of older patients with breast cancer receiving surgery is decreasing. The reason for this decline is unknown, but it might be due to fear of complications. To better inform patients about the benefits and risks of surgery, the aim of this study was to develop a prediction model for complications after surgery. Another important aspect, especially for older adults with breast cancer, is quality of life, functional capacity, and ability to carry out daily tasks (functional status) after therapy. This study showed that quality of life and functional status did not decline after breast surgery, irrespective of the occurrence of postoperative complications.

Effect of omission of surgery on survival in patients aged 80 years and older with early-stage hormone receptor-positive breast cancer.

BACKGROUND: Surgery is increasingly being omitted in older patients with operable breast cancer in the Netherlands. Although omission of surgery can be considered in frail older patients, it may lead to inferior outcomes in non-frail patients. Therefore, the aim of this study was to evaluate the effect of omission of surgery on relative and overall survival in older patients with operable breast cancer. METHODS: Patients aged 80 years or older diagnosed with stage I-II hormone receptor-positive breast cancer between 2003 and 2009 were selected from the Netherlands Cancer Registry. An instrumental variable approach was applied to minimize confounding, using hospital variation in rate of primary surgery. Relative and overall survival was compared between patients treated in hospitals with different rates of surgery. RESULTS: Overall, 6464 patients were included. Relative survival was lower for patients treated in hospitals with lower compared with higher surgical rates (90·2 versus 92·4 per cent respectively after 5 years; 71·6 versus 88·2 per cent after 10 years). The relative excess risk for patients treated in hospitals with lower surgical rates was 2·00 (95 per cent c.i. 1·17 to 3·40). Overall survival rates were also lower among patients treated in hospitals with lower compared with higher surgical rates (48·3 versus 51·3 per cent after 5 years; 15·0 versus 19·7 per cent after 10 years respectively; adjusted hazard ratio 1·07, 95 per cent c.i. 1·00 to 1·14). CONCLUSION: Omission of surgery is associated with worse relative and overall survival in patients aged 80 years or more with stage I-II hormone receptor-positive breast cancer. Future research should focus on the effect on quality of life and physical functioning.

ANTECEDENTES: En los Países Bajos cada vez es más frecuente descartar la cirugía en pacientes mayores con cáncer de mama operable. Aunque la omisión de la cirugía puede ser adecuada en pacientes mayores frágiles, ello puede determinar peores resultados en pacientes no frágiles. Por tanto, el objetivo de este estudio fue evaluar el efecto de omitir la cirugía en la supervivencia relativa y en la supervivencia global en pacientes mayores con cáncer de mama operable. MÉTODOS: A partir del Registro de Cáncer de los Países Bajos se seleccionaron las pacientes de ≥ 80 años de edad diagnosticadas de cáncer de mama entre 2003-2009 en estadios 1-2 y con receptores hormonales positivos. Se aplicó un método de variables instrumentales para minimizar los factores de confusión utilizando la tasa de variación hospitalaria de la cirugía primaria. Se compararon las supervivencias relativa y global de las pacientes tratadas en hospitales con diferentes tasas de cirugía. RESULTADOS: Se incluyeron 6.464 pacientes. La supervivencia relativa fue menor en las pacientes tratadas en hospitales con tasas quirúrgicas más bajas en comparación con las tratadas en hospitales con tasas altas (90,2% versus 92,4% a los 5 años y 71,6% versus 88,2% a los 10 años, respectivamente). El exceso de riesgo relativo para las pacientes tratadas en hospitales con tasas quirúrgicas más bajas fue de 2,00 (i.c. del 95% 1,17-3,40). La supervivencia global también fue menor para las pacientes tratadas en hospitales con tasas quirúrgicas más bajas en comparación con las más altas (48,3% versus 51,3% a los 5 años y 15,0% versus 19,7% a los 10 años, respectivamente, cociente de riesgos instantáneos, hazard ratio, HR, ajustado 1,07) i.c. del 95% 1,00-1,14)). CONCLUSIÓN: Omitir la cirugía se asocia con una peor supervivencia relativa y global en pacientes de ≥ 80 años con cáncer de mama en estadios 1-2 y receptores hormonales positivos. Las investigaciones futuras deberían centrarse en el efecto de este enfoque en la calidad de vida y la funcionalidad física.

Treatment strategies and overall survival for incurable metastatic colorectal cancer - A EURECCA international comparison including 21,196 patients from the Netherlands and Norway.

BACKGROUND: The potential benefit of surgery of the primary tumour in patients with asymptomatic metastatic colorectal cancer is debated. This EURECCA international comparison analyses treatment strategies and overall survival in the Netherlands and Norway in patients with incurable metastatic colorectal cancer. METHODS: National cohorts (2007-2013) from the Netherlands and Norway including all patients with synchronous metastatic colorectal cancer were compared on treatment strategy and overall survival. Using country as an instrumental variable, we assessed the effect of different treatment strategies on mortality in the first year. RESULTS: Of 21,196 patients (16,144 Dutch and 5052 Norwegian), 38.6% Dutch and 51.5% (p < 0.001) Norwegian patients underwent resection of the primary tumour. In the Netherlands, 58.2% received chemotherapy compared with 21.4% in Norway. Radiotherapy was given in 9.5% of Dutch patients and 7.2% of Norwegian patients. Using the Netherlands as reference, the adjusted HR for overall survival was 0.96 (95% CI 0.93-0.99; p = 0.024). Instrumental variable analysis showed an adjusted OR of 1.00 (95% CI 0.99-1.02; p = 0.741). CONCLUSIONS: Treatment strategies varied significantly between the Netherlands and Norway, with more surgery and less radiotherapy in Norway. Adjusted overall survival was better in Norway for all patients and patients <75 years, but not for patients ≥75 years. Instrumental variable analysis showed no benefit in one-year mortality for a treatment strategy with a higher proportion of surgery and a lower proportion of radiotherapy. Our findings emphasise the need for further research to select patients with incurable metastatic colorectal cancer for different treatment options.

National cohort study on postoperative risks after surgery for submucosal invasive colorectal cancer.

Background: The decision to perform surgery for patients with T1 colorectal cancer hinges on the estimated risk of lymph node metastasis, residual tumour and risks of surgery. The aim of this observational study was to compare surgical outcomes for T1 colorectal cancer with those for more advanced colorectal cancer. Methods: This was a population-based cohort study of patients treated surgically for pT1-3 colorectal cancer between 2009 and 2016, using data from the Dutch ColoRectal Audit. Postoperative complications (overall, surgical, severe complications and mortality) were compared using multivariable logistic regression. A risk stratification table was developed based on factors independently associated with severe complications (reintervention and/or mortality) after elective surgery. Results: Of 39 813 patients, 5170 had pT1 colorectal cancer. No statistically significant differences were observed between patients with pT1 and pT2-3 disease in the rate of severe complications (8·3 versus 9·5 per cent respectively; odds ratio (OR) 0·89, 95 per cent c.i. 0·80 to 1·01, P = 0·061), surgical complications (12·6 versus 13·5 per cent; OR 0·93, 0·84 to 1·02, P = 0·119) or mortality (1·7 versus 2·5 per cent; OR 0·94, 0·74 to 1·19, P = 0·604). Male sex, higher ASA grade, previous abdominal surgery, open approach and type of procedure were associated with a higher severe complication rate in patients with pT1 colorectal cancer. Conclusion: Elective bowel resection was associated with similar morbidity and mortality rates in patients with pT1 and those with pT2-3 colorectal carcinoma.

Time trends of short-term mortality for octogenarians undergoing a colorectal resection in North Europe.

BACKGROUND: Decreased cancer specific survival in older colorectal patients is mainly due to mortality in the first year, emphasizing the importance of the first postoperative year. This study aims to gain an overview and time trends of short-term mortality in octogenarians (≥80 years) with colorectal cancer across four North European countries. METHODS: Patients of 80 years or older, operated for colorectal cancer (stage I-III) between 2005 and 2014, were included. Population-based cohorts from Belgium, Denmark, the Netherlands, and Sweden were collected. Separately for colon- and rectal cancer, 30-day, 90-day, one-year, and excess one-year mortality were calculated. Also, short-term mortality over three time periods (2005-2008, 2009-2011, 2012-2014) was analyzed. RESULTS: In total, 35,158 colon cancer patients and 10,144 rectal cancer patients were included. For colon cancer, 90-day mortality rate was highest in Denmark (15%) and lowest in Sweden (8%). For rectal cancer, 90-day mortality rate was highest in Belgium (11%) and lowest in Sweden (7%). One-year excess mortality rate of colon cancer patients decreased from 2005 to 2008 to 2012-2014 for all countries (Belgium: 17%-11%, Denmark: 21%-15%, the Netherlands: 18%-10%, and Sweden: 10%-8%). For rectal cancer, from 2005 to 2008 to 2012-2014 one-year excess mortality rate decreased in the Netherlands from 16% to 7% and Sweden: 8%-2%). CONCLUSIONS: Short-term mortality rates were high in octogenarians operated for colorectal cancer. Short-term mortality rates differ across four North European countries, but decreased over time for both colon and rectal cancer patients in all countries.

Meta-analysis of long-term survival after elective endovascular or open repair of abdominal aortic aneurysm.

BACKGROUND: Endovascular aneurysm repair (EVAR) has become the preferred strategy for elective repair of abdominal aortic aneurysm (AAA) for many patients. However, the superiority of the endovascular procedure has recently been challenged by reports of impaired long-term survival in patients who underwent EVAR. A systematic review of long-term survival following AAA repair was therefore undertaken. METHODS: A systematic review was performed according to PRISMA guidelines. Articles reporting short- and/or long-term mortality of EVAR and open surgical repair (OSR) of AAA were identified. Pooled overall survival estimates (hazard ratios (HRs) with corresponding 95 per cent c.i. for EVAR versus OSR) were calculated using a random-effects model. Possible confounding owing to age differences between patients receiving EVAR or OSR was addressed by estimating relative survival. RESULTS: Some 53 studies were identified. The 30-day mortality rate was lower for EVAR compared with OSR: 1·16 (95 per cent c.i. 0·92 to 1·39) versus 3·27 (2·71 to 3·83) per cent. Long-term survival rates were similar for EVAR versus OSR (HRs 1·01, 1·00 and 0·98 for 3, 5 and 10 years respectively; P = 0·721, P = 0·912 and P = 0·777). Correction of age inequality by means of relative survival analysis showed equal long-term survival: 0·94, 0·91 and 0·76 at 3, 5 and 10 years for EVAR, and 0·96, 0·91 and 0·76 respectively for OSR. CONCLUSION: Long-term overall survival rates were similar for EVAR and OSR. Available data do not allow extension beyond the 10-year survival window or analysis of specific subgroups.

International comparison of treatment strategy and survival in metastatic gastric cancer.

Background: In the randomized Asian REGATTA trial, no survival benefit was shown for additional gastrectomy over chemotherapy alone in patients with advanced gastric cancer with a single incurable factor, thereby discouraging surgery for these patients. The purpose of this study was to evaluate treatment strategies for patients with metastatic gastric cancer in daily practice in five European countries, along with relative survival in each country. Methods: Nationwide population-based data from Belgium, Denmark, the Netherlands, Norway and Sweden were combined. Patients with primary metastatic gastric cancer diagnosed between 2006 and 2014 were included. The proportion of gastric resections performed and the administration of chemotherapy (irrespective of surgery) within each country were determined. Relative survival according to country was calculated. Results: Overall, 15 057 patients with gastric cancer were included. The proportion of gastric resections varied from 8·1 per cent in the Netherlands and Denmark to 18·3 per cent in Belgium. Administration of chemotherapy was 39·2 per cent in the Netherlands, compared with 63·2 per cent in Belgium. The 6-month relative survival rate was between 39·0 (95 per cent c.i. 37·8 to 40·2) per cent in the Netherlands and 54·1 (52·1 to 56·9) per cent in Belgium. Conclusion: There is variation in the use of gastrectomy and chemotherapy in patients with metastatic gastric cancer, and subsequent differences in survival.

The Prognostic Value of a Geriatric Risk Score for Older Patients with Colorectal Cancer.

INTRODUCTION: VMS is a Dutch risk assessment tool for hospitalized older adults that includes a short evaluation of four geriatric domains: risk for delirium, risk for undernutrition, risk for physical impairments, and fall risk. We investigated whether the information derived from this tool has prognostic value for outcomes of colorectal surgery. METHODS: All consecutive patients over age 70 years who underwent elective colorectal cancer surgery in three Dutch hospitals (2014-2016) were studied. The presence of risk was scored prior to surgery and per geriatric domain as either 0 (risk absent) or 1 (risk present). The total number of geriatric risk factors was summed. The primary outcome was long-term survival. Secondary outcomes were postoperative complications, including delirium. Cox proportional hazards models were used to evaluate the sumscore and risk factors associated with overall survival. RESULTS: Five hundred fifty patients were included. Median age was 76.5 years, and median follow-up was 870 days. Patients with intermediate (1-2) or high (3-4) sumscore were independently associated with lower overall survival, with hazard ratio (HR) of 1.9 [95% confidence interval (CI) 1.1-3.5; p = 0.03] and 8.7 (95% CI 4.0-19.2; p < 0.001), respectively. Sumscores were also associated with postoperative complications (intermediate sumscore OR 1.8; 95% CI 1.2-2.7; high sumscore OR 2.4; 95% CI 1.02-5.5). CONCLUSIONS: This easy-to-use geriatric sumscore has strong associations with long-term outcome and morbidity after colorectal cancer surgery. This information may be included in risk models for morbidity and mortality and can be used in shared decision-making.

North European comparison of treatment strategy and survival in older patients with resectable gastric cancer: A EURECCA upper gastrointestinal group analysis.

BACKGROUND: As older gastric cancer patients are often excluded from randomized clinical trials, the most appropriate treatment strategy for these patients remains unclear. The current study aimed to gain more insight in treatment strategies and relative survival of older patients with resectable gastric cancer across Europe. METHODS: Population-based cohorts from Belgium, Denmark, The Netherlands, Norway, and Sweden were combined. Patients ≥70 years with resectable gastric cancer (cT1-4a, cN0-2, cM0), diagnosed between 2004 and 2014 were included. Resection rates, administration of chemotherapy (irrespective of surgery), and relative survival within a country according to stage were determined. RESULTS: Overall, 6698 patients were included. The percentage of operated patients was highest in Belgium and lowest in Sweden for both stage II (74% versus 56%) and stage III disease (57% versus 25%). For stage III, chemotherapy administration was highest in Belgium (44%) and lowest in Sweden (2%). Three year relative survival for stage I, II, and III disease in Belgium was 67.8% (95% CI:62.8-72.6), 41.2% (95% CI:37.3-45.2), 17.8% (95% CI:12.5-24.0), compared with 56.7% (95% CI:51.5-61.7), 31.3% (95% CI:27.6-35.2), 8.2% (95% CI:4.4-13.4) in Sweden. There were no significant differences in treatment strategies of patients with stage I disease. CONCLUSION: Substantial treatment differences are observed across North European countries for patients with stages II and III resectable gastric cancer aged 70 years or older. In the present comparison, treatment strategies with a higher proportion of patients undergoing surgery seemed to be associated with higher survival rates for patients with stages II or III disease.

Decrease in 30-day and one-year mortality over time in patients aged ≥75 years with stage I-III colon cancer: A population-based study.

BACKGROUND: Monitoring time trends of cancer mortality is essential. Thirty-day mortality is an important surgical outcome measure, though postoperative mortality exceeds to one year after surgery in patients with colorectal cancer. The aim of this nationwide observational study was to assess changes over time in 30-day and one-year mortality in patients with stage I-III colorectal cancer. METHODS: All surgically treated patients with stage I-III colorectal cancer, diagnosed between 2009 and 2013 were selected from the Netherlands Cancer Registry. Changes in 30-day and one-year mortality were assessed using logistic regression by tumour localisation (colon, rectum) and age group (<75 years, ≥75 years). RESULTS: Overall, 41,186 patients were included. Among patients with colon cancer ≥75 years, 30-day mortality decreased from 8.3% in 2009 to 6.2% in 2013 (p-value for trend = 0.011), and one-year mortality from 18.5% in 2009 to 15.0% in 2013 (p-value for trend = 0.007). No significant differences in mortality over time were observed for patients <75 years with colon cancer and for patients with rectal cancer. CONCLUSION: Thirty-day and one-year mortality decreased over time in patients ≥75 years with stage I-III colon cancer, though the absolute decrease is small. However, 30-day mortality and in particular the one-year mortality are both still high in older patients with colorectal cancer and will need to be focused on to further improve outcomes for these patient subgroups.

Comprehensive multidisciplinary care program for elderly colorectal cancer patients: "From prehabilitation to independence".

BACKGROUND: We implemented a multidisciplinary pre- and rehabilitation program for elderly patients (≥75 years of age) in a single center consisting of prehabilitation, laparoscopic surgery and early rehabilitation with the intention to lower 1-year overall mortality. METHODS: In this study we compared all patients that underwent elective surgery for stage I-III colorectal cancer before and during development and after implementation of the program (2010-2011, 2012-2013 and 2014-2015). Primary endpoint was 1-year overall mortality, the secondary endpoint was 30-day postoperative outcome. RESULTS: Eighty-six consecutive patients were included in the study cohort and compared to 63 patients from 2010 to 2011 and 75 patients from 2012 to 2013. Patient characteristics were comparable; median age in the study cohort was 80.6. Seventy-three patients (85%) participated in the program, 54 (63%) of whom followed a prehabilitation program, 46 (53%) of whom were discharged to a rehabilitation center. Laparoscopic surgery increased over the years from 70% to 83% in the study cohort. There was a trend in lower 1-year overall mortality: 11% versus 3% (p=0.08). There was a significant reduction in cardiac complications and the number of patients with a prolonged length of stay (p < 0.01). CONCLUSIONS: Multidisciplinary care for elderly colorectal cancer patients that includes prehabilitation and rehabilitation is feasible and may contribute to lower complications and reduced length of stay. This study did not show a clear benefit of implementing a comprehensive care program including both prehabilitation and rehabilitation. Dedicated multidisciplinary care seems the key attributer to favorable outcomes of CRC surgery in elderly patients.

Differences in Treatment and Outcome of Pancreatic Adenocarcinoma Stage I and II in the EURECCA Pancreas Consortium.

BACKGROUND: The EUropean REgistration of Cancer CAre (EURECCA) consortium aims to investigate differences in treatment and to improve cancer care through Europe. The purpose of this study was to compare neo- and adjuvant chemotherapy (ACT) and outcome after tumor resection for pancreatic adenocarcinoma stage I and II in the EURECCA Pancreas consortium. METHODS: The eight, collaborating national, regional, and single-center partners shared their anonymized dataset. Patients diagnosed in 2012-2013 who underwent tumor resection for pancreatic adenocarcinoma stage I and II were investigated with respect to treatment and survival and compared using uni- and multivariable logistic and Cox regression analyses. All comparisons were performed separately per registry type: national, regional, and single-center registries. RESULTS: In total, 2052 patients were included. Stage II was present in the majority of patients. The use of neo-ACT was limited in most registries (range 2.8-15.5%) and was only different between Belgium and The Netherlands after adjustment for potential confounders. The use of ACT was different between the registries (range 40.5-70.0%), even after adjustment for potential confounders. Ninety-day mortality was also different between the registries (range 0.9-13.6%). In multivariable analyses for overall survival, differences were observed between the national and regional registries. Furthermore, patients in ascending age groups and patients with stage II showed a significant worse overall survival. CONCLUSIONS: This study provides a clear insight in clinical practice in the EURECCA Pancreas consortium. The differences observed in (neo-)ACT and outcome give us the chance to further investigate the best practices and improve outcome of pancreatic adenocarcinoma.

Oncologic treatment strategies and relative survival of patients with stage I-III rectal cancer - A EURECCA international comparison between the Netherlands, Belgium, Denmark, Sweden, England, Ireland, Spain, and Lithuania.

INTRODUCTION: The aim of this EURECCA international comparison is to compare oncologic treatment strategies and relative survival of patients with stage I-III rectal cancer between European countries. MATERIAL AND METHODS: Population-based national cohort data from the Netherlands (NL), Belgium (BE), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), Spain (ES), and single-centre data from Lithuania (LT) were obtained. All operated patients with (y)pTNM stage I-III rectal cancer diagnosed between 2004 and 2009 were included. Oncologic treatment strategies and relative survival were calculated and compared between neighbouring countries. RESULTS: We included 57,120 patients. Treatment strategies differed between NL and BE (p < 0.001), DK and SE (p < 0.001), and ENG and IE (p < 0.001). More preoperative radiotherapy as single treatment before surgery was administered in NL compared with BE (59.7% vs. 13.1%), in SE compared with DK (55.1% vs. 10.4%), and in ENG compared with IE (15.2% vs. 9.6%). Less postoperative chemotherapy was given in NL (9.6% vs. 39.1%), in SE (7.9% vs. 14.1%), and in IE (12.6% vs. 18.5%) compared with their neighbouring country. In ES, 55.1% of patients received preoperative chemoradiation and 62.3% postoperative chemotherapy. There were no significant differences in relative survival between neighbouring countries. CONCLUSION: Large differences in oncologic treatment strategies for patients with (y)pTNM I-III rectal cancer were observed across European countries. No clear relation between oncologic treatment strategies and relative survival was observed. Further research into selection criteria for specific treatments could eventually lead to individualised and optimal treatment for patients with non-metastasised rectal cancer.

Introduction of a colorectal cancer screening programme: results from a single-centre study.

AIM: In 2014, a national colorectal cancer (CRC) screening programme was launched in the Netherlands. It is difficult to assess for the individual patients with CRC whether the oncological benefits of surgery will outweigh the morbidity of the procedure, especially in early lesions. This study compares patient and tumour characteristics between screen-detected and nonscreen-detected patients. Also, we present an overview of treatment options and clinical dilemmas when treating patients with early-stage colorectal disease. METHOD: Between January 2014 and December 2016, all patients with nonmalignant polyps or CRC who were referred to the Department of Surgery of the Leiden University Medical Centre in the Netherlands were included. Baseline characteristics, type of treatment and short-term outcomes of patients with screen-detected and nonscreen-detected colorectal tumours were compared. RESULTS: A total of 426 patients were included, of whom 240 (56.3%) were identified by screening. Nonscreen-detected patients more often had comorbidity (P = 0.03), the primary tumour was more often located in the rectum (P = 0.001) and there was a higher rate of metastatic disease (P < 0.001). Of 354 surgically treated patients, postoperative adverse events did not significantly differ between the two groups (P = 0.38). Of 46 patients with T1 CRC in the endoscopic resection specimen, 23 underwent surgical resection of whom only 30.4% had residual invasive disease at colectomy. CONCLUSION: Despite differences in comorbidity, stage and surgical outcome of patients with screen-detected tumours compared to nonscreen-detected tumours were not significantly different. Considering its limited oncological benefits as well as the rate of adverse events, surgery for nonmalignant polyps and T1 CRC should be considered carefully.

Impact of age on breast cancer mortality and competing causes of death at 10 years follow-up in the adjuvant TEAM trial.

AIM: Due to increasing life expectancy, patients with breast cancer remain at risk of dying due to breast cancer over a long time. This study aims to assess the impact of age on breast cancer mortality and other cause mortality 10 years after diagnosis. METHODS: Postmenopausal patients with hormone-receptor positive breast cancer were included in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial between 2001 and 2006. Age at diagnosis was categorised as <65 years (n = 3369), 65-74 years (n = 1896) and ≥75 years (n = 854). Breast cancer mortality was assessed considering other cause mortality as competing event using competing risk analysis. RESULTS: After a median follow-up of 9.8 years (interquartile range 8.0-10.3), cumulative incidence of breast cancer mortality increased with increasing age (age <65 years, 11.7% [95% confidence interval {CI}: 10.2-13.2]; 65-74 years, 12.7% (11.2-14.2) and ≥75 years, 15.6% (13.1-18.0)). Univariate subdistribution hazard ratio (sHR) increased with increasing age (age: 65-74 years, sHR: 1.08, 95% CI: 0.92-1.27 and ≥75 years sHR: 1.30, 95% CI: 1.06-1.58, P = 0.013). Multivariable sHR adjusted for tumour and treatment characteristics increased with age but did not reach significance (age 65-74 years, sHR: 1.11, 95% CI: 0.94-1.31; ≥75 years, sHR: 1.18, 95% CI: 0.94-1.48, P = 0.055). CONCLUSION: Ten years after diagnosis, older age at diagnosis is associated with increasing breast cancer mortality in univariate analysis, but it did not reach significance in multivariable analysis. This is not outweighed by a substantially higher other cause mortality with older age. This underlines the need to improve the balance between undertreatment and overtreatment in older patients with breast cancer. The trial was registered in International Trial Databases (ClinicalTrials.govNCT00279448, NCT00032136, and NCT00036270; the Netherlands Trial Registry NTR267).

Systematic review of the clinical and economic value of gene expression profiles for invasive early breast cancer available in Europe.

Gene expression profiles with prognostic capacities have shown good performance in multiple clinical trials. However, with multiple assays available and numerous types of validation studies performed, the added value for daily clinical practice is still unclear. In Europe, the MammaPrint, OncotypeDX, PAM50/Prosigna and Endopredict assays are commercially available. In this systematic review, we aim to assess these assays on four important criteria: Assay development and methodology, clinical validation, clinical utility and economic value. We performed a literature search covering PubMed, Embase, Web of Science and Cochrane, for studies related to one or more of the four selected assays. We identified 147 papers for inclusion in this review. MammaPrint and OncotypeDX both have evidence available, including level IA clinical trial results for both assays. Both assays provide prognostic information. Predictive value has only been shown for OncotypeDX. In the clinical utility studies, a higher reduction in chemotherapy was achieved by OncotypeDX, although the number of available studies differ considerably between tests. On average, economic evaluations estimate that genomic testing results in a moderate increase in total costs, but that these costs are acceptable in relation to the expected improved patient outcome. PAM50/prosigna and EndoPredict showed comparable prognostic capacities, but with less economical and clinical utility studies. Furthermore, for these assays no level IA trial data are available yet. In summary, all assays have shown excellent prognostic capacities. The differences in the quantity and quality of evidence are discussed. Future studies shall focus on the selection of appropriate subgroups for testing and long-term outcome of validation trials, in order to determine the place of these assays in daily clinical practice.