Objective: Compare oncological long-term and short-term outcomes between patients with distal cT2NO rectal cancer treated with chemoradio-therapy and local excision (CRT + LE) and patients treated... Show moreObjective: Compare oncological long-term and short-term outcomes between patients with distal cT2NO rectal cancer treated with chemoradio-therapy and local excision (CRT + LE) and patients treated with total mesorectal excision (TME). Summary Background Data: Previous studies showed that CRT + LE is equivalent to TME in local tumor control and survival for T2N0 rectal cancer. Methods: Seventy-nine patients with cT2N0 rectal adenocarcinoma treated with CRT + LE in the ACOSOG Z6041 trial were compared to a cohort of 79 patients with pT2N0 tumors treated with upfront TME in the Dutch TME trial. Survival, short-term outcomes, and health-related quality of life (HRQOL) were compared between groups. Results:Three patients (4%) in the CRT + LE group required abdominoperineal resection, compared with 31 (40%) in the TME group. Forty TME patients (51%) required a permanent stoma. CRT-related toxicity occurred in 43% of the CRT + LE patients; however, TME patients had a higher rate of complications requiring reoperation (1 vs 9%; P = 0.03). Five-year disease-free survival {88.2% [confidence interval (CI), 77.7%-93.9%] vs 88.3% [CI, 78.7%-93.7%]; P = 0.88} and overall survival [90.3% (CI, 80.8%-95.3%) vs 88.4% (CI, 78.9%-93.8%); P = 0.82] were similar in the 2 groups. Compared to baseline, overall HRQOL decreased in the CRT + LE group and improved in the TME group. In both groups, patients with sphincter preservation had worse HRQOL scores 1 year after surgery. Conclusions: In patients who underwent CRT + LE, oncological outcomes were similar to those of patients who underwent TME, with fewer complications requiring reoperation but significant CRT toxicity. Although overall HRQOL decreased in the CRT + LE group and improved in TME patients, when considering anorectal function, results were worse in both groups. Show less
Background: Muscle attenuation (MA) and visceral adipose tissue (VAT) have not yet been included in the currently used alternative Fistula Risk Score (a-FRS). The aim of this study was to examine... Show moreBackground: Muscle attenuation (MA) and visceral adipose tissue (VAT) have not yet been included in the currently used alternative Fistula Risk Score (a-FRS). The aim of this study was to examine the added value of these parameters as predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) in the a-FRS after pancreatoduodenectomy compared to Body Mass Index (BMI). Methods: A single center retrospective cohort study was performed in patients who underwent pancreatoduodenectomy between 2009 and 2018. The a-FRS model was reproduced, MA and VAT were both combined and separately added to the model instead of BMI using logistic regression analysis. Model discrimination was assessed by ROC-curves. Results: In total, 329 patients were included of which 55 (16.7%) developed CR-POPF. The a-FRS model showed an AUC of 0.74 (95%CI: 0.68-0.80). In this model, BMI was not significantly associated with CR-POPF (p = 0.16). The MA + VAT model showed an AUC of 0.81 (95%CI: 0.75-0.86). VAT was significantly associated with CR-POPF (per cm2, OR: 1.01; 95%CI: 1.00-1.01; p < 0.001). The AUC of the MA + VAT model differed significantly from the AUC of the a-FRS model (p = 0.001). Conclusion: Visceral adipose tissue is of added value in the a-FRS compared to BMI in predicting CRPOPF in patients undergoing pancreatoduodenectomy. Show less
Ziel, D. van der; Derks, M.G.M.; Kapiteijn, E.; Bastiaannet, E.; Louwman, M.; Bos, F. van den; ... ; Glas, N.A. de 2022
Simple Summary Immunotherapy has strongly improved outcomes of patients with metastatic melanoma in recent years, but previous studies have shown that survival of older patients often lacks behind.... Show moreSimple Summary Immunotherapy has strongly improved outcomes of patients with metastatic melanoma in recent years, but previous studies have shown that survival of older patients often lacks behind. In this study, we investigated treatment prescription of immunotherapy over time in relation to age and survival. We showed that overall survival has improved in patients with synchronous metastasised melanoma aged <75 years, but not in patients aged 75 years or older. This might be explained by lower prescription rates of immunotherapy in this age group. Around 45% of patients with melanoma are older than 65 years. In recent years, immunotherapy has proven very effective for metastasised melanoma. The aim of this study was to investigate the time trends in treatment strategies and survival in older versus younger patients with synchronous metastasised melanoma. We included all patients diagnosed between 2000 and 2019 from the Netherlands cancer registry. We analysed changes in first-line systemic treatment using multivariable logistic regression models, stratified by age (<65, 65-75, and >= 75). Changes in overall survival were studied using multivariable Cox regression analysis. A total of 2967 patients were included. Immunotherapy prescription increased significantly over time for all age groups (<65 years: 11.8% to 64.9%, p < 0.001; 65-75 years: 0% to 68.6%, p < 0.001; >75 years: 0% to 39.5%, p < 0.001). In multivariable analyses, overall survival improved for patients aged <65 and 65-75 (HR 0.96, 95% CI 0.92-1.00 and HR 0.95, 95% CI 0.89-1.00, respectively), but not in patients over 75 (HR 0.98, 95% CI 0.91-1.05). In conclusion, overall survival has improved in patients with synchronous metastasised melanoma aged <75 years, but not in patients aged 75 years or older. This might be explained by lower prescription rates of immunotherapy in this age group. Show less
Introduction: In older patients with breast cancer, the risk of dying from other causes than breast cancer strongly increases after the age of 70. The aim of this study was to assess contributions... Show moreIntroduction: In older patients with breast cancer, the risk of dying from other causes than breast cancer strongly increases after the age of 70. The aim of this study was to assess contributions of breast cancer mortality versus other-cause mortality after locoregio-nal or distant recurrence in a population-based cohort of older patients analysed by multi-state models. Methods: Surgically treated patients >70 years diagnosed with stage I-III breast cancer in 2003-2009 were selected from the Netherlands Cancer Registry. A novel multi-state model with locoregional and distant recurrence that incorporates relative survival was fitted. Other-cause and breast cancer mortality were indicated as population and excess mortality. Results: Overall, 18,419 patients were included. Ten-year cumulative incidences of locoregio-nal and distant recurrence were 2.8% (95%CI 2.6-3.1%) and 12.5% (95%CI 11.9-13.1%). Other-cause mortality increased from 23.9% (95%CI 23.7-24.2%) in patients 70-74 years to 73.8% (95%CI 72.2-75.4%) in those >80 years. Ten-year probabilities of locoregional or distant recurrence with subsequent breast cancer death were 0.4-1.3% and 10.2-14.6%, respectively. For patients with a distant recurrence in the first two years after diagnosis, breast cancer death probabilities were 95.3% (95%CI 94.2-96.4%), 93.1% (95%CI 91.6-94.6%), and 88.6% (95%CI 86.5-90.8%) in patients 70-74, 75-79, and >80 years. Conclusion: In older patients without recurrence, prognosis is driven by other-cause mortality. Although locoregional recurrence is a predictor for worse outcome, given its low incidence it contributes little to breast cancer mortality after diagnosis. For patients who develop a distant recurrence, breast cancer remains the dominant cause of death, even at old age.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Schaapherder, A.F.; Kaisar, M.; Mumford, L.; Robb, M.; Johnson, R.; Kok, M.J.C.D.; ... ; Lindeman, J.H.N. 2022
Background: Donor-characteristics and donor characteristics-based decision algorithms are being progressively used in the decision process whether or not to accept an available donor kidney graft... Show moreBackground: Donor-characteristics and donor characteristics-based decision algorithms are being progressively used in the decision process whether or not to accept an available donor kidney graft for transplantation. While this may improve outcomes, the performance characteristics of the algorithms remains moderate. To estimate the impact of donor factors of grafts accepted for transplantation on transplant outcomes, and to test whether implementation of donor-characteristics-based algorithms in clinical decision-making is justified, we applied an instrumental variable analysis to outcomes for kidney donor pairs transplanted in different individuals. Methods: This analysis used (dis)congruent outcomes of kidney donor pairs as an instrument and was based on national transplantation registry data for all donor kidney pairs transplanted in separate individuals in the Netherlands (1990-2018, 2,845 donor pairs), and the United Kingdom (UK, 2000-2018, 11,450 pairs). Incident early graft loss (EGL) was used as the primary discriminatory factor. It was reasoned that a scenario with a dominant impact of donor variables on transplantation outcomes would result in high concordance of EGL in both recipients, whilst dominance of asymmetrical outcomes could indicate a more complex scenario, involving an interaction of donor, procedural and recipient factors. Findings: Incidences of congruent EGL (Netherlands: 1.2%, UK: 0.7%) were slightly lower than the arithmetical (stochastic) incidences, suggesting that once a graft has been accepted for transplantation, donor factors minimally contribute to incident EGL. A long-term impact of donor factors was explored by comparing outcomes for functional grafts from donor pairs with asymmetrical vs. symmetrical outcomes. Recipient survival was similar for both groups, but a slightly compromised graft survival was observed for grafts with asymmetrical outcomes in the UK cohort: (10 years Hazard Ratio for graft loss: 1.18 [1.03-1.35] p < 0.018); and 5 years eGFR (48.6 [48.3-49.0] vs. 46.0 [44.5-47.6] ml/min in the symmetrical outcome group, p < 0.001). Interpretation: Our results suggest that donor factors for kidney grafts deemed acceptable for transplantation impact minimally on transplantation outcomes. A strong reliance on donor factors and/or donor-characteristics-based decision algorithms could result in unjustified rejection of grafts. Future efforts to optimize transplant outcomes should focus on a better understanding of the recipient factors underlying transplant outcomes. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Show less
Background: A decade ago, it was demonstrated that the difference in survival between older patients and younger patients with colorectal cancer (CRC) was mainly due to mortality in the first... Show moreBackground: A decade ago, it was demonstrated that the difference in survival between older patients and younger patients with colorectal cancer (CRC) was mainly due to mortality in the first postoperative year. Over the last few years, improvements -especially in perioperative care-have increased survival. The current research investigates whether a survival gap between younger and older patients with CRC still exists on a national level in four European countries. Methods: Population-based data from Belgium, the Netherlands, Norway, and Sweden were collected from patients that underwent surgical resection for primary stage I-III CRC between 2007 and 2016. Relative survival and conditional relative survival (CS), with the condition of surviving the first postoperative year, were calculated for colon and rectal cancer separately, stratified for country and age category (< 65, 65-75, >= 75 years). In addition, relative excess risk of death (RER) was estimated, and one-year excess mortality was calculated. Results: Data of 206,024 patients were analyzed. In general, compared to patients < 65 years, patients >= 75 years had a worse survival during the first year after surgery, which was most pronounced in Belgium (RER colon cancer 2.5 [95% confidence interval (CI) 2.3-2.8] and RER rectal cancer 2.6 [95% CI 2.3-2.9]). After surviving the first year, CS was mostly not statistically different between patients < 65 years and patients >= 75 years with stage I-II, with the exception of stage II colon cancer in Belgium. However, CS remained worse in the largest part of the patients & GE;75 years with stage III colon or rectal cancer (except for rectal cancer in Norway). Conclusions: Although differences exist between the countries, the survival gap between young and older patients is based mainly on early mortality and remains only for stage III disease after surviving the first year. Show less
Hulst, H.C.V.; Dekker, J.W.T.; Bastiaannet, E.; Bol, J.M. van der; Bos, F. van den; Hamaker, M.E.; ... ; Souwer, E.T.D. 2022
Background: For clinical decision making it is important to identify patients at risk for adverse outcomes after co-lorectal cancer (CRC) surgery, especially in the older population. Because the... Show moreBackground: For clinical decision making it is important to identify patients at risk for adverse outcomes after co-lorectal cancer (CRC) surgery, especially in the older population. Because the American College of Surgeons Na-tional Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator is potentially useful in clinical practice, we performed an external validation in a Dutch multicenter cohort of patients >= 70 years undergoing elective non-metastatic CRC surgery.Methods: We compared the ACS NSQIP calculator mean predicted risk to the overall observed rate of anastomotic leakage, return to operation room, pneumonia, discharge not to home, and readmission in our cohort using a one-sample Z-test. Calibration plots and receiver operating characteristic (ROC) curves were used to determine the calculator's performance.Results: Six hundred eighty-two patients were included. Median age was 76.2 years. The ACS NSQIP calculator ac-curately predicted the overall readmission rate (predicted: 8.6% vs. observed: 7.8%, p = 0.456), overestimated the rate of discharge not to home (predicted:11.2% vs. observed: 7.0% p = 0.005) and underestimated the observed rate of all other outcomes. The calibration plots showed poor calibration for all outcomes. The ROC-curve showed an area under the curve (AUC) of 0.75 (95% confidence interval [CI] 0.67-0.83) for pneumonia and 0.70 (0.62-0.78) for discharge not to home. The AUC for all other outcomes was poor.Conclusions: The ACS NSQIP surgical risk calculator had a poor individual risk prediction (calibration) for all out-comes and only a fair discriminative ability (discrimination) to predict pneumonia and discharge not to home. The calculator might be considered to identify patients at high risk of pneumonia and discharge not to home to initiate additional preoperative interventions. (c) 2022 Elsevier Ltd. All rights reserved. Show less
Argillander, T.E.; Hulst, H.C. van der; Zaag-loonen, H.J. van der; Duijvendijk, P. van; Dekker, J.W.T.; Bol, J.M. van der; ... ; Munster, B.C. van 2022
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... Show moreIntroduction: 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. Show less
Lemij, A.A.; Plas-Krijgsman, W.G. van der; Bastiaannet, E.; Merkus, J.W.S.; Dalen, T. van; Vulink, A.J.E.; ... ; Liefers, G.J. 2022
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... Show moreBackground 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. Lay summary 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.Some 41.0 per cent of older patients with breast cancer developed a postoperative complication within 30 days after surgery. The authors designed a prediction tool that can predict complication risk, with a good internal and external validity. Postoperative complications did not affect functional status or quality of life in the first year after surgery after adjustment for confounders. Show less
Purpose: Side effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation... Show morePurpose: Side effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation of adjuvant endocrine therapy within the first 2 years after initiation, and to study the association between early discontinuation and functional status and quality of life (QoL). Methods: Patients aged >= 70 years with stage I-III breast cancer who received adjuvant endocrine therapy were included. The primary endpoint was discontinuation of endocrine therapy within 2 years. Risk factors for discontinuation were assessed using univariate logistic regression models. Linear mixed models were used to assess QoL and functional status over time. Results: Overall, 258 patients were included, of whom 36% discontinued therapy within 2 years after initiation. No geriatric predictive factors for treatment discontinuation were found. Tumour stage was inversely associated with early discontinuation. Patients who discontinued had a worse breast cancer-specific QoL (b = - 4.37; 95% CI - 7.96 to - 0.78; p = 0.017) over the first 2 years, in particular on the future perspective subscale (b = - 11.10; 95% CI - 18.80 to - 3.40; p = 0.005), which did not recover after discontinuation. Treatment discontinuation was not associated with functional improvement. Conclusion: A large proportion of older patients discontinue adjuvant endocrine treatment within 2 years after initiation, but geriatric characteristics are not predictive of early discontinuation of treatment. Discontinuation of adjuvant endocrine therapy did not positively affect QoL and functional status, which implies that the observed poorer QoL in this group is probably not caused by adverse effects of endocrine therapy. Show less
Background: Previous studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has... Show moreBackground: Previous studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been hypothesised that these differences in survival outcomes could be related to treatment variation. Objectives: We aimed to compare patient and tumour characteristics, treatment selection and survival outcomes between two large prospective cohorts of older patients with operable breast cancer from the United Kingdom (UK) and The Netherlands.Methods: Women diagnosed with operable breast cancer aged >70 years were included. A baseline comprehensive geriatric assessment was performed in both cohorts, with data collected on age, comorbidities, cognition, nutritional and functional status. Baseline tumour characteristics and treatment type were collected. Univariable and multivariable Cox regression models were used to compare overall survival between the cohorts. Results: 3262 patients from the UK Age Gap cohort and 618 patients from the Dutch Climb cohort were included, with median ages of 77.0 (IQR: 72.0-81.0) and 75.0 (IQR: 72.0-81.0) years, respectively. The cohorts were generally comparable, with slight differences in rates of comorbidity and frailty. Median follow-up for overall survival was 4.1 years (IQR 2.9-5.4) in Age Gap and 4.3 years (IQR 2.9-5.5) in Climb. In Age Gap, both the rates of primary endocrine therapy and adjuvant hormonal therapy after surgery were approximately twice those in Climb (16.6% versus 7.3%, p < 0.001 for primary endocrine therapy, and 62.2% versus 38.8%, p < 0.001 for adjuvant hormonal therapy). There was no evidence of a difference in overall survival between the cohorts (adjusted HR 0.94, 95% CI 0.74-1.17, p Z 0.568). Conclusions: In contrast to previous studies, this comparison of two large national prospective longitudinal multi-centre cohort studies demonstrated comparable survival outcomes between older patients with breast cancer treated in the UK and The Netherlands, despite differences in treatment allocation.(C) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Purpose Integrin subunit beta 4 (beta 4) has been proposed to play an important role in colon cancer progression through its involvement in hemidesmosome disassembly processes and tumor cell... Show morePurpose Integrin subunit beta 4 (beta 4) has been proposed to play an important role in colon cancer progression through its involvement in hemidesmosome disassembly processes and tumor cell migration. However, the association between beta 4 expression and clinicopathological outcomes in colon cancer remains unclear.Methods Expression of beta 4 was assessed by immunohistochemistry in a large cohort of 651 colon cancer patients, the largest colon cancer cohort so far. Chi-squared tests were used to study the association between beta 4 expression and clinicopathological features. Overall and disease-free survival were assessed by Cox proportional hazard models.Results Loss of beta 4 expression was associated with local tumor invasion. Only 17.9% of the pT1 tumors displayed weak beta 4 expression level versus 28.1% of pT4 tumors, and 25.0% of the pT1 tumors had a high expression level versus 8.6% of the pT4 tumors (p = 0.012). No association between beta 4 expression and overall (p = 0.845) or disease-free survival (p = 0.767) was encountered, which disputes the role of beta 4 as a biomarker of malignant behavior in colon cancer.Conclusion Contradictory reports have suggested opposite roles for beta 4 expression in (colon) cancer progression. In the present large cohort of colon cancer patients, we found that beta 4 expression was not associated with worse clinical prognosis, but decreased with advanced pathological tumor stage. Future studies should establish whether loss of beta 4 expression promotes invasive characteristics of colon cancer cells. Show less
Background: Young-onset rectal cancer, in patients less than 50 years, is expected to increase in the coming years. A watch-and-wait strategy is nowadays increasingly practised in patients with a... Show moreBackground: Young-onset rectal cancer, in patients less than 50 years, is expected to increase in the coming years. A watch-and-wait strategy is nowadays increasingly practised in patients with a clinical complete response (cCR) after neoadjuvant treatment. Nevertheless, there may be reluctance to offer organ preservation treatment to young patients owing to a potentially higher oncological risk. This study compared patients aged less than 50 years with those aged 50 years or more to identify possible differences in oncological outcomes of watch and wait.Methods: The study analysed data from patients with a cCR after neoadjuvant therapy in whom surgery was omitted, registered in the retrospective-prospective, multicentre International Watch & Wait Database (IWWD).Results: In the IWWD, 1552 patients met the inclusion criteria, of whom 199 (12.8 per cent) were aged less than 50 years. Patients younger than 50 years had a higher T category of disease at diagnosis (P = 0.011). The disease-specific survival rate at 3 years was 98 (95 per cent c.i. 93 to 99) per cent in this group, compared with 97 (95 to 98) per cent in patients aged over 50 years (hazard ratio (HR) 1.67, 95 per cent c.i. 0.76 to 3.64; P = 0.199). The cumulative probability of local regrowth at 3 years was 24 (95 per cent c.i. 18 to 31) per cent in patients less than 50 years and 26 (23 to 29) per cent among those aged 50 years or more (HR 1.09, 0.79 to 1.49; P = 0.603). Both groups had a cumulative probability of distant metastases of 10 per cent at 3 years (HR 1.00, 0.62 to 1.62; P = 0.998).Conclusion: There is no additional oncological risk in young patients compared with their older counterparts when following a watch-and-wait strategy after a cCR. In light of a shared decision-making process, watch and wait should be also be discussed with young patients who have a cCR after neoadjuvant treatment. Show less
Background Young-onset rectal cancer, in patients less than 50 years, is expected to increase in the coming years. A watch-and-wait strategy is nowadays increasingly practised in patients with a... Show moreBackground Young-onset rectal cancer, in patients less than 50 years, is expected to increase in the coming years. A watch-and-wait strategy is nowadays increasingly practised in patients with a clinical complete response (cCR) after neoadjuvant treatment. Nevertheless, there may be reluctance to offer organ preservation treatment to young patients owing to a potentially higher oncological risk. This study compared patients aged less than 50 years with those aged 50 years or more to identify possible differences in oncological outcomes of watch and wait. Methods The study analysed data from patients with a cCR after neoadjuvant therapy in whom surgery was omitted, registered in the retrospective-prospective, multicentre International Watch & Wait Database (IWWD). Results In the IWWD, 1552 patients met the inclusion criteria, of whom 199 (12.8 per cent) were aged less than 50 years. Patients younger than 50 years had a higher T category of disease at diagnosis (P = 0.011). The disease-specific survival rate at 3 years was 98 (95 per cent c.i. 93 to 99) per cent in this group, compared with 97 (95 to 98) per cent in patients aged over 50 years (hazard ratio (HR) 1.67, 95 per cent c.i. 0.76 to 3.64; P = 0.199). The cumulative probability of local regrowth at 3 years was 24 (95 per cent c.i. 18 to 31) per cent in patients less than 50 years and 26 (23 to 29) per cent among those aged 50 years or more (HR 1.09, 0.79 to 1.49; P = 0.603). Both groups had a cumulative probability of distant metastases of 10 per cent at 3 years (HR 1.00, 0.62 to 1.62; P = 0.998). Conclusion There is no additional oncological risk in young patients compared with their older counterparts when following a watch-and-wait strategy after a cCR. In light of a shared decision-making process, watch and wait should be also be discussed with young patients who have a cCR after neoadjuvant treatment.Data from the International Watch and Wait Database have been analysed. There is no additional oncological risk in patients younger than 50 years compared with their older counterparts when following watch and wait after the achievement of a clinical complete response following neoadjuvant treatment for rectal cancer. Show less
When comparing hospitals on their readmission rates as currently done in the Hospital Readmission and Reduction Program (HRRP) in the USA, should we include the competing risk of mortality after... Show moreWhen comparing hospitals on their readmission rates as currently done in the Hospital Readmission and Reduction Program (HRRP) in the USA, should we include the competing risk of mortality after discharge, which precludes the readmission, in the analysis? Not including competing risks in current HRRP metrics was raised recently as a limitation with possible unintended consequences, as financial penalties for higher readmission rates are more severe than for higher mortality rates. Incorrectly including or ignoring competing risks can both induce bias. In this paper, we present a framework to clarify situations when competing risks should be taken into account and when they should not. We argue that the research question and the perspective from which it is asked determine whether the competing risk is also of interest and should be included in the analysis, or if only the event of interest should be considered. This information is often not explicitly reported but is needed to interpret whether the results are valid. Using the examples of readmissions and cancer, we show how different research questions fit different perspectives from which these are asked (patient, system, regulatory/insurance). Slightly changing the research question or perspective may thus change the analysis. Even though some may argue that any introduced bias is likely to be small, in the context of the HRRP, even small changes may mean that a hospital will face (higher) financial penalties. The impact of getting it wrong matters. Show less
Hulst, H.C. van der; Bastiaannet, E.; Portielje, J.E.A.; Bol, J.M. van der; Dekker, J.W.T. 2021
Introduction: Frail patients with colorectal cancer (CRC) are at increased risk of complications after surgery. Prehabilitation seems promising to improve this outcome and therefore we evaluated... Show moreIntroduction: Frail patients with colorectal cancer (CRC) are at increased risk of complications after surgery. Prehabilitation seems promising to improve this outcome and therefore we evaluated the effect of physical prehabilitation on postoperative complications in a retrospective cohort of frail CRC patients. Methods: The study consisted of all consecutive non-metastatic CRC patients >70 years who had elective surgery from 2014 to 2019 in a teaching hospital in the Netherlands, where a physical prehabilitation program was implemented from 2014 on. We performed both an intention-to-treat and per protocol analysis to evaluate postoperative complications in the physical prehabilitation (PhP) and non-prehabilitation (NP) group. Results: Eventually, 334 elective patients were included. The 124 (37.1%) patients in the PhP-group presented with higher age, higher comorbidity scores and walking-aid use compared to the NP-group. Medical complications occurred in 26.6% of the PhP-group and in 20.5% of the NP-group (p = 0.20) and surgical complications in 19.4% and 14.3% (p = 0.22) respectively. In all frailty subgroups, the medical complications were lower in the PhP-group compared to the NP-group (35.9% vs. 45.5% for patients with >2 comorbidities, 36.2% vs. 39.1% for ASA score > III, 29.2% vs. 45.8% for walking-aid use). Differences were not significant. Conclusions: In this study, patients selected for physical prehabilitation had a worse frailty profile and therefore a higher a priori risk of postoperative complications. However, the postoperative complication rate was not increased compared to patients who were less frail at baseline and without prehabilitation. Hence, physical prehabilitation may prevent postoperative complications in frail CRC patients >70 years. (c) 2021 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Plas-Krijgsman, W.G. van der; Giardiello, D.; Putter, H.; Steyerberg, E.W.; Bastiaannet, E.; Stiggelbout, A.M.; ... ; Glas, N.A. de 2021
Background Current prediction tools for breast cancer outcomes are not tailored to the older patient, in whom competing risk strongly influences treatment effects. We aimed to develop and validate... Show moreBackground Current prediction tools for breast cancer outcomes are not tailored to the older patient, in whom competing risk strongly influences treatment effects. We aimed to develop and validate a prediction tool for 5-year recurrence, overall mortality, and other-cause mortality for older patients (aged >= 65 years) with early invasive breast cancer and to estimate individualised expected benefits of adjuvant systemic treatment.Methods We selected surgically treated patients with early invasive breast cancer (stage I-III) aged 65 years or older from the population-based FOCUS cohort in the Netherlands. We developed prediction models for 5-year recurrence, overall mortality, and other-cause mortality using cause-specific Cox proportional hazard models. External validation was performed in a Dutch Cancer registry cohort. Performance was evaluated with discrimination accuracy and calibration plots.Findings We included 2744 female patients in the development cohort and 13631 female patients in the validation cohort. Median age was 74.8 years (range 65-98) in the development cohort and 76.0 years (70-101) in the validation cohort. 5-year follow-up was complete for more than 99% of all patients. We observed 343 and 1462 recurrences, and 831 and 3594 deaths, of which 586 and 2565 were without recurrence, in the development and validation cohort, respectively. The area under the receiver-operating-characteristic curve at 5 years in the external dataset was 0.76 (95% CI 0.75-0.76) for overall mortality, 0.76 (0.76-0.77) for recurrence, and 0.75 (0.74-0.75) for other-cause mortality.Interpretation The PORTRET tool can accurately predict 5-year recurrence, overall mortality, and other-cause mortality in older patients with breast cancer. The tool can support shared decision making, especially since it provides individualised estimated benefits of adjuvant treatment. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd. Show less
Background Long-term use of statins is associated with a small reduced risk of colorectal cancer but their mechanism of action is not well understood. While they are generally believed to act on... Show moreBackground Long-term use of statins is associated with a small reduced risk of colorectal cancer but their mechanism of action is not well understood. While they are generally believed to act on KRAS, we have previously proposed that they act via influencing the BMP pathway. The objective of this study was to look for associations between statin use and the risk of developing colorectal cancer of a particular molecular subtype. Methods By linking two registries unique to the Netherlands, 69,272 statin users and 94,753 controls were identified and, if they developed colorectal cancer, their specimens traced. Colorectal cancers were molecularly subtyped according to the expression of SMAD4 and the mutation status of KRAS and BRAF. Results Statin use was associated with a reduction in the risk of developing colorectal cancer regardless of molecular subtype (HR 0.77; 95% CI 0.66-0.89) and a larger reduction in the risk of developing SMAD4-positive colorectal cancer (OR 0.64; 95% CI 0.42-0.82). There was no relationship between statin use and the risk of developing colorectal cancer with a mutation in KRAS and/or BRAF. Conclusions Statin use is associated with a reduced risk of developing colorectal cancer with intact SMAD4 expression. Show less
Background: The incidence of metastatic melanoma is increasing in all ages. Multiple trials with targeted drugs and immune checkpoint inhibitors showed improved survival in metastatic melanoma.... Show moreBackground: The incidence of metastatic melanoma is increasing in all ages. Multiple trials with targeted drugs and immune checkpoint inhibitors showed improved survival in metastatic melanoma. However, patients aged >_75 years are often under-represented in clinical trials, therefore raising questions on safety and efficacy of treatment. Patients and methods: We analyzed a real-world cohort of 3054 patients with metastatic melanoma stratified for age (<_65 years, 66-74 years and >_ 75 years), and BRAF status, providing data on treatment strategies, toxicity, and survival. Kaplan Meier curves and Cox Proportional Hazard Models were used to present overall survival (OS) and Melanoma Specific Survival (MSS). Results: Overall, 52.2% of patients were <_ 65 years and 18.4% of patients >_75 years. BRAF mutated tumors were found less often in patients >_75 years: 34.5% versus 65% in patients <_65 years. Patients >_75 years received systemic therapy less frequently compared to their younger counterparts independent of the BRAF status. When receiving treatment, no statistical significant difference in grade 3 or 4 toxicity was observed. Three year Overall Survival rate was 13.7% (9.1-19.3) in patients >_75 years versus 26.7% (23.1-30.4) in patients <_65 years, with a Hazard Ratio (HR) of 1.71 (95%CI 1.50-1.95), p < 0.001. Three year Melanoma Specific Survival was 30.4% (22.0-39.2) versus 34.0% (29.7-38.2), HR 1.26 (95% CI 1.07-1.49), p = 0.005 with an adjusted HR of 1.21 (1.00-1.47), p = 0.049 Conclusion: Patients with metastatic melanoma >_75 years are less frequently treated, but when treated there is no statistical significant increase in toxicity and only a borderline statistical significant difference in Melanoma Specific Survival was seen, compared to younger patients. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
