Adjuvant Chemotherapy Among Elderly Colon Cancer Patients : from gut feeling towards evidence-based use in clinical practice

Elderly represent a substantial part of the colon cancer patients and this will increase even further in the near future due to demographic developments. This thesis provides a substantial contribution to the limited available evidence on the use and effectiveness of adjuvant chemotherapy among unselected elderly patients with stage III colon cancer treated in everyday clinical practice. It was shown that elderly derive comparable benefit from adjuvant chemotherapy as their younger counterparts, indicating that consideration of adjuvant chemotherapy is warranted for all patients. It was also shown that capecitabine monotherapy is better tolerated and less toxic, without limiting the recurrence-free and overall survival benefit, compared to a combination of capecitabine and oxaliplatin. Therefore, the addition of oxaliplatin should not be standard care for the majority of elderly stage III colon cancer patients treated in daily clinical practice

Modeling Personalized Adjuvant TreaTment in EaRly stage coloN cancer (PATTERN)

Aim: To develop a decision model for the population-level evaluation of strategies to improve the selection of stage II colon cancer (CC) patients who benefit from adjuvant chemotherapy. Methods: A Markov cohort model with a one-month cycle length and a lifelong time horizon was developed. Five health states were included; diagnosis, 90-day mortality, death other causes, recurrence and CC death. Data from the Netherlands Cancer Registry were used to parameterize the model. Transition probabilities were estimated using parametric survival models including relevant clinical and pathological covariates. Subsequently, biomarker status was implemented using external data. Treatment effect was incorporated using pooled trial data. Model development, data sources used, parameter estimation, and internal and external validation are described in detail. To illustrate the use of the model, three example strategies were evaluated in which allocation of treatment was based on (A) 100% adherence to the Dutch guidelines, (B) observed adherence to guideline recommendations and (C) a biomarker-driven strategy. Results: Overall, the model showed good internal and external validity. Age, tumor growth, tumor sidedness, evaluated lymph nodes, and biomarker status were included as covariates. For the example strategies, the model predicted 83, 87 and 77 CC deaths after 5 years in a cohort of 1000 patients for strategies A, B and C, respectively. Conclusion: This model can be used to evaluate strategies for the allocation of adjuvant chemotherapy in stage II CC patients. In future studies, the model will be used to estimate population-level long-term health gain and cost-effectiveness of biomarker-based selection strategies

Association of the location of pancreatic ductal adenocarcinoma (head, body, tail) with tumor stage, treatment, and survival: a population-based analysis

Background: The association between pancreatic ductal adenocarcinoma (PDAC) location (head, body, tail) and tumor stage, treatment and overall survival (OS) is unclear. Methods: Patients with PDAC diagnosed between 2005 and 2015 were included from the population-based Netherlands Cancer Registry. Patient, tumor and treatment characteristics were compared with the tumor locations. Multivariable logistic and Cox regression analyses were used. Results: Overall, 19,023 patients were included. PDAC locations were 13,451 (71%) head, 2429 (13%) body and 3143 (16%) tail. Differences were found regarding metastasized disease (head 42%, body 69%, tail 84%, p 4 cm: 21%, 40%, 51%, p <.001) and resection rate (17%, 4%, 7%, p <.001). For patients without metastases, median OS did not differ between head, body, tail (after resection: 16.8, 15.0, 17.3 months, without resection: 5.2, 6.1, 4.6 months, respectively). For patients with metastases, median OS differed slightly (2.6, 2.4, 1.9 months, respectively, adjusted HR body versus head 1.17 (95%CI 1.10–1.23), tail versus head 1.35 (95%CI 1.29–1.41)). Conclusions: PDAC locations in body and tail are larger, more often metastasized and less often resectable than in the pancreatic head. Whereas survival is similar after resection, survival in metastasized disease is somewhat less for PDAC in the pancreatic body and tail

Adjuvant chemotherapy is not associated with improved survival for all high-risk factors in stage II colon cancer

Adjuvant chemotherapy can be considered in high-risk stage II colon cancer comprising pT4, poor/undifferentiated grade, vascular invasion, emergency surgery and/or <10 evaluated lymph nodes (LNs). Adjuvant chemotherapy administration and its effect on survival was evaluated for each known risk factor. All patients with high-risk stage II colon cancer who underwent resection and were diagnosed in the Netherlands between 2008 and 2012 were included. After stratification by risk factor(s) (vascular invasion could not be included), Cox regression was used to discriminate the independent association of adjuvant chemotherapy with the probability of death. Relative survival was used to estimate disease-specific survival. A total of 4,940 of 10,935 patients with stage II colon cancer were identified as high risk, of whom 790 (16%) patients received adjuvant chemotherapy. Patients with a pT4 received adjuvant chemotherapy more often (37%). Probability of death in pT4 patients receiving chemotherapy was lower compared to non-recipients (3-year overall survival 91% vs. 73%, HR 0.43, 95% CI 0.28-0.66). The relative excess risk (RER) of dying was also lower for pT4 patients receiving chemotherapy compared to non-recipients (3-year relative survival 94% vs. 85%, RER 0.36, 95% CI 0.17-0.74). For patients with only poor/undifferentiated grade, emergency surgery or <10 LNs evaluated, no association between receipt of adjuvant chemotherapy and survival was observed. In high-risk stage II colon cancer, adjuvant chemotherapy was associated with higher survival in pT4 only. To prevent unnecessary chemotherapy-induced toxicity, further refinement of patient subgroups within stage II colon cancer who could benefit from adjuvant chemotherapy seems indicated

No change in lymph node positivity rate despite increased lymph node yield and improved survival in colon cancer

Contains fulltext : 139183.pdf (publisher's version ) (Closed access)AIM: To analyse trends over time in the number of lymph nodes evaluated and in the proportion of node positivity and to investigate the impact on survival for patients with colon cancer. PATIENTS AND METHODS: 8616 patients resected for M0 colon cancer diagnosed in the Southern Netherlands between 2000 and 2011 were included in this study. Trends in nodal evaluation and node positivity were analysed. Multivariable logistic regressions were used to assess the influence of period of diagnosis on adequate nodal evaluation (12lymph nodes) and node positivity after adjusting for patient and tumour characteristics. Crude 5-year relative survival was used as an estimate for disease-specific survival. RESULTS: Overall, the proportion adequate nodal evaluation increased from 13% in 2000-2002 to 59% in 2009-2011 (p<0.0001), whereas the proportion node positivity remained similar across study periods (approximately 35%). Patients diagnosed in later periods were more likely to have received adequate nodal yield (adjusted Odds ratio (OR) 2009-2011 versus 2000-2002 9.8, 95% Confidence interval (CI) 8.3-11.6). However, the adjusted odds of having node positive disease did not differ between periods of diagnosis. Relative excess risk of dying was independently correlated with the number of lymph nodes evaluated (1-8LNs versus 12LNs, N0: 2.2, 95% CI 1.7-2.9; N+: 1.7, 95% CI 1.4-2.0) and period of diagnosis (2009-2011 versus 2000-2002, N+ only: 0.8, 95% CI 0.6-1.0). CONCLUSION: The reason for improved survival with increased nodal yield is different from simple understaging as the proportion of lymph node positivity remained constant

Updated Incidence, Treatment and Survival of a Nationwide Cohort of Patients with Peritoneal Metastases of Unknown Origin

The aim of this study was to investigate the incidence, treatment and survival of patients with peritoneal metastases (PM) of unknown origin. All Dutch patients diagnosed in 2017 and 2018 with PM of unknown origin (PM-CUP) were evaluated. Data were extracted from the Netherlands Cancer Registry (NCR). Patients with PM-CUP were categorized into the following histological subtypes: 1) adenocarcinoma, 2) mucinous adenocarcinoma, 3) carcinoid, 4) unspecified carcinoma and 5) other. Treatments were compared between the different histological subtypes in patients with PM-CUP. Overall survival (OS) was calculated using the Kaplan-Meier method for all patients with cancer of unknown origin and between histological subtypes in patients with PM-CUP. Significant differences in OS were assessed by using the log-rank test. In total, 3026 patients were diagnosed with cancer of unknown origin, 513 (17%) among them were diagnosed with PM-CUP. Most PM-CUP patients received best supportive care only (76%), whereas 22% received systemic treatment and 4% underwent metastasectomy. Median OS was 1.1 months for all patients with PM-CUP but varied from 0.6 months to 30.5 months depending on the underlying histology. In this study, PM-CUP were diagnosed in 17% of all patients with cancer of unknown primary and the reported survival in this cohort was extremely poor. Since survival differed among histological subtypes and recently more treatment options became available for a selected group of patients with peritoneal malignancies, it is of great importance to identify the histology of the metastases and whenever possible the primary tumor