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