Evolutionary therapy (ET) applies principles of evolutionary biology to steer tumour dynamics and forestall or delay treatment resistance, typically guided by data-driven mathematical models. Our aim is to assess whether ET protocols, and specifically Zhang et al.’s protocol proposed for metastatic castrate-resistant prostate cancer, can be theoretically effective for fast-growing metastatic cancers such as stage IV non-small-cell lung cancer (NSCLC). Using longitudinal tumour-burden data from NSCLC patients treated with erlotinib, we systematically evaluate 26 two-population differential-equation models based on classical tumour-growth dynamics, with varying assumptions about density- and frequency-dependent interactions, pharmacokinetics, and treatment-induced death. Previous work by Yin et al. on the same dataset employed an exponential model that omitted density- and frequency-dependent interactions; although it provided a good fit to tumour-burden data, its structure would theoretically lead to poorer outcomes under ET protocols. In contrast, our analysis identifies the minimal model structure required to reproduce the resistance-driven regrowth observed in NSCLC, with the Gompertzian model featuring log-kill dynamics and both density- and frequency-dependent interactions providing the best fit. In this model, Zhang et al.’s protocol prolonged median time-to-progression to 42.3 months compared with 24.8 months under maximum tolerated dose. These results indicate that ET is theoretically a viable treatment strategy for NSCLC. This study offers a practical framework for assessing ET feasibility using clinical data and supports future clinical translation of ET in NSCLC.

Evolutionary cancer therapy (ECT) delays or forestalls the progression of metastatic cancer by adjusting treatment based on individual patient and disease characteristics. Clinical implementation of ECT can improve patient outcomes but faces technical and cultural challenges. To address those, we propose a systems approach incorporating systems modeling, problem structuring, and stakeholder engagement. This approach identifies and addresses barriers to implementation, ensuring the feasibility of ECT in clinical practice and enabling better metastatic cancer care.

Background: Physicians have complex and demanding jobs that may negatively affect their sustainable employability (SE) and quality of care. Despite its societal and occupational relevance, empirical research on physicians’ SE is scarce. To further advance our understanding of physicians’ SE, this study explores how physicians perceive their employment context to affect their SE, how physicians self-regulate with the intent to sustain their employability, and how self-regulations affect physicians’ SE and their employment context. Methods: Twenty Dutch physicians from different specialisms were narratively interviewed between March and September 2021 by a researcher with a similar background (surgeon) to allow participants to speak in their own jargon. The interviews were analyzed collaboratively by the research team in accordance with theory-led thematic analysis. Results: According to the interviewees, group dynamics, whether positive or negative, and (mis)matches between personal professional standards and group norms on professionalism, affect their SE in the long run. Interviewees self-regulate with the intent to sustain their employability by (I) influencing work; (II) influencing themselves; and (III) influencing others. Interviewees also reflect on long-term, unintended, and dysfunctional consequences of their self-regulations. Conclusions: We conclude that physicians’ SE develops from the interplay between the employment context in which they function and their self-regulations intended to sustain employability. As self-regulations may unintentionally contribute to dysfunctional work practices in the employment context, there is a potential for a vicious cycle. Insights from this study can be used to understand and appraise how physicians self-regulate to face complex challenges at work and to prevent both dysfunctional work practices that incite self-regulation and dysfunctional consequences resulting from self-regulations.

Background Surgical resection with restoration of bowel continuity is the cornerstone of treatment for patients with colonic cancer. The aim of this study was to identify risk factors for anastomotic leakage (AL) and subsequent death after colonic cancer surgery. Methods Data were retrieved from the Dutch Surgical Colorectal Audit. Patients undergoing colonic cancer resection with creation of an anastomosis between January 2009 to December 2011 were included. Outcomes were AL requiring reintervention and postoperative mortality following AL. Results AL occurred in 7·5 per cent of 15 667 patients. Multivariable analyses identified male sex, high American Society of Anesthesiologists (ASA) fitness grade, extensive tumour resection, emergency surgery, and surgical resection types such as transverse resection, left colectomy and subtotal colectomy as independent risk factors for AL. A defunctioning stoma was created in a small group of patients, leading to a lower risk of leakage. The mortality rate was 4·1 per cent overall, and was significantly higher in patients with AL than in those without leakage (16·4 versus 3·1 per cent; P < 0·001). Multivariable analyses identified older age, high ASA grade, high Charlson score and emergency surgery as independent risk factors for death after AL. The adjusted risk of death after AL was twice as high following right compared with left colectomy. Conclusion The elderly and patients with co-morbidity have a higher risk of death after AL. Accurate preoperative patient selection, intensive postoperative surveillance for AL, and early and aggressive treatment of suspected leakage is important, especially in patients undergoing right colectomy.

Background Due to changes in staging, (neo)-adjuvant treatment and surgical techniques for colorectal cancer (CRC), it is expected that the recurrence pattern will change as well. This study aims to report the current incidence of, and time to recurrent disease (RD), further the localization(s) and the eligibility for successive curative treatment. Methods A consecutive cohort of CRC patients, whom were routinely staged with CT and underwent curative treatment according to the national guidelines, was analyzed (n = 526). Results After a mean and median FU of 39 months, 20% of all patients and 16% of all AJCC stage 0-III patients had developed RD. The annual incidences were the highest in the first two years but tend to retain in the succeeding years for stage 0-III patients. The majority of RD was confined to one organ (58%) and 28% of these patients were again treated with curative intent. Conclusions In follow-up nowadays, less recurrences are found than reported in historical studies but these can more often be treated with curative intent. A main cause for the decreased incidence of RD, next to improvements in treatment, is probably stage shift elicited by pre-operative staging. The outcomes support continuation of follow-up in colorectal cancer.

Background: The present paper is a first evaluation of the use of "CEAwatch", a clinical support software system for surgeons for the follow-up of colorectal cancer (CRC) patients. This system gathers Carcino-Embryonic Antigen (CEA) values and automatically returns a recommendation based on the latest values. Methods. Consecutive patients receiving follow-up care for CRC fulfilling our in- and exclusion criteria were identified to participate in this study. From August 2008, when the software was introduced, patients were asked to undergo the software-supported follow-up. Safety of the follow-up, experiences of working with the software, and technical issues were analyzed. Results: 245 patients were identified. The software-supported group contained 184 patients; the control group contained 61 patients. The software was safe in finding the same amount of recurrent disease with fewer outpatient visits, and revealed few technical problems. Clinicians experienced a decrease in follow-up workload of up to 50% with high adherence to the follow-up scheme. Conclusion: CEAwatch is an efficient software tool helping clinicians working with large numbers of follow-up patients. The number of outpatient visits can safely be reduced, thus significantly decreasing workload for clinicians.

Background: Advanced colorectal cancer (CRC), either locally advanced, metastasized (mCRC) or both, is present in a relevant proportion of patients. The chances on curation of advanced CRC are continuously improving with modern multi-modality treatment options. For incurable CRC the focus lies on palliation of symptoms, which is not necessarily a resection of the primary tumor. Both situations motivate adequate staging before treatment in CRC. This prospective observational study evaluates the outcomes after the introduction of routine staging with abdominal CT before treatment.Methods: In a prospective observational study of 612 consecutive patients (2007-2009), the ability of abdominal CT to find liver metastases (LM), peritoneal carcinomatosis (PC) and T4 stage in colon cancer (CC) was analysed.Results: Advanced CRC was present in 58% of patients, mCRC in 31%. The ability to find LM was excellent (99%), cT4 stage CC good (86%) and PC poor (33%). In the group of surgical patients with emergency presentations, the incidences of both mCRC (51%) and locally advanced colon cancer (LACC) (69%) were higher than in the elective group (20% and 26% respectively). Staging tended to be omitted more often in the emergency group (35% versus 12% in elective surgery).Conclusions: The strengths of staging with abdominal CT are to find LM and LACC, however it fails in diagnosing PC. On grounds of the incidence of advanced CRC, staging is warranted in patients with emergency presentations as well.

Following curative treatment for colorectal cancer (CRC), 30% to 50% of patients will develop recurrent disease. For CRC there are several lines of evidence supporting the hypothesis that early detection of meta chronous disease offers a second opportunity for cure. This paper revisits the potential role of serum carcinoem bryonic antigen (CEA) in follow-up. A comprehensive review of the literature (1978-2008) demonstrates that the initial promise of serum CEA as an effective surveillance tool has been tarnished through perpetuation of poorly designed studies. Specific limitations included: testing CEA as only an 'add-on' diagnostic tool; lack of standardization of threshold values; use of static thresholds; too low measurement frequency. Major changes in localizing imaging techniques and treatment of metastatic CRC further cause a decrease of clinical applicability of past trial outcomes. In 1982, Staab hypothesized that the optimal benefit of serum CEA as a surveillance tool is through high-frequency triage using a dynamic threshold (HiDT). Evidence supporting this hypothesis was found in the biochemical characteristics of serum CEA and retrospective studies showing the superior predictive value of a dynamic threshold. A multi-centred randomized phase III study optimizing the usage of HiDT against resectability of recurrent disease is commencing recruitment in the Netherlands.