Cancer dormancy and criticality from a game theory perspective

The presence of driver mutations and subsequent clonal expansion by Darwinian evolution does not explain dormancy and re-emergence of cancer from a community of cancer and host cells (including stromal and immune cells). Dormancy appears to be a slow-driven, interaction-dominated, threshold system which is poorly prognosed. At the simplest level, we view cancer cells interacting with host cells via complex, non-linear population dynamics, which can lead to very non-intuitive but perhaps deterministic and understandable progression dynamics of cancer. We explore here the dynamics of host-cancer cell populations in the presence of (1) payoffs gradients and (2) perturbation due to cell migration to determine to what extent the time-dependence of the populations can be quantitatively understood in spite of the underlying complexity of the individual agents. The population dynamics presented here provide a model system for the clinic to map the payoffs matrices and suggest new avenues to predict drug dosages. Citation Format: Robert H. Austin. Game theory and personalized cancer treatment. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA04.

e24062 Background: Our aim was to determine the frequency of health-related problems faced by breast cancer patients before and six months after the initiation of breast cancer treatment. Methods: This prospective study involved 600 female breast cancer patients (26-65 years, mean 52), who participated in the pilot study in the novel individualized integrated rehabilitation programme in 2019-2022 and were followed for at least six months. The patients completed three questionnaires (EORTC QLQ - C30, B23 and NCCN) before the initiation of cancer treatment and six months after. The patients received neoadjuvant chemotherapy in 22% of the cases, tumorectomy in 53%, mastectomy in 39%, breast reconstruction in 27%, sentinel node biopsy in 67%, lymphadenectomy in 23%, external beam radiotherapy in 73%, chemotherapy in 45%, anti-HER-2 therapy in 11% and hormonal therapy in 74% of the cases. Data on the patients’ demographics, disease extent, cancer treatment and problems reported in the questionnaires were collected and analysed using descriptive analysis. Results: The problems reported by patients before the initiation of cancer treatment and after six months are presented in Table. In 14 out of 22 parameters, the frequency of problems increased in the six months after the initiation of treatment: fatigue, insomnia, lymphedema, shoulder movement impairment, disturbing scars, heart problems, hot flashes/sweating, gynaecological problems, sexual problems, body image worries, inappropriate nutrition, pain in the shoulder or arm, alopecia and concerns about returning to work. On the other hand, the frequency of problems decreased six months after the initiation of cancer treatment in 6 out of 22 parameters. Our patients less often had depression or anxiety, were too little physically active, smoked, consumed alcohol or used food supplements than before. Conclusions: Six months after the initiation of breast cancer treatment patients have more problems than at the time before treatment.[Table: see text]

Patients report strong preferences regarding which provider-oncologist or primary care provider (PCP)-handles their primary care after initial cancer treatment (eg, other cancer screenings, preventive care, comorbidity management). Little is known about associations between provider involvement during initial cancer treatment and patient preferences for provider roles after initial treatment. Women who received a diagnosis of early-stage breast cancer in 2014 to 2015 were identified from the Georgia and Los Angeles County SEER registries and surveyed (N = 2,502; 68% response rate). Women reported the level of their providers' involvement in their care during initial cancer treatment. Associations between level of medical oncologist's participation and PCP's engagement during initial cancer treatment and patient preferences for oncologist led ( v PCP led) other cancer screenings after initial treatment were examined using multivariable logistic regression models. During their initial cancer treatment, 20% of women reported medical oncologists participated substantially in delivering primary care and 66% reported PCPs were highly engaged in their cancer care. Two-thirds (66%) of women preferred medical oncologists to handle other cancer screenings after initial treatment. Women who reported substantial medical oncologist participation in primary care were more likely (adjusted odds ratio, 1.42; 95% CI, 1.05 to 1.91) and those who reported high PCP engagement in cancer care were less likely (adjusted odds ratio, 0.41; 95% CI, 0.31 to 0.53) to prefer oncologist-led other cancer screenings after initial treatment. Providers' involvement during initial cancer treatment may affect patient preferences regarding provision of follow-up primary care. Clarifying provider roles as early as during cancer treatment may help to better delineate their roles throughout survivorship.

To examine the association between types of chronic conditions combinations and initial cancer treatment among elderly Medicare beneficiaries with localised prostate cancer. A population-based retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. The study cohort consisted of elderly men (≥ 66 years) with localised prostate cancer diagnosed between 2002 and 2009 (N = 98,264). The initial cancer treatment received during the 6 months after cancer diagnosis consisted of (i) radical prostatectomy (RP); (ii) radiation therapy (RT); (iii) hormone therapy; and (iv) no treatment. Pre-existing chronic conditions were classified into the following eight groups: (i) only cardiometabolic conditions (CM); (ii) only mental health conditions (MH); (iii) only respiratory conditions (RESP); (iv) CM and MH; (v) CM and RESP; (vi) MH and RESP; (vii) all three conditions, CM, MH and RESP; and (viii) none of the three types of conditions. Only 20% did not receive any cancer treatment; 47.4%, 22.1% and 10.5% received RT, RP, and hormone therapy, respectively. In multinomial logistic regression, elderly men with only RESP were more likely to receive RP as compared with those with all the three types of chronic conditions; those with only CM, only RESP, CM and MH or CM and RESP were more likely to receive RT. No significant associations were observed between the receipt of hormone therapy and types of chronic conditions. A significant proportion of elderly men with chronic conditions have received aggressive initial cancer treatment. Our study findings suggest a conservative approach for the initial prostate cancer treatment among elderly men with significant chronic conditions and localised prostate cancer.

Nonlinear dynamics, where a change in the input is not proportional to a change in the output, are often found throughout nature, for example in biochemical kinetics. Because of the complex suite of interacting abiotic and biotic variables present in ecosystems, animal population dynamics are often thought to be driven in a nonlinear, state-dependent fashion. However, so far these have only been identified in model organisms and some natural systems. Here we show that nonlinear population dynamics are ubiquitous in nature. We use nonlinear forecasting to analyse 747 datasets of 228 species to find that insect population trends were highly nonlinear (74%), followed by mammals (58%), bony fish (49%) and birds (35%). This indicates that linear, equilibrium-based model assumptions may fail at predicting population dynamics across a wide range of animal taxa. We show that faster-reproducing animals are more likely to have nonlinear and high-dimensional dynamics, supporting past ecological theory. Lastly, only a third of time series were predictable beyond two years; therefore, the ability to predict animal population trends using these methods may be limited. Our results suggest that the complex dynamics necessary to cause regime shifts and other transitions may be inherent in a wide variety of animals.

Mammalian cell proliferation depends essentially on intercellular interactions, provision of humoral growth regulators, and attachment to the extracellular growth substrate. In order to be able to control and manipulate separately these essential interactions of the cell with its environment, profitable use has been made of culturing mammalian cells in vitro. If the cells are cultured in vitro on a defined and reproducible growth substrate, and fresh medium containing humoral growth factors is supplied sufficiently often, the external environment of the cell population may be approximated as constant. Under these conditions, the population dynamics of the cells in a good approximation may be considered as determined by intercellular interactions [1]. Taking a more general view, the systems considered presently are composed of (largely) identical subunits (the cells), which can exist in different states, the balance of subsystems in these different states being determined by a constant influx of energy (here: of nutrients and growth factors), as well as by effects of specific interactions between the sub-units. Systems of this general nature are encountered in very different fields of physics, chemistry, biology, and sociology [2]. Due to the interactions between subunits, such systems often exhibit quite interesting population dynamics, which in many cases can be described quantitatively by theoretical approaches resembling each other, and are the subject of a new field termed “synergetics” [2]. In this sense, the nonlinear population dynamics studied here and in earlier work [1,3] may be designated as “cellular synergetics”.KeywordsSaturation DensityMedium RenewalNewborn Calf SerumIntercellular InteractionCompetence FactorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

BackgroundBreast cancer is the most frequent and fatal cancer type globally. The fatality rate of breast cancer is mostly due to disease complications like hematological alterations. Therefore, this study aimed to assess the hematological abnormalities before, during, and after the initiation of cancer treatment in breast cancer patients at the University of Gondar comprehensive specialized hospital.MethodologyHematological profiles were collected from 267 breast cancer patients who attended the cancer treatment center from September 2017 to August 2021. A data extraction sheet was used to extract data from the patient’s medical chart, including sociodemography, clinical, and hematological profiles. EPI info version 3.5.1 and SPSS Version 25 softwares were used for data entrance and analysis, respectively. Descriptive statistics were summarized using frequency and percentage. The Friedman test followed by a Wilcoxon signed rank test was used to compare the mean difference between the hematological profiles at zero and after the 4th and 8th cycles of treatment.ResultOf the total participants, 91% were females, and the median age of the study participants was 45 (IQR = 36, 55) years. Red blood cell, white blood cell, and lymphocyte counts, as well as hematocrit and hemoglobin values, were significantly reduced after the initiation of cancer treatment, while the platelet count and red cell distribution width were significantly increased. The prevalence of anemia was 21.7% (95% CI: 16.6, 26.8), 22.7% (95% CI: 17.6, 27.8), and 26.4% (95% CI: 21.3, 31.5) before, during, and after the initiation of cancer treatment, respectively. The prevalence of leukopenia before, during, and after treatment was 9.7%, 18.8%, and 15.1%, respectively. Finally the prevalence of thrombocytopenia was 6.3%, 3.4%, and 8% at before, during, and after treatment, respectively.ConclusionThis study concluded that many hematological parameters were significantly affected by the breast cancer treatment. Therefore, proper patient follow-up and provide appropriate interventions related to their hematological abnormalities is crucial. It is also important to conduct further prospective studies to confirm the findings of this study.

BackgroundThe lac operon genetic switch is considered as a paradigm of genetic regulation. This system has a positive feedback loop due to the LacY permease boosting its own production by the facilitated transport of inducer into the cell and the subsequent de-repression of the lac operon genes. Previously, we have investigated the effect of stochasticity in an artificial lac operon network at the single cell level by comparing corresponding deterministic and stochastic kinetic models.ResultsThis work focuses on the dynamics of cell populations by incorporating the above kinetic scheme into two Monte Carlo (MC) simulation frameworks. The first MC framework assumes stochastic reaction occurrence, accounts for stochastic DNA duplication, division and partitioning and tracks all daughter cells to obtain the statistics of the entire cell population. In order to better understand how stochastic effects shape cell population distributions, we develop a second framework that assumes deterministic reaction dynamics. By comparing the predictions of the two frameworks, we conclude that stochasticity can create or destroy bimodality, and may enhance phenotypic heterogeneity.ConclusionsOur results show how various sources of stochasticity act in synergy with the positive feedback architecture, thereby shaping the behavior at the cell population level. Further, the insights obtained from the present study allow us to construct simpler and less computationally intensive models that can closely approximate the dynamics of heterogeneous cell populations.

According to the National Cancer Plan in Germany, all cancer patients should receive high-quality care in accordance with evidence-based treatment guidelines. Certification programs were established for this purpose but have not yet been comprehensively evaluated. In the WiZen project, which was supported by the Innovation Fund (supported project number 01VSF17020), controlled cohort studies were performed to investigate whether initial treatment in hospitals with or without a certificate from the German Cancer Society was associated with a difference in overall survival (primary endpoint) in patients with cancer of the colon, rectum, lung, pancreas, breast, cervix, prostate, endometrium, and ovary, head and neck cancer, and neuro-oncological tumors. The studies were based on nationwide data from adult insurees of the AOK statutory health insurance carrier for the years 2009-2017. The majority of patients with all entities except breast cancer received their initial treatment in non-certified hospitals. Initial treatment in a certified hospital was found to be beneficial in terms of overall survival for all cancer entities, even after extensive adjustment for patient- and hospital-related confounders. The hazard ratio (HR) ranged from 0.97 (95% CI: [0.94; 1.00]) for lung cancer to 0.77 [0.74; 0.81] for breast cancer, corresponding to an absolute risk reduction (ARR) for overall survival of 0.62 months for lung cancer to 4.61 months for cervical cancer. The WiZen study shows for the entities studied that initial cancer treatment in a certified center is associated with lower mortality. Despite the recommendations of the National Cancer Plan, however, more than 40% of all cancer patients still receive their initial treatment in a non-certified hospital. The preferential provision of initial care in certified hospitals would be likely to improve overall survival. Although the study design does not permit any conclusion with regard to causality, the findings seem robust considering that a control group was used, confounders were taken into account, and the study population was of large size.

Purpose: Prostate cancer death rates are higher in blacks than whites. Using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database, we evaluated whether racial disparities exist in the receipt of initial prostate cancer treatment. Methods: We analyzed data on prostate cancer cases diagnosed in 2004-2009 and linked with Medicare claims data from 2003-2010. We focused on cases with SEER race coded as white or black; and enrolled in both Medicare Parts A and B continuously during 12 months before diagnosis to 24 months after diagnosis, death, or December 2010, whichever was earliest. We defined prostate cancer recurrence risk categories using tumor stage, prostate specific antigen (PSA), and Gleason scores. We identified initial prostate cancer treatment using: radical prostatectomy, radiation therapy, or androgen deprivation therapy within 1 month before to 6 months after diagnosis; or evidence of active surveillance based on prostate biopsies or PSA tests from 1 to 18 months after diagnosis. We used multivariate logistic regression to determine adjusted odds ratios (OR) and 95% confidence intervals (CI). The outcome variable was receipt of initial treatment. Explanatory variables were: race; prostate cancer disease recurrence risk category; asymptomatic or symptomatic at time of first diagnosis; life expectancy from the man's age at diagnosis; comorbidity; census tract poverty; and census region. Results: Our final study cohort included 70,254 white men and 8,653 black men with prostate cancer. After adjustment for multiple variables, men were less likely to receive initial treatment if: expected survival < 5 years (OR, 0.36; 95% CI, 0.33–0.40; ref.= > 10 years); black race (OR, 0.54; 95% CI, 0.50–0.57; ref. = white); or symptomatic at time of diagnosis (OR, 0.77, 95% CI, 0.74–0.81; ref.=asymptomatic). Men were more likely to receive initial treatment if: high recurrence risk (OR, 2.75; 95% CI, 2.55–2.96; ref.= low); resided in Northeast (OR, 1.30; 95% CI 1.24–1.38; ref.= West); comorbidity score > 2 (OR, 1.24; 95% CI, 1.17–1.31; ref. = 0); or lived in a census tract with <5% poverty (OR, 1.14; 95% CI, 1.07–1.22; ref.= > 19%). Conclusion: Low expected survival and black race were relatively important reasons that older men did not receive initial treatment for prostate cancer. Citation Format: Thomas B. Richards, Serban Negoita, Timothy S. McNeel, Jun Li, Chunyu Li. Racial disparities in receipt of initial prostate cancer treatment, SEER Medicare, 2004-2009. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C55. doi:10.1158/1538-7755.DISP13-C55

As an important tool of urban public works evaluation and a result of redistribution of public interests and private interests after power game between each evaluating subject of urban public works, it focus on comprehensive evaluation of urban public works benefits. Owing to complicated relations of each evaluating subject' interests of urban public works and unequal power positions of each subject, a game between groups of high power positions and that of low power positions occurs and results in distorting behavior of urban public works evaluation so that urban public works supply is lacked or excess meanwhile urban public interest is eroded. This paper suggests that some institutional evaluating indexes should be added into the current normal indexes of urban public works evaluation from the perspective of game theory; and points out that mathematical evaluating model of urban public works could be improved based on those new evaluating indexes, consequently, bias conclusion of urban public works evaluation caused by the power game could be corrected. The innovation of this paper is that it attempts to evaluating urban public works from the perspective of power game theory, and then to design some new evaluating indicators of evaluating institutions of urban public works, and finally to establish a better mathematical evaluation model.

The aim was to compare self-rated independence in childhood cancer survivors 5 years after diagnosis with corresponding ratings during initial cancer treatment and those in a comparison group. A further aim was to determine whether and how certain clinical and demographic variables affected self-rated independence. Self-rated independence, a dimension included in the health-related quality of life (HRQoL) measure DISABKIDS Chronic Generic Measure (DCGM-37), was assessed in a Swedish cohort of survivors (n = 63, aged 12-22 years) and compared with ratings during initial cancer treatment and those in an age-matched comparison group (n = 257). Potential predictors of self-rated independence were estimated using multiple regression analysis. Survivors rated their independence significantly higher 5 years after diagnosis than during initial cancer treatment and higher than the comparison group. Neither demographic nor clinical variables (age, sex, diagnosis, initial cancer treatment) predicted self-rated independence 5 years post diagnosis. Five years after diagnosis, survivors of childhood cancer appear to have reached a satisfactory level of independence. However, survivors are likely to experience complications over the longer term, and therefore continued follow-up is warranted to follow possible changes in self-reported independence.

Robust analyses of noisy, stage-structured, irregularly spaced, field-scale data incorporating multiple sources of variability and nonlinear dynamics remain very limited, hindering understanding of how small-scale studies relate to large-scale population dynamics. We used a novel, complementary Bayesian and frequentist state-space model analysis to ask how density, temperature, plant nitrogen, and predators affect cotton aphid (Aphis gossypii) population dynamics in weekly data from 18 field-years and whether estimated effects are consistent with small-scale studies. We found clear roles of density and temperature but not of plant nitrogen or predators, for which Bayesian and frequentist evidence differed. However, overall predictability of field-scale dynamics remained low. This study demonstrates stage-structured state-space model analysis incorporating bottom-up, top-down, and density-dependent effects for within-season (nearly continuous time), nonlinear population dynamics. The analysis combines Bayesian posterior evidence with maximum-likelihood estimation and frequentist hypothesis testing using average one-step-ahead residuals.

Purpose To develop multi-compartment mechanistic models of dynamics of stem and functional cell populations in epithelium after irradiation. Methods and materials: We present two models, with three (3C) and four (4C) compartments respectively. We use delay differential equations, and include accelerated proliferation, loss of division asymmetry, progressive death of abortive stem cells, and turnover of functional cells. The models are used to fit experimental data on the variations of the number of cells in mice mucosa after irradiation with 13 Gy and 20 Gy. Akaike information criteria (AIC) was used to evaluate the performance of each model. Results Both 3C and 4C models provide good fits to experimental data for 13 Gy. Fits for 20 Gy are slightly poorer and may be affected by larger uncertainties and fluctuations of experimental data. Best fits are obtained by imposing constraints on the fitting parameters, so to have values that are within experimental ranges. There is some degeneration in the fits, as different sets of parameters provide similarly good fits. Conclusions The models provide good fits to experimental data. Mechanistic approaches like this can facilitate the development of mucositis response models to nonstandard schedules/treatment combinations not covered by datasets to which phenomenological models have been fitted. Studying the dynamics of cell populations in multifraction treatments, and finding links with induced toxicity, is the next step of this work.

Social science disciplines have used decision theory and game theory to provide metaphorical understanding and analytical rigour in their particular domains. The paper explores whether a similar perspective can be applied to operational research (OR) in order to provide an integrating theme for both theory and practice. It is argued that, while the methods of OR are instrumentally rational, OR interventions embrace non-instrumental aspects as well. A case study of an application of decision theory is described and analysed from a decision and game theory (DGT) perspective. The case demonstrates that although the model developed was instrumental, the structure and content of the model reflected the normative and communicative aspects of the decision context. The paper concludes that OR could use a DGT perspective as a conceptual framework for the teaching, research and practice of OR.