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Simple Summary: Neuroblastoma is a rare type of cancer that usually affects children. The high-risk patients' expected survival rate is less than 50%. One reason is the lack of precision in the standard treatment protocol: a one-size-fits-all multi-modal therapy. The study presented in this paper was designed to address this deficit by optimising the use of two chemotherapeutic agents—vincristine and cyclophosphamide—during induction chemotherapy—the part of the protocol that shrinks the primary tumour before surgical removal. We combined a mathematical model and an optimisation algorithm to identify the best chemotherapy schedules for a cohort of virtual patients with different initial tumour compositions. Our results reveal novel strategies to exploit a pair of drugs with different levels of efficacy, provide a platform on which to individualise induction chemotherapy, and lay the foundation for a personalised therapy that leverages targeted therapies, multi-region sequencing, liquid biopsies, and modern computational methods to improve today's multi-modal therapy. Neuroblastoma is the most common extra-cranial solid tumour in children. Despite multi-modal therapy, over half of the high-risk patients will succumb. One contributing factor is the one-size-fits-all nature of multi-modal therapy. For example, during the first step (induction chemotherapy), the standard regimen (rapid COJEC) administers fixed doses of chemotherapeutic agents in eight two-week cycles. Perhaps because of differences in resistance, this standard regimen results in highly heterogeneous outcomes in different tumours. In this study, we formulated a mathematical model comprising ordinary differential equations. The equations describe the clonal evolution within a neuroblastoma tumour being treated with vincristine and cyclophosphamide, which are used in the rapid COJEC regimen, including genetically conferred and phenotypic drug resistance. The equations also describe the agents' pharmacokinetics. We devised an optimisation algorithm to find the best chemotherapy schedules for tumours with different pre-treatment clonal compositions. The optimised chemotherapy schedules exploit the cytotoxic difference between the two drugs and intra-tumoural clonal competition to shrink the tumours as much as possible during induction chemotherapy and before surgical removal. They indicate that induction chemotherapy can be improved by finding and using personalised schedules. More broadly, we propose that the overall multi-modal therapy can be enhanced by employing targeted therapies against the mutations and oncogenic pathways enriched and activated by the chemotherapeutic agents. To translate the proposed personalised multi-modal therapy into clinical use, patient-specific model calibration and treatment optimisation are necessary. This entails a decision support system informed by emerging medical technologies such as multi-region sequencing and liquid biopsies. The results and tools presented in this paper could be the foundation of this decision support system. [ABSTRACT FROM AUTHOR]

Simple Summary: A significant proportion of people with cancer use forms of complementary medicine. Many factors contribute to cancer including some which are modifiable by the patient, such as stress, poor nutrition, vitamin D deficiency, poor sleep and lack of physical activity. This paper discusses why it is important that oncologists help cancer patients to address such factors, and why an integrative approach which combines evidence-based complementary medicines or therapies with orthodox treatment might lead to better outcomes for cancer patients. A significant proportion of cancer patients use forms of complementary medicine or therapies. An integrative approach to cancer management combines conventional medicine with evidence-based complementary medicines/therapies and lifestyle interventions, for the treatment and prevention of disease and the optimisation of health. Its basis is a holistic one; to treat the whole person, not just the disease. It makes use of adjunct technologies which may assist the clinician in diagnosis of early carcinogenesis and monitoring of treatment effectiveness. Many factors contribute to the development of cancer including some which are largely modifiable by the patient and which oncologists may be in a position to advise on, such as stress, poor nutrition, lack of physical activity, poor sleep, and Vitamin D deficiency. An integrative approach to addressing these factors may contribute to better overall health of the patient and better outcomes. Evidence-based complementary medicine approaches include the use of supplements, herbal medicine, various practices that reduce stress, and physical therapies. Individualised to the patient, these can also help address the symptoms and signs associated with cancer and its orthodox treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Complementary and alternative medicine (CAM) therapies include a wide range of procedures and products that are often used by cancer patients to directly combat cancer and to protect normal cells from the toxic effects of conventional therapies. Most often, their use is self-prescribed based on a collection of scattered information from websites and advice from relatives or friends. In this paper, we examined the potential known benefits and harms associated with the most commonly used alternative treatments to provide a practical guide for caregivers and patients. CAM is used by about 40% of cancer patients in Western Countries, with peaks of 80% for breast cancer patients. Cancer patients use CAM to boost immune function, to control cancer symptoms and treatment-related side effects, and to improve health-related quality of life (HR-QoL) and survival. Unfortunately, self-prescription of natural remedies in cancer patients can lead to unexpected toxicities and can reduce the effectiveness of cancer therapy. Although CAM usually refers to all the "natural or organic" products/methods that are generally considered less toxic, there are concerns about drug interactions, especially in patients participating in clinical trials with experimental agents. Despite the claims of the promising and potential benefits made by prescribers, many CAMs lack clear scientific evidence of their safety and efficacy. Given the widespread use of CAM—both clearly declared and overt—in this review, we focused on the most important known data on the risk of interactions between biologics and oncology drugs with the goal of opening up CAM in accordance with the meaning of integrative medicine. [ABSTRACT FROM AUTHOR]