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Simple Summary: There is a large gap in knowledge amongst the oncology community of moderate hyperthermia use in cancer management. This review provides an overview of clinical data on the use of loco-regional and superficial hyperthermia in the adjunct management of cancers. It is updated using higher-level evidence from prospective, comparative studies and meta-analyses. The methodology and results are summarised and tabulated according to tumour type for easy reference. Regional hyperthermia therapy (RHT) is a treatment that applies moderate heat to tumours in an attempt to potentiate the effects of oncological treatments and improve responses. Although it has been used for many years, the mechanisms of action are not fully understood. Heterogenous practices, poor quality assurance, conflicting clinical evidence and lack of familiarity have hindered its use. Despite this, several centres recognise its potential and have adopted it in their standard treatment protocols. In recent times, significant technical improvements have been made and there is an increasing pool of evidence that could revolutionise its use. Our narrative review aims to summarise the recently published prospective trial evidence and present the clinical effects of RHT when added to standard cancer treatments. In total, 31 studies with higher-quality evidence across various subsites are discussed herein. Although not all of these studies are level 1 evidence, benefits of moderate RHT in improving local tumour control, survival outcomes and quality of life scores were observed across the different cancer subsites with minimal increase in toxicities. This paper may serve as a reference when considering this technique for specific indications. [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]

Simple Summary: The recent approval of [177Lu]Lu-prostate-specific membrane antigen (PSMA) for managing metastatic castration-resistant prostate cancer (mCRPC) has catalyzed the innovation of various PSMA-targeted radiopharmaceuticals. In our retrospective study, we explored both safety and efficacy of two beta-emitting PSMA radioligands, [177Lu]Lu and [161Tb]Tb, for mCRPC therapy. Our study included 53 patients and reinforced prior evidence validating the clinical safety and efficacy of these radioligands. Our research suggested that these treatments are characterized by a favorable safety profile with negligible toxicity. Moreover, [161Tb]Tb-PSMA recipients, though trialed in a smaller patient sample, yielded concordant outcomes on par with those receiving [177Lu]Lu-PSMA, highlighting its promise as an alternative therapy and warrants additional investigation. The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [177Lu]Lu and [161Tb]Tb, in heavily treated patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 148 cycles of beta-emitting PSMA radioligand therapy were given to 53 patients at a specialized cancer care center in Amman, Jordan. This treatment was offered following the exhaustion of all prior treatment modalities. Approximately half of the cases (n = 26) demonstrated an initial partial response to PSMA radioligand therapy. Moreover, roughly one-fourth of the patients (n = 13) exhibited a sustained satisfactory biochemical response, which qualified them to receive a total of six PSMA radioligand therapy cycles and maintain continued follow-up for additional treatment cycles. This was reflected by an adequate prostate-specific antigen (PSA) decline and a concomitant partial response evident on [68Ga]Ga-PSMA positron emission tomography/computed tomography imaging. A minority of patients (n= 18; 34%) experienced side effects. Generally, these were low-grade and self-limiting toxicities. This study endorses previous research evidence about PSMA radioligand therapy's safety and efficacy. It also provides the first clinical insight from patients of Arab ethnicity. This should facilitate and promote further evidence, both regionally and internationally. [ABSTRACT FROM AUTHOR]

Simple Summary: Pseudomyxoma peritonei (PMP) is a rare disease and has, thus, been the focus of relatively few studies in the field of digestive system research. Even experts and scholars in this field have certain deficiencies in their understanding of the disease. Although the standard treatment of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved patient prognosis, problems such as the difficulty of operation, tumor recurrence, single treatment method, and poor quality of life cannot be properly solved. This review mainly examines the progress of biological research and the existing or potential treatment strategies in relation to pseudomyxoma peritonei. It is expected to help scholars in related fields to understand the disease and provide potential directions for research into more effective and personalized treatment strategies. Pseudomyxoma peritonei (PMP) is a rare disease characterized by extensive peritoneal implantation and mass secretion of mucus after primary mucinous tumors of the appendix or other organ ruptures. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is currently the preferred treatment, with excellent efficacy and safety, and is associated with breakthrough progress in long-term disease control and prolonged survival. However, the high recurrence rate of PMP is the key challenge in its treatment, which limits the clinical application of multiple rounds of CRS-HIPEC and does not benefit from conventional systemic chemotherapy. Therefore, the development of alternative therapies for patients with refractory or relapsing PMP is critical. The literature related to PMP research progress and treatment was searched in the Web of Science, PubMed, and Google Scholar databases, and a literature review was conducted. The overview of the biological research, treatment status, potential therapeutic strategies, current research limitations, and future directions associated with PMP are presented, focuses on CRS-HIPEC therapy and alternative or combination therapy strategies, and emphasizes the clinical transformation prospects of potential therapeutic strategies such as mucolytic agents and targeted therapy. It provides a theoretical reference for the treatment of PMP and the main directions for future research. [ABSTRACT FROM AUTHOR]

Simple Summary: "Precision medicine" is a therapeutic strategy launched over two decades ago. It relies on drugs that inhibit key molecular mechanisms/pathways or induce anti-tumour effects by modulating immune suppression. During this time, the complexity of advanced breast cancer disease has been increasingly elucidated and many clinical trials, sponsored by multinational drug companies, have been carried out. Nevertheless, patients have seen limited benefits from these clinical trials and the few approved drugs are costly. Concomitant, although other therapeutic strategies have been proposed by researchers over time, the resources available for alternative research have been restrained. As to this, while drug repurposing is an obvious answer to expensive targeted therapies, counteracting micro-metastatic disease represents a new field and seems to be the "way beyond" the current research. "Targeted therapy" or "precision medicine" is a therapeutic strategy launched over two decades ago. It relies on drugs that inhibit key molecular mechanisms/pathways or genetic/epigenetic alterations that promote different cancer hallmarks. Many clinical trials, sponsored by multinational drug companies, have been carried out. During this time, research has increasingly uncovered the complexity of advanced breast cancer disease. Despite high expectations, patients have seen limited benefits from these clinical trials. Commonly, only a minority of trials are successful, and the few approved drugs are costly. The spread of this expensive therapeutic strategy has constrained the resources available for alternative research. Meanwhile, due to the high cost/benefit ratio, other therapeutic strategies have been proposed by researchers over time, though they are often not pursued due to a focus on precision medicine. Notable among these are drug repurposing and counteracting micrometastatic disease. The former provides an obvious answer to expensive targeted therapies, while the latter represents a new field to which efforts have recently been devoted, offering a "way beyond" the current research. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic cancer-related fatigue is a critical problem for breast cancer survivors and effective and sustained management is a key for improvement. A six-week tango Argentino program showed to be effective in reducing fatigue and improving quality of life, here we examined the sustainability of this effect over a twelve month period. It was observed that in the tango cohort, breast cancer survivors experienced a sustained improvement in physical functioning and a reduction in fatigue symptoms for at least six months, but not in a control cohort. Tango may be an appropriate activity to promote quality of life and also eventually to improve long-term clinical outcomes of cancer survivors. Background: Chronic cancer-related fatigue is difficult to manage in breast cancer survivors. The tango trial showed that a six-week tango Argentino program was effective in reducing fatigue and improving quality of life, and here we investigated the sustainability of this tango program for breast cancer survivors. Methods: Stage I–III breast cancer survivors with increased fatigue symptoms were analyzed. The fifty participants in the tango trial were compared with a control cohort (n = 108) who did not participate in the tango program. Using the European Organization for Research and Treatment of Cancer Questionnaire C30 (EORTC-QLQ-C30) and the German version of the cancer fatigue scale (CFS-D) self-reported quality of life parameters were assessed and longitudinal changes, correlations, and association factors were calculated. Results: Significant improvements in fatigue (p = 0.006), physical functioning (p = 0.01), and diarrhea (p = 0.04) persisted in the 50 Tango participants at 6 months, but not in the control cohort. Twelve months after joining the tango program, increased fatigue was associated with reduced sporting activities (p = 0.0005), but this was not the case for tango dancing. Conclusions: The present results suggest that tango may be appropriate as a component of early supportive and follow-up care programs, to promote health-related quality of life and physical activity and also eventually to improve long-term clinical outcomes of breast cancer survivors. Trial registration: Trial registration numbers DRKS00013335 on 27 November 2017 and DRKS00021601 on 21 August 2020 retrospectively registered. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the use of novel agents in the first-line therapeutic setting, such as PD-1/PDL1 axis blockers for non-oncogene addicted non-small-cell lung cancer, most patients with advanced disease experience progression will succumb to the illness within a short period of time. Currently, the standard second-line treatment consists primarily of systemic cytotoxic therapies, which typically yield poor outcomes. Recently, several novel therapeutic strategies have emerged that may improve patient outcomes. This article reviews current state-of-the-art treatments in this scenario and highlights potential future options. Immune checkpoint inhibitors (ICIs) have revolutionized the management of non-oncogene addicted non-small-cell lung cancer (NSCLC). Blocking the anti-PD-1 axis represents the current standard of care in the first-line setting, with drugs administered either as monotherapy or in combination with chemotherapy. Despite notable successes achieved with ICIs, most of their long-term benefits are restricted to approximately 20% of patients. Consequently, the post-failure treatment landscape after failure to first-line treatment remains a complex challenge. Currently, docetaxel remains the preferred option, although its benefits remain modest as most patients do not respond or progress promptly. In recent times, novel agents and treatment combinations have emerged, offering fresh opportunities to improve patient outcomes. ICIs combined either with antiangiogenic or other novel immunotherapeutic compounds have shown promising preliminary activity. However, more mature data concerning specific combinations do not support their benefit over standard of care. In addition, antibody–drug conjugates seem to be the most promising alternative among all available compounds according to already-published phase I/II data that will be confirmed in soon-to-be-published phase III trial data. In this report, we provide a comprehensive overview of the current second-line treatment options and discuss future therapeutic perspectives. [ABSTRACT FROM AUTHOR]

Simple Summary: Neurofibromatosis type 1 (Nf1) is a genetically determined neurodevelopmental disorder and tumor syndrome with an incidence of approximately 1/3000 live births. It is caused by loss of function mutations in the neurofibromin gene (Nf1) and is estimated to affect 100,000 people in the US. Approximately 50% of the patients inherited the condition in an autosomal dominant pattern; the remaining 50% are the result of de novo mutations. Behavioral alterations and cognitive deficits have been found in 50–70% of children with Nf1. These behavioral alterations and cognitive deficits include specific problems with attention, visual perception, language, learning, attention, and executive function. Inhibition of the anaplastic lymphoma kinase (Alk), a kinase which is negatively regulated by neurofibromin, allows for testing the hypothesis that this inhibition may be therapeutically beneficial in Nf1. In this review, we discuss this area of research and directions for the development of alternative therapeutic strategies to inhibit Alk. Neurofibromatosis type 1 (Nf1) is a neurodevelopmental disorder and tumor syndrome caused by loss of function mutations in the neurofibromin gene (Nf1) and is estimated to affect 100,000 people in the US. Behavioral alterations and cognitive deficits have been found in 50–70% of children with Nf1 and include specific problems with attention, visual perception, language, learning, attention, and executive function. These behavioral alterations and cognitive deficits are observed in the absence of tumors or macroscopic structural abnormalities in the central nervous system. No effective treatments for the behavioral and cognitive disabilities of Nf1 exist. Inhibition of the anaplastic lymphoma kinase (Alk), a kinase which is negatively regulated by neurofibromin, allows for testing the hypothesis that this inhibition may be therapeutically beneficial in Nf1. In this review, we discuss this area of research and directions for the development of alternative therapeutic strategies to inhibit Alk. Even if the incidence of adverse reactions of currently available Alk inhibitors was reduced to half the dose, we anticipate that a long-term treatment would pose challenges for efficacy, safety, and tolerability. Therefore, future efforts are warranted to investigate alternative, potentially less toxic and more specific strategies to inhibit Alk function. [ABSTRACT FROM AUTHOR]

Simple Summary: Complementary therapies, such as acupuncture, yoga and herbal medicine are used by many patients with cancer to relieve symptoms and side effects from anti-cancer treatment. Clinicians in oncology often lack the knowledge to adequately advise patients about the potential benefits and risks of complementary therapies. This study aims to provide an overview of recently published systematic reviews of the effects of complementary therapies on patient-reported health outcomes in patients with cancer. One hundred systematic reviews were included, and the results suggest that several complementary therapies can improve patient-reported health outcomes in patients with cancer. For instance, acupuncture to relieve pain and yoga to improve cancer-related fatigue. The results remain inconclusive for other complementary therapies. Many included systematic reviews did not assess the impact of bias on their results. Nonetheless, the results from this study can help clinicians to find information about the evidence base for complementary therapies when counselling patients on this topic. Many patients with cancer make use of complementary medicine alongside conventional medicine, but clinicians in oncology often lack the knowledge to adequately advise patients on the evidence base for complementary therapies. This study aims to provide an overview of recently published systematic reviews that assess the effects of complementary therapies on patient-reported health outcomes in patients with cancer. Systematic reviews, including a meta-analysis of at least two randomized controlled trials, were identified from the PubMed, Embase, Cochrane Library, CINAHL and PsycINFO databases. The methodological quality was assessed with AMSTAR 2. One hundred systematic reviews were included. The results suggest that several complementary therapies can improve health outcomes reported by patients with cancer, such as acupuncture to relieve pain, music interventions to reduce anxiety and yoga to improve cancer-related fatigue. The side effects related to complementary therapy use are generally mild. The results remain inconclusive for some intervention–outcome combinations. Many of the included systematic reviews insufficiently assessed the causes and impact of bias in their interpretation of the results. This overview of systematic reviews can support clinicians in counselling their patients on this topic and provide directions for future research and clinical practice guidelines in the field of complementary medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemotherapy-induced peripheral neuropathy is highly relevant in breast cancer because of the symptoms it triggers and its corresponding negative impact on health status. The foot is the most affected part of the body by this adverse effect. However, little is known about its implications and the most relevant complementary therapies to deal with it. Hence, this scoping review aimed to summarize the impact of this side effect on quality of life and foot health of people with breast cancer as well as describe the main assessment strategies and complementary therapies that may be used in clinical practice. Subsequently, by summarizing these findings, the aim was to communicate the key gaps in current knowledge and provide directions for new research as well as contribute to developing evidence-based practice in this highlighted field. Background: Chemotherapy-induced peripheral neuropathy is a multidimensional health problem. Up to now, little evidence has been found concerning its impact on quality of life and foot health. Evaluation tools and prevention and treatment strategies must be reported. This study aimed to map the literature on the impact of this side effect on the wellbeing and foot health of people with breast cancer and to describe their main assessment strategies and complementary therapies. Methods: A scoping review was carried out while following the PRISMA-ScR and Arksey and O'Malley guidelines. Different databases (Cochrane Plus, Scopus, Web of Science, and Pubmed) were used. A total of 221 results were identified. Sixteen articles were included. Results: The thematic analysis obtained the following categories: the impact of peripheral neuropathy on quality of life and foot health, complementary therapies as a path for new strategies, and the need for clinicians and researchers to get involved in researching this side effect. Conclusions: Peripheral neuropathy has a negative impact on people's quality of life. Implications for foot health and maintaining an active and healthy lifestyle have not been previously reported. Complementary therapies are recommended by scientific evidence, highlighting exercise. However, there is a need to develop more research that will help to incorporate them into evidence-based practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Hemangiosarcoma is a mesenchymal neoplasm that originates in the endothelial cells of blood vessels. According to the location of origin, they can be classified as non-visceral and visceral types. Hemangiosarcoma can be very aggressive and metastasize to distant organs. The aim of this critical review is to present data on the epidemiology, etiology, diagnosis, staging, therapeutic modalities, and prognosis of canine hemangiosarcoma based on a consensus meeting organized by the Brazilian Association of Veterinary Oncology (ABROVET) in September 2022. Recent information from the literature, as well as new results from consensus participants, are presented and discussed. Hemangiosarcoma is a mesenchymal neoplasm originating in the endothelial cells of blood vessels; they can be classified as non-visceral and visceral types. Non-visceral hemangiosarcomas can affect the skin, subcutaneous tissues, and muscle tissues; visceral hemangiosarcomas can affect the spleen, liver, heart, lungs, kidneys, oral cavity, bones, bladder, uterus, tongue, and retroperitoneum. Among domestic species, dogs are most affected by cutaneous HSA. Cutaneous HSA represents approximately 14% of all HSA diagnosed in this species and less than 5% of dermal tumors, according to North American studies. However, Brazilian epidemiological data demonstrate a higher prevalence, which may represent 27 to 80% of all canine HSAs and 13.9% of all skin neoplasms diagnosed in this species. Cutaneous HSA most commonly affects middle-aged to elderly dogs (between 8 and 15 years old), with no gender predisposition for either the actinic or non-actinic forms. The higher prevalence of cutaneous HSA in some canine breeds is related to lower protection from solar radiation, as low skin pigmentation and hair coverage lead to greater sun exposure. Actinic changes, such as solar dermatosis, are frequent in these patients, confirming the influence of solar radiation on the development of this neoplasm. There are multiple clinical manifestations of hemangiosarcoma in canines. The diagnostic approach and staging classification of cutaneous HSAs are similar between the different subtypes. The definitive diagnosis is obtained through histopathological analysis of incisional or excisional biopsies. Cytology can be used as a presurgical screening test; however, it has little diagnostic utility in cases of HSA because there is a high risk of blood contamination and sample hemodilution. Surgery is generally the treatment of choice for dogs with localized non-visceral HSA without evidence of metastatic disease. Recently, electrochemotherapy (ECT) has emerged as an alternative therapy for the local ablative treatment of different neoplastic types; the use of radiotherapy for the treatment of dogs with cutaneous HSA is uncommon. There is greater consensus in the literature regarding the indications for adjuvant chemotherapy in subcutaneous and muscular HSA; doxorubicin is the most frequently used antineoplastic agent for subcutaneous and muscular subtypes and can be administered alone or in combination with other drugs. Other therapies include antiangiogenic therapy, photodynamic therapy, the association of chemotherapy with the metronomic dose, targeted therapies, and natural products. The benefits of these therapies are presented and discussed. In general, the prognosis of splenic and cardiac HSA is unfavorable. As a challenging neoplasm, studies of new protocols and treatment modalities are necessary to control this aggressive disease. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, the aim of conducting the network meta-analysis (NMA) was to explore the efficacy of different exercises and their respective ranks in the context of reducing cancer-related fatigue (CRF) in women with breast cancer (BC) during the inter-treatment and post-treatment periods. We found that yoga, resistance exercise, and aerobic resistance were the top three recommended exercise modes for the purposes of reducing CRF during the inter-treatment period among women with BC; moreover, Qigong ranked last in terms of efficacy. Yoga, aerobic yoga, and aerobic resistance were the top three exercise options that should be performed in order to relieve CRF during the post-treatment period; conversely, relaxation ranked last in this respect. Aerobic plus resistance, resistance exercise, and yoga were conducted via using a supervisor, as well as short-time sessions. Objective measures are recommended in order to examine the causal relationship of vigorous exercise or yoga on physical functions. This was performed in order to obtain clarity in respect to the optimal therapeutic management strategies that will best aid with the reduction in CRF among women with BC. Context: Cancer-related fatigue (CRF) is the most common cause of physical powerlessness in women with breast cancer (BC). The practice of continuous effective exercise is beneficial with respect to reducing CRF. Objective: To explore exercise efficacy and respective ranks with respect to reducing CRF in women with BC within the inter-treatment and post-treatment periods. Methods: Throughout this systematic review and network meta-analysis, articles published from 2000 to March 2022 were included. Article searches were conducted on the MEDLINE, Embase, CINAHL, and CENTRAL databases. Adult women with BC and different exercise programs were compared with those involved in regular care as a control during or after treatment. In addition, randomized controlled trials (RCT) were also included. A risk-of-bias assessment, with the revised Cochrane risk-of-bias tool regarding RCT and probability-based ranking, was established based on the surface under the cumulative rank (SUCRA) method via network meta-analysis. Results: a total of 5747 women with BC followed seven exercise interventions. Yoga (SMD = −0.54, 95% CI [−0.86, −0.22]) was ranked first (94.5%), with significant effects in respect of mitigating CRF, followed by resistance exercise (66.2%), and aerobic resistance (63.3%), while Qigong ranked last (22.2%) among the 36 RCT in inter-treatment. Aerobic resistance exercise (SMD = −0.52, 95% CI [−0.98, −0.07]) induced significant effects in respect of mitigating CRF in the 38 RCTs in the post-treatment period. Yoga, aerobic yoga, and aerobic resistance exercise ranked as the top three (75.5%, 75.0%, and 72.4%, respectively), whereas relaxation ranked last (38.8%) in the post-treatment period. Conclusion: Yoga, aerobic resistance, and aerobic yoga are recommended for the purposes of inter- and post-treatment exercise to reduce CRF in women with BC by enhancing their physical resilience and long-term quality of life. [ABSTRACT FROM AUTHOR]

Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in human radiotherapy, which allows a high dose to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinics takes advantage of this feature due to the small target volumes and distances between the target and the OAR. Sparing the OAR permits dose escalation, and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding missing the target. Additionally, the elaborate treatment plan must pursue hard constraints and objectives, and its feasibility must be evaluated with a per patient quality control. The aim of this work is to report results with regard to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal tumors with vascular invasion and rabbit thymomas, in comparison with literature to determine if VMAT is a safe and viable alternative to surgery or chemotherapy alone, or as an adjuvant therapy in pets. [ABSTRACT FROM AUTHOR]

The epithelial cell adhesion molecule (EpCAM), or CD326, was one of the first cancer associated biomarkers to be discovered. In the last forty years, this biomarker has been investigated for use in personalized cancer therapy, with the first monoclonal antibody, edrecolomab, being trialled in humans more than thirty years ago. Since then, several other monoclonal antibodies have been raised to EpCAM and tested in clinical trials. However, while monoclonal antibody therapy has been investigated against EpCAM for almost 40 years as primary or adjuvant therapy, it has not shown as much promise as initially heralded. In this review, we look at the reasons why and consider alternative targeting options, such as aptamers, to turn this almost ubiquitously expressed epithelial cancer biomarker into a viable target for future personalized therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma is a devastating disease that is very hard to treat. Here, we advance and evaluate the notion that the best possible management currently would be possible by combining clinical procedures with evidence-based complementary measures. We evaluate three categories of such complementary measures: Diet (background and specific), nutraceutical agents and lifestyle factors. Altogether, these include alkalinity, low-glycemic index, low-cholesterol, red meat, fish, fruit/vegetables, dairy, honey, coffee, vitamins A, C, D, E, genistein and curcumin (dietary issues); propolis, triptolide and cannabidiol (nutraceuticals); and obesity, diabetes, smoking, alcohol and exercise (lifestyle factors). The available evidence is considered by four criteria: clinical trials, meta-analyses and in vivo and in vitro data. A total of nine agents satisfy these criteria. These are combined and divided into two groups. Finally, a scheme is proposed for integrating the two groups with gemcitabine chemotherapy on a weekly cycle. The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which comprises some 85% of all cases. Currently, this is the fourth highest cause of cancer mortality worldwide and its incidence is rising steeply. Commonly applied clinical therapies offer limited chance of a lasting cure and the five-year survival rate is one of the lowest of the commonly occurring cancers. This review cultivates the hypothesis that the best management of PDAC would be possible by integrating 'western' clinical medicine with evidence-based complementary measures. Protecting the liver, where PDAC frequently first spreads, is also given some consideration. Overall, the complementary measures are divided into three groups: dietary factors, nutraceutical agents and lifestyle. In turn, dietary factors are considered as general conditioners, multi-factorial foodstuffs and specific compounds. The general conditioners are alkalinity, low-glycemic index and low-cholesterol. The multi-factorial foodstuffs comprise red meat, fish, fruit/vegetables, dairy, honey and coffee. The available evidence for the beneficial effects of the specific dietary and nutraceutical agents was considered at four levels (in order of prominence): clinical trials, meta-analyses, in vivo tests and in vitro studies. Thus, 9 specific agents were identified (6 dietary and 3 nutraceutical) as acceptable for integration with gemcitabine chemotherapy, the first-line treatment for pancreatic cancer. The specific dietary agents were the following: Vitamins A, C, D and E, genistein and curcumin. As nutraceutical compounds, propolis, triptolide and cannabidiol were accepted. The 9 complementary agents were sub-grouped into two with reference to the main 'hallmarks of cancer'. Lifestyle factors covered obesity, diabetes, smoking, alcohol and exercise. An integrative treatment regimen was devised for the management of PDAC patients. This involved combining first-line gemcitabine chemotherapy with the two sub-groups of complementary agents alternately in weekly cycles. The review concludes that integrated management currently offers the best patient outcome. Opportunities to be investigated in the future include emerging modalities, precision medicine, the nerve input to tumors and, importantly, clinical trials. [ABSTRACT FROM AUTHOR]