Advances in oncology are occurring in leaps and bounds in various areas of pharmaceuticals, devices and surgical techniques. Non-invasive technologies such as wearables and artificial intelligence are making in-roads into this area and impacting the lives of cancer patients as they are rapidly being incorporated into clinical research and patient care. The objective of this Research Topic is to evaluate the latest non-invasive technologies that are emerging in oncology. For clarity, we define non-invasive as any procedure or technology used in cancer care (including diagnostics and therapeutics) that does not require the insertion of a device through the skin or into a bodily orifice. We encourage scientists and researchers to submit original research, reviews or opinions in this area.

Yale University

Cork University Hospital - CUH

National University of Singapore

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Frontiers in Digital Health

Personalized Medicine

Non-Invasive Technology Advances in Oncology

Breakthrough non-invasive technologies are swiftly being incorporated in oncology clinical care and research. Broadly, the innovations in this field can be classified by their role(s) in disease and patient management: (1) diagnosis, monitoring, and prognostication, (2) treatment and supportive care, (3) patient self-management and education. In this Research Topic titled &#x201c;Non-Invasive Technology Advances in Oncology&#x201d; in Frontiers in Digital Health, we have included recent contributions to this area of research.Aided by ongoing progress in genomic and molecular methods (<a href="#B1">1</a>), liquid biopsy is rapidly emerging as one of the kingpins of non-invasive diagnostics and prognostics in oncology. <a href="https://doi.org/10.3389/fdgth.2020.573010">Openshaw and McVeigh</a> comprehensively review the emerging roles of tumor-derived components including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA), messenger and microRNAs, and extracellular vesicles (EVs) in ovarian and endometrial cancer. Compared to conventional tumor biopsies, liquid biopsies offer a non-invasive, high-frequency method of assessing inter- and intra-tumoral heterogeneity to detect, prognosticate and treat cancer. Regarding cancer screening, the authors highlight the absence of a non-invasive screening test with proven survival benefit for patients at risk of ovarian and endometrial cancer, in notable contrast to cervical cancer where Papanicolaou (Pap) smears and human papillomavirus (HPV) tests are routine. Liquid biopsies can supplement existing techniques in detecting ovarian and endometrial cancer, by detecting ctDNA alongside conventional blood biomarkers (CancerSEEK) to improve sensitivity (<a href="#B2">2</a>), or by detecting ctDNA and exosomes in Pap smear samples routinely taken for cervical cancer screening (PapSEEK) (<a href="#B3">3</a>). As for disease prognostication, the detection of CTCs in apparently optimally debulked ovarian cancer patients has been shown to predict disease mortality (<a href="#B4">4</a>), while the presence of ctDNA post-operatively predicts tumor relapse (<a href="#B5">5</a>–<a href="#B7">7</a>). Liquid biopsies are useful even for treatment selection, with studies showing that cfDNA BRCA reversion mutations can predict resistance to platinum-based chemotherapy and Poly ADP-ribose Polymerase (PARP) inhibitors. Interestingly, the authors also noted a relative scarcity of evidence on specific liquid biopsy components, such as cell free messenger RNAs (cfmRNA) and cell free microRNAs (cf.miRNA). This highlights the potential for further translational research in liquid biopsy, and on a broader front, in non-invasive technology for cancer diagnostics and prognostics.In the realm of cancer therapeutics, non-invasive technologies are being harnessed for disease treatment and supportive care. Scalp cooling, now established as a safe and efficacious method of preventing chemotherapy-induced alopecia (<a href="#B8">8</a>), is one example of a successful non-invasive intervention in supportive care. Efforts in preventing chemotherapy-related adverse effects have now turned to chemotherapy-induced peripheral neuropathy (CIPN), which is a common, dose-limiting and potentially irreversible side-effect of taxane, platinum, and vinca alkaloid-based chemotherapy. Existing interventions for CIPN prevention such as neuroprotective agents and acupuncture have not been proven effective (<a href="#B9">9</a>–<a href="#B11">11</a>). Cryotherapy-induced vasoconstriction is an alternative promising non-invasive approach to limit peripheral exposure to toxic chemotherapeutics. While recent landmark trials have supported the use of frozen gloves in preventing CIPN (<a href="#B12">12</a>, <a href="#B13">13</a>), the frozen gloves used in the earlier trial were later recalled due to frostbite and other issues with patient safety and tolerability (<a href="#B14">14</a>). Here, <a href="https://doi.org/10.3389/fdgth.2020.573234">Binder et al.</a> report a novel mixed-methods approach in the design and development of a limb cryocompression system for CIPN prevention. They identified limb cryocompression (continuous-flow cooling combined with cyclic compression) as a potential alternative to frozen gloves for preventing CIPN, based on early clinical studies that have demonstrated safety, tolerability and potential efficacy (<a href="#B15">15</a>–<a href="#B17">17</a>). In designing their protective device, the authors adopted a collaborative approach, which facilitates the integration of evidence-based and user-centered techniques to meet the unique challenges of cross-sector medical device development. This novel approach, named HudPAX, integrates existing design and development methods to overcome the major challenges faced in medical product development such as industrial commercial awareness, medical regulatory standards and market considerations. Today's medical device development endeavors are often best accomplished in a multidisciplinary setting to allow design teams to capitalize on the respective expertise and forte of the clinical, academic, and industry sectors. Centered on cross-sector partnership, the proposed HudPAX approach is highly suited to today's medical innovation climate and can potentially be applied to streamline the development of various other non-invasive technologies for cancer care and beyond.Apart from the traditional fields of diagnostics and therapeutics, the use of non-invasive digital technology in patient self-management and education is gaining traction. With the increasing pervasiveness of the Internet, online health information, and services are becoming essential for patient self-management in oncology. Despite the burgeoning amount of web-based healthcare information, the probability of accessing health-related information without frustration has not changed significantly over the last decade (<a href="#B18">18</a>). <a href="https://doi.org/10.3389/fdgth.2020.578792">Hanai et al.</a> thus sought to understand the levels of satisfaction and the factors predicting satisfaction in a cross-sectional study of 412 cancer survivors who used web-based healthcare content. Participants reported using these resources to either record their health or therapy status, relieve their anxiety or stress, or to devise activities of daily living during cancer therapy. Among the 238 participants who used web content to relieve their anxiety or stress, interactive web content (such as social networking services or private blogs, where users had to respond in some form) was associated with significantly increased satisfaction. The authors found no relationship between clinical or demographic factors with the level of satisfaction with web content. Additionally, none of the respondents used evidence-based web healthcare applications backed by clinical trial data. With existing evidence suggesting beneficial effects of self-management interventions on physical and emotional distress and quality of life in cancer patients (<a href="#B19">19</a>–<a href="#B22">22</a>), we can expect further progress on the use of internet-enabled technologies to improve holistic care and patient empowerment in oncology. We particularly await the results of randomized trials using wearable technology for patient self-monitoring and for encouraging physical activity in cancer patients (<a href="#B23">23</a>).We look forward to receiving the results of additional research in the above fields, as well as in the other aspects that have yet to be covered in this Research Topic. We hope the reader will find this collection a relevant resource that showcases the frontiers of non-invasive technology in oncology.CT and BT wrote the editorial. DC undertook editorial revision and final approval. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Editorial: Non-invasive Technology Advances in Oncology

Health-related web content is constantly increasing, and cancer survivors use it to manage their health and activities of daily living. However, the actual usage of and satisfaction with web contents among cancer survivors is unclear. Therefore, we conducted a web-based cross-sectional survey to understand the satisfaction with web content in those cancer survivors who use the Internet to cope with their anxiety/stress, sleeplessness, or cognitive difficulties. The survey questionnaire was e-mailed to 1.2 million voluntary registrants at a research company. Cancer survivors who accessed any content via the Internet and experienced anxiety/stress, sleeplessness, or cognitive difficulties were included in the study. Out of the 412 survivors who completed the survey, 357 experienced some degree of anxiety or stress, 258 experienced sleeplessness, and 161 experienced some cognitive difficulties, such as forgetfulness or lack of attention. They used web contents to record their health or (n = 205), relieve their anxiety or stress (n = 238), and devise activities of daily living (n = 232) during cancer therapy, including surgery, chemotherapy, and radiation. The web contents included “interactive contents” (users engage with the web content by responding to it in some form), “non-interactive contents” (information medium without any user engagement), “web-storage,” or “scrolling.” Multivariate logistic regression revealed greater satisfaction with “interactive contents” in cancer survivors. This reflects that the sharing of personal experiences as well as objective information should be considered to create satisfying and effective web contents.

Health-related web content is constantly increasing, and cancer survivors use it to manage their health and activities of daily living. However, the actual usage of and satisfaction with web contents among cancer survivors is unclear. Therefore, we conducted a web-based cross-sectional survey to understand the satisfaction with web content in those cancer survivors who use the Internet to cope with their anxiety/stress, sleeplessness, or cognitive difficulties. The survey questionnaire was e-mailed to 1.2 million voluntary registrants at a research company. Cancer survivors who accessed any content via the Internet and experienced anxiety/stress, sleeplessness, or cognitive difficulties were included in the study. Out of the 412 survivors who completed the survey, 357 experienced some degree of anxiety or stress, 258 experienced sleeplessness, and 161 experienced some cognitive difficulties, such as forgetfulness or lack of attention. They used web contents to record their health or (n = 205), relieve their anxiety or stress (n = 238), and devise activities of daily living (n = 232) during cancer therapy, including surgery, chemotherapy, and radiation. The web contents included “interactive contents” (users engage with the web content by responding to it in some form), “non-interactive contents” (information medium without any user engagement), “web-storage,” or “scrolling.” Multivariate logistic regression revealed greater satisfaction with “interactive contents” in cancer survivors. This reflects that the sharing of personal experiences as well as objective information should be considered to create satisfying and effective web contents.

Satisfaction With Web-Based Healthcare Content in Cancer Survivors: A Cross-Sectional Survey

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common dose-limiting side-effect of taxane-based chemotherapy, causing progressive and often irreversible pain/sensitivity in the hands and feet. Prevention/treatments for CIPN are not well-developed and urgently needed. Limb cryocompression during chemotherapy has demonstrated promising early data of preventing/reducing CIPN severity. Currently there are no medical devices available that are dedicated to the specific requirements of CIPN prevention. As part of our ongoing development of a dedicated CIPN-prevention limb cryocompression system, this study documents the design & development of the wearable arm wrap, a central component of the system, from initial concept to a trial-ready prototype. A collaborative and multidisciplinary approach was adopted to address the complex and high-risk nature of this SME (Small Medium Enterprise)-centered medical device design & development process. The complementary collaboration unites multidisciplinary expertise spanning the scope of the project. Alongside the clinical, academic, and design & development expertise, the integration of commercial expertise is imperative to promote the market viability, and ultimate success, of the development. As the global leading experts in scalp cooling specializing in the prevention of chemotherapy-induced alopecia, UK-based SME Paxman Coolers Ltd is optimally positioned to support the commercial and regulatory dimensions. Development and adoption of a novel mixed-methodology (HudPAX) facilitated the integration of evidence-based and user-centered techniques to optimize the design & development approach and ensure integration of all critical design inputs. Alpha prototypes were designed through evidence-based approaches, with data from existing clinical trials utilized to determine the preliminary design inputs, alongside 3D ergonomic data. Investigations utilized computer-aided design, rapid prototyping, additive manufacturing, sketch modeling, and fast ideation. User-based approaches facilitated stakeholder-feedback through expert focus groups, informing further design & development and projecting the design into the next stage, Beta prototyping, for use in large-scale efficacy trials and upscaling manufacturing. This paper demonstrates a novel mixed-methods approach, which promotes cross-sector multidisciplinary collaboration, to address the complex multi-layered challenges posed by an early-stage medical device design & development process.

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common dose-limiting side-effect of taxane-based chemotherapy, causing progressive and often irreversible pain/sensitivity in the hands and feet. Prevention/treatments for CIPN are not well-developed and urgently needed. Limb cryocompression during chemotherapy has demonstrated promising early data of preventing/reducing CIPN severity. Currently there are no medical devices available that are dedicated to the specific requirements of CIPN prevention. As part of our ongoing development of a dedicated CIPN-prevention limb cryocompression system, this study documents the design &amp; development of the wearable arm wrap, a central component of the system, from initial concept to a trial-ready prototype. A collaborative and multidisciplinary approach was adopted to address the complex and high-risk nature of this SME (Small Medium Enterprise)-centered medical device design &amp; development process. The complementary collaboration unites multidisciplinary expertise spanning the scope of the project. Alongside the clinical, academic, and design &amp; development expertise, the integration of commercial expertise is imperative to promote the market viability, and ultimate success, of the development. As the global leading experts in scalp cooling specializing in the prevention of chemotherapy-induced alopecia, UK-based SME Paxman Coolers Ltd is optimally positioned to support the commercial and regulatory dimensions. Development and adoption of a novel mixed-methodology (HudPAX) facilitated the integration of evidence-based and user-centered techniques to optimize the design &amp; development approach and ensure integration of all critical design inputs. Alpha prototypes were designed through evidence-based approaches, with data from existing clinical trials utilized to determine the preliminary design inputs, alongside 3D ergonomic data. Investigations utilized computer-aided design, rapid prototyping, additive manufacturing, sketch modeling, and fast ideation. User-based approaches facilitated stakeholder-feedback through expert focus groups, informing further design &amp; development and projecting the design into the next stage, Beta prototyping, for use in large-scale efficacy trials and upscaling manufacturing. This paper demonstrates a novel mixed-methods approach, which promotes cross-sector multidisciplinary collaboration, to address the complex multi-layered challenges posed by an early-stage medical device design &amp; development process.

A Limb Hypothermia Wearable for Chemotherapy-Induced Peripheral Neuropathy: A Mixed-Methods Approach in Medical Product Development

Improving cancer survival rates globally requires improvements in disease detection and monitoring, with the aim of improving early diagnosis and prediction of disease relapse. Traditional means of detecting and monitoring cancers rely largely on imaging and, where possible, blood-based protein biomarkers, many of which are non-specific. Treatments are being improved by identification of inherited and acquired genomic aberrations in tumors, some of which can be targeted by newly developed therapeutic interventions. Treatment of gynecological malignancy is progressively moving toward personalized therapy, as exemplified by application of PARP-inhibition for patients with BRCA-deficient tubo-ovarian cancers, or checkpoint inhibition in patients with mismatch repair-deficient disease. However, the more recent discovery of a group of biomarkers described under the umbrella term of “liquid biopsy” promises significant improvement in our ability to detect and monitor cancers. The term “liquid biopsy” is used to describe an array of tumor-derived material found in blood plasma and other bodily fluids such as ascites, pleural fluid, saliva, and urine. It includes circulating tumors cells (CTCs), circulating nucleic acids including DNA, messenger RNA and micro RNAs, and extracellular vesicles (EVs). In this review, we discuss recent advancements in liquid biopsy for biomarker detection to help in diagnosis, prognosis, and planning of treatment of ovarian and endometrial cancer.

Improving cancer survival rates globally requires improvements in disease detection and monitoring, with the aim of improving early diagnosis and prediction of disease relapse. Traditional means of detecting and monitoring cancers rely largely on imaging and, where possible, blood-based protein biomarkers, many of which are non-specific. Treatments are being improved by identification of inherited and acquired genomic aberrations in tumors, some of which can be targeted by newly developed therapeutic interventions. Treatment of gynecological malignancy is progressively moving toward personalized therapy, as exemplified by application of PARP-inhibition for patients with BRCA-deficient tubo-ovarian cancers, or checkpoint inhibition in patients with mismatch repair-deficient disease. However, the more recent discovery of a group of biomarkers described under the umbrella term of &#x201c;liquid biopsy&#x201d; promises significant improvement in our ability to detect and monitor cancers. The term &#x201c;liquid biopsy&#x201d; is used to describe an array of tumor-derived material found in blood plasma and other bodily fluids such as ascites, pleural fluid, saliva, and urine. It includes circulating tumors cells (CTCs), circulating nucleic acids including DNA, messenger RNA and micro RNAs, and extracellular vesicles (EVs). In this review, we discuss recent advancements in liquid biopsy for biomarker detection to help in diagnosis, prognosis, and planning of treatment of ovarian and endometrial cancer.