A systematic review of rehabilitation and exercise recommendations in oncology guidelines.

Guidelines promote high quality cancer care. Rehabilitation recommendations in oncology guidelines have not been characterized and may provide insight to improve integration of rehabilitation into oncology care. This report was developed as a part of the World Health Organization (WHO) Rehabilitation 2030 initiative to identify rehabilitation-specific recommendations in guidelines for oncology care. A systematic review of guidelines was conducted. Only guidelines published in English, for adults with cancer, providing recommendations for rehabilitation referral and assessment or interventions between 2009 and 2019 were included. 13840 articles were identified. After duplicates and applied filters, 4897 articles were screened. 69 guidelines were identified with rehabilitation-specific recommendations. Thirty-seven of the 69 guidelines endorsed referral to rehabilitation services but provided no specific recommendations regarding assessment or interventions. Thirty-two of the 69 guidelines met the full inclusion criteria and were assessed using the AGREE II tool. Twenty-one of these guidelines achieved an AGREE II quality score of ≥ 45 and were fully extracted. Guidelines exclusive to pharmacologic interventions and complementary and alternative interventions were excluded. Findings identify guidelines that recommend rehabilitation services across many cancer types and for various consequences of cancer treatment signifying that rehabilitation is a recognized component of oncology care. However, these findings are at odds with clinical reports of low rehabilitation utilization rates suggesting that guideline recommendations may be overlooked. Considering that functional morbidity negatively affects a majority of cancer survivors, improving guideline concordant rehabilitative care could have substantial impact on function and quality of life among cancer survivors.

Circulating tumor DNA in advanced solid tumors: Clinical relevance and future directions.

The application of genomic profiling assays using plasma circulating tumor DNA (ctDNA) is rapidly evolving in the management of patients with advanced solid tumors. Diverse plasma ctDNA technologies in both commercial and academic laboratories are in routine or emerging use. The increasing integration of such testing to inform treatment decision making by oncology clinicians has complexities and challenges but holds significant potential to substantially improve patient outcomes. In this review, the authors discuss the current role of plasma ctDNA assays in oncology care and provide an overview of ongoing research that may inform real-world clinical applications in the near future.

Exercise is medicine in oncology: Engaging clinicians to help patients move through cancer.

Multiple organizations around the world have issued evidence-based exercise guidance for patients with cancer and cancer survivors. Recently, the American College of Sports Medicine has updated its exercise guidance for cancer prevention as well as for the prevention and treatment of a variety of cancer health-related outcomes (eg, fatigue, anxiety, depression, function, and quality of life). Despite these guidelines, the majority of people living with and beyond cancer are not regularly physically active. Among the reasons for this is a lack of clarity on the part of those who work in oncology clinical settings of their role in assessing, advising, and referring patients to exercise. The authors propose using the American College of Sports Medicine's Exercise Is Medicine initiative to address this practice gap. The simple proposal is for clinicians to assess, advise, and refer patients to either home-based or community-based exercise or for further evaluation and intervention in outpatient rehabilitation. To do this will require care coordination with appropriate professionals as well as change in the behaviors of clinicians, patients, and those who deliver the rehabilitation and exercise programming. Behavior change is one of many challenges to enacting the proposed practice changes. Other implementation challenges include capacity for triage and referral, the need for a program registry, costs and compensation, and workforce development. In conclusion, there is a call to action for key stakeholders to create the infrastructure and cultural adaptations needed so that all people living with and beyond cancer can be as active as is possible for them.

Gastroenteropancreatic Neuroendocrine Tumors.

Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from the diffuse neuroendocrine system. They frequently originate in the gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their incidence has steadily increased in the last 3 decades. Fundamental biologic and genomic differences underlie the clinical heterogeneity of NETs, and distinct molecular features characterize NETs of different grades and different primary sites. Although surgery remains the cornerstone of treatment for localized tumors, systemic treatment options for patients with metastatic NETs have expanded considerably. Somatostatin analogs have demonstrated both antisecretory and antitumor efficacy. Peptide receptor radionuclide therapy with lutetium-177 dotatate (177 Lu-DOTATATE) has been approved for advanced GEP-NETs. The antitumor activity of everolimus has been demonstrated across a wide spectrum of NETs, and the antiangiogenic agent sunitinib has been approved for pancreatic NETs (pNETs). Chemotherapy with temozolomide and capecitabine has recently demonstrated an unprecedented prolongation of progression-free survival in a randomized trial of pNETs. Multiple retrospective series have reported the efficacy of liver-directed therapies both for palliating symptoms of hormone excess and for controlling tumor growth. Telotristat, an oral inhibitor of tryptophan hydroxylase, has been shown to reduce diarrhea in patients with carcinoid syndrome. Defining the therapeutic algorithm and identifying biomarkers predictive of response to treatments are among the main priorities for the next decade of research in the NET field.

Artificial Intelligence for Response Assessment in Neuro Oncology (AI-RANO), part 2: recommendations for standardisation, validation, and good clinical practice.

Technological advancements have enabled the extended investigation, development, and application of computational approaches in various domains, including health care. A burgeoning number of diagnostic, predictive, prognostic, and monitoring biomarkers are continuously being explored to improve clinical decision making in neuro-oncology. These advancements describe the increasing incorporation of artificial intelligence (AI) algorithms, including the use of radiomics. However, the broad applicability and clinical translation of AI are restricted by concerns about generalisability, reproducibility, scalability, and validation. This Policy Review intends to serve as the leading resource of recommendations for the standardisation and good clinical practice of AI approaches in health care, particularly in neuro-oncology. To this end, we investigate the repeatability, reproducibility, and stability of AI in response assessment in neuro-oncology in studies on factors affecting such computational approaches, and in publicly available open-source data and computational software tools facilitating these goals. The pathway for standardisation and validation of these approaches is discussed with the view of trustworthy AI enabling the next generation of clinical trials. We conclude with an outlook on the future of AI-enabled neuro-oncology.

Lost in the plot: missing visual elements in Kaplan-Meier plots of phase III oncology trials.

Missing visual elements (MVE) in Kaplan-Meier (KM) curves can misrepresent data, preclude curve reconstruction, and hamper transparency. This study evaluated KM plots of phase III oncology trials. MVE were defined as an incomplete y-axis range or missing number at risk table in a KM curve. Surrogate endpoint KM curves were additionally evaluated for complete interpretability, defined by (1) reporting the number of censored patients and (2) correspondence of the disease assessment interval with the number at risk interval. Among 641 trials enrolling 518 235 patients, 116 trials (18%) had MVE in KM curves. Industry sponsorship, larger trials, and more recently published trials were correlated with lower odds of MVE. Only 3% of trials (15 of 574) published surrogate endpoint KM plots with complete interpretability. Improvements in the quality of KM curves of phase III oncology trials, particularly for surrogate endpoints, are needed for greater interpretability, reproducibility, and transparency in oncology research.

Health equity principles for oncology real world evidence studies.

BACKGROUND: Real-world research on cancer care in the community should address social determinants of health (SDOH) to advance health equity in cancer diagnosis, treatment, and survivorship. We sought patient and stakeholder perspectives to co-develop research principles to guide researchers when using patient record data to address health equity in their research protocols. MATERIALS AND METHODS: Key informant interviews with 13 individuals elicited perspectives and insights related to health equity and SDOH when conducting research using data from community-based oncology care. Interviews included a brief overview of a prior scoping review and related questions in the interview guide. Key informants included experts in health equity and SDOH, and patient and community advisory board members. Rapid qualitative analysis was used to identify key themes, patterns, and insights from the interview data. Principles were developed based on the results of the analysis. RESULTS: Three overarching categories for promoting health equity were (1) education; (2) community engagement; and (3) research design and implementation. Education principles highlight the necessity of training in relevant skills to address health equity. Community engagement principles highlight various actions that researchers can take to conduct research inclusive of community concerns regarding health equity. The research design and implementation category provides practical guidelines for researchers in planning, conducting, and disseminating community-based oncology research to address health equity. CONCLUSION: Our principles guide oncology real-world research protocols to address SDOH in community settings and promote health equity. These principles should be tailored to specific cancer topics and communities.

Evolving assessment pathways for precision oncology medicines to improve patient access: a tumor-agnostic lens.

BACKGROUND: Genomic and molecular alterations are increasingly important in cancer diagnosis, and scientific advances are opening new treatment avenues. Precision oncology (PO) uses a patient's genomic profile to determine optimal treatment, promising fewer side effects and higher success rates. Within PO, tumor-agnostic (TA) therapies target genomic alterations irrespective of tumor location. However, traditional value frameworks and approval pathways pose challenges which may limit patient access to PO therapies. OBJECTIVES: This study describes challenges in assessing PO and TA medicines, explores possible solutions, and provides actionable recommendations to facilitate an iterative life-cycle assessment of these medicines. METHODS: After reviewing the published literature, we obtained insights from key stakeholders and European experts across a range of disciplines, through individual interviews and an industry workshop. The research was guided and refined by an international expert committee through 2 sounding board meetings. RESULTS: The current challenges faced by PO and TA medicines are multiple and can be demonstrated through real-world examples of the current barriers and opportunities. A life-cycle approach to assessment should be taken, including key actions at the early stages of evidence generation, regulatory and reimbursement stage, as well as payment and adoption solutions that make use of the evolving evidence base. Working toward these solutions to maximize PO medicine value is a shared responsibility and stands to benefit all stakeholders. CONCLUSIONS: Our call to action is to expand access to comprehensive genomic testing, foster a learning health care system, enable fast and equitable access to cost-effective treatments, and ultimately improve health outcomes.

Comparison of Large Language Models in Answering Immuno-Oncology Questions: A Cross-Sectional Study.

BACKGROUND: The capability of large language models (LLMs) to understand and generate human-readable text has prompted the investigation of their potential as educational and management tools for patients with cancer and healthcare providers. MATERIALS AND METHODS: We conducted a cross-sectional study aimed at evaluating the ability of ChatGPT-4, ChatGPT-3.5, and Google Bard to answer questions related to 4 domains of immuno-oncology (Mechanisms, Indications, Toxicities, and Prognosis). We generated 60 open-ended questions (15 for each section). Questions were manually submitted to LLMs, and responses were collected on June 30, 2023. Two reviewers evaluated the answers independently. RESULTS: ChatGPT-4 and ChatGPT-3.5 answered all questions, whereas Google Bard answered only 53.3% (P < .0001). The number of questions with reproducible answers was higher for ChatGPT-4 (95%) and ChatGPT3.5 (88.3%) than for Google Bard (50%) (P < .0001). In terms of accuracy, the number of answers deemed fully correct were 75.4%, 58.5%, and 43.8% for ChatGPT-4, ChatGPT-3.5, and Google Bard, respectively (P = .03). Furthermore, the number of responses deemed highly relevant was 71.9%, 77.4%, and 43.8% for ChatGPT-4, ChatGPT-3.5, and Google Bard, respectively (P = .04). Regarding readability, the number of highly readable was higher for ChatGPT-4 and ChatGPT-3.5 (98.1%) and (100%) compared to Google Bard (87.5%) (P = .02). CONCLUSION: ChatGPT-4 and ChatGPT-3.5 are potentially powerful tools in immuno-oncology, whereas Google Bard demonstrated relatively poorer performance. However, the risk of inaccuracy or incompleteness in the responses was evident in all 3 LLMs, highlighting the importance of expert-driven verification of the outputs returned by these technologies.

ESMO Recommendations on clinical reporting of genomic test results for solid cancers.

BACKGROUND: Genomic tumour profiling has a crucial role in the management of patients with solid cancers, as it helps selecting and prioritising therapeutic interventions based on prognostic and predictive biomarkers, as well as identifying markers of hereditary cancers. Harmonised approaches to interpret the results of genomic testing are needed to support physicians in their decision making, prevent inequalities in precision medicine and maximise patient benefit from available cancer management options. METHODS: The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group assembled a group of international experts to propose recommendations for preparing clinical genomic reports for solid cancers. These recommendations aim to foster best practices in integrating genomic testing within clinical settings. After review of available evidence, several rounds of surveys and focused discussions were conducted to reach consensus on the recommendation statements. Only consensus recommendations were reported. Recommendation statements were graded in two tiers based on their clinical importance: level A (required to maintain common standards in reporting) and level B (optional but necessary to achieve ideal practice). RESULTS: Genomics reports should present key information in a front page(s) followed by supplementary information in one or more appendices. Reports should be structured into sections: (i) patient and sample details; (ii) assay and data analysis characteristics; (iii) sample-specific assay performance and quality control; (iv) genomic alterations and their functional annotation; (v) clinical actionability assessment and matching to potential therapy indications; and (vi) summary of the main findings. Specific recommendations to prepare each of these sections are made. CONCLUSIONS: We present a set of recommendations aimed at structuring genomics reports to enhance physician comprehension of genomic profiling results for solid cancers. Communication between ordering physicians and professionals reporting genomic data is key to minimise uncertainties and to optimise the impact of genomic tests in patient care.

The ESMO Tumour-Agnostic Classifier and Screener (ETAC-S): a tool for assessing tumour-agnostic potential of molecularly guided therapies and for steering drug development.

BACKGROUND: Advances in precision oncology led to approval of tumour-agnostic molecularly guided treatment options (MGTOs). The minimum requirements for claiming tumour-agnostic potential remain elusive. METHODS: The European Society for Medical Oncology (ESMO) Precision Medicine Working Group (PMWG) coordinated a project to optimise tumour-agnostic drug development. International experts examined and summarised the publicly available data used for regulatory assessment of the tumour-agnostic indications approved by the US Food and Drug Administration and/or the European Medicines Agency as of December 2023. Different scenarios of minimum objective response rate (ORR), number of tumour types investigated, and number of evaluable patients per tumour type were assessed for developing a screening tool for tumour-agnostic potential. This tool was tested using the tumour-agnostic indications approved during the first half of 2024. A taxonomy for MGTOs and a framework for tumour-agnostic drug development were conceptualised. RESULTS: Each tumour-agnostic indication had data establishing objective response in at least one out of five patients (ORR ≥ 20%) in two-thirds (≥4) of the investigated tumour types, with at least five evaluable patients in each tumour type. These minimum requirements were met by tested indications and may serve as a screening tool for tumour-agnostic potential, requiring further validation. We propose a conceptual taxonomy classifying MGTOs based on the therapeutic effect obtained by targeting a driver molecular aberration across tumours and its modulation by tumour-specific biology: tumour-agnostic, tumour-modulated, or tumour-restricted. The presence of biology-informed mechanistic rationale, early regulatory advice, and adequate trial design demonstrating signs of biology-driven tumour-agnostic activity, followed by confirmatory evidence, should be the principles for tumour-agnostic drug development. CONCLUSION: The ESMO Tumour-Agnostic Classifier (ETAC) focuses on the interplay of targeted driver molecular aberration and tumour-specific biology modulating the therapeutic effect of MGTOs. We propose minimum requirements to screen for tumour-agnostic potential (ETAC-S) as part of tumour-agnostic drug development. Definition of ETAC cut-offs is warranted.

Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

Review of Nutrition Guidelines and Evidence on Diet and Survival Outcomes for Cancer Survivors: Call for Integrating Nutrition into Oncology Care.

Several organizations have published nutrition guidelines for cancer survivors during and after treatment. This review compared nutrition guidelines for cancer survivors published in the United States for the topics that are covered in the guidelines and evaluated the evidence that these guidelines are based upon. A team of researchers, patient stakeholders, and healthcare providers collectively identified 5 nutrition guidelines for cancer survivors in the United States: the 2022 American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors, the 2018 American Institute for Cancer Research Cancer Nutrition Guide, the 2022 National Cancer Institute Physician Data Query and Eating Hints, the 2024 National Comprehensive Cancer Network Guidelines for Cancer Survivors, and the 2020 American Society for Clinical Oncology Guidelines. The 5 guidelines cover a comprehensive list of nutrition topics but overall promote to follow those recommendations for cancer prevention. This review also evaluated the current evidence from meta-analyses on dietary patterns and intakes of foods and nutrients in relation to survival outcomes among cancer survivors. Although the evidence on dietary patterns is strong, the evidence on most dietary factors is still limited and the current research was primarily conducted among breast and colorectal cancer survivors. Although nutrition recommendations are available for cancer survivors, practical strategies need to be implemented to integrate nutrition into oncology care and help cancer survivors follow these recommendations. Further research is warranted to provide additional evidence on the role of nutrition in the health outcomes of cancer survivors and guide the development of evidence-based nutrition recommendations. The protocol is registered in PROSPERO: CRD42023429240.

System-level recommendations for improved wellness for gynecologic oncologists: A Society of Gynecologic Oncology Review.

Burnout and its negative sequelae are a persistent problem in gynecologic oncology, threatening the health of our physician workforce. Individual-level interventions such as stress management training, physical activity, and sleep hygiene only partially address this widespread, systemic crisis rooted in the extended work hours and stressful situations associated with gynecologic oncology practice. There is an urgent need for systematic, institution-level changes to allow gynecologic oncologists to continue the crucial work of caring for people with gynecologic cancer. We present recommendations for institution-level changes which are grounded in the framework presented by the National Plan for Health Workforce Well-Being by the National Academy of Medicine. These are aimed at facilitating gynecologic oncologists' well-being and reduction of burnout. Recommendations include efforts to create a more positive and inclusive work environment, decrease administrative barriers, promote mental health, optimize electronic medical record use, and support a diverse workforce. Implementation and regular evaluation of these interventions, with specific attention to at-risk groups, is an important next step.

NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024.

Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.

Neuroblastoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.

Rehabilitation in Oncology Care Guidelines: A Gap Analysis.

BACKGROUND: Cancer survivors experience a high prevalence of functional impairments. Rehabilitation interventions include an expansive array of services that can help optimize function, address pain, decrease symptom burden, and improve quality of life. Nonetheless, rehabilitation services remain underutilized. Thus, it is important to enhance the understanding of and establish guidelines for specific rehabilitation disciplines and interventions. METHODS: This is a gap analysis of rehabilitation recommendations in published oncology guidelines from selected nationally recognized organizations. Symptom-specific guidelines and cancer type-specific guidelines were analyzed for inclusion of common functional impairments (fatigue, pain, peripheral neuropathy, cognitive dysfunction, and lymphedema) and the rehabilitation discipline recommendations. RESULTS: The prevalence of recommendations for rehabilitation in cancer type-specific guidelines was 29%, and was higher in symptom-specific guidelines at 60%. However, the frequency of specific rehabilitation disciplines (physiatry, physical therapy, occupational therapy, speech-language pathology, and rehabilitation psychology/neuropsychology) was notably lower. Overall rehabilitation was mentioned in 33% and physiatry in 18%. Nonrehabilitation specialties were recommended in 18% of the guidelines. No specialty referral was endorsed in 53% of guidelines in which 1 of 5 symptoms were discussed. This highlights the relative paucity of recommendations for specific rehabilitation disciplines in oncology guidelines. The more general term "rehabilitation" was included more frequently but lacks critical guidance for oncology providers. Other crucial rehabilitation services may be underrecognized and underutilized. Rehabilitation specialists must work to improve patient access and the presence of indicated specific rehabilitation disciplines and goals within guidelines. CONCLUSIONS: Most oncology guidelines do not include specific recommendations for rehabilitation disciplines. However, including specific rehabilitation disciplines is more common in symptom-specific guidelines. With a stronger evidence base and increased involvement of rehabilitation specialists in guideline development, rehabilitation recommendations in oncologic guidelines may be more precise, leading to improved utilization of rehabilitation services to optimize function and quality of life.

Acute Lymphoblastic Leukemia, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for acute lymphoblastic leukemia (ALL) provide recommendations for management of ALL, with a focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. This selection from the NCCN Guidelines for ALL focuses on treatment recommendations for adults with newly diagnosed Ph-negative ALL based on current evidence.

Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024.

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.