Establishing an Integrative Oncology Service: Essential Aspects of Program Development.

PURPOSE OF REVIEW: Over the last 2 decades, integrative oncology (IO) has seen exponential growth within cancer care. It aims to combine evidence-based complementary therapies with conventional treatments to improve the well-being and quality of life for individuals dealing with cancer. The proliferation of integrative medicine programs in major cancer centers globally reflects varying approaches shaped by cultural, demographic, and resource-based factors. RECENT FINDINGS: Drawing upon the expertise of leaders in IO from the Society for Integrative Oncology (SIO) Clinical Practice Committee, this manuscript serves as a practical guide for establishing an IO practice. Collating insights from diverse professionals, including oncologists, integrative oncologists, supportive care physicians, researchers, and clinicians, the paper aims to provide a comprehensive roadmap for initiating and advancing IO services. The primary objective is to bridge the gap between conventional cancer care and complementary therapies, fostering a patient-centric approach to address the multifaceted challenges encountered by individuals with cancer. This paper delineates several key sections elucidating different aspects of IO practice. It delves into the core components necessary for an IO service's foundation, outlines the initial medical consultation process, and presents crucial tools essential for successful consultations. By consolidating insights and expertise, this manuscript seeks to facilitate the integration of IO into mainstream cancer care, ultimately enhancing patient outcomes and experiences.

Machine learning models for 180-day mortality prediction of patients with advanced cancer using patient-reported symptom data.

PURPOSE: The objective of the current study was to develop and test the performances of different ML algorithms which were trained using patient-reported symptom severity data to predict mortality within 180 days for patients with advanced cancer. METHODS: We randomly selected 630 of 689 patients with advanced cancer at our institution who completed symptom PRO measures as part of routine care between 2009 and 2020. Using clinical, demographic, and PRO data, we trained and tested four ML algorithms: generalized regression with elastic net regularization (GLM), extreme gradient boosting (XGBoost) trees, support vector machines (SVM), and a single hidden layer neural network (NNET). We assessed the performance of algorithms individually as well as part of an unweighted voting ensemble on the hold-out testing sample. Performance was assessed using area under the receiver-operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The starting cohort of 630 patients was randomly partitioned into training (n = 504) and testing (n = 126) samples. Of the four ML models, the XGBoost algorithm demonstrated the best performance for 180-day mortality prediction in testing data (AUROC = 0.69, sensitivity = 0.68, specificity = 0.62, PPV = 0.66, NPV = 0.64). Ensemble of all algorithms performed worst (AUROC = 0.65, sensitivity = 0.65, specificity = 0.62, PPV = 0.65, NPV = 0.62). Of individual PRO symptoms, shortness of breath emerged as the variable of highest impact on the XGBoost 180-mortality prediction (1-AUROC = 0.30). CONCLUSION: Our findings support ML models driven by patient-reported symptom severity as accurate predictors of short-term mortality in patients with advanced cancer, highlighting the opportunity to integrate these models prospectively into future studies of goal-concordant care.

The Careers and Professional Well-Being of Women Oncologists During the COVID-19 Pandemic: Responding for Tomorrow.

The COVID-19 pandemic exacerbated gender inequity in medicine, with women physicians reporting greater household responsibilities than their men counterparts and steeper barriers to career advancement. The pandemic highlighted the systemic assumptions and challenges faced by women physicians, which we anticipate is also true in our field of oncology. Prior literature suggests that women physicians were tasked with increased personal and professional responsibilities without compensation for their additional work, as well as derailments in career progression and significant burnout. Our aims are to highlight areas of opportunity to optimize the workplace experience of the oncology workforce and to invest in the professional well-being and sustainability of women oncologists as a step toward global workplace equity and future pandemic preparedness.

NCCN Guidelines® Insights: Older Adult Oncology, Version 1.2021.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Visitation policies at NCI-designated comprehensive cancer centers during the COVID-19 pandemic.

PURPOSE: Family/caregiver visitation provides critical support for patients confronting cancer and is associated with positive outcomes. However, the COVID-19 pandemic brought historic disruptions including widespread visitation restrictions. Here, we characterize in-depth the visitor policies of NCI-designated comprehensive cancer centers (CCCs) and analyze geographic/temporal patterns across CCCs. METHODS: The public-facing CCC websites, including archived webpages, were reviewed to abstract initial visitation policies and revisions, including end-of-life (EoL) exceptions and timing of visitation restrictions relative to regional lockdowns. Chi-squared and Fisher's exact tests were employed to analyze associations between geographic region, timing, and severity of restrictions. RESULTS: Most CCCs (n=43, 86%) enacted visitation restrictions between March 15 and April 15, 2020. About half barred all visitors for COVID-negative inpatients (n=24, 48%) or outpatients (n=26, 52%). Most (n=36, 72%) prohibited visitors for patients with confirmed/suspected COVID-19. Most (n=40, 80%) published EoL exceptions but the specifics were highly variable. The median time from initial restrictions to government-mandated lockdowns was 1 day, with a wide range (25 days before to 26 days after). There was no association between timing of initial restrictions and geographic location (p=0.14) or severity of inpatient policies (p=1.0), even among centers in the same city. Outpatient policies published reactively (after lockdown) were more restrictive than those published proactively (p=0.04). CONCLUSION: CCCs enacted strict but strikingly variable COVID-19 visitation restrictions, with important implications for patients/families seeking cancer care. A unified, evidence-based approach to visitation policies is needed to balance proven infection control measures with the needs of patients and families.

Performance Status Restriction in Phase III Cancer Clinical Trials.

BACKGROUND: Patients with good performance status (PS) tend to be favored in randomized clinical trials (RCTs), possibly limiting the generalizability of trial findings. We aimed to characterize trial-related factors associated with the use of PS eligibility criteria and analyze patient accrual breakdown by PS. METHODS: Adult, therapeutic, multiarm phase III cancer-specific RCTs were identified through ClinicalTrials.gov. PS data were extracted from articles. Trials with a PS restriction ECOG score ≤1 were identified. Factors associated with PS restriction were determined, and the use of PS restrictions was analyzed over time. RESULTS: In total, 600 trials were included and 238,213 patients had PS data. Of those trials, 527 studies (87.8%) specified a PS restriction cutoff, with 237 (39.5%) having a strict inclusion criterion (ECOG PS ≤1). Enrollment criteria restrictions based on PS (ECOG PS ≤1) were more common among industry-supported trials (P<.001) and lung cancer trials (P<.001). Nearly half of trials that led to FDA approval included strict PS restrictions. Most patients enrolled across all trials had an ECOG PS of 0 to 1 (96.3%). Even among trials that allowed patients with ECOG PS ≥2, only 8.1% of those enrolled had a poor PS. Trials of lung, breast, gastrointestinal, and genitourinary cancers all included <5% of patients with poor PS. Finally, only 4.7% of patients enrolled in trials that led to subsequent FDA approval had poor PS. CONCLUSIONS: Use of PS restrictions in oncologic RCTs is pervasive, and exceedingly few patients with poor PS are enrolled. The selective accrual of healthier patients has the potential to severely limit and bias trial results. Future trials should consider a wider cancer population with close toxicity monitoring to ensure the generalizability of results while maintaining patient safety.

Artificial Intelligence Systems Assisting Oncologists? Resist and Desist or Enlist and Coexist.

The use of artificial intelligence (AI) has become an integral part of patient care, but there are concerns about the impact of non­human decision assistance on patient outcomes. This commentary focuses on how AI can assist oncologists and benefit patients.

Development of a prognostic scoring system for patients with advanced cancer enrolled in immune checkpoint inhibitor phase 1 clinical trials.

This corrects the article DOI: 10.1038/bjc.2017.85.

Outcomes of patients ≥65 years old with advanced cancer treated on phase I trials at MD ANDERSON CANCER CENTER.

Patients ≥65 years with cancer remain underrepresented in clinical trials, particularly in phase I clinical trials. We analyzed the clinical course of patients ≥65 years treated on phase I clinical trials with particular emphasis on toxicities. We identified 347 consecutive patients ≥65 years with advanced cancer in our phase I clinic from 01/2004-12/2009 and analyzed disease characteristics, toxicities, survival and response. Overall, 251 patients received a targeted agent, of whom 241 (96%) received an investigational, non-FDA-approved drug. Clinical benefit (complete response + partial response + stable disease ≥ 6 months) was noted in 61 patients (18%). Eighty-nine patients (26%) had grade 3/4 toxicity, commonly hematologic, including 6 dose-limiting toxicities and 1 treatment-related death (<0.01%). Median overall survival from first Phase I Clinic visit was 8.8 months (95% CI: 7.8-10.6); median time to treatment failure was 1.9 months (95% CI: 1.8-2.1). Multivariable analyses revealed 4 indicators of lack of clinical benefit (liver metastases, performance status [PS] >1, prior radiation, ≥5 prior treatments; p <0.0001). Patients age 70-79 years had a greater risk of grade 3/4 toxicities when treated with combinations (≥2 drugs) compared to monotherapy (p = 0.006). Predictors of shorter time to treatment failure and overall survival included PS >1, thrombocytosis, >2 metastatic sites, and elevated lactate dehydrogenase (p <0.05). Our results suggest that phase I clinical trials are well tolerated in patients ≥65 years. Additionally, we identified risk factors that may facilitate patient selection for clinical trial participation.

Advances and future directions in the targeting of HER2-positive breast cancer: implications for the future.

OPINION STATEMENT: The natural history of HER2-positive breast cancer significantly changed in the past 15 years. Form being the most aggressive type of breast cancer, it became treatable with important cure rates. However, with new and successful drugs, resistance emerges. Progress in research and drug development continues to make available effective anti-HER2 therapies. Our challenge today is to use these tools correctly by looking at the data that support the indications of each compound and to continue clinical trial participation.

A Vision for Democratizing Next-Generation Oncology Clinical Trials.

SUMMARY: Revolutionary advancements in oncology have transformed lives, but the clinical trials ecosystem encounters challenges, including restricted access to innovative therapies and a lack of diversity in participant representation. A vision emerges for democratized, globally accessible oncology trials, necessitating collaboration among researchers, clinicians, patients, and policymakers to shift from converting complex, exclusive trials into a dynamic, inclusive force against cancer.

Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline.

PURPOSE: To guide clinicians, adults with cancer, caregivers, researchers, and oncology institutions on the medical use of cannabis and cannabinoids, including synthetic cannabinoids and herbal cannabis derivatives; single, purified cannabinoids; combinations of cannabis ingredients; and full-spectrum cannabis. METHODS: A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and cohort studies on the efficacy and safety of cannabis and cannabinoids when used by adults with cancer. Outcomes of interest included antineoplastic effects, cancer treatment toxicity, symptoms, and quality of life. PubMed and the Cochrane Library were searched from database inception to January 27, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: The evidence base consisted of 13 systematic reviews and five additional primary studies (four RCTs and one cohort study). The certainty of evidence for most outcomes was low or very low. RECOMMENDATIONS: Cannabis and/or cannabinoid access and use by adults with cancer has outpaced the science supporting their clinical use. This guideline provides strategies for open, nonjudgmental communication between clinicians and adults with cancer about the use of cannabis and/or cannabinoids. Clinicians should recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within the context of a clinical trial. Cannabis and/or cannabinoids may improve refractory, chemotherapy-induced nausea and vomiting when added to guideline-concordant antiemetic regimens. Whether cannabis and/or cannabinoids can improve other supportive care outcomes remains uncertain. This guideline also highlights the critical need for more cannabis and/or cannabinoid research.Additional information is available at www.asco.org/supportive-care-guidelines.

Prognostic indicators and treatment outcome in 94 cases of fibrolamellar hepatocellular carcinoma.

OBJECTIVE: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare variant of HCC. We report an analysis of the clinicopathologic features, treatment outcomes, and prognostic indicators of 94 cases. METHODS: We retrospectively collected clinicopathologic and treatment outcome data from 94 FLHCC patients (48 males and 46 females). Median overall survival (OS) and recurrence-free survival (RFS) were calculated using Kaplan-Meier curves, and survival rates were compared by the log-rank test. The Cox proportional hazard model was used for univariate and multivariate estimation of hazard risk ratios and 95% confidence intervals (CI) for factors that correlated with survival and disease recurrence after resection. RESULTS: Median age was 23 years (14-75); median OS was 57.2 months (95% CI, 36.4-77.9), and median RFS was 13.9 months (95% CI, 8.8-18.9). White race, female gender, early tumor stage, and tumor resection including metastasectomy were positively associated with longer OS, while female gender was the only significant positive predictor of longer RFS. Finally, the 5-fluorouracil-interferon combination was the most frequently used systemic therapy. CONCLUSIONS: Our analyses indicate that surgical approaches including metastasectomy as the first-line treatment in FLHCC correlated with better outcome. Multimodality approaches, including neoadjuvant and adjuvant therapies, prolonged patient survival.

Frequency, barriers, outcomes, and consequences of reporting sexual harassment in clinical oncology.

Sexual harassment is increasingly recognized as widely prevalent in medicine. Broad efforts at the organizational and society level are working to address this inequity, but many of these efforts rely on reporting to eradicate problematic behaviors and shift culture. We examined, among oncologists experiencing sexual harassment, the frequency of reporting, as well as barriers, outcomes, and consequences of reporting. Among 271 survey respondents, 217 reported sexual harassment from peers or superiors or from patients or families. Most harassed oncologists (n = 148, 68%) did not report the event to authority because of concerns about future negative consequences for themselves. Among the minority who reported harassment (n = 31, 14%), 52% felt their concerns were not taken seriously and 55% reported no action was taken as a result of their report. Furthermore, 52% experienced retaliatory behavior. Addressing these findings may help to inform the change necessary to create an antiharassment culture in oncology.

Practice Patterns on the Incorporation of Integrative Medicine Into the Oncologic Care of Patients With Cancer.

BACKGROUND: With rising interest in complementary approaches to symptom management, awareness of real-world practice patterns in the incorporation of integrative oncology (IO) into cancer care is limited. Therefore, we examined the reasons for referral, symptom burdens, and clinical outcomes for cancer patients who underwent initial IO consultations. METHODS: The records of adult patients with cancer who underwent initial outpatient IO consultations at our cancer center for a representative 10-day period at the start of each month for 12 months starting January 1, 2017, were reviewed retrospectively. Patient demographic and medical characteristics and outpatient IO consultation details, including patient-reported outcome measures of symptom burden, were extracted. Descriptive summary statistics and logistic regression were used to analyze the data. RESULTS: Among the 473 study patients, 71% were women, breast cancer (42%) was the most common cancer type, and 31% had metastatic cancer. Referring clinicians listed an integrative approach (57%) as the most common reason for referral, followed by diet (26%), pain (19%), discussion of herbs and supplements (18%), and stress (18%). In comparison, patients listed their primary concerns as diet (16%), pain (15%), and an integrative approach to overall health (11%). After the IO consultations, the highest likelihood of subsequent recommendations were acupuncture for hot flashes (odds ratio [OR], P = .002) or peripheral neuropathy (OR = 6.59, P < .001), oncology massage for pain (OR = 3.04, P < .001), psychology referral for patient's self-reported anxiety (OR = 2.35, P < .001), and mind-body therapies for stress (OR = 2.57, P < .001). CONCLUSION: Cancer patients' top concerns regarding IO consultation may not always match providers' reasons for referral. Longitudinal data analysis is needed to determine the effect of integrative interventions on symptom burden.

Long COVID in cancer patients: preponderance of symptoms in majority of patients over long time period.

Background: An increasing number of observational studies have reported the persistence of symptoms following recovery from acute COVID-19 disease in non-cancer patients. The long-term consequences of COVID-19 are not fully understood particularly in the cancer patient population. The purpose of this study is to assess post-acute sequelae of SARS-CoV-2 infection (PASC) in cancer patients following acute COVID-19 recovery. Methods: We identified cancer patients at MD Anderson Cancer Center who were diagnosed with COVID-19 disease between March 1, 2020, and September 1, 2020, and followed them till May 2021. To assess PASC, we collected patients reported outcomes through questionnaires that were sent to patients daily for 14 days after COVID-19 diagnosis then weekly for 3 months, and then monthly thereafter. We also reviewed patients' electronic medical records to capture the persistence or emergence of new COVID19-related symptoms reported during any clinic or hospital encounter beyond 30 days of the acute illness and up to 14 months. Results: We included 312 cancer patients with a median age of 57 years (18-86). The majority of patients had solid tumors (75%). Of the 312 patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis. The most common symptoms reported included fatigue (82%), sleep disturbances (78%), myalgias (67%), and gastrointestinal symptoms (61%), followed by headache, altered smell or taste, dyspnea (47%), and cough (46%). A higher number of females reported a persistence of symptoms compared to males (63% vs. 37%; p=0.036). Cancer type, neutropenia, lymphocytopenia, and hospital admission during acute COVID-19 disease were comparable in both groups. Among the 188 patients with PASC, only 16 (8.5%) were re-admitted for COVID-related reasons. Conclusions: More than one out of two cancer patients, and more likely females, report PASC that may persist beyond 6 months and even 1 year. The most common symptoms are non-respiratory and consist of fatigue, sleep disturbance, myalgia, and gastrointestinal symptoms. Most of the cancer patients with PASC were managed on outpatient basis with only 8.5% requiring a COVID-19-related re-admission. Funding: This research is supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports the MD Anderson Cancer Center Clinical Trials Office. The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.

Measuring symptom burden in patients with cancer during a pandemic: the MD Anderson symptom inventory for COVID-19 (MDASI-COVID).

BACKGROUND: Symptom expression in SARS-CoV-2 infection (COVID-19) may affect patients already symptomatic with cancer. Patient-reported outcomes (PROs) can describe symptom burden during the acute and postacute stages of COVID-19 and support risk stratification for levels of care. At the start of the COVID-19 pandemic, our purpose was to rapidly develop, launch through an electronic patient portal, and provide initial validation for a PRO measure of COVID-19 symptom burden in patients with cancer. METHODS: We conducted a CDC/WHO web-based scan for COVID-19 symptoms and a relevance review of symptoms by an expert panel of clinicians treating cancer patients with COVID-19 to create a provisional MD Anderson Symptom Inventory for COVID-19 (MDASI-COVID). English-speaking adults with cancer who tested positive for COVID-19 participated in the psychometric testing phase. Patients completed longitudinal assessments of the MDASI-COVID and the EuroQOL 5 Dimensions 5 Levels (EQ-5D-5L) utility index and visual analog scale, which were presented through an electronic health record patient portal. To test the validity of the MDASI-COVID to distinguish between known groups of patients, we hypothesized that patients hospitalized, including having a hospitalization extended, for COVID-19 versus those not hospitalized would experience higher symptom burden. Correlation of mean symptom severity and interference scores with relevant EQ-5D-5L scores tested concurrent validity. The reliability of the MDASI-COVID was evaluated by calculating Cronbach alpha coefficients and test-retest reliability was evaluated by calculating Pearson correlation coefficients between the initial assessment and a second assessment no more than 14 days later. RESULTS: The web-based scan found 31 COVID-19-related symptoms; rankings of a 14-clinician expert panel reduced this list to 11 COVID-specific items to be added to the core MDASI. Time from literature scan start in March 2020 to instrument launch in May 2020 was 2 months. Psychometric analysis established the MDASI-COVID's reliability, known-group validity, and concurrent validity. CONCLUSIONS: We were able to rapidly develop and electronically launch a PRO measure of COVID-19 symptom burden in patients with cancer. Additional research is needed to confirm the content domain and predictive validity of the MDASI-COVID and define the symptom burden trajectory of COVID-19.

Feasibility and acceptability of an online intervention to enhance hopefulness among oncology professionals.

BACKGROUND: Patients prefer medical communication including both hopefulness and realism, though health-care professional (HCPs) struggle to balance these. Providers could thus benefit from a detailed personal understanding of hope, allowing them to model and convey it to patients. Additionally, given that hope is associated with lower levels of burnout, HCPs may benefit from tools designed to enhance their own personal hopefulness. Several investigators have proposed offering HCPs interventions to augment hope. We developed an online workshop for this purpose. METHODS: Feasibility and acceptability of the workshop were assessed in members of the SWOG Cancer Research Network. Three measures were used: the Was-It-Worth-It scale, a survey based on the Kirkpatrick Training Evaluation Model, and a single item prompting participants to rate the degree to which they believe concepts from the workshop should be integrated into SWOG studies. RESULTS: Twenty-nine individuals signed up for the intervention, which consisted of a single 2-hour session, and 23 completed measures. Results from Was-It-Worth-It items indicate that nearly all participants found the intervention relevant, engaging, and helpful. Mean ratings for Kirkpatrick Training Evaluation Model items were high, ranging from 6.91 to 7.70 on 8-point scales. Finally, participants provided a mean rating of 4.44 on a 5-point scale to the item "To what degree do you believe it may be useful to integrate concepts from this workshop into SWOG trials/studies?" CONCLUSIONS: An online workshop to enhance hopefulness is feasible and acceptable to oncology HCPs. The tool will be integrated into SWOG studies evaluating provider and patient well-being.