ABSTRACT
Prostate cancer survivors approach 2.8 million in number and represent 1 in 5 of all cancer survivors in the United States. While guidelines exist for timely treatment and surveillance for recurrent disease, there is limited availability of guidelines that facilitate the provision of posttreatment clinical follow-up care to address the myriad of long-term and late effects that survivors may face. Based on recommendations set forth by a National Cancer Survivorship Resource Center expert panel, the American Cancer Society developed clinical follow-up care guidelines to facilitate the provision of posttreatment care by primary care clinicians. These guidelines were developed using a combined approach of evidence synthesis and expert consensus. Existing guidelines for health promotion, surveillance, and screening for second primary cancers were referenced when available. To promote comprehensive follow-up care and optimal health and quality of life for the posttreatment survivor, the guidelines address health promotion, surveillance for prostate cancer recurrence, screening for second primary cancers, long-term and late effects assessment and management, psychosocial issues, and care coordination among the oncology team, primary care clinicians, and nononcology specialists. A key challenge to the development of these guidelines was the limited availability of published evidence for management of prostate cancer survivors after treatment. Much of the evidence relies on studies with small sample sizes and retrospective analyses of facility-specific and population databases.
Subject(s)
Continuity of Patient Care/standards , Primary Health Care/standards , Prostatic Neoplasms/therapy , Survivors , American Cancer Society , Evidence-Based Medicine , Health Promotion/standards , Humans , Male , Population Surveillance , Quality of Life , United StatesABSTRACT
African-American (AA) cancer patients have long-experienced worse outcomes compared to non-Hispanic whites (NHW). No studies to date have evaluated the prognostic impact of sickle cell trait (SCT) and other inherited haemoglobinopathies, of which several are disproportionately high in the AA population. In a cohort analysis of treated patients diagnosed with breast or prostate cancer in the linked SEER-Medicare database, the relative risk (RR) for ≥1 serious adverse events (AEs), defined as hospitalisations or emergency department visits, was estimated for 371 AA patients with a haemoglobinopathy (AA+) compared to patients without haemoglobinopathies (17,303 AA-; 144,863 NHW-). AA+ patients had significantly increased risk for ≥1 AEs compared to AA- (RR = 1.19; 95% CI 1.11-1.27) and NHW- (RR = 1.23; 95% CI 1.15-1.31) patients. The magnitude of effect was similar by cancer type, and in analyses of AA+ with SCT only. Our findings suggest a novel hypothesis for disparities in cancer outcomes.
Subject(s)
Black or African American , Hemoglobinopathies/epidemiology , Neoplasms/epidemiology , Sickle Cell Trait/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Hemoglobinopathies/blood , Hemoglobinopathies/complications , Hemoglobinopathies/pathology , Humans , Male , Medicare , Neoplasms/blood , Neoplasms/complications , Neoplasms/pathology , Patients , Risk Factors , SEER Program , Sickle Cell Trait/blood , Sickle Cell Trait/complications , Sickle Cell Trait/pathology , United States/epidemiology , White PeopleABSTRACT
OBJECTIVE: Adjuvant endocrine therapy (AET) significantly reduces risk of breast cancer recurrence in those patients whose tumor tests hormone (estrogen and/or progesterone) receptor positive. Many who are prescribed AET do not adhere adequately. Studies have sought to examine the effects of interventions to enhance patients' AET adherence, with strikingly mixed results. In order to reconcile a disparate literature, this paper aims to (1) quantitatively review the aggregate effect of interventions designed to optimize AET adherence within the current literature and (2) meta-analyze these effects across studies' by intervention design. METHODS: Duplicate searches were conducted using multiple electronic databases as well as hand searches of recent year conference abstracts. Studies were included that (1) tested an intervention to promote AET adherence; (2) reported at least one measure of medication adherence; and (3) reported (or provided upon request) data sufficient to calculate effect size. Effect sizes were calculated using random effects models. RESULTS: Seven studies representing eight unique interventions were included. We observed an overall null effect across all interventions (k = 8; d [95% CI] = 0.28 [-0.05, 0.61]); however, sensitivity analyses showed that interventions that used bi-directional communication showed statistically significant effects relative to control groups within each study (k = 4; d [95% CI] = 0.59 [0.23, 0.95]) while those relying only on providing information to the patient (one-way communication) did not (k = 4; d [95% CI] = -0.03 [-0.27, 0.20]). CONCLUSIONS: Interventions that promote patient self-report may improve AET adherence through enhancing patient engagement. Investigators and clinicians who wish to optimize medication adherence in this population can consider this approach.
Subject(s)
Breast Neoplasms/therapy , Cancer Survivors/statistics & numerical data , Chemotherapy, Adjuvant/statistics & numerical data , Medication Adherence/statistics & numerical data , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/metabolism , Breast Neoplasms/psychology , Combined Modality Therapy , Female , Humans , Neoplasm Recurrence, Local/prevention & control , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolismABSTRACT
PURPOSE: Although breast cancer survivors' lifestyle choices affect their subsequent health, a majority do not engage in healthy behaviors. Because treatment end is a "teachable moment" for potentially altering lifestyle change for breast cancer survivors, we developed and tested two mail-based interventions for women who recently completed primary treatment. METHODS: One hundred seventy-three survivors were randomly assigned to (1) Targeting the Teachable Moment (TTMI, n = 57), (2) Standard Lifestyle Management (SLM, n = 58), or (3) usual care (UC, n = 58) control group. Participants who were assigned to TTMI and SLM received relevant treatment materials biweekly for 4 months. Participants were assessed at baseline (T1, before randomization), post-treatment (T2, 4 months), and follow-up (T3, 7 months). Fruit and vegetable (F/V) intake, fat intake, and moderate-to-vigorous physical activity (MVPA) were assessed. RESULTS: Results showed promise for these mail-based interventions for changes in health behaviors: Survivors in TTMI (+.47) and SLM (+.45) reported increased F/V intake, whereas those in UC (-.1) reported decreased F/V intake from T1 to T2. Changes in minutes of MVPA from T1 to T2 were higher in SLM than UC and marginally higher in TTMI than UC. However, these differences were due to decreased MVPA in UC rather than increased MVPA in the intervention groups. There were no group differences regarding fat intake. Survivors reported high satisfaction and preference for mail-based interventions, supporting feasibility. CONCLUSIONS: Mail-based lifestyle interventions for breast cancer survivors may benefit F/V intake and physical activity. Further testing and optimizing of these interventions is warranted.
Subject(s)
Breast Neoplasms/therapy , Health Behavior , Life Style , Postal Service/methods , Breast Neoplasms/mortality , Breast Neoplasms/psychology , Breast Neoplasms/rehabilitation , Female , Humans , Middle Aged , SurvivorsABSTRACT
BACKGROUND: The Institute of Medicine recommended that survivors of cancer and their primary care providers receive survivorship care plans (SCPs) to summarize cancer treatment and plan ongoing care. However, the use of SCPs remains limited. METHODS: Oncology providers at 14 National Cancer Institute Community Cancer Centers Program hospitals completed a survey regarding their perceptions of SCPs, including barriers to implementation, strategies for implementation, the role of oncology providers, and the importance of topics in SCPs (diagnosis, treatment, recommended ongoing care, and the aspects of ongoing care that the oncology practice will provide). RESULTS: Among 245 providers (response rate of 70%), 52% reported ever providing any component of an SCP to patients. The most widely reported barriers were lack of personnel and time to create SCPs (69% and 64% of respondents, respectively). The most widely endorsed strategy among those using SCPs was the use of a template with prespecified fields; 94% of those who used templates found them helpful. For each topic of an SCP, although 87% to 89% of oncology providers believed it was very important for primary care providers to receive the information, only 58% to 65% of respondents believed it was very important for patients to receive the information. Furthermore, 33% to 38% of respondents reported mixed feelings regarding whether it was the responsibility of oncology providers to provide SCPs. CONCLUSIONS: Practices need additional resources to overcome barriers to implementing SCPs. We found resistance toward SCPs, particularly the perceived value for the survivor and the idea that oncology providers are responsible for SCP dissemination.
Subject(s)
Community Health Services , Medical Oncology/trends , Neoplasms , Patient Care Planning , Physician's Role , Practice Patterns, Physicians' , Survivors , Adult , Aged , Continuity of Patient Care , Female , Health Services Needs and Demand , Humans , Male , Medical Oncology/standards , Middle Aged , Neoplasms/therapy , Patient Care Planning/standards , Patient Care Planning/trendsABSTRACT
Importance: For patients with nonspine bone metastases, short-course radiotherapy (RT) can reduce patient burden without sacrificing clinical benefit. However, there is great variation in uptake of short-course RT across practice settings. Objective: To evaluate whether a set of 3 implementation strategies facilitates increased adoption of a consensus recommendation to treat nonspine bone metastases with short-course RT (ie, ≤5 fractions). Design, Setting, and Participants: This prospective, stepped-wedge, cluster randomized quality improvement study was conducted at 3 community-based cancer centers within an existing academic-community partnership. Rollout was initiated in 3-month increments between October 2021 and May 2022. Participants included treating physicians and patients receiving RT for nonspine bone metastases. Data analysis was performed from October 2022 to May 2023. Exposures: Three implementation strategies-(1) dissemination of published consensus guidelines, (2) personalized audit-and-feedback reports, and (3) an email-based electronic consultation platform (eConsult)-were rolled out to physicians. Main Outcomes and Measures: The primary outcome was adherence to the consensus recommendation of short-course RT for nonspine bone metastases. Mixed-effects logistic regression at the bone metastasis level was used to model associations between the exposure of physicians to the set of strategies (preimplementation vs postimplementation) and short-course RT, while accounting for patient and physician characteristics and calendar time, with a random effect for physician. Physician surveys were administered before implementation and after implementation to assess feasibility, acceptability, and appropriateness of each strategy. Results: Forty-five physicians treated 714 patients (median [IQR] age at treatment start, 67 [59-75] years; 343 women [48%]) with 838 unique nonspine bone metastases during the study period. Implementing the set of strategies was not associated with use of short-course RT (odds ratio, 0.78; 95% CI, 0.45-1.34; P = .40), with unadjusted adherence rates of 53% (444 lesions) preimplementation vs 56% (469 lesions) postimplementation; however, the adjusted odds of adherence increased with calendar time (odds ratio, 1.68; 95% CI, 1.20-2.36; P = .003). All 3 implementation strategies were perceived as being feasible, acceptable, and appropriate; only the perception of audit-and-feedback appropriateness changed before vs after implementation (19 of 29 physicians [66%] vs 27 of 30 physicians [90%]; P = .03, Fisher exact test), with 20 physicians (67%) preferring reports quarterly. Conclusions and Relevance: In this quality improvement study, a multicomponent set of implementation strategies was not associated with increased use of short-course RT within an academic-community partnership. However, practice improved with time, perhaps owing to secular trends or physician awareness of the study. Audit-and-feedback was more appropriate than anticipated. Findings support the need to investigate optimal approaches for promoting evidence-based radiation practice across settings.
Subject(s)
Bone Neoplasms , Quality Improvement , Humans , Bone Neoplasms/secondary , Bone Neoplasms/radiotherapy , Female , Male , Middle Aged , Prospective Studies , Aged , Guideline Adherence/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical dataABSTRACT
BACKGROUND: Routine colorectal screening, decreases in incidence, and advances in treatment have lowered colorectal cancer mortality rates over the past three decades. Nevertheless, it remains the second most common cause of cancer death amongst men and women combined in U.S. Most cases of colon cancer are diagnosed at a late stage leading to poor survival outcomes for patients. After extensive research of publically available data, it would appear that the state of Connecticut does not have available state-wide data on patient wait times for routine colonoscopy screening. Furthermore, there are no publicly available, or Connecticut-specific, reports on Medicaid participation rates for colorectal screening amongst gastroenterologists (GI) in Connecticut. In 2012, the American Cancer Society report on Colorectal Cancer Screening Rates confirmed barriers to health-care access and disparities in health outcomes and survival rates for colon cancer patients based on race, ethnicity, and low socioeconomic status. Given this information, one could conjecture that low Medicaid participation rates among GIs could potentially have a more severe impact on health-care access and outcomes for underserved populations. At present, funding and human resources are being employed across the state of Connecticut to address bottlenecks in colorectal cancer screening. More specifically, patient navigation and outreach programs are emerging and expanding to address the gaps in services for hard-to-reach populations and the medically underserved. Low Medicaid participation rates and increased wait times for colonoscopy screening may impair the efficacy of colorectal cancer patient navigation and outreach efforts and potentially funding for future interventions. In this study, we report the results of our secret-shopper telephone survey comprising of 93 group and independent gastroenterologist (GI) practices in different counties of Connecticut. METHODS: Reviewing online resources and yellow pages, researchers compiled a county-specific list of GI practices throughout Connecticut and conducted a secret-shopper survey by telephone. A standard script and set of questions was formulated and used for each telephone call to GI practices. Data was analyzed in context of statistics available to the public at large from the U.S. Census Bureau. RESULTS: Overall, 46% of all 93 practices and 62% of individual GIs from all 93 practices state-wide reported Medicaid participation. About 35% of surveyed practices were independent practices; 41% of these reported Medicaid participation. About 65% of surveyed practices were group practices; 49% of these reported Medicaid participation. Approximately, 85% of all practices are in Fairfield, Hartford, orNew Haven counties. Of all three counties, New Haven reported the highest Medicaid participation rate by practices; 62% of all practices in New Haven reported participation. Fairfield reported the lowest Medicaid participation rate by practices; 29% of all practices in Fairfield reported participation. When Medicaid participation rates were calculated for total number of gastroenterologists from all practices in a given county (as opposed to participation rates by number of practices), Medicaid participation rates were 80% and 44% for New Haven and Fairfield, respectively. Of all practices in Hartford, only 50% reported Medicaid participation, whereas 67% of the total number of gastroenterologists (as opposed to practices) reported Medicaid participation. According to a recent national survey, 47% of gastroenterologists reported stopping accepting new Medicaid patients. Overall minimum and maximum wait times were reported to be the highest for Hartford, but wait times were long even for smaller counties, reflecting a possible imbalance in supply and demand or inefficiency in allocating the available resources. CONCLUSIONS: Only a limited number of gastroenterology practices in Connecticut accept Medicaid patients, notably in selected counties, but in all counties, and this may add to access barriers. It is yet unclear whether these disparities are significant enough to create a supply-demand imbalance and thus, have a significantly negative impact on health outcomes for the underserved. Nevertheless, with the high unemployment rates and impending implementation of mandated state-wide health-care reform as outlined in the Affordable Care Act, the Medicaid population in the state of Connecticut will increase, increasing future demand for services. In addition, based on the survey findings, longer wait times for colonoscopy screening are reported for the many of GI practices in Connecticut for Medicaid-insured as well as non-Medicaid patients. Longer wait times may have an impact on patient compliance, especially for the underserved populations that are hard to reach and ensure follow-up, contributing to potential delayed diagnosis. A Medicaid-associated disparity in this area will serve to exacerbate the problem for the underserved compared to those relatively well served. Those currently not seeking screening are at even higher risk of contributing to the higher mortality rate, and we need to find out how best to ensure that we can more uniformly apply screening and have the capacity to do so.
Subject(s)
Colorectal Neoplasms/diagnosis , Early Detection of Cancer/statistics & numerical data , Gastroenterology/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Medicaid/statistics & numerical data , Waiting Lists , Connecticut , Humans , Time Factors , United StatesABSTRACT
OBJECTIVES: To characterize the needs and preferences for pain self-management support (SMS) among patients with cancer during the transition of cancer care from the hospital to the home setting. SAMPLE & SETTING: 38 participants with cancer pain at a research-intensive cancer center in New England. METHODS & VARIABLES: A descriptive, cross-sectional survey study was conducted to investigate relationships among preferred and received support, extent and management of transitional change, and pain outcomes. Pain intensity and interference were measured using the Brief Pain Inventory-Short Form, transitional change was measured using the Measurement of Transitions in Cancer Scale, and SMS was measured using dichotomous questions. RESULTS: About half of participants reported concordance between preferred and received cancer pain SMS in the hospital and at home. The extent of transitional change in cancer care was found to be a significant predictor of average pain intensity in the hospital and pain interference at home. Satisfaction with cancer pain SMS was a significant predictor of pain intensity at home. IMPLICATIONS FOR NURSING: The extent of change during care transitions should be considered when fulfilling patient needs and preferences for cancer pain SMS to optimize outcomes.
Subject(s)
Cancer Pain , Neoplasms , Self-Management , Humans , Cancer Pain/therapy , Cross-Sectional Studies , Neoplasms/complications , Neoplasms/therapy , Pain/etiologyABSTRACT
Purpose: Local treatment for bone metastases is becoming increasingly complex. National guidelines traditionally focus only on radiation therapy (RT), leaving a gap in clinical decision support resources available to clinicians. The objective of this study was to reach expert consensus regarding multidisciplinary management of non-spine bone metastases, which would facilitate standardizing treatment within an academic-community partnership. Methods and Materials: A multidisciplinary panel of physicians treating metastatic disease across the Memorial Sloan Kettering (MSK) Cancer Alliance, including community-based partner sites, was convened. Clinical questions rated of high importance in the management of non-spine bone metastases were identified via survey. A literature review was conducted, and panel physicians drafted initial recommendation statements. Consensus was gathered on recommendation statements through a modified Delphi process from a full panel of 17 physicians from radiation oncology, orthopaedic surgery, medical oncology, interventional radiology, and anesthesia pain. Consensus was defined a priori as 75% of respondents indicating "agree" or "strongly agree" with the consensus statement. Strength of Recommendation Taxonomy was employed to assign evidence strength for each statement. Results: Seventeen clinical questions were identified, of which 11 (65%) were selected for the consensus process. Consensus was reached for 16 of 17 answer statements (94%), of which 12 were approved after Round 1 and additional 4 approved after Round 2 of the modified Delphi voting process. Topics included indications for referral to surgery or interventional radiology, radiation fractionation and appropriate use of stereotactic approaches, and the handling of systemic therapies during radiation. Evidence strength was most commonly C (n = 7), followed by B (n = 5) and A (n = 3). Conclusions: Consensus among a multidisciplinary panel of community and academic physicians treating non-spine bone metastases was feasible. Recommendations will assist clinicians and potentially provide measures to reduce variation across diverse practice settings. Findings highlight areas for further research such as pathologic fracture risk estimation, pre-operative radiation, and percutaneous ablation.
ABSTRACT
PURPOSE: Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted community-based partner sites with a high potential to improve diverse population accrual. This study evaluates the effectiveness of a set of implementation strategies for increasing overall community-based enrollment and the resulting proportional enrollment of Hispanic patients on trials on the basis of availability in community-based partner sites. METHODS: An interrupted time series analysis evaluating implementation strategies was conducted from April 2018 to September 2021. Descriptive analysis ofHispanic enrollment on investigator-initiated randomized therapeutic radiation trials open at community-based sites was compared with those open only at themain academic center. RESULTS: Overall, 84 patients were enrolled in clinical trials in the MSK Alliance, of which 48 (56%) identified as Hispanic. The quarterly patient enrollment pre- vs postimplementation increased from 1.39 (95% CI, -3.67 to 6.46) to 9.42 (95% CI, 2.05 to 16.78; P5 .017). In the investigator-initiated randomized therapeutic radiation trials open in the MSK Alliance, Hispanic representation was 11.5% and 35.9% in twometastatic trials and 14.2% in a proton versus photon trial. Inmatched trials open only at the main academic center, Hispanic representation was 5.6%, 6.0%, and 4.0%, respectively. CONCLUSION: A combination of practice-level and physician-level strategies implemented at community-based partner sites was associated with increased clinical trial enrollment, which translated to improved Hispanic representation. This supports the role Q:2 of strategic community-academic partnerships in addressing disparities in clinical trial enrollment.
Subject(s)
Clinical Trials as Topic , Hispanic or Latino , Patient Participation , Humans , Interrupted Time Series Analysis , Physicians , Research PersonnelABSTRACT
PURPOSE: Lutetium Lu-177 dotatate is the first peptide receptor radionuclide therapy approved by the US Food and Drug Administration. Well-designed studies in Europe have shown dramatic effectiveness in improving progression-free survival in patients with gastroenteropancreatic neuroendocrine tumors, which are progressive and generally metastatic. This therapy is a molecular targeted therapy linking a beta-emitting radioisotope to dotatate, which binds tightly to somatostatin receptors on neuroendocrine tumors cells. Various adverse effects of this therapy have been reported in the literature, including potential toxicity to renal, hepatic, and hematologic tissues and risk of second malignancy. Our study sought to explore acute adverse effects in this patient population. METHODS AND MATERIALS: We tracked adverse effects and patient experience in our first year of therapy experience with this new agent. RESULTS: In our first 12 patients who received Lutetium Lu-177 dotatate, tumor flare reactions occurred in 5 patients due to worsening symptoms of bone or soft tissue metastasis. This flare reaction can be mitigated with short course of corticosteroid therapy or other strategies. CONCLUSIONS: Flare reaction is common in patients with progressive metastatic gastroenteropancreatic neuroendocrine tumors and can be managed successfully with several strategies.
ABSTRACT
PURPOSE: A substantial portion of breast cancer survivors are active in the workforce, yet factors that allow survivors to balance work with cancer management and to return to work are poorly understood. We examined breast cancer survivors' most valued/desired types of support in early survivorship. METHODS: Seventy-six employed breast cancer survivors answered an open-ended survey question assessing the most valued/desired support to receive from healthcare providers during early survivorship to manage work and health. Cutrona's (Journal of Social and Clinical Psychology 9:3-14, 1990) optimal matching theory and House's (1981) conceptualization of social support types informed our analyses. Data were content-analyzed to identify themes related to support, whether needed support was received or not, and the types of healthcare providers who provided support. RESULTS: We identified six themes related to types of support. Informational support was valued and mostly received by survivors, but they expected more guidance related to work. Emotional support was valued but lacking, attributed mainly to providers' lack of personal connection and mental health support. Instrumental (practical) support was valued but received by a small number of participants. Quality of life support to promote well-being and functionality was valued and often received. Other themes included non-specific support and non-support. CONCLUSIONS: This study expands our understanding of how breast cancer survivors perceive work-related support from healthcare professionals. Findings will inform targeted interventions designed to improve the support provided by healthcare professionals. IMPLICATIONS FOR CANCER SURVIVORS: Breast cancer survivors managing work and health challenges may benefit by having their unmet support needs fulfilled.
Subject(s)
Breast Neoplasms , Cancer Survivors , Breast Neoplasms/therapy , Female , Humans , Qualitative Research , Quality of Life , Social Support , SurvivorsABSTRACT
Survivors of head and neck cancer (HNC) can have multiple health concerns. To facilitate their care, we developed and pilot-tested a clinical informatics intervention, HN-STAR. HN-STAR elicits concerns online from HNC survivors prior to a routine oncology clinic visit. HN-STAR then presents tailored evidence-based clinical recommendations as a clinical decision support tool to be used during the visit where the oncology clinician and survivor select symptom management strategies and other actions. This generates a survivorship care plan (SCP). Online elicitation of health concerns occurs 3, 6, and 9 months after the clinic visit, generating an updated SCP each time. HN-STAR encompasses important methods of improving survivorship care (e.g., needs assessment, tailored interventions, dissemination of guidelines) and will be evaluated in a pragmatic trial to maximize external validity. This hybrid type 1 implementation-effectiveness trial tests HN-STAR effectiveness while studying barriers and facilitators to implementation in community oncology practices within the National Cancer Institute Community Oncology Research Program. Effectiveness will be measured as differences in key survivorship outcomes between HNC participants who do and do not use HN-STAR over one year after the clinic visit. The primary endpoint is HNC-specific quality of life; other outcomes include patient-centered measures and receipt of guideline-concordant care. Implementation outcomes will be assessed of survivors, providers, and clinic stakeholders. The hybrid design will provide insight into a dose-response relationship between the extent of implementation fidelity and effectiveness outcomes, as well as how to incorporate HN-STAR into standard practice outside the research setting.
Subject(s)
Head and Neck Neoplasms , Survivorship , Aftercare , Head and Neck Neoplasms/therapy , Humans , Pragmatic Clinical Trials as Topic , Quality of Life , Randomized Controlled Trials as Topic , SurvivorsABSTRACT
Oral candidiasis is a common side effect of cancer chemotherapy. To better understand predisposing factors, we followed forty-five subjects who received 5-fluorouracil- or doxorubicin-based treatment, during one chemotherapy cycle. Subjects were evaluated at baseline, prior to the first infusion, and at three additional visits within a two-week window. We assessed the demographic, medical and oral health parameters, neutrophil surveillance, and characterized the salivary bacteriome and mycobiome communities through amplicon high throughput sequencing. Twenty percent of all subjects developed oral candidiasis. Using multivariate statistics, we identified smoking, amount of dental plaque, low bacteriome and mycobiome alpha-diversity, and the proportions of specific bacterial and fungal taxa as baseline predictors of oral candidiasis development during the treatment cycle. All subjects who developed oral candidiasis had baseline microbiome communities dominated by Candida and enriched in aciduric bacteria. Longitudinally, oral candidiasis was associated with a decrease in salivary flow prior to lesion development, and occurred simultaneously or before oral mucositis. Candidiasis was also longitudinally associated with a decrease in peripheral neutrophils but increased the neutrophil killing capacity of Candida albicans. Oral candidiasis was not found to be associated with mycobiome structure shifts during the cycle but was the result of an increase in Candida load, with C. albicans and Candida dubliniensis being the most abundant species comprising the salivary mycobiome of the affected subjects. In conclusion, we identified a set of clinical and microbiome baseline factors associated with susceptibility to oral candidiasis, which might be useful tools in identifying at risk individuals, prior to chemotherapy.
ABSTRACT
BACKGROUND: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. RESULTS: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. CONCLUSIONS: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis.
Subject(s)
Drug-Related Side Effects and Adverse Reactions/microbiology , Dysbiosis/etiology , Microbiota/drug effects , Mouth Mucosa/microbiology , Mouth Mucosa/pathology , Stomatitis/etiology , Antineoplastic Agents/adverse effects , Bacteria/drug effects , Drug Therapy , Dysbiosis/microbiology , Fluorouracil/adverse effects , Fungi/drug effects , Humans , Inflammation , Longitudinal Studies , Mouth/microbiology , Mouth Mucosa/drug effects , Prospective Studies , Stomatitis/microbiologyABSTRACT
PURPOSE: To improve the care of survivors of head and neck cancer, we developed the Head and Neck Survivorship Tool: Assessment and Recommendations (HN-STAR). HN-STAR is an electronic platform that incorporates patient-reported outcomes into a clinical decision support tool for use at a survivorship visit. Selections in the clinical decision support tool automatically populate a survivorship care plan (SCP). We aimed to refine HN-STAR by eliciting and incorporating feedback on its ease of use and usefulness. METHODS: Human-computer interaction (HCI) experts reviewed HN-STAR using think-aloud testing and the Nielsen Heuristic Checklist. Nurse practitioners (NPs) thought aloud while reviewing the clinical decision support tool and SCP and responded to an interview. Survivors used HN-STAR as part of a routine visit and were interviewed afterward. We analyzed themes from the feedback. We described how we addressed each theme to improve the usability of HN-STAR. RESULTS: Five HCI experts, 10 NPs, and 10 cancer survivors provided complementary usability insight that we categorized into themes of improvements. For ease of use, themes included technical design considerations to enhance user interface, ease of completion of a self-assessment, streamlining text, disruption of the clinic visit, and threshold for symptoms to appear on the SCP. The theme addressing usefulness was efficiency and comprehensiveness of the clinic visit. For each theme, we report revisions to HN-STAR in response to the feedback. CONCLUSION: HCI experts provided key technical design insights into HN-STAR, whereas NPs and survivors provided usability feedback and clinical perspectives. We incorporated the feedback into the preparation for additional testing of HN-STAR. This method can inform and improve the ease of use and usefulness of the survivorship applications.
Subject(s)
Cancer Survivors/psychology , Head and Neck Neoplasms/nursing , Survivorship , User-Computer Interface , Decision Support Systems, Clinical , Female , Head and Neck Neoplasms/psychology , Humans , Interviews as Topic , Male , Middle Aged , Patient Reported Outcome Measures , SoftwareABSTRACT
BACKGROUND: Intravenously (IV)-injected gold nanoparticles (AuNPs) powerfully enhance the efficacy of X-ray therapy of tumors including advanced gliomas. However, pharmacokinetic issues, such as slow tissue clearance and skin discoloration, may impede clinical translation. The direct infusion of AuNPs into the tumor might be an alternative mode of delivery. MATERIALS AND METHODS: Using the advanced, invasive, and difficult-to-treat F98 rat glioma model, we have studied the biodistribution of the AuNPs in the tumor and surrounding brain after either IV injection or direct intratumoral infusion by convection-enhanced delivery using light microscopy immunofluorescence and direct gold visualization. RESULTS: IV-injected AuNPs localize more specifically to intracerebral tumor cells, both in the main tumor mass and in the migrated tumor cells as well as the tumor edema, than do the directly infused AuNPs. Although some of the directly infused AuNPs do access the main tumor region, such access is largely restricted. CONCLUSION: These data suggest that IV-injected AuNPs are likely to have a greater therapeutic benefit when combined with radiation therapy than after the direct infusion of AuNPs.
Subject(s)
Brain Neoplasms/drug therapy , Convection , Drug Delivery Systems , Glioma/drug therapy , Gold/chemistry , Metal Nanoparticles/chemistry , Animals , Astrocytes/pathology , Brain Neoplasms/blood supply , Brain Neoplasms/pathology , Cell Line, Tumor , Edema/pathology , Glioma/blood supply , Glioma/pathology , Injections, Intravenous , Microglia/pathology , Neoplasm Invasiveness , Rats , Rats, Inbred F344 , Stereotaxic Techniques , Tissue DistributionABSTRACT
Purpose This guideline provides recommendations on the management of adults after head and neck cancer (HNC) treatment, focusing on surveillance and screening for recurrence or second primary cancers, assessment and management of long-term and late effects, health promotion, care coordination, and practice implications. Methods ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. The American Cancer Society (ACS) HNC Survivorship Care Guideline was reviewed for developmental rigor by methodologists. An ASCO Expert Panel reviewed the content and recommendations, offering modifications and/or qualifying statements when deemed necessary. Results The ASCO Expert Panel determined that the ACS HNC Survivorship Care Guideline, published in 2016, is clear, thorough, clinically practical, and helpful, despite the limited availability of high-quality evidence to support many of the recommendations. ASCO endorsed the ACS HNC Survivorship Care Guideline, adding qualifying statements aimed at promoting team-based, multispecialty, multidisciplinary, collaborative head and neck survivorship care. Recommendations The ASCO Expert Panel emphasized that caring for HNC survivors requires a team-based approach that includes primary care clinicians, oncology specialists, otolaryngologists, dentists, and other allied professionals. The HNC treatment team should educate the primary care clinicians and patients about the type(s) of treatment received, the likelihood of potential recurrence, and the potential late and long-term complications. Primary care clinicians should recognize symptoms of recurrence and coordinate a prompt evaluation. They should also be prepared to manage late effects either directly or by referral to appropriate specialists. Health promotion is critical, particularly regarding tobacco cessation and dental care. Additional information is available at www.asco.org/HNC-Survivorship-endorsement and www.asco.org/guidelineswiki .