Real-World Use of Electronic Patient-Reported Outcome (ePRO) Tools Integrated in the Electronic Medical Record During Radiation Therapy for Head and Neck Cancer: Feasibility Study.

Purpose Use of electronic patient-reported outcome (ePRO) tools in routine oncology practice can be challenging despite evidence showing they can improve survival, improve patient and practitioner satisfaction, and reduce medical resource utilization. Head and neck cancer (HNC) patients receiving radiation therapy (RT) may be a group that would particularly benefit from interventions focused on early symptom management. Methods Patients undergoing definitive RT for HNC were enrolled in a feasibility study and received ePRO surveys integrated within the electronic medical record (EMR) on a weekly basis during RT. After completion of each ePRO survey, a radiation oncology registered nurse documented the findings and subsequent interventions within the EMR. Results Thirty-four patients with HNC who received curative RT at a single center were enrolled. The total number of surveys completed was 194 with a median of 7 surveys per patient (range 1-8). There was a total of 887 individual abnormal findings reported on the ePROs, and the authors found that all 887 had a corresponding documented intervention. Post-treatment practitioner questionnaires highlighted that ePROs were felt to be helpful for the care team in providing care to HNC patients. Conclusion For patients with HNC receiving RT, ePROs can be effectively utilized to address patient symptoms within an integrated health care system. Creating an infrastructure for the use of ePROs integrated within the EMR in routine care requires an approach that accounts for local workflows and buy-in from patients and the entire care team.

Preoperative Treatment of Locally Advanced Rectal Cancer.

BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048).

PURPOSE: The standard of care for locally advanced rectal cancer in North America is neoadjuvant pelvic chemoradiation with fluorouracil (5FUCRT). Neoadjuvant chemotherapy with fluorouracil and oxaliplatin (FOLFOX) is an alternative that may spare patients the morbidity of radiation. Understanding the relative patient experiences with these options is necessary to inform treatment decisions. METHODS: PROSPECT was a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX versus 5FUCRT, which enrolled adults with rectal cancer clinically staged as T2N+, cT3N-, or cT3N+ who were candidates for sphincter-sparing surgery. Neoadjuvant FOLFOX was given in six cycles over 12 weeks, followed by surgery. Neoadjuvant 5FUCRT was delivered in 28 fractions over 5.5 weeks, followed by surgery. Adjuvant chemotherapy was suggested but not mandated in both groups. Enrolled patients were asked to provide patient-reported outcomes (PROs) at baseline, during neoadjuvant treatment, and at 12 months after surgery. PROs included 14 symptoms from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Additional PRO instruments measured bowel, bladder, sexual function, and health-related quality of life (HRQL). RESULTS: From June 2012 to December 2018, 1,194 patients were randomly assigned, 1,128 initiated treatment, and 940 contributed PRO-CTCAE data (493 FOLFOX; 447 5FUCRT). During neoadjuvant treatment, patients reported significantly lower rates of diarrhea and better overall bowel function with FOLFOX while anxiety, appetite loss, constipation, depression, dysphagia, dyspnea, edema, fatigue, mucositis, nausea, neuropathy, and vomiting were lower with 5FUCRT (all multiplicity adjusted P < .05). At 12 months after surgery, patients randomly assigned to FOLFOX reported significantly lower rates of fatigue and neuropathy and better sexual function versus 5FUCRT (all multiplicity adjusted P < .05). Neither bladder function nor HRQL differed between groups at any time point. CONCLUSION: For patients with locally advanced rectal cancer choosing between neoadjuvant FOLFOX and 5FUCRT, the distinctive PRO profiles inform treatment selection and shared decision making.

Pediatric lymphoma patients in Malawi present with poor health-related quality of life at diagnosis and improve throughout treatment and follow-up across all Pediatric PROMIS-25 domains.

BACKGROUND: Patient-reportedoutcomes (PROs) that assess health-related quality of life (HRQoL) are increasingly important components of cancer care and research that are infrequently used in sub-Saharan Africa (SSA). METHODS: We administered the Chichewa Pediatric Patient-Reported Outcome Measurement Information System Pediatric (PROMIS)-25 at diagnosis, active treatment, and follow-up among pediatric lymphoma patients in Lilongwe, Malawi. Mean scores were calculated for the six PROMIS-25 HRQoL domains (Mobility, Anxiety, Depressive Symptoms, Fatigue, Peer Relationships, Pain Interference). Differences in HRQoL throughout treatment were compared using the minimally important difference (MID) and an ANOVA analysis. Kaplan-Meier survival estimates and Cox hazard ratios for mortality are reported. RESULTS: Seventy-five children completed PROMIS-25 surveys at diagnosis, 35 (47%) during active treatment, and 24 (32%) at follow-up. The majority of patients died (n = 37, 49%) or were lost to follow-up (n = 6, 8%). Most (n = 51, 68%) were male, median age was 10 (interquartile range [IQR] 8-12), 48/73 (66%) presented with advanced stage III/IV, 61 (81%) were diagnosed with Burkitt lymphoma and 14 (19%) Hodgkin lymphoma. At diagnosis, HRQoL was poor across all domains, except for Peer Relationships. Improvements in HRQoL during active treatment and follow-up exceeded the MID. On exploratory analysis, fair-poor PROMIS Mobility <40 and severe Pain Intensity = 10 at diagnosis were associated with increased mortality risk and worse survival, but were not statistically significant. CONCLUSIONS: Pediatric lymphoma patients in Malawi present with poor HRQoL that improves throughout treatment and survivorship. Baseline PROMIS scores may provide important prognostic information. PROs offer an opportunity to include patient voices and prioritize holistic patient-centered care in low-resource settings.

Patient-Reported Outcomes Integrated Within an Electronic Medical Record in Patients With Head and Neck Cancer.

PURPOSE: Patient-reported outcome (PRO) tools lead to clinical benefits, including improved overall survival for patients with cancer. However, routine implementation of PROs in clinical practice within the electronic medical record (EMR) by integrated health care delivery systems remains limited. We studied the use of a PRO tool for patients with head and neck cancer (HNC) integrated in an EMR at Kaiser Permanente in Northern California. METHODS: Between August 2017 and December 2019, patients with newly diagnosed HNC were surveyed at baseline, then every 3 months using the Functional Assessment of Cancer Therapy-General 7 and Functional Assessment of Cancer Therapy-Head and Neck (version 4). A medical assistant performed a baseline survey on diagnosis and then notified patients electronically per surveillance protocol. Patients who did not respond to online PRO surveys could complete them via telephone or in-person appointments with medical assistants. Abnormal findings on PRO surveys were referred to appropriate members of the care team or the treating Otolaryngology-Head and Neck Surgery physicians. RESULTS: Two hundred ninety patients received baseline surveys. Patients received up to a maximum of eight subsequent surveys. Of a total of 597 electronic surveys, 585 (97.9%) were completed. The percentage of patients completing each interval survey ranged from 92% to 100%. Multivariate Poisson regression analysis showed patients with English as their primary language and an online secure account were the most likely to complete surveys compared with those patients with non-English as a primary language and without an online account. CONCLUSION: PRO tools can be effectively used within the EMR for patients with HNC with a high response rate provided there is strong engagement from a dedicated member of the care team. This has important implications for designing clinical trials and symptom monitoring in clinical practices that incorporate EMRs.

Feasibility and delivery of patient-reported outcomes in clinical practice among racially diverse bladder and prostate cancer patients.

OBJECTIVE: To assess the feasibility of enrollment and collecting patient-reported outcome (PRO) data as part of routine clinical urologic care for bladder and prostate cancer patients and examine overall patterns and racial variations in PRO use and symptom reports over time. SUBJECTS/PATIENTS AND METHODS: We recruited 76 patients (n = 29 Black and n = 47 White) with prostate or bladder cancer at a single, comprehensive cancer center. The majority of prostate cancer patients had intermediate risk (57%) disease and underwent either radiation or prostatectomy. Over half (58%) of bladder cancer patients had muscle invasive disease and underwent cystectomy. Patients were asked to complete PRO symptom surveys using their preferred mode [web- or phone-based interactive voice response (IVR)]. Symptom summary reports were shared with providers during visits. Surveys were completed at 3 time points and assessed urinary, sexual, gastrointestinal, anxiety/depression, and sleep symptoms. Feasibility of enrollment and survey completion were calculated, and linear mixed effects models estimated differences in outcomes by race and time. RESULTS: Sixty three percent of study participants completed all PRO measures at all 3 time points. Black patients were more likely to select IVR as their survey mode (40% vs. 13%, P < 0.05), and less likely to complete all surveys (55% vs. 74%, P = 0.13). Patients using IVR were also less likely to complete all surveys (41% vs. 69%, P = 0.046). CONCLUSIONS: Reported preferences for survey mode and completion rates differ by race, which may influence survey completion rates and highlight potential obstacles for equitable implementation of PROs into clinical care.

Older Adults with Cancer: A Randomized Controlled Trial of Occupational and Physical Therapy.

OBJECTIVES: The impact of occupational therapy (OT) and physical therapy (PT) on functional outcomes in older adults with cancer is unknown. DESIGN: Two-arm single-institution randomized controlled trial of outpatient OT/PT. SETTING: Comprehensive cancer center with two off-site OT/PT clinics. PARTICIPANTS: We recruited adults 65 years and older with a recent diagnosis or recurrence of cancer within 5 years, with at least one functional limitation as identified by a geriatric assessment. Participants were randomized to OT/PT or usual care. INTERVENTION: Rehabilitation consisted of individualized OT and PT that addressed functional activities and strength/endurance needs. MEASUREMENTS: Primary outcome was functional status as measured by the Nottingham Extended Activities of Daily Living scale. Secondary outcomes were Patient-Reported Outcomes Measurement Information System-Global Mental Health (GMH) and Global Physical Health (GPH), ability to participate in Social Roles (SR), physical function, and activity expectations and self-efficacy (Possibilities for Activity Scale [PActS]). RESULTS: Among those recruited (N = 63), only 45 patients (71%) were evaluable due to loss of follow-up and/or nonreceipt of intervention. The median age was 74 years; 53% were female, and 91% were white. Overall, 30% patients had hematologic malignancies, 30% breast cancer, and 16% colorectal cancers. A total of 65% were in active treatment; 49% had stage 3 or 4 disease. At follow-up, both OT/PT (P = .02) and usual care (P = .03) groups experienced a decline in functional status. PActS scores between groups (P = .04) was significantly improved in the intervention group. GMH and SR met criteria for minimally important clinical difference favoring the intervention, but not statistical significance. Several barriers were noted in the implementation of the intervention program: recruitment, concerns about cost, distance, scheduling, and limited treatment provided. CONCLUSION: OT/PT may positively influence activity expectations and self-efficacy. Future research needs to address significant barriers to implementation to increase use of OT/PT services and access to quality care. J Am Geriatr Soc 67:953-960, 2019.

Challenges and solutions in the design and execution of the PROSPECT Phase II/III neoadjuvant rectal cancer trial (NCCTG N1048/Alliance).

BACKGROUND: More than half of the 40,000 incident rectal cancer patients in the United States each year are diagnosed at clinical stage II and III (locally advanced stage). For this group, high rates of cure can be achieved with the combination of pelvic radiation and sensitizing 5-fluorouracil (chemoradiation), surgery and chemotherapy, but treatment is long, arduous and toxicities are substantial. The PROSPECT trial (N1048, NCT01515787) was designed to determine whether neoadjuvant chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX) could be used as an alternative to neoadjuvant chemoradiation without compromising treatment outcomes and to spare these patients excess toxicity. The statistical design balanced the twin co-primary goals of achieving low local and distant recurrence rates. Study design features contended with the need for stringent safeguards given limited phase II data, the need for straightforward criteria to facilitate both accrual and protocol fidelity and the importance of patients' perspectives on symptom burden and treatment toxicity. METHODS: PROSPECT is an ongoing multi-site two-group seamless phase II/III randomized trial comparing standard neoadjuvant chemoradiation versus neoadjuvant chemotherapy with selective use of chemoradiation for patients with locally advanced rectal cancer. Challenges addressed in the design and conduct of PROSPECT have included the following: (1) setting safety thresholds given limited single-center phase II data, (2) establishing workable eligibility criteria, (3) balancing competing time to local and distant recurrence as co-primary endpoints and (4) obtaining reliable and complete data for patients' symptom burden. The design and implementation challenges, choices, modifications and their implications for the design of future national cooperative group clinical trials are presented. RESULTS: PROSPECT incorporated stringent thresholds for both complete surgical resection (R0) and the time to local recurrence as early stopping rules. When predetermined stopping criteria were not met after evaluation of the first 366 participants in the randomized phase II, the study transitioned seamlessly to phase III with cumulative accrual of over 1000 participants. Eligibility criteria stipulating rectal tumor location based on distance from the anal verge were unworkable, and the protocol was amended to a more pragmatic approach that assigned surgeons with primary responsibility for determining eligibility. Central radiology review was feasible and in some cases prompted discontinuation of protocol treatment. Participation in toxicity reporting using the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events was uniformly high and was well accepted by participants from over 200 sites in the United States, Canada and Switzerland. CONCLUSION: The strategies used to overcome these obstacles may inform the design of other studies that involve multi-modality treatment interventions, particularly trials where implementation of consistent criteria for eligibility and outcomes across hundreds of practice settings is necessary.

Sorafenib for Advanced and Refractory Desmoid Tumors.

BACKGROUND: Desmoid tumors (also referred to as aggressive fibromatosis) are connective tissue neoplasms that can arise in any anatomical location and infiltrate the mesentery, neurovascular structures, and visceral organs. There is no standard of care. METHODS: In this double-blind, phase 3 trial, we randomly assigned 87 patients with progressive, symptomatic, or recurrent desmoid tumors to receive either sorafenib (400-mg tablet once daily) or matching placebo. Crossover to the sorafenib group was permitted for patients in the placebo group who had disease progression. The primary end point was investigator-assessed progression-free survival; rates of objective response and adverse events were also evaluated. RESULTS: With a median follow-up of 27.2 months, the 2-year progression-free survival rate was 81% (95% confidence interval [CI], 69 to 96) in the sorafenib group and 36% (95% CI, 22 to 57) in the placebo group (hazard ratio for progression or death, 0.13; 95% CI, 0.05 to 0.31; P<0.001). Before crossover, the objective response rate was 33% (95% CI, 20 to 48) in the sorafenib group and 20% (95% CI, 8 to 38) in the placebo group. The median time to an objective response among patients who had a response was 9.6 months (interquartile range, 6.6 to 16.7) in the sorafenib group and 13.3 months (interquartile range, 11.2 to 31.1) in the placebo group. The objective responses are ongoing. Among patients who received sorafenib, the most frequently reported adverse events were grade 1 or 2 events of rash (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). CONCLUSIONS: Among patients with progressive, refractory, or symptomatic desmoid tumors, sorafenib significantly prolonged progression-free survival and induced durable responses. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT02066181 .).

Pharmaceutical assistance programs for cancer patients in the era of orally administered chemotherapeutics.

Introduction The rising cost of cancer drugs may make treatment unaffordable for some patients. Patients often rely on drug manufacturer-administered Pharmaceutical Assistance Programs (PAPs) to obtain drugs and reduced or no cost. The overall usage of PAPs within cancer care delivery is unknown. Methods We included all cancer patients across an academically affiliated, integrated health system in North Carolina during 2014 ( N = 8591). We identified the subset of patients receiving PAP assistance to afford one or more cancer drugs, in order to calculate the proportion of patients receiving PAP assistance, and the retail value of the assistance. Results Among 8591 cancer patients, 215 unique patients submitted a total of 478 successful PAP requests for cancer drugs. 40% of PAP-utilizing patients were uninsured, 23% had Medicaid coverage, 20% had Medicare coverage, 2% were dual Medicare/Medicaid eligible, and 14% were commercially insured. Among all cancer patients who received medical treatment, 6.0% required PAP assistance, whereas 10.6% receiving an oral agent required PAP assistance. The proportion receiving PAP assistance varied substantially by drug, ranging from <1% of patients (e.g. carboplatin, methotrexate) to 50% of patients (e.g. ponatinib, temsirolimus). The majority of the retail value obtained was for oral agents, including $1,556,575 of imatinib and $1,449,633 of dasatinib, which were the two drugs with the highest aggregate retail value. Conclusions A substantial proportion of cancer patients receive private charitable assistance to obtain standard-of-care treatments. This includes patients with federal and private insurance, suggesting an inability of patients to meet cost-sharing requirements.

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial.

PURPOSE: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). METHODS AND MATERIALS: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. RESULTS: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." CONCLUSIONS: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.

Financial Relationships With Industry Among National Comprehensive Cancer Network Guideline Authors.

IMPORTANCE: Financial conflicts of interest (FCOIs) among authors of clinical practice guidelines have the potential to influence treatment recommendations. OBJECTIVE: To quantify FCOIs with industry among authors of the National Comprehensive Cancer Network (NCCN) guidelines. DESIGN, SETTING, AND PARTICIPANTS: We assessed FCOIs occurring during 2014 among NCCN guideline authors in the United States. All were physician members of the NCCN guideline committees for lung, breast, prostate, and colorectal cancer as of the end of 2014. The data source for FCOIs was Open Payments, which is publically reported by the Centers for Medicare and Medicaid Services. This study was cross-sectional. MAIN OUTCOMES AND MEASURES: The proportion of NCCN authors having FCOIs with industry; the average amount received from industry sources per author. RESULTS: Of 125 guideline authors, 108 (86%) had at least 1 reported FCOI. Authors received an average of $10 011 (range, $0-$106 859) in general payments (GPs), which include consulting, meals, lodging, and similar transfers of value, and $236 066 (range $0-$2 756 713) in industry research payments (RPs), including funding associated with clinical trials. Approximately 84% of authors received GPs, while 47% received RPs. Eight (6%) had FCOIs in excess of the $50 000 net and/or $20 000 single-company maximums stipulated by NCCN. CONCLUSIONS AND RELEVANCE: Among NCCN guideline authors, FCOIs involving RPs were of greater value, while those involving GPs were more prevalent. Although FCOIs may result from engaging in important scholarship, FCOIs may still influence guideline authors in counterproductive ways. Research is needed to understand how best to manage author FCOIs during guideline creation.

Statewide geographic variation in outcomes for adults with acute myeloid leukemia in North Carolina.

BACKGROUND: Population-based studies have demonstrated survival disparities related to socioeconomic factors for patients with acute myeloid leukemia (AML). The objective of the current study was to determine whether the local health care infrastructure, represented by Area Health Education Centers (AHEC) region, or treating center experience, represented by National Cancer Institute Comprehensive Cancer Center (NCICCC) designation, were associated with outcomes among patients with AML in North Carolina. METHODS: Patients who were diagnosed with AML from 2003 to 2009 were identified using the University of North Carolina Lineberger Integrated Cancer Information and Surveillance System, a database linking insurance claims to the North Carolina Cancer Registry. A Cox proportional-hazards model was used to explore survival based on AHEC region. A subset of patients who received inpatient chemotherapy was examined to evaluate the impact of treatment at an NCICCC. RESULTS: Nine hundred patients were identified in the study period, 553 of whom received inpatient chemotherapy therapy within 30 days of diagnosis. Almost one-half of these patients (n = 294) received chemotherapy at a non-NCICCC. Among the patients who received intensive inpatient therapy, residence in 3 of 9 AHEC regions was associated with a higher risk of mortality (hazard ratio: range, 1.97-4.03; P < .01) at 1 year in multivariate analysis. Treatment at a non-NCICCC was not associated with an increased risk of mortality at 1 year (hazard ratio, 1.25; 95% confidence interval, 0.95-1.65). CONCLUSIONS: Survival among patients with AML in North Carolina varies according to geographic region. Further examination of local practice and referral patterns may inform strategies to improve AML outcomes across the state. Cancer 2016;122:3041-3050. © 2016 American Cancer Society.

An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration.

An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Prevalence of pain and analgesic use in men with metastatic prostate cancer using a patient-reported outcome measure.

PURPOSE: Contemporary tumor-directed therapies for metastatic castration-resistant prostate cancer (mCRPC) are approved to prolong life, but their effects on symptoms such as pain are less well understood as a result of the lack of analytically valid assessments of pain prevalence and severity, clinically meaningful definitions of therapeutic benefit, and methodologic standards of trial conduct. This study establishes pain characteristics in the mCRPC population using a PRO measure. MATERIALS AND METHODS: Patients with prostate cancer participated in an anonymous survey at five US comprehensive cancer centers in the Prostate Cancer Clinical Trials Consortium that incorporated the Brief Pain Inventory (BPI), analgesic use, and interference with daily activities. Prevalence and severity of cancer-related pain and analgesic use were tabulated according to castration-resistant status and exposure to docetaxel chemotherapy. RESULTS: Four hundred sixty-one patients with prostate cancer participated, of whom 147 had mCRPC involving bone (61% [89 of 147] docetaxel exposed, 39% [58 of 147] docetaxel naive). Pain of any level was more common among docetaxel-exposed versus docetaxel-naive patients with mCRPC (70% [62 of 89] v 38% [22 of 58], respectively; P<.001). BPI score≥4 was reported by 38% (34 of 89) of docetaxel-pretreated and 24% (14 of 58) of docetaxel-naive patients with mCRPC; 40% of these patients with pain intensity≥4 reported no current narcotic analgesic. CONCLUSION: Pain prevalence and severity were higher in patients with prior docetaxel exposure. Analgesics were underutilized. These results provide a method for estimating accruals along the disease continuum, and for enabling design of trials appropriately powered to assess pain.

An evidence-based systematic review of vitamin A by the natural standard research collaboration.

An evidence-based systematic review of vitamin A by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated and reproducible grading rationale. This paper includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

An evidence-based systematic review of gymnema (Gymnema sylvestre R. Br.) by the Natural Standard Research Collaboration.

An evidence-based systematic review of gymnema (Gymnema sylvestre R. Br.), including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Maitake mushroom (Grifola frondosa): systematic review by the natural standard research collaboration.

The objective of this study was to evaluate the scientific evidence on maitake, including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. This review serves as a clinical support tool. Electronic searches were conducted in 10 databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on the language or quality of the publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy and lactation, interactions, alteration of laboratory assays, and mechanisms of action. Standardized inclusion and exclusion criteria were used for selection. Grades were assigned using an evidence-based grading rationale. There was a lack of systematic study on the safety and effectiveness of maitake in humans. However, based on popular use and supportive scientific data, three indications are discussed in this review: cancer, diabetes, and immunostimulation. Despite the lack of scientific evidence, maitake mushroom remains a popular agent in commercial products. Future randomized controlled trials are warranted.

An evidence-based systematic review of bilberry (Vaccinium myrtillus) by the Natural Standard Research Collaboration.

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.