Associations of daily weight management-focused social support with weight loss, activity behaviors, and eating regulation in the context of metabolic and bariatric surgery.

Objective: Greater perceived social support (PSS) is associated with more favorable changes in weight loss, activity behaviors, and eating regulation after metabolic and bariatric surgery (MBS). However, studies have relied on generic, retrospective PSS measures, and stability of PSS levels and relations with weight loss and weight-related behaviors over time is unknown. Using smartphone-based Ecological Momentary Assessment, this study evaluated pre-to 1-year post-MBS changes in daily weight management-focused PSS and associations with weight loss, device-measured activity behaviors, and eating regulation before and during the initial year after MBS. Method: Adult MBS patients (n = 71) received (1) an accelerometer to measure daily moderate-to-vigorous intensity physical activity (MVPA) and sedentary time (ST) minutes/day, and (2) a smartphone to complete morning weight-focused PSS ratings and eating regulation (dietary restraint/disinhibition) ratings at four semi-random times daily for 10 days at pre- and 3, 6, and 12-month postoperative. Generalized linear mixed models analyzed the associations of PSS with total weight loss (%TWL) and activity/eating outcomes. Results: Participants on average reported relatively stable moderate-to-high PSS (3.98 on one to five scale) across assessments. Perceived social support was not related to %TWL, MVPA, or ST. Participants with higher PSS reported lower disinhibition and higher restraint than those with lower PSS (ps < 0.05); however, participants reported higher restraint on days that PSS was lower than their usual levels (p = 0.009). Conclusions: MBS patients on average had stable PSS levels across time. Higher PSS levels were associated with greater resistance to overeating cues (disinhibition) and cognitive control to restrict food intake (restraint) over time. Additionally, participants reported higher restraint when PSS levels were lower than usual. Overall, weight-focused PSS appeared to hold greater importance in relation to regulating eating behavior than engaging in activity behaviors or weight loss among MBS patients during the initial postoperative year. Clinical Trial Registration: NCT02777177.

The prognostic value of Eastern Cooperative Oncology Group performance status on overall survival among patients with metastatic prostate cancer: a systematic review and meta-analysis.

Background: There is heterogeneity in the literature regarding the strength of association between Eastern Cooperative Oncology Group performance status (ECOG PS) and mortality. We conducted a systematic review and meta-analysis of studies reporting the prognostic value of ECOG PS on overall survival (OS) in metastatic prostate cancer (mPC). Methods: PubMed was searched from inception to March 21, 2022. A meta-analysis pooling the effect of ECOG PS categories (≥2 vs. <2, 2 vs. <2, and ≥1 vs. <1) on OS was performed separately for studies including patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC) using a random-effects model. Analyses were stratified by prior chemotherapy and study type. Results: Overall, 75 studies, comprising 32,298 patients, were included. Most studies (72/75) included patients with mCRPC. Higher ECOG PS was associated with a significant increase in mortality risk, with the highest estimate observed among patients with mCRPC with an ECOG PS of ≥2 versus <2 (hazard ratio [HR]: 2.10, 95% confidence interval [CI]: 1.87-2.37). When stratifying by study type, there was a higher risk estimate of mortality among patients with mCRPC with an ECOG PS of ≥1 versus <1 in real-world data studies (HR: 1.98, 95% CI: 1.72-2.26) compared with clinical trials (HR: 1.32, 95% CI: 1.13-1.54; p < 0.001). There were no significant differences in the HR of OS stratified by previous chemotherapy. Conclusion: ECOG PS was a significant predictor of OS regardless of category, previous chemotherapy, and mPC population. Additional studies are needed to better characterize the effect of ECOG PS on OS in mCSPC.

Associations of physical activity and sedentary behavior with appetite sensations and eating regulation behaviors before and during the initial year following bariatric surgery.

Background: Bariatric surgery produces weight loss in part by impacting appetite and eating behavior. Research suggests physical activity (PA) assists with regulation of appetite and eating during non-surgical weight loss, although whether PA carries similar benefits in the context of bariatric surgery is unknown. Objective: Evaluate associations of moderate-to-vigorous intensity PA (MVPA) and sedentary time (ST) with appetite sensations (hunger [homeostatic/hedonic], satiety) and eating regulation behaviors (restraint, disinhibition) before and during the initial year following bariatric surgery. Method: Adult bariatric patients received an accelerometer to measure MVPA/ST and a smartphone to complete appetite/eating ratings at four semi-random times daily for 10 days at pre- and 3-, 6-, and 12-months post-surgery. Data were analyzed using generalized linear mixed models. Results: Higher MVPA levels related to more satiety across time (p = 0.045) and more restraint at 3-months post-surgery (p < 0.001). At pre-surgery, higher MVPA levels also related to more disinhibition (p's < 0.01), although participants reported more disinhibition on days they performed less MVPA than usual (p = 0.017). MVPA did not relate to hunger. Lower ST levels related to more hedonic hunger (p = 0.003), especially at 12-months post-surgery (p < 0.001), and participants reported more homeostatic hunger on days they accumulated more ST than usual (p = 0.044). Additionally, higher ST levels related to more disinhibition at 3-months post-surgery (p's < 0.01) and lower restraint at pre-surgery (p's < 0.05). ST did not relate to satiety. Conclusions: This study is the first to show that MVPA and ST each associate with appetite and eating regulation in daily life before and during post-surgical weight loss. Results, while preliminary and requiring experimental confirmation, highlight potential for targeting bariatric patients' activity behaviors to enhance modulation of appetite, control of food intake, and resistance to overeating.

Tumor Lysis Syndrome: Implications for Oncology Nursing Practice.

OBJECTIVES: To provide an overview of tumor lysis syndrome, which is one of the metabolic oncologic emergencies. DATA SOURCES: A review and synthesis of empirical articles. CONCLUSION: One of the metabolic oncologic emergencies identified by the Oncology Nursing Society is tumor lysis syndrome. This condition is life-threatening and is characterized by metabolic derangements that can lead to acute kidney injury and multiple organ dysfunction. Normal intracellular components (potassium, phosphorus, and nucleic acids) spill into the bloodstream when cancer cells die. If the tumor is large and highly responsive to chemotherapy, the resulting cascade of dead tumor cells may overwhelm normal homeostatic mechanisms. The cells enter the bloodstream faster than they can be cleared by the kidneys. This results in hyperkalemia and hyperphosphatemia. Nucleic acids convert to uric acid in the liver with a resultant hyperuricemia. Excess uric acid in the kidneys can lead to uric acid nephropathy and renal insufficiency. Phosphorus binds with calcium, leading to hypocalcemia from the formation of calcium phosphate precipitate or crystals. These crystals can also lead to renal insufficiency or acute kidney injury, which can lead to a metabolic acidosis and exacerbation of the hyperkalemic state. These metabolic derangements define presence of tumor lysis syndrome. IMPLICATIONS FOR NURSING PRACTICE: Multidisciplinary collaboration and communication is essential to identifying patients at risk prior to treatment. Meticulous nursing care in terms of prevention and treatment is critical to patient survival.

Comprehensive Genomic Profiling of Adult Renal Sarcomas Provides Insight into Disease Biology and Opportunities for Targeted Therapies.

BACKGROUND: Primary adult renal sarcomas (RSs) are rare aggressive neoplasms. Clinical outcomes are extremely poor, and optimal treatment remains challenging. OBJECTIVE: To identify genomic alterations (GAs) in patients with RSs. DESIGN, SETTING, AND PARTICIPANTS: Comprehensive genomic profiling (CGP) was conducted on DNA/RNA extracted from formalin-fixed paraffin-embedded tissue using the FoundationOne Heme/Sarcoma assay in 13 adult, locally advanced or metastatic RSs of various histologic types. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All classes of GAs, including base substitutions, small indels, rearrangements, copy number alterations, tumor mutational burden (TMB), and microsatellite instability (MSI), were analyzed. RESULTS AND LIMITATIONS: CGP revealed 55 GAs (4.2 per tumor), 29 of which were clinically relevant genomic alterations (CRGAs; 2.2 per tumor). At least one CRGA was detected in nine (69%) cases. High-level amplifications (more than six copies) involving 4q12 amplicon of the KIT and PDGFRA genes were identified in four (31%) cases (two undifferentiated pleomorphic sarcomas [UPSs], one sarcomatoid renal cell carcinoma, and one myxofibrosarcoma). Both UPSs also had KDR gene amplification in addition to KIT and PDGFRA. Additional CRGAs were found in CDKN2A/B (23%), NF1 (23%), and MET (8%). All RSs were MSI stable, the mean TMB was 3.5 mutations/megabase (Mb), and none (0%) featured TMB >10 mutations/Mb. Limitations include the small sample size. CONCLUSIONS: RSs are characterized by diverse histology and genomic profiles including 31% of cases with 4q12 amplification harboring the KIT/PDGFRA/KDR genes. Of the tumors, 69% carry CRGAs, which could lead to potential benefit from targeted therapies; however, a low TMB also suggests that these cases are unlikely to respond to checkpoint inhibitors. PATIENT SUMMARY: This study provides insights into molecular biology of renal sarcoma, a rare aggressive subtype of kidney tumors. We demonstrated that renal sarcomas harbor unique, recurrent, clinically relevant molecular abnormalities that provide new opportunities for targeted therapies.

Ecological momentary assessment of gastrointestinal symptoms and risky eating behaviors in Roux-en-Y gastric bypass and sleeve gastrectomy patients.

BACKGROUND: Gastrointestinal symptoms (GIS) are common after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). However, little is known about frequencies of GIS and their co-occurrence with risky eating behaviors. OBJECTIVES: Compare RYGB and SG on GIS and risky eating behaviors, and test associations between GIS and behaviors. SETTING: Two university hospitals in Northeastern United States. METHODS: RYGB (n = 18) and SG (n = 53) patients completed smartphone-based ecological momentary assessment of GIS and risky eating behaviors at 4 semi-random times daily for 10 days preoperatively and at 3, 6, and 12 months postoperatively. Study objectives were evaluated using generalized linear mixed-effects models. RESULTS: All available data from each assessment were included in the analysis: participant attrition was 18%, 30%, and 38% at 3, 6, and 12 months. All GIS were reduced at 12 months postoperative. Bloating decreased consistently whereas cramping, dehydration, and dumping first increased at 3 to 6 months then decreased to 12 months. Diarrhea, nausea, reflux, and vomiting decreased to 12 months for RYGB, but first increased at 3 to 6 months then decreased to 12 months for SG. Consumption of carbonated and sugar-sweetened beverages, fatty meats, and sweets decreased to 6 months then rebounded at 12 months. Eating past the first sign of fullness, drinking liquids with meals, not starting meals with protein, and fried foods consumption decreased to 6 months and then rebounded for RYGB only at 12 months. Alcohol consumption did not change. Sweets consumption and eating past the first sign of fullness were most consistently associated with GIS for both RYGB and SG patients. CONCLUSION: GIS and risky eating behaviors improved postoperatively, although patterns of change were variable and occasionally differed between RYGB and SG. Pending replication, patients may benefit from intervention to limit risky behaviors that are tailored to their surgery type.

Oral Cytokine Levels Are More Linked to Levels of Plasma and Oral HIV-1 RNA Than to CD4+ T-Cell Counts in People With HIV.

BACKGROUND: We determined the levels of 11 soluble immune mediators in oral washings of AIDS Clinical Trials Group A5254 participants with varying degrees of plasma viremia and CD4 T-cell counts to characterize the mucosal immune response at different stages of HIV-1 infection. METHODS: A5254 was a multicenter, cross-sectional study in people with HIV (PWH) recruited into 4 strata based on CD4 count and levels of plasma viremia: stratum (St) A: CD4 ≤200 cells/mm3, HIV-1 RNA (viral load [VL]) >1000 cps/mL; St B: CD4 ≤200, VL ≤1000; St C: CD4 >200, VL >1000; St D: CD4 >200, VL ≤1000. Oral/throat washings were obtained from all participants. Soluble markers were tested in oral/throat washings using a multibead fluorescent platform and were compared across strata. Linear regression was used to determine the associations between cytokines and HIV-1 in plasma and oral fluid. RESULTS: St A participants had higher levels of interleukin (IL)-1ß, IL-6, IL-17, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) compared with St B and D (P = .02; P < .0001) but were not different from St C. IL-8, IL-10, and IL-12 were elevated in St A compared with the other 3 strata (P = .046; P < .0001). Linear regression demonstrated that oral HIV-1 levels were associated with IL-1ß, IL-6, IL-8, and TNFα production (R > .40; P < .001) when controlling for CD4 count and opportunistic infections. CONCLUSIONS: Our results show that high levels of oral HIV-1, rather than low CD4 counts, were linked to the production of oral immune mediators. Participants with AIDS and uncontrolled viremia demonstrated higher levels of pro- and anti-inflammatory soluble immune mediators compared with participants with lower HIV-1 RNA. The interplay of HIV-1 and these immune mediators could be important in the oral health of PWH.

Prolonged sedentary time adversely relates to physical activity and obesity among preoperative bariatric surgery patients.

BACKGROUND: Bariatric surgery patients spend much of their waking time sedentary. Yet, little is known about their patterns of accumulation of sedentary time (ST) and whether more prolonged ST is associated with lower physical activity (PA), independent of total ST, or obesity severity. OBJECTIVES: To characterize variability in prolonged ST among bariatric patients preoperatively and assess the importance of a "prolonger" pattern in relation to PA and weight status. SETTING: Two university hospital clinics, United States. METHODS: Adult patients (n = 76) wore a wrist-based accelerometer for 10 days preoperatively. ST and time spent in light and moderate-to-vigorous PA was determined using validated thresholds. Percent of total ST accumulated in ≥30-consecutive ST minute bouts was calculated, and participants were trichotomized into low, medium, and high "prolongers" based on this value. The associations of prolonged ST with PA and obesity were examined. RESULTS: On average, participants accumulated a mean ± standard deviation of 10.5 ± 2.1 hours of ST per day, 30% of which was prolonged (prolonger groups: low = 7.2%-24.5%, medium = 24.5%-33.0%, and high = 34.0%-52.6% of ST in ≥30-min bouts). Adjusting for covariates including total ST, high prolongers had fewer light PA minutes per day (P < .01), and a greater percentage of prolonged ST related to lower likelihood of meeting the national guideline of ≥150 moderate-to-vigorous PA minutes per week (P = .012). High (versus low) prolongers had more severe obesity (P < .05). CONCLUSIONS: Accumulating a greater percentage of ST in prolonged bouts appears to be adversely related to PA and obesity severity among bariatric patients. Future research should determine whether interrupting prolonged ST with brief breaks can favorably modify PA and weight in this population.

The Pan-Cancer Landscape of Coamplification of the Tyrosine Kinases KIT, KDR, and PDGFRA.

PURPOSE: Amplifications of receptor tyrosine kinases (RTKS) are therapeutic targets in multiple tumor types (e.g. HER2 in breast cancer), and amplification of the chromosome 4 segment harboring the three RTKs KIT, PDGFRA, and KDR (4q12amp) may be similarly targetable. The presence of 4q12amp has been sporadically reported in small tumor specific series but a large-scale analysis is lacking. We assess the pan-cancer landscape of 4q12amp and provide early clinical support for the feasibility of targeting this amplicon. EXPERIMENTAL DESIGN: Tumor specimens from 132,872 patients with advanced cancer were assayed with hybrid capture based comprehensive genomic profiling which assays 186-315 genes for all classes of genomic alterations, including amplifications. Baseline demographic data were abstracted, and presence of 4q12amp was defined as 6 or more copies of KIT/KDR/PDGFRA. Concurrent alterations and treatment outcomes with matched therapies were explored in a subset of cases. RESULTS: Overall 0.65% of cases harbored 4q12amp at a median copy number of 10 (range 6-344). Among cancers with >100 cases in this series, glioblastomas, angiosarcomas, and osteosarcomas were enriched for 4q12amp at 4.7%, 4.8%, and 6.4%, respectively (all p < 0.001), giving an overall sarcoma (n = 6,885) incidence of 1.9%. Among 99 pulmonary adenocarcinoma cases harboring 4q12amp, 50 (50%) lacked any other known driver of NSLCC. Four index cases plus a previously reported case on treatment with empirical TKIs monotherapy had stable disease on average exceeding 20 months. CONCLUSION: We define 4q12amp as a significant event across the pan-cancer landscape, comparable to known pan-cancer targets such as NTRK and microsatellite instability, with notable enrichment in several cancers such as osteosarcoma where standard treatment is limited. The responses to available TKIs observed in index cases strongly suggest 4q12amp is a druggable oncogenic target across cancers that warrants a focused drug development strategy. IMPLICATIONS FOR PRACTICE: Coamplification of the receptor tyrosine kinases (rtks) KIT/KDR/PDGFRA (4q12amp) is present broadly across cancers (0.65%), with enrichment in osteosarcoma and gliomas. Evidence for this amplicon having an oncogenic role is the mutual exclusivity of 4q12amp to other known drivers in 50% of pulmonary adenocarcinoma cases. Furthermore, preliminary clinical evidence for driver status comes from four index cases of patients empirically treated with commercially available tyrosine kinase inhibitors with activity against KIT/KDR/PDGFRA who had stable disease for 20 months on average. The sum of these lines of evidence suggests further clinical and preclinical investigation of 4q12amp is warranted as the possible basis for a pan-cancer drug development strategy.

Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study.

Cancer treatments have evolved from indiscriminate cytotoxic agents to selective genome- and immune-targeted drugs that have transformed the outcomes of some malignancies1. Tumor complexity and heterogeneity suggest that the 'precision medicine' paradigm of cancer therapy requires treatment to be personalized to the individual patient2-6. To date, precision oncology trials have been based on molecular matching with predetermined monotherapies7-14. Several of these trials have been hindered by very low matching rates, often in the 5-10% range15, and low response rates. Low matching rates may be due to the use of limited gene panels, restrictive molecular matching algorithms, lack of drug availability, or the deterioration and death of end-stage patients before therapy can be implemented. We hypothesized that personalized treatment with combination therapies would improve outcomes in patients with refractory malignancies. As a first test of this concept, we implemented a cross-institutional prospective study (I-PREDICT, NCT02534675 ) that used tumor DNA sequencing and timely recommendations for individualized treatment with combination therapies. We found that administration of customized multidrug regimens was feasible, with 49% of consented patients receiving personalized treatment. Targeting of a larger fraction of identified molecular alterations, yielding a higher 'matching score', was correlated with significantly improved disease control rates, as well as longer progression-free and overall survival rates, compared to targeting of fewer somatic alterations. Our findings suggest that the current clinical trial paradigm for precision oncology, which pairs one driver mutation with one drug, may be optimized by treating molecularly complex and heterogeneous cancers with combinations of customized agents.

Multi-sensor ecological momentary assessment of behavioral and psychosocial predictors of weight loss following bariatric surgery: study protocol for a multicenter prospective longitudinal evaluation.

BACKGROUND: Bariatric surgery is currently the most effective strategy for producing significant and durable weight loss. Yet, not all patients achieve initial weight loss success and some degree of weight regain is very common, sometimes as early as 1-2 years post-surgery. Suboptimal weight loss not fully explained by surgical, demographic, and medical factors has led to greater emphasis on patient behaviors evidenced by clinical guidelines for appropriate eating and physical activity. However, research to inform such guidelines has often relied on imprecise measures or not been specific to bariatric surgery. There is also little understanding of what psychosocial factors and environmental contexts impact outcomes. To address research gaps and measurement limitations, we designed a protocol that innovatively integrates multiple measurement tools to determine which behaviors, environmental contexts, and psychosocial factors are related to outcomes and explore how psychosocial factors/environmental contexts influence weight. This paper provides a detailed description of our study protocol with a focus on developing and deploying a multi-sensor assessment tool to meet our study aims. METHODS: This NIH-funded prospective cohort study evaluates behavioral, psychosocial, and environmental predictors of weight loss after bariatric surgery using a multi-sensor platform that integrates objective sensors and self-report information collected via smartphone in real-time in patients' natural environment. A target sample of 100 adult, bariatric surgery patients (ages 21-70) use this multi-sensor platform at preoperative baseline, as well as 3, 6, and 12 months postoperatively, to assess recommended behaviors (e.g., meal frequency, physical activity), psychosocial indicators with prior evidence of an association with surgical outcomes (e.g., mood/depression), and key environmental factors (e.g., type/quality of food environment). Weight also is measured at each assessment point. DISCUSSION: This project has the potential to build a more sophisticated and valid understanding of behavioral and psychosocial factors contributing to success and risk after bariatric surgery. This new understanding could directly contribute to improved (i.e., specific, consistent, and validated) guidelines for recommended pre- and postoperative behaviors, which could lead to improved surgical outcomes. These data will also inform behavioral, psychosocial, and environmental targets for adjunctive interventions to improve surgical outcomes. TRIAL REGISTRATION: Registered trial NCT02777177 on 5/19/2016.

Greater Adherence to Recommended Morning Physical Activity is Associated With Greater Total Intervention-Related Physical Activity Changes in Bariatric Surgery Patients.

BACKGROUND: This study examines whether performance of bout-related physical activity (PA) during morning hours is related to greater overall bout-related PA increases within a preoperative PA intervention for bariatric surgery (BS) patients. METHODS: Participants with severe obesity (n = 33; mean age = 45.6 ± 9.6 years; BMI = 45.7 ± 7.0 kg/m2) seeking BS were randomized to and completed 6 weeks of preoperative PA counseling (retention = 82.5%). Participants were encouraged to walk daily at a moderate intensity in bouts ≥ 10 minutes during morning hours to overcome time-related obstacles and establish a PA habit. Timing and amount of bout-related moderate-to-vigorous PA (MVPA) was assessed via objective monitor at pre- and postintervention. RESULTS: Greater proportion of bout-related MVPA performed during morning hours (4:00 AM-12:00 PM) at postintervention was associated with larger total increases in bout-related MVPA minutes/day (ß = .40, P = .03). At postintervention, a greater proportion of participants whose longest MVPA bouts occurred during morning hours (n = 11) achieved the public health guideline (ie, ≥150 bout-related MVPA minutes/week) versus those whose longest MVPA bouts occurred during nonmorning hours (n = 19; 63.6% vs. 26.3%, P = .04). CONCLUSIONS: Intervention-related increases in PA tended to be greatest when PA was performed in the morning. Morning exercise may be a viable strategy for promoting habitual PA in inactive BS patients.

Changes in enjoyment, self-efficacy, and motivation during a randomized trial to promote habitual physical activity adoption in bariatric surgery patients.

BACKGROUND: The Bari-Active trial found that a physical activity (PA) intervention (PAI), versus standard presurgical care control (SC), produced significant increases in daily bout-related moderate-to-vigorous PA (MVPA, in≥10-min bouts) preoperatively. The present study examined whether PAI also produces superior improvements in psychological and/or motivational processes that may be important for PA adoption. OBJECTIVES: Compare PAI and SC on baseline to postintervention changes in PA-related enjoyment, self-efficacy, and motivations, and examine whether greater bout-related MVPA changes are associated with greater improvements in these variables. SETTING: University hospital, United States. METHODS: Participants (87% female; body mass index = 45.0±6.5 kg/m(2)) were randomly assigned to 6 weeks of PAI (n = 40) or SC (n = 35). PAI received weekly counseling sessions to increase daily walking exercise. At baseline and postintervention, both groups completed 7-day objective PA monitoring and questionnaires to evaluate changes in bout-related MVPA and PA enjoyment, self-efficacy, and motivation. RESULTS: Retention was 84% at postintervention. Intent-to-treat analyses showed that PAI on average reported more favorable changes than SC in PA enjoyment, self-efficacy, amotivation (i.e., lack of PA motivation), and identified and intrinsic regulations (i.e., more autonomous PA motivations; P<.01). In PAI completers (n = 33), changes in bout-related MVPA and psychological/motivational variables were unrelated. CONCLUSION: PAI produced greater improvements in PA-related enjoyment, self-efficacy, and motivations than SC. The lack of association between objectively measured PA changes and psychological/motivational processes highlights the need for future research to identify which processes are most important for PA adoption and maintenance in bariatric surgery patients, and to determine whether the method used to measure PA affects the pattern of association.

Community Oncology Medical Homes: Physician-Driven Change to Improve Patient Care and Reduce Costs.

Although the patient-centered medical home is a well-established model of care for primary care providers, adoption by specialty providers has been relatively limited. Recently, there has been particular interest in developing specialty medical homes in medical oncology because of practice variation, care fragmentation, and high overall costs of care. In 2012, the Center for Medicare and Medicaid Innovation awarded Innovative Oncology Business Solutions a 3-year grant for their Community Oncology Medical Home (COME HOME) program to implement specialty medical homes in seven oncology practices across the country. We report our early experience and lessons learned.Through September 30, 2014, COME HOME has touched 16,353 unique patients through triage encounters, patient education visits, or application of clinical pathways. We describe the COME HOME model and implementation timeline, profile use of key services, and report patient satisfaction. Using feedback from practice sites, we highlight patient-centered innovations and overall lessons learned.COME HOME incorporates best practices care driven by triage and clinical pathways, team-based care, active disease management, enhanced access and care, as well as financial support for the medical home infrastructure. Information technology plays a central role, supporting both delivery of care and performance monitoring. Volume of service use has grown steadily over time, leveling out in second quarter 2014. The program currently averages 1,265 triage encounters, 440 extended hours visits, and 655 patient education encounters per month.COME HOME offers a patient-centered model of care to improve quality and continuity of care.

Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample.

PURPOSE: Epidermal growth factor receptor (EGFR) inhibitors are approved for treating metastatic colorectal cancer (CRC); KRAS mutation testing is recommended prior to treatment. We conducted a non-inferiority analysis to examine whether KRAS testing has impacted survival in CRC patients. PATIENTS AND METHODS: We included 1186 metastatic CRC cases from seven health plans. A cutpoint of July, 2008, was used to define two KRAS testing time period groups: "pre-testing" (n = 760 cases) and "post-testing" (n = 426 cases). Overall survival (OS) was estimated, and the difference in median OS between the groups was calculated. The lower bound of the one-sided 95% confidence interval (CI) for the difference in survival was used to test the null hypothesis of post-testing inferiority. Multivariable Cox regression models were constructed to adjust for covariates. RESULTS: The median unadjusted OS was 15.4 months (95% CI: 14.0-17.5) and 12.8 months (95% CI: 10.0-15.2) in the pre- and post-testing groups, respectively. The OS difference was -2.6 months with one-sided 95% lower confidence bound of -5.13 months, which was less than the non-inferiority margin (-5.0 months, unadjusted p = 0.06), leading to a failure to reject inferiority of OS in the post-testing period. In contrast, in the adjusted analysis, OS non-inferiority was identified in the post-testing period (p = 0.001). Sensitivity analyses using cutpoints before and after July, 2008, also met the criteria for non-inferiority. CONCLUSION: Implementation of KRAS testing did not influence CRC OS. Our data support the use of KRAS testing to guide administration of EGFR inhibitors for treatment of metastatic CRC without diminished OS.

Underutilization of Lynch syndrome screening in a multisite study of patients with colorectal cancer.

PURPOSE: The aim of this study was to examine Lynch syndrome screening of patients with metastatic colorectal cancer in integrated health-care-delivery organizations. METHODS: We determined the availability of Lynch syndrome screening criteria and actual Lynch syndrome screening in the medical records of 1,188 patients diagnosed with metastatic colorectal cancer between 2004 and 2009 at seven institutions in the Cancer Research Network. RESULTS: We found infrequent use of Lynch syndrome screening (41/1,188). Family history was available for 937 of the 1,188 patients (79%). There was sufficient information to assess Lynch syndrome risk using family history-based criteria in 719 of the 937 patients (77%) with family history documentation. In 391 individuals with a family history of a Lynch syndrome-associated cancer, 107 (27%) could not be evaluated due to missing information such as age of cancer onset. Eleven percent of patients who met the Bethesda criteria and 25% of individuals who met the Amsterdam II criteria were screened for Lynch syndrome. Recommended guidelines were adhered to during screening, but no testing method was preferred. CONCLUSION: The information required for Lynch syndrome screening decisions is routinely collected but seldom used. There is a critical gap between collection of family history and its use to guide Lynch syndrome screening, which may support a case for implementation of universal screening guidelines.

Description and pilot results from a novel method for evaluating return of incidental findings from next-generation sequencing technologies.

PURPOSE: The aim of this study was to develop, operationalize, and pilot test a transparent, reproducible, and evidence-informed method to determine when to report incidental findings from next-generation sequencing technologies. METHODS: Using evidence-based principles, we proposed a three-stage process. Stage I "rules out" incidental findings below a minimal threshold of evidence and is evaluated using inter-rater agreement and comparison with an expert-based approach. Stage II documents criteria for clinical actionability using a standardized approach to allow experts to consistently consider and recommend whether results should be routinely reported (stage III). We used expert opinion to determine the face validity of stages II and III using three case studies. We evaluated the time and effort for stages I and II. RESULTS: For stage I, we assessed 99 conditions and found high inter-rater agreement (89%), and strong agreement with a separate expert-based method. Case studies for familial adenomatous polyposis, hereditary hemochromatosis, and α1-antitrypsin deficiency were all recommended for routine reporting as incidental findings. The method requires <3 days per topic. CONCLUSION: We establish an operational definition of clinically actionable incidental findings and provide documentation and pilot testing of a feasible method that is scalable to the whole genome.

KRAS testing and epidermal growth factor receptor inhibitor treatment for colorectal cancer in community settings.

BACKGROUND: In metastatic colorectal cancer (mCRC), mutations in the KRAS gene predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our study investigates the clinical uptake and utilization of KRAS testing. METHODS: We included 1,188 patients with mCRCs diagnosed from 2004 to 2009, from seven integrated health care delivery systems with a combined membership of 5.5 million. We used electronic medical records and targeted manual chart review to capture the complexity and breadth of real-world clinical oncology care. RESULTS: Overall, 428 patients (36%) received KRAS testing during their clinical care, and 266 (22%) were treated with EGFR inhibitors. Age at diagnosis (P = 0.0034), comorbid conditions (P = 0.0316), and survival time from diagnosis (P < 0.0001) influence KRAS testing and EGFR inhibitor prescribing. The proportion who received KRAS testing increased from 7% to 97% for those treated in 2006 and 2010, respectively, and 83% of all treated patients had a KRAS wild-type genotype. Most patients with a KRAS mutation (86%) were not treated with EGFR inhibitors. The interval between mCRC diagnosis and receipt of KRAS testing decreased from 26 months (2006) to 10 months (2009). CONCLUSIONS: These findings show rapid uptake and incorporation of this predictive biomarker into clinical oncology care. IMPACT: In this delivery setting, KRAS testing is widely used to guide treatment decisions with EGFR inhibitors in patients with mCRCs. An important future research goal is to evaluate utilization of KRAS testing in other delivery settings in the United States.

Utilization of HER2 genetic testing in a multi-institutional observational study.

INTRODUCTION: Human epidermal growth factor receptor 2 (HER2) expression is amplified in about 20% of breast cancer tumors, and evaluation of HER2 status should influence therapy selection. A critical gap in our knowledge is the real-world implementation of HER2 testing and its impact on treatment decisions for women diagnosed with breast cancer. OBJECTIVES: To assess use of HER2 testing, to describe characteristics of patients who do or do not receive HER2 testing, to describe which HER2 tests were used (fluorescence in situ hybridization or immunohistochemistry), and to evaluate trastuzumab use as a function of HER2 results. STUDY DESIGN: The population included 6460 women diagnosed with invasive breast cancer between 1999 and 2007 at 8 geographically distributed Cancer Research Network healthcare delivery systems in the United States. METHODS: Electronic records were used to identify patient and tumor characteristics and treatment with trastuzumab. Chart abstraction was performed for 400 women (50 per site) to identify receipt of HER2 testing and results. RESULTS: More than 90% of study participants received HER2 testing. Everyone who received trastuzumab had a HER2 test, and nearly all (>95%) who received trastuzumab had a positive HER2 test result recorded in their medical chart. Most (77%) eligible patients with a positive HER2 test result diagnosed after 2005 received trastuzumab. This study expands upon previous work in individual health plans. CONCLUSIONS: HER2 status has been successfully incorporated into medical practice to guide treatment decisions for breast cancer patients in diverse integrated healthcare delivery settings.