Citations

PURPOSE: Routine use of extended-fraction (> 10 fractions) radiation therapy (RT) for palliation of bone metastases is recognized as a low-value intervention by the American Society for Radiation Oncology. We examined contemporary practice patterns of, and physician characteristics associated with extended-fraction RT use. MATERIALS AND METHODS: We conducted a retrospective cohort study using Medicare fee-for-service data. We included patients who underwent 2- or 3-dimensional external-beam RT for bone metastases between January 1, 2016, and December 31, 2018. Physicians treating > 10 patients over the study period were analyzed for their individual practice. Hierarchic logistic regression modeling was used to identify patient- and physician-level factors associated with extended-fraction RT use. RESULTS: A total of 12,221 patients (median age, 75.6 years; 40.9% women, 87.6% white) were included. The rate of extended-fraction RT was 23.4%. A total of 1,432 physicians treated any patient. Among the 382 physicians treating > 10 patients, 127 (33.2%) used extended-fraction RT > 30% (consensus threshold). Physician factors associated with decreased odds of extended-fraction RT were years since medical school graduation (≤ 10 years and 11-20 years v ≥ 31 years: adjusted odds ratio [aOR], 0.32 [95% CI, 0.20 to 0.51] and 0.64 [95% CI, 0.44 to 0.93]) and practicing in the Northeast or Midwest versus the South (aOR, 0.36 [95% CI, 0.22 to 0.58] and 0.48 [95% CI, 0.31 to 0.74]). Physicians treating > 20 patients ( v 11-14 patients) over the study period had increased odds of delivering extended-fraction RT (aOR, 1.53 [95% CI, 1.10 to 2.12]). CONCLUSION: In this study, almost one fourth of patients received extended-fraction RT, and one third of physicians had an extended-fraction RT use rate of > 30%. Personalized feedback of performance data, clinical pathways and peer review, and updated reimbursement models are potential mechanisms to address this low-value care.

6133 Background: Patient (pt) trial experience may give insight to quality of life (QOL) factors affecting accrual, retention and outcome. While pts are vital to clinical trial success, we know little about their post-trial opinions. This trial examined pt opinion of their trial and treatment decision making (TDM). Methods: Pts enrolled on designated North Central Cancer Treatment Group (NCCTG) phase II or III treatment trials completed the TDM Control Preferences Scale at baseline and the Was It Worth It (WIWI) satisfaction assessment at the ends of cycle 1 and active protocol treatment. The primary endpoint was the proportion of pts reporting worthwhile participation. Fisher Exact tests compared pt opinion across subgroups. Results: As of 01/15/2012, 264 pts were enrolled on 25 protocols and treated at 79 sites. 86% of pts were in phase II studies and 89% had stage IV disease. At the end of cycle 1, pts felt the trial was worthwhile (74%), would do it again (85%), and would recommend it to others (82%). 85% of pts reported undiminished QOL and only 7% rated the trial worse than expected. End of treatment responses were similar. Satisfaction rates varied by tumor site (p=0.04). 11% of pts having tumor response rated the trial as not worthwhile, and 66% of pts with progressive disease rated it worthwhile (see table). Pts with concordant preferred and actual TDM roles rated participation higher than pts with discordant TDM roles (see table). Conclusions: Most pts endorsed their clinical trial experience. Contrary to popular beliefs, treatment outcome did not have an overwhelming impact on pt satisfaction, and was just one of many factors such as TDM role discordance. Assessing pt satisfaction will inform future study design that can potentially improve pt accrual and retention. [Table: see text]

Abstract Abstract 3008 Poster Board II-984 Introduction: The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients (pts) with cancer chemotherapy-associated anemia (CAA). Extended-interval ESA dosing (i.e., administration less than once weekly) is a common practice with DA, which is FDA approved for dosing once every 3 weeks (q3wks); a previous study of the North Central Cancer Treatment Group suggested that EA can also be given less often than the FDA-approved once weekly schedule (Steensma DP et al, J Clin Onc 2006; 24:1079). The present study compared 2 different q3wks extended-interval EA regimens with weekly fixed-dose EA and with q3wks DA in pts with CAA. Patients and Methods: Eligible pts were receiving chemotherapy for a non-myeloid malignancy and had Hb <10.5 g/dL, ferritin >20 ng/mL, weight >40 kg and <150 kg, and ECOG performance score £2. Pts were randomized 1:1:1:1 to receive EA 40,000 Units subcutaneously (SC) once weekly (40K arm), EA 80,000 Units SC q3wks (80K arm), EA 120,000 Units SC q3wks (120K arm), or DA 500 mcg SC q3wks (DA arm), for 15 weeks. EA and DA were held for Hb >12 g/dL and restarted at a lower dose when Hb fell to '11.5 g/dL. All pts received ferrous sulfate 325 mg orally once daily, if tolerated. Quality of life (QOL) was measured using the Symptom Distress Scale (SDS), Brief Fatigue Inventory (BFI), FACT-An, and Linear Analogue Self Assessment (LASA) tools. The primary endpoint was the proportion of pts achieving Hb≥11.5 g/dL or increment of Hb>2.0 g/dL from baseline. Secondary endpoints included RBC transfusion requirements, adverse events (AEs), and QOL. Results: 239 pts (236 evaluable) enrolled at 10 MCCRC sites between Feb. 2007 and Dec. 2008; 62% of pts completed all study interventions. The median age of enrolled pts was 66 years; 42.4% were men, 91.5% had solid tumors, 26.7% had severe anemia (Hb <9.5 g/dL), and 44.9% were receiving platinum-containing regimens. Baseline characteristics were balanced between study arms, with the exception of gender (39% female for 40K, 60% for 80K, 43% for 120K, 26% for DA). There were no significant differences between treatment arms in the proportion of pts achieving a Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; p>0.41 for all comparisons), but the median Hb increment from baseline was higher in the 40K and DA arms compared to the 2 extended dosing EA arms (40K-2.8 g/dL, 80K-2.0 g/dL, 120K-2.1 g/dL, DA-2.6 g/dL; p=0.005 for 40K vs 80K). Hb response was achieved more quickly in the weekly EA arm, but the difference was not significant (40K-32 days, 80K-50 days, 120K-49 days, DA-49 days; p>0.13). The proportion of patients transfused was similar between arms (40K-27.9%, 80K-33.3%, 120K-22.4%, DA-29.8%; p>0.49). There were no significant differences in QOL changes. Deaths were also similar between arms (40K-5 pts, 80K-7 pts, 120K-7 pts, DA-1 pt, p>0.10) and were primarily due to disease progression. AEs and serious AEs were comparable between study groups; grade 3/4 AEs were observed in 22% of pts in the 40K arm, 22% on 80K, 17% on 120K, and 13% on DA; p>0.56. The median total dose of EA used was highest in the 120K arm (40K-265,000 U; 80K-240,000 U; 120K-360,000 U; p=0.0009 for 40K vs 120K), while pts on the 40K arm were more likely to omit a dose due to a high Hb (40K-63.9% of pts omitted at least one dose; 80K-30.0%; 120K-34.5%; DA-43.6%, p<0.0001 for 40K vs 80K). Conclusion: Although there was no significant difference in the proportion of responding pts (the primary endpoint), Hb increments from baseline were moderately higher with the 2 FDA-approved regimens – weekly EA 40,000 Units, and q3wk DA 500 mcg – than with the extended dosing regimens. This study was supported by a grant from Centocor Ortho Biotech, Inc. to the MCCRC. Disclosures: No relevant conflicts of interest to declare.

Abstract We have taken a genetic strategy to define the mechanisms underlying the increased risk of VTE in myeloma patient treated with thalidomide using clinical trial data derived from the MRC, ECOG, Little Rock and HOVON trial groups. Baseline VTE rates in the MRC IX study, (CTD vs CVAD; n=748 no prophylactic anticoagulation), were 14%. Rates in both arms were equal but in the thalidomide arm, thrombotic events were all DVT’s or PE’s, whereas in the CVAD arm they split equally between line related and VTE’s. In the other comparison (CTD vs MP; n=542), the VTE rate was 17%, all in the thalidomide arm. Rates were similar or higher (30%) in the other trials depending on the intensity of treatment used. We carried out a nested case control on DNA from MRC IX on 90 VTE (45 thalidomide, 45 non-thalidomide related), matched to 180 controls. SNPlex analysis for 60 SNPs in the coagulation cascade, DNA repair, thalidomide, metabolism and myeloma specific pathways, identified 7 genes which affected risk (NBS1, MTHFR, Ku80, Cyp3A5, LGAL52 and IL12B). This suggests three major pathways contribute to the risk of thalidomide related VTE, metabolism of thalidomide, tumour responsiveness and some pro-thrombotic factors. These factors differ from non-thalidomide related risk where a strong pro-inflammatory response is most relevant. We tested this hypothesis further using an expanded panel of 3,404 SNPs (BOAC panel), using the Megalle system. Statistical analysis of this data defined the top 20 thalidomide and non-thalidomide associated SNPs, which were consistent with the initial hypothesis, the results of which exclude variation in the coagulation cascade as being a significant risk factor. We explored this hypothesis further using pathway-based analysis focussing on the MTHFR, DNA repair and WNT pathways on data from the ECOG, HOVON and Little Rock data sets. The biological relevance of the SNPs and genes identified was validated by correlating the level of expression using the Affymetrix U133 CHIP with genetic variation at the DNA level. To verify the relevance of DNA repair variability to tumour response further, we correlated gene expression profiling with response and again Ku80 was identified as one of a cluster of genes defining increased risk. The data suggests that the risk of thalidomide related VTE relates to rapid tumour lysis combined with a prothrombotic tendency, whereas in line related thrombosis, risk is dependent upon a strong proinflammatory response. We are building this genetic data into a clinical risk model in order to allow us to develop a rationale for intervention strategies.

2002 Background: This study sought to update the predictive significance of the three WHO-defined molecular glioma subgroups ( IDHwt, IDHmt/noncodel, and IDHmt/codel) in the subset of specimens available for analysis in NRG Oncology/RTOG 9802, a phase III trial of high-risk low-grade gliomas (LGGs) treated with radiation (RT) with and without PCV after biopsy/surgical resection. Notably, this is the first phase III study to evaluate the predictive value of the WHO subgroups in LGGs using prospectively-collected, well-annotated long-term overall survival data, in a post-hoc analysis. Methods: IDH1/2 mutation status was determined by immunohistochemistry and/or next-generation sequencing. 1p/19q status was determined by Oncoscan and/or 450K methylation data. Treatment effects on overall survival (OS) and progression-free survival (PFS) by marker status were determined by the Cox proportional hazard model and tested using the log-rank test in a secondary and exploratory analysis. Results: Of all the randomized eligible high-risk G2 patients (N = 251) in NRG Oncology/RTOG 9802, 106(42%) patients had tissue available with sufficient quality DNA for profiling. Of these, 80(75%) were IDHmut; 43(41%) were IDHmut/non-co-deleted, 37(35%) were IDHmut/co-deleted, and 26(24%) were IDHwt. Upon univariate analyses, no significant difference in either PFS or OS was observed with the addition of PCV in the IDHwt subgroup. Both the IDHmut/non-co-deleted and IDHmut/co-deleted subgroups were significantly correlated with longer PFS (HR = 0.32; p = 0.003; HR = 0.13; p < 0.001) and OS (HR = 0.38; p = 0.013; HR = 0.21; p = 0.029) in the RT plus PCV arm, respectively. Conclusions: Our analyses suggest that both IDHmut/non-co-deleted and IDHmut/co-deleted subgroups received benefit from treatment with PCV although sample size is limited and analyses are post-hoc. Our results also support the notion that IDHwt high-risk LGG patients do not benefit from the addition of PCV to RT. Funding: U10CA180868, U10CA180822, and U24CA196067. Also, R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01, BTFC, OSU-CCC (all to AC). Clinical trial information: NCT00003375.

ABSTRACTAimPatients with autosomal dominant polycystic kidney disease (ADPKD) are at increased risk of premature mortality, morbidities and complications, which severely impair quality of life. However, patient‐centered outcomes are not consistently reported in trials in ADPKD, which can limit shared decision‐making. We aimed to identify outcomes important to patients and caregivers and the reasons for their priorities.MethodsNominal group technique was adopted involving patients with ADPKD and caregivers who were purposively selected from eight centres across Australia, France and the Republic of Korea. Participants identified, ranked and discussed outcomes for trials in ADPKD. We calculated an importance score (0–1) for each outcome and conducted thematic analyses.ResultsAcross 17 groups, 154 participants (121 patients, 33 caregivers) aged 19 to 78 (mean 54.5 years) identified 55 outcomes. The 10 highest ranked outcomes were: kidney function (importance score 0.36), end‐stage kidney disease (0.32), survival (0.21), cyst size/growth (0.20), cyst pain/bleeding (0.18), blood pressure (0.17), ability to work (0.16), cerebral aneurysm/stroke (0.14), mobility/physical function (0.12), and fatigue (0.12). Three themes were identified: threatening semblance of normality, inability to control and making sense of diverse risks.ConclusionFor patients with ADPKD and their caregivers, kidney function, delayed progression to end‐stage kidney disease and survival were the highest priorities, and were focused on achieving normality, and maintaining control over health and lifestyle. Implementing these patient‐important outcomes may improve the meaning and relevance of trials to inform clinical care in ADPKD.

Background: Glenoid bone loss is a well-accepted risk factor for failure after arthroscopic stabilization of anterior glenohumeral instability. Glenoid bone loss in posterior instability has been noted relative to its existence in posterior instability surgery. Its effect on outcomes after arthroscopic stabilization has not been specifically evaluated and reported. Purpose: The purpose was to evaluate the presence of posterior glenoid bone loss in a series of patients who had undergone arthroscopic isolated stabilization of the posterior labrum. Bone loss was then correlated to return-to-duty rates, complications, and validated patient-reported outcomes. Study Design: Case-control study; Level of evidence, 3. Methods: A retrospective review was conducted at a single military treatment facility over a 4-year period (2010-2013). Patients with primary posterior instability who underwent arthroscopic isolated posterior labral repair were included. Preoperative magnetic resonance imaging was used to calculate posterior glenoid bone loss using a standardized “perfect circle” technique. Demographics, return to duty, complications, and reoperations, as well as outcomes scores including the Single Assessment Numeric Evaluation and the Western Ontario Shoulder Instability Index (WOSI) scores, were obtained. Outcomes were analyzed across all patients based on percentage of posterior glenoid bone loss. Bone loss was then categorized as below or above the subcritical threshold of 13.5% to determine if bone loss effected outcomes similar to what has been shown in anterior instability. Results: There were 43 consecutive patients with primary, isolated posterior instability, and 32 (74.4%) completed WOSI scoring. Mean follow-up was 53.7 months (range, 25-82 months) The mean posterior glenoid bone loss was 7.3% (0%-21.5%). Ten of 32 patients (31%) had no appreciable bone loss. Bone loss exceeded 13.5% in 7 of 32 patients (22%), and 2 patients (6%) exceeded 20% bone loss. Return to full duty or activity was nearly 90% overall. However, those with >13.5%, subcritical glenoid bone loss, were statistically less likely to return to full duty (relative risk = 1.8), but outcomes scores, complications, and revision rates were otherwise not different in those with no or minimal bone loss versus those with more significant amounts. Conclusion: Posterior glenoid bone loss has not previously been evaluated independently relative to patients with shoulder instability repairs. Sixty-nine percent of our patients had measurable bone loss, and 22% had greater than 13.5%, or above subcritical bone loss. While these patients were statistically less likely to return to full duty, the reoperation rate, complications, and patient-reported outcomes between groups were not different.

704 Background: Inpatients with gastrointestinal (GI) malignancies are at a high risk for Clostridium difficile infection (CDI) but the impact of CDI on outcomes in these patients needs elucidation. We analyzed the incidence of CDI and its impact on outcomes in GI cancer patients using the National Hospital Discharge Survey (NHDS) database from 2001 - 2010. Methods: NHDS collects clinical information on patients dismissed from non-Federal short-stay United States hospitals. Demographics, diagnoses (GI malignancies, CDI and comorbidities), length of stay (LOS), and dismissal information were abstracted using ICD-9 diagnosis and procedure codes. Weighted analyses were performed using SAS version 9.4. Results: Of an estimated 317.9 million unique hospitalizations; 4.6 million had a diagnosis of a GI malignancy (1.4%); median age 68 years, 46.1% female. CDI was more common in patients with GI malignancies compared to patients with no GI malignancy (1.05% vs 0.69%, aOR 1.16, 95% CI 1.15- 1.17, p < 0.0001). There was a significant increase in CDI incidence in GI cancer patients over the 10-year study period (72.7 in 2001-2002 to 109.1 in 2009-2010, per 10,000 discharges, p < 0001). In multivariable analysis, compared to GI cancer patients without CDI, GI cancer patients with CDI had a longer mean LOS (3.94 more days, 95% CI 3.31-4.56) and dismissal to a care facility (adjusted OR, 1.75; 95% CI, 1.71-1.79), but lower all-cause in-hospital mortality (adjusted OR, 0.76; 95% CI, 0.74-0.79), all p < 0.0001 Conclusions: In this national database of hospitalized patients, an increasing incidence of CDI in patients with GI malignancies was noted over the study period. CDI prolonged hospitalization, and was associated with increased dismissal to a care-facility. Lower rates of in-hospital mortality may represent early diagnosis due to vigilance or a milder form of CDI. Despite increased attention over the last few decades, CDI remained a serious infection in GI cancer patients, and merits appropriate prevention, management and follow-up.