National Comprehensive Cancer Network Centers Research Articles

Comparative outcome of initial therapy for younger patients with mantle cell lymphoma: an analysis from the NCCN NHL Database

AbstractFew randomized trials have compared therapies in mantle cell lymphoma (MCL), and the role of aggressive induction is unclear. The National Comprehensive Cancer Network (NCCN) Non-Hodgkin Lymphoma (NHL) Database, a prospective cohort study collecting clinical, treatment, and outcome data at 7 NCCN centers, provides a unique opportunity to compare the effectiveness of initial therapies in MCL. Patients younger than 65 diagnosed between 2000 and 2008 were included if they received RHCVAD (rituximab fractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone), RCHOP+HDT/ASCR (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone + high-dose therapy/autologous stem cell rescue), RHCVAD+HDT/ASCR, or RCHOP. Clinical parameters were similar for patients treated with RHCVAD (n = 83, 50%), RCHOP+HDT/ASCR (n = 34, 20%), RCHOP (n = 29, 17%), or RHCVAD+HDT/ASCR (n = 21, 13%). Overall, 70 (42%) of the 167 patients progressed and 25 (15%) expired with a median follow-up of 33 months. There was no difference in progression-free survival (PFS) between aggressive regimens (P > .57), which all demonstrated superior PFS compared with RCHOP (P < .004). There was no difference in overall survival (OS) between the RHCVAD and RCHOP+HDT/ASCR (P = .98). RCHOP was inferior to RHCVAD and RCHOP+HDT/ASCR, which had similar PFS and OS. Despite aggressive regimens, the median PFS was 3 to 4 years. Future trials should focus on novel agents rather than comparing current approaches.

Systemic therapy for advanced appendiceal adenocarcinoma: An analysis from the National Comprehensive Cancer Network (NCCN) database.

562 Background: Appendiceal neoplasms are rare and represent 1% of intestinal tumors in the United States. The role and efficacy of modern systemic therapy in advanced appendiceal adenocarcinoma has not been established. Methods: Patients with recurrent or metastatic appendiceal adenocarcinoma in the NCCN Colorectal Database (2005-2010) were analyzed. Study objectives were to describe and evaluate the efficacy of systemic therapy and investigate relationships with clinicopathologic features. Cox regression analysis was performed to identify predictors of PFS and OS. The hazard ratio and 95% CI from Cox models and median PFS and OS from Kaplan-Meier curves were reported. Results: Of 177 patients with advanced appendiceal carcinoma, 81 (46%) received systemic therapy for measurable disease and are the focus of this report (patients undergoing IP chemotherapy excluded). Patient/tumor characteristics: median age 50 (range 20-82), ECOG PS 0/1 (67%/22%), mucinous/non-mucinous (44 %/ 51%), 91% peritoneal and 15% liver metastases. 70% of patients had primary surgical debulking. Common chemotherapy regimens included FOLFOX with or without bevacizumab (n=30 and n=28), FOLFIRI (n=11), and single-agent fluoropyrimidine (n=7). Among 70 patients with a recorded best response, the response rate (RR) was 46% with 31% stable disease. Median PFS was 1.0 year (95% CI: 0.7-1.9) and OS was 2.1 years (95% CI: 1.7-2.6). Patients with non-mucinous histology, high grade tumors and non-debulking surgery had worse PFS and OS (Table). Conclusions: Treatment of advanced appendiceal adenocarcinoma at NCCN centers commonly incorporates agents utilized for colorectal cancer. RR, PFS and OS are comparable to those achieved in the treatment of metastatic CRC and support routine use of these regimens in clinical practice. Poor prognostic factors include non-mucinous histology, high grade and not undergoing debulking surgery. [Table: see text]

Outcomes with Autologous (Auto) and Allogeneic (Allo) Stem Cell Transplantation (SCT) for Relapsed/Refractory Follicular Lymphoma (FL) in the Post-Rituximab Era: A Comparative Analysis From the National Comprehensive Cancer Network (NCCN) Non-Hodgkin's Lymphoma (NHL) Outcomes Database Project,

Abstract 4112 Background:AutoSCT and AlloSCT have both been shown to be effective for the treatment of relapsed/refractory FL. However, outcomes with either modality are not well defined in the post-rituximab era, especially regarding autoSCT. The NCCN NHL Outcomes Database was utilized to examine survival for FL patients (pts) refractory or relapsed after rituximab-based therapy who underwent subsequent autoSCT or alloSCT. Further, prognostic factors were investigated. Methods:The NCCN NHL Outcomes Database is a prospective cohort study collecting comprehensive clinical, treatment, and outcomes data for NHL pts at 7 participating NCCN centers. Among all NHL pts in the database (n=5,395), 1,670 had FL, of whom 240 had SCT during the study observation period of 1/1/00 to 12/31/09 (follow-up through May 2011). Pts were excluded if they 1) did not have relapsed/refractory FL (n=13) or 2) had not received prior rituximab (n=11). In total, 216 pts (autoSCT n=158, alloSCT n=58) were included for analysis. Median follow-up was 2.9 years. Univariate Cox proportional hazards regression was used to assess associations of prognostic factors within each type of SCT for overall survival (OS) and failure free survival (FFS). OS was defined as years from SCT to death; FFS was defined as relapse, transformation, disease progression, or death. Variables with a p <0.20 were entered into a multivariate Cox model within each type of SCT. In a similar fashion, Cox regression was used to assess OS and FFS between type of SCT. Results:There were several notable differences in pt and disease characteristics between SCT modalities. Pts who received autoSCT were significantly older at initial FL diagnosis compared with alloSCT (median 51 vs 46 years, p=0.002) and older at time of SCT (median 55 vs 51 years, p=0.005). However, median time from initial FL diagnosis to SCT was shorter for alloSCT vs autoSCT (3.3 vs 4.1 years, p=0.02). AlloSCT pts received a median of 4 prior therapies vs 3 for the autoSCT cohort (p<0.001). Further, pts who had alloSCT had a higher proportion of resistant disease at time of SCT than autoSCT pts (19% vs 7%, p=0.01), while autoSCT pts were more likely to have grade 3 FL compared with alloSCT (36% vs 9%, p=0.001). There were no comparative differences among gender, race, stage at SCT or performance status. 59% of alloSCT pts had a matched-sibling donor, while 42% had an unrelated donor. The most common conditioning regimens for autoSCT were CBV 50%, BEAM 30%, and TBI-based 16%, while for alloSCT were Flu/Mel 31%, TBI-based 28% (Flu-TBI or Cy-TBI), and Bu/Flu 24%. The cumulative rate of relapse, progression, and/or transformation was 33% for autoSCT pts compared with 16% for alloSCT (p=0.01), while the overall non-relapse mortality (NRM) rate for alloSCT was 33% vs 10% for autoSCT (p<0.0001). There was no difference in FFS between type of SCT (p=0.30) with 3-year FFS of 55% (95%CI 46%-63%) for autoSCT vs 56% (95%CI 42%-70%) for alloSCT (Figure 1). However, OS was significantly different between type of SCT (p<0.001); the 3-year OS was 85% (95%CI 79%-91%) for autoSCT compared with 64% (95%CI 50%-77%) for alloSCT (Figure 2). Factors that predicted survival on univariate analysis for pts who had autoSCT were increasing age (continuous variable, years) and >3 prior therapies, while age > 50 years and resistant disease status at SCT predicted survival for alloSCT. Further, these factors remained significant on Cox regression multivariate analysis (Table 1). Additionally, multivariate analysis including all SCT pts (n=216) was performed to compare survival between autoSCT and alloSCT. After adjusting for age, number of prior therapies, and disease status, alloSCT still showed increased risk of death compared with autoSCT (HR 2.2, 95%CI 1.2–4.1, p=0.01); no significant difference was noted for FFS (p=0.72). [Display omitted] [Display omitted] [Display omitted] Conclusion:To our knowledge, this represents the largest analysis of autoSCT and alloSCT among FL pts relapsed/refractory s/p prior rituximab. Within this multicenter prospective cohort analysis, we identified prognostic factors that predicted survival within autoSCT and alloSCT cohorts. Furthermore, autoSCT and alloSCT were associated with comparable FFS, however including adjustment for competing prognostic factors, OS was improved among pts who had autoSCT. Based on these data, we conclude that autoSCT remains a viable therapy for relapsed/refractory FL in the post-rituximab era. Disclosures:No relevant conflicts of interest to declare.

The impact of obesity on receipt of adjuvant chemotherapy for breast cancer in the National Comprehensive Cancer Network (NCCN) centers

Disparities in the receipt of adjuvant chemotherapy for early stage breast cancer is an important factor influencing mortality. We investigated whether greater body mass index (BMI) decreases receipt of adjuvant chemotherapy among women with operable breast cancer. In the NCCN breast cancer outcomes database, we identified women aged ≤ 70 with newly diagnosed stage I, II, or III breast cancer between 1997 and 2007, for whom use of adjuvant chemotherapy was classified as either standard-of-care or discretionary based on their clinical characteristics. Body mass index was assessed in categories (<18.5 kg/m(2) [underweight], 18.5 to <25 kg/m(2) [normal], 25 to <30 kg/m(2) [overweight], 30-39 kg/m(2) [obese], ≥ 40 kg/m(2) [extreme obese]). Multivariable logistic regression analysis was used to examine the association between BMI and receipt of chemotherapy in each classification group. 9,527 women were eligible for the study; 40% normal weight or less; 31% overweight; 24% obese; and 5% extremely obese. In multivariable analysis, there was no significant association between BMI and receipt of chemotherapy in either classification group. Among women for whom chemotherapy would be considered standard-of-care, older age (P < 0.001), comorbidity (P < 0.001), and non-Hispanic black ethnicity (P = 0.002) were associated with a lower likelihood of receipt of chemotherapy; however, the effect of ethnicity was not modified by obesity. Among women treated for operable breast cancer in the NCCN centers, BMI had no impact on receipt of adjuvant chemotherapy and did not modify the lower likelihood of chemotherapy among non-Hispanic black patients. Further investigation is needed into other factors that contribute to patient disparities in the receipt of chemotherapy in major academic centers.

Timing in adjuvant chemotherapy (CTX) initiation among women with breast cancer (BC) at National Comprehensive Cancer Network (NCCN) centers: An analysis from the NCCN Outcomes Database.

6022 Background: Receipt of quality care has two important dimensions: that patients receive both appropriate and timely care. The primary aim was to examine time from BC diagnosis to CTX and identify factors associated with longer time. Methods: In the NCCN Outcomes Database, we identified 5,583 women with stage I-III BC diagnosed in 2003-2008 who received adjuvant CTX at 10 NCCN centers within 32 weeks (wks) of diagnosis. Patients with neoadjuvant therapy were excluded. Multivariate ANCOVA models were constructed to examine adjusted mean Time to Chemotherapy (TTC) from the date of pathological diagnosis. Results: Mean TTC was 11.8 wks. Many sociodemographic and clinical factors were associated with longer TTC. Factors with the largest effects are listed in Table 1. Minimal prolongation of TTC was associated with initial mastectomy versus lumpectomy (3 day greater TTC, p=0.01). Greater prolongation of TTC was observed between Caucasian and African American (AA) women diagnosed at another center prior to presentation (2.1 wks, p<0.001) than at the NCCN center (1.0 wk, p=0.13), and among patients with Medicare (2.7 wks, p<0.001) versus Managed Care (MCO, 1.2 wks, p<0.001) or Medicaid (0.9 wks, p=0.99). Interactions were significant between ethnicity and both insurance (p=0.03) and diagnosing institution (p=0.02). Conclusions: Some delay in TTC associated with clinical factors (21 gene RT PCR assay or number of excisions) may be unavoidable but should be minimized. Opportunities for improvement at the system level (insurance and transfers in care) were observed. Observed disparity in TTC for AA women appears to be exacerbated by transferring care and insurance related issues. % patients Mean TTC difference, wks Race/ethnicity Caucasian 78 Ref Hispanic 7 +0.7** AA 9 +1.6*** Asian 4 0.5 Other 2 0.0 Insurance MCO 78 Ref Medicare 10 +0.6* Medicaid 7 +2.6*** Other 4 0.4 Diagnosing institution NCCN 26 Ref Non-NCCN 74 +1.2*** Excisional procedures 1 64 Ref 2 31 +2.1*** ≥3 5 +5.6*** Reconstruction prior to CTX No 82 Ref Yes 18 +2.5*** 21-gene RT PCR assay No 94 Ref Yes 6 +2.2*** *p<0.05, **p<0.01, ***p<0.001

The 2010 National Comprehensive Cancer Network (NCCN) research benchmarking survey (RBS): Clinical trials in the academic cancer center.

6116 Background: The 2010 NCCN RBS focused on therapeutic clinical trial volume, accrual rates, and protocol review processes at NCCN centers. The primary aim was to benchmark clinical trials activity including trial sponsorship, patient accrual, and the steps involved in protocol review. Methods: The survey collected quantitative and descriptive data on therapeutic trials, accruals, and sponsors. In addition, because the steps required for activation of clinical trials may result in delays and increase costs, the 2010 RBS focused on the processes and timeframes involved in protocol review. Results: Of newly reportable patients (105,917) from 19 centers reporting accruals over a 12-month period, 16,018 (15.1%) were recruited to therapeutic clinical trials; 6,097 trials (all phases) were reported. The average number of accruals per trial (all sponsors) was 2.63. 39% of trials (2,367) were sponsored by National Cancer Institute Cooperative Groups (NCI CGs), with 19% (2,866) of patient accruals attributed to NCI CG trials (1.21 accruals/trial). Comparatively, 22% of trials (1,364) were institutionally sponsored, while 40% of accruals (6,087) were enrolled in these trials (4.46 accruals/trial). 30% of trials (1,827) were industry sponsored (1,827), and accounted for 27% of accruals (4,016), or 2.20 per trial. Other peer-reviewed mechanisms accounted for the balance of trials and accruals. A broad range of timelines were reported for the steps involved in protocol review and activation indicating that 1) there are likely best practices that merit investigation and 2) further refinement and standardization of timeline definitions are warranted. An analysis of protocol review timelines is underway. Conclusions: Clinical research constitutes a core mission of NCCN centers. NCCN benchmarking efforts are undertaken to improve clinical trials operations and ultimately to impact the delivery of new therapies to patients. Accruals per trial for all sponsors appear low; the rate of 1.21 accruals per NCI CG trial is of particular concern. Further development of benchmarks and best practices will promote enhanced operations, timely review processes, and increased patient accrual.

What do 1281 distress screeners tell us about cancer patients in a community cancer center?

The 2008 Institute of Medicine's Report, Cancer Care for the Whole Patient (IOM, 2008), recommends screening cancer patients for distress. Cancer programs throughout the United States are struggling to achieve this standard. The IOM report indicates that only 14% of 1000 randomly selected American Society of Clinical Oncology (ASCO) members and eight of 15 National Comprehensive Cancer Network (NCCN) centers reported screening for distress in at least some of their patients [J Natl Compr Cancer Netw 2007;5:99-103]. Without adequate screening, distress often goes unnoticed by cancer professionals and there is little information about the prevalence of distress. The main objective of this article is to present data from 1281 distress screenings completed by patients treated within a community cancer center. Specifically, this article reports the intensity of distress, frequency of problem endorsement, and requests for specific psychosocial providers by cancer patients. Medical and radiation oncology patients completed a distress screener before their first physician appointment. The screening instrument included the Distress Thermometer, a symptom checklist, and a list of psychosocial providers that the patient could request to meet. Thirty-two percent of this sample rated distress above the threshold level. Worry was the most common problem endorsed followed by financial issues. Emotional concerns were endorsed by 59% of the sample. The cancer dietitian was the psychosocial professional most frequently requested by patients. Distress screening can be accomplished within a community cancer center but the provision of psychosocial services is difficult given the high volume of need.

Patterns of Use of FDG-PET for the Initial Staging of Follicular Lymphoma (FL) and Its Impact on Initial Treatment Strategy and Outcomes In the National Comprehensive Cancer Network (NCCN) Lymphoma Database

AbstractAbstract 81 Background:The management of follicular lymphoma (FL) can vary according to stage at presentation. The use of 18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for initial staging of FL may result in upstaging and/or changes in treatment strategy. In this study, we describe the patterns of use of FDG-PET for the initial staging of patients with newly diagnosed FL and its potential impact on treatment. Methods:Data were obtained from the NCCN Non-Hodgkin's Lymphoma Outcomes Database, a prospective cohort study collecting comprehensive clinical, treatment, and outcome data for patients treated at 7 participating NCCN centers. Patients who presented between January 1, 2001 and September 30, 2009 with newly diagnosed low grade FL (grade 1, 2), received staging imaging within 6 weeks of diagnosis, and with at least 6 months of follow-up were included. We compared baseline and clinical characteristics as well as treatment among patients by receipt of FDG-PET for initial staging. Results:We identified 953 eligible FL patients with a mean age of 56 years; 532 (56%) underwent FDG-PET as part of initial staging. Use of FDG-PET varied significantly across NCCN centers (p<0.0001). Among patients who underwent FDG-PET for initial staging, 438 (82%) received early treatment (defined as treatment within 180 days of diagnosis) compared to 259 (61.5%) who were staged with conventional CT scanning only (p<0.0001).Among 189 patients with early stage FL (ESFL), 120 (63.5%) underwent FDG-PET for initial staging. Significant differences in use were observed across NCCN centers (p<0.0001). Of all ESFL, 55 (29.1%) were treated with radiotherapy (RT) alone, 68 (36%) with chemotherapy/immunotherapy (CIT) alone, 28 (14.8%) with combined RT and CIT and 38 (20.1%) were observed. Initial treatment strategy for ESFL varied significantly according to NCCN centers (p<0.001). Choice of initial treatment strategy for ESFL did not vary significantly by use of FDG-PET (p=0.09). Conclusions:The use of FDG-PET for staging of FL varies by center and is widespread despite a paucity of evidence supporting its use in this disease. Patients who undergo FDG-PET scan for initial staging appear more likely to receive early therapy although this may not be directly attributed to FDG-PET results. The management of ESFL is surprisingly heterogeneous and varies across NCCN centers but is not influenced by the use of FDG-PET scan at staging. Given the widespread use and high cost of FDG-PET, its clinical utility in ESFL should be further evaluated. Disclosures:No relevant conflicts of interest to declare.

Incidence, Method and Covariates of Central Nervous System (CNS) Prophylaxis for Diffuse Large B-Cell Lymphoma In the National Comprehensive Cancer Network (NCCN) Lymphoma Database

AbstractAbstract 1756 Background:The optimal criteria to determine which patients with diffuse large B-cell lymphoma (DLBCL) should receive central nervous system (CNS) prophylaxis remain controversial. We aimed to characterize patterns of CNS prophylaxis administration in patients with DLBCL in a large multi-institutional database. Methods:The National Comprehensive Cancer Network (NCCN) Non-Hodgkin's Lymphoma Outcomes Database is a prospective cohort study collecting clinical, treatment, and outcomes data for patients at seven participating NCCN centers. Patients who presented between January 1, 2001 and July 1, 2008 with newly-diagnosed DLBCL, without CNS disease at baseline, and who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) within 180 days of diagnosis were eligible for this analysis. We assessed clinical and sociodemographic covariates of receipt of CNS prophylaxis and type of prophylaxis received (either ≥2 doses of intrathecal methotrexate and/or cytarabine or ≥1 dose of systemic methotrexate). Extrapolating from prior studies (e.g., Boehme et al, Ann Oncol, 2007), we defined high-risk features as >1 extranodal site involvement, elevated lactate dehydrogenase (LDH), bone marrow involvement, or other high-risk site involvement (orbit, testis, peripheral blood, bone/vertebrae, nasal/paranasal sinuses), and assessed rates of CNS prophylaxis in patients with ≥1 high-risk feature. We also determined rates of CNS recurrence for patients with ≥ 2 high-risk features who received prophylaxis versus those who did not. Results:Of a total of 989 patients with DLBCL (mean age 56; 44.4 % female; 70.2% with low or low-intermediate international prognostic index (IPI) score), 117 received CNS prophylaxis (11.8% [95% Confidence Interval (CI) 9.8%-13.8%]). Considered individually, patients with bone marrow involvement, other high-risk site involvement, >1 extranodal site involvement, high versus low IPI score, and advanced stage (III or IV) were significantly more likely to receive CNS prophylaxis (all p<0.0001); those with elevated LDH or presence of B-symptoms were not. In addition, age, gender, race/ethnicity, performance status, and cancer center were not associated with CNS prophylaxis receipt. Rates of CNS prophylaxis, in descending order of frequency, are shown below for significant clinical factors:Individual Clinical Factor+ CNS prophylaxisOther high-risk site involvement36.0%Bone marrow involvement28.2%>1 Extranodal site involvement23.1%High IPI18.6%Stage III/IV15.8%Of those who received CNS prophylaxis, 71.8% received intrathecal therapy and 28.2% received systemic therapy. There were significant center-specific differences regarding type of CNS prophylaxis used (p<0.0001). In addition, other high-risk site involvement was associated with use of systemic versus intrathecal prophylaxis (p=0.04), while higher mean age was associated with the reverse (p=0.05). Patients with increasing number of the four specific high-risk features (>1 extranodal site involvement, elevated LDH, bone marrow involvement, or other high-risk site involvement) were increasingly likely to receive CNS prophylaxis (0 features: 4.3%; 1 feature: 8.1%; 2 features: 20.1%; 3 features: 31.0%; 4 features: 61.1%; p<0.0001). Of all patients with ≥1 high-risk feature (n= 617), 16.4% received CNS prophylaxis. With median follow-up of 2.5 years, there were 20 CNS recurrences (2.0% [95% CI 1.1%-2.9%]). For those with ≥2 high-risk features (n=284), rates of CNS relapse were not significantly different in those who did and did not receive prophylaxis. Conclusion:In our cohort, several classic clinical high-risk variables were associated with receipt of CNS prophylaxis. The modality of prophylaxis used, whether intrathecal or systemic, appeared predominantly mediated by site-specific clinician preference rather than clinical or sociodemographic factors. While an increasing number of widely-accepted high-risk features was associated with higher rates of CNS prophylaxis, surprisingly, a minority of patients with high-risk features received CNS prophylaxis. In conclusion, we found no standard of care for administration of CNS prophylaxis in DLBCL; moreover, as the rate of CNS recurrence was low, our data suggest the need for further evaluation of the efficacy of CNS prophylaxis in the R-CHOP era. Disclosures:No relevant conflicts of interest to declare.

Utilization of adjuvant therapy among completely resected non-small cell lung cancer (NSCLC) patients in the National Comprehensive Cancer Network (NCCN) Outcomes Database Project.

7017 Background: In recent years, adjuvant chemotherapy has become the standard of care for completely resected (R0) stage II and IIIA NSCLC patients, while the use of adjuvant therapy in stage IB remains controversial. We evaluated the use of adjuvant therapy among R0 stage IA-IIIA NSCLC patients in the NCCN Outcomes Database Project. Methods: Completely resected stage I-IIIA NSCLC patients who did not receive preoperative therapy were selected for analysis. Eligible patients received adjuvant treatment at 8 participating NCCN institutions between 01/2007 and 06/2009 and were at least 90 days postsurgery. Adjuvant therapy was defined as therapy initiated within 3 months of surgery. Analyses were done on 12/11/09. Results: A total of 498 patients met the inclusion criteria. Patient characteristics were: male 42%; median age 67 yrs; stage IA 39%, IB 35%, II 16%, IIIA 10%; lobectomy (uni or bi) 84% (N=416); adenocarcinoma 58% (N=289); performance status (PS) 0-1 54% (N=271), PS ≥2 3% (N=16), and undocumented PS 42% (N=211). Adjuvant treatment category is presented by stage in the Table. Of patients receiving adjuvant therapy, 5 (4%) did so on a clinical trial. The most common reason for not receiving adjuvant systemic therapy in stage II-IIIA was patient refusal (26%). Conclusions: Adjuvant therapy was commonly administered to stage II and IIIA patients. Radiation was most common among stage IIIA patients. While the majority of R0 NSCLC patients received treatment that follows NCCN guidelines, relatively few patients at these NCCN centers are participating in clinical trials. Adjuvant treatment category by stage Treatment category Stage IA (N=193) IB (N=174) II (N=79) IIIA (N=52) No treatment 190 (98%) 126 (72%) 25 (32%) 14 (27%) Chemotherapy 2 (1%) 43 (25%) 43 (54%) 20 (38%) Cisplatin-based 2 (100%) 25 (58%) 25 (58%) 10 (50%) Carboplatin-based 0 (0%) 14 (33%) 17 (40%) 8 (40%) Other 0 (0%) 4 (9%) 1 (2%) 2 (10%) Chemotherapy + targeted therapy 0 (0%) 2 (1%) 0 (0%) 0 (0%) Targeted therapy alone 0 (0%) 2 (1%) 2 (3%) 1 (2%) Sequential chemo/RT 1 (<1%) 0 (0%) 6 (8%) 13 (25%) Concurrent chemo/RT 0 (0%) 0 (0%) 1 (1%) 3 (6%) RT alone 0 (0%) 1 (<1%) 2 (3%) 1 (2%) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience

The 2008 National Comprehensive Cancer Network (NCCN) Research Benchmarking Survey (RBS): Clinical trials (CTs) operations in the academic center.

6154 Background: The 2008 NCCN RBS focused on the operations of clinical trials offices (CTOs) at NCCN Institutions. The survey utilized clinical trials benchmarking metrics based on CTO budgets, full-time equivalents (FTEs), and patient accruals. The primary aims were benchmarking and improvement of CTO operations and processes and identification of best practices in academic cancer center clinical research. Methods: A survey instrument was developed by the NCCN Best Practices Committee based on prior 2004 and 2006 surveys, which will allow for future analysis of longitudinal data. The survey collected quantitative and descriptive data on CTO organization, research infrastructure, staffing and clinical trials management, and included questions on innovative approaches to increasing accrual to CTs. Results: 20/21 NCCN institutions participated, for a response rate of 95%. The proportion of therapeutic trials varied across sponsor (mean, range): Cooperative Group (42%, 24%-66%), Industry Sponsored (29%, 18%-38%), Institutional (19%, 8-33%), Other Peer Reviewed (10%, 2%-27%). Of the 17/20 responding centers submitting patient accrual data, over 16,000 patients were accrued to therapeutic CTs. Patients were accrued to CTs as follows: Institutional (34%), Industry Sponsored (27%), Cooperative Group (23%) and Other Peer Reviewed (16%). CT accrual rates ranged from 10% to 24%; minority accrual rates ranged from 6 to 28 %. The mean annual operating budget for 15 centers was $4.7 million. The range of sources of support for CT management was from 43% for Sponsored Industry to 5% for Sponsored Cooperatives. The mean number of therapeutic accruals per CTO FTE was 10.6. 7/20 (35%) centers demonstrated Best Practices in implementing a value stream analysis of the protocol approval process. Conclusions: Clinical Research is at the heart of NCCN center operations, as it constitutes a core mission of NCCN institutions. It also represents one of the most significant challenges with many opportunities for improvement. Development of benchmark data and Best Practices across these institutions will promote enhanced operations and patient accrual in therapeutic CTs. No significant financial relationships to disclose.

Practice and Attitudes towards CYP2D6 Testing for Patients on Tamoxifen among US Oncologists.

Abstract Background: CYP2D6 genotype has been associated with breast cancer outcomes for patients on Tamoxifen (TAM) and testing is commercially available. In the context of emerging data regarding the clinical relevance of CYP2D6 testing (CYPT) and uncertainty regarding how test results should be used in practice, we evaluated current practice and attitudes with regard to this novel pharmacogenomic test among U.S. oncologists.Methods: A survey was mailed to all breast cancer oncologists identified at National Comprehensive Cancer Network (NCCNO) centers and a random sample of community based oncologists (CBO) identified from the American Society of Clinical Oncology directory. The survey evaluated knowledge of the CYP2D test, use of the test, requests for the test by patients and third parties, and response to hypothetical test results. Associations between practice setting and CYP2D6 knowledge, CYPT, and practice patterns were evaluated. All statistical tests were two-sided.Results: 201 of 459 (44%) oncologists responded, including 97/173 (56%) of NCCNO and 104/286 (36%) of CBO. While 90% of all oncologists were aware of CYPT, only 31% had ever ordered CYPT, and only 14% used CYPT for ≥ 10% of patients on TAM. 22% had received a request for CYPT from a 3rd party. While NCCNO were more likely to be aware of CYPT (98% vs. 82%, p &amp;lt; 0.001), and to receive requests for CYPT (33% vs. 12%, p &amp;lt; 0.001), CBO reported higher frequency of CYPT in routine practice (21% vs. 11%, p = 0.06). Despite rare use, 66% of CBO and 44% of NCCNO reported they would order the test upon patient request (p &amp;lt; 0.001). In hypothetical scenarios involving CYPT for patients on TAM, for premenopausal women with poor metabolism, 33% would make no change, while 38% would switch to ovarian suppression (OS) plus aromatase inhibitor (AI), 9% would switch to OS alone, and 8% would add OS to TAM. CBO were more likely to switch to OS + AI in this setting (47% vs. 31%, p &amp;lt; 0.02), while NCCNO were more likely to recommend no change (50% vs. 18%, p &amp;lt; 0.001). For premenopausal intermediate metabolizers, 33% of CBO would change management, compared to 8% of NCCN (p &amp;lt; 0.001), with addition of OS to TAM being most frequent among both groups. For postmenopausal women with poor metabolism the majority of both CBO and NCCNO would switch to AI (82% vs. 71%, p = 0.08). Among oncologists who indicated they might change management based on CYPT results, 43% had never ordered the test. Respondents cited data from randomized trials, and professional guidelines as most influential for decisions regarding ordering tests.Conclusion: Despite calls for increased CYP2D6 testing at academic meetings and occasional requests by 3rd parties, use of CYPT is currently infrequent in oncology practice. Greater familiarity with breast cancer management correlated with lower use of CYPT and greater reluctance to change management based on test results at this time. Diversity in practice patterns and knowledge suggests a need for greater consensus on CYPT in routine practice, and highlights the need for further clinical research in this area. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1077.

Variations in Surveillance Imaging for Patients with Treated Diffuse Large B-Cell Lymphoma in the National Comprehensive Cancer Network (NCCN) Lymphoma Database.

Abstract 1387Poster Board I-409 BACKGROUND:Utility and optimal timing of surveillance imaging for patients with treated diffuse large B-cell lymphoma (DLBCL) remains uncertain, especially in the era of positron emission tomography. METHODS:Data were obtained from the NCCN Non-Hodgkin's Lymphoma Outcomes Database, a prospective cohort study collecting comprehensive clinical, treatment, and outcome data for patients seen at 7 participating NCCN centers. Patients who presented between January 1, 2001 and June 30, 2007 with a new diagnosis of DLBCL in remission for at least three months after the completion of initial therapy were eligible for this study. For those patients with at least two years of follow-up, we assessed overall number and modality of imaging studies performed starting 90 days after the end date of their first-line therapy until documented relapse or end of two-year follow-up window. We then created three subcategories depending upon surveillance strategy: “PET” = positron emission tomography scans or combined positron emission tomography/limited computed tomography scans only; “CT”= computed tomography scans only; or “BOTH PET AND CT” = combination of both “PET” and “CT” at different times. For those who relapsed after being in primary remission for at least 90 days, we assessed the nature of the visit where relapse was first documented, recent accompanying imaging, and the presence of a confirmatory biopsy within one month before or after that relapse. RESULTS:As of July 1, 2009, 433 newly-diagnosed DLBCL patients had at least two years of follow-up from 6 of the 7 participating NCCN centers; median age was 56 and 57% were male. Initial stage and International Prognostic Index (IPI) were as follows: I = 24%; II= 24%; III= 16%; IV=36%; and low= 47%; low-intermediate= 26%; high-intermediate= 19% and high= 8%. For surveillance imaging as defined above, 14% received PET, 48% received CT, and 38% received BOTH PET AND CT. Range of median frequencies across NCCN centers are reported below, both overall and by test type. Overall median number of tests received per year differed significantly across NCCN centers (p for Kruskal-Wallis < 0.0001).Surveillance StrategyMedian tests/year across all NCCN centersMedian tests/year, NCCN center rangeMean tests/year across all NCCN centersAll tests2.81.5 – 3.52.8PET2.01.5 – 2.752.2CT2.51.5 – 3.52.6BOTH PET AND CT3.01.5 – 4.03.3Of 990 patients in primary remission for at least 90 days, there were 108 (11%) documented relapses. Of those, 20% were found at non-routine visits with symptoms, 41% at routine visits with symptoms, 37% at routine visits without symptoms and 2% were unclear. Of those found at routine visits without symptoms, 73% had undergone imaging within one month before and up to the date of relapse. Finally, 77% of those with relapse underwent confirmatory biopsy within one month before or after relapse. CONCLUSIONS:The frequency of surveillance imaging for patients with treated DLBCL is highly variable, even within the context of tertiary care academic centers. Despite controversy surrounding its use, a high proportion of DLBCL patients in remission are followed with PET modalities. Those being followed exclusively with PET modalities tend to have less frequent imaging, which may have implications for comparative effectiveness. Routine imaging likely identifies relapse in about a quarter of patients with DLBCL; the impact on ultimate outcome remains to be further evaluated. Disclosures:Friedberg: Genentech: Membership on an entity's Board of Directors or advisory committees. Blayney: American Society of Clinical Oncology: Membership on an entity's Board of Directors or advisory committees; BlueCross Blue Shield of Michigan: Research Funding; NCCN: Honoraria; University of Michigan Health System: Employment.

R-CHOP, Followed by High Dose Therapy and Autologous Stem Cell Rescue (HDT/ASCR), and R-Hypercvad Have Equivalent Progression-Free Survival and Are Superior to R-CHOP Alone in Younger Patients with Mantle Cell Lymphoma: a Comparative Effectiveness Analysis From the National Comprehensive Cancer Network (NCCN) Non-Hodgkin's Lymphoma Outcomes Database Project.

Abstract 403 Background:Mantle Cell Lymphoma (MCL) is an uncommon histology of non-Hodgkin's lymphoma (NHL) with an unfavorable prognosis for which optimal initial therapy has not been clearly defined. Despite a number of single center studies and uncontrolled trials examining first-line therapy options in MCL, no randomized clinical trials or observational studies have directly compared initial therapeutic options in a single cohort of patients. The role of aggressive induction therapy versus sequential standard chemotherapy remains uncertain, particularly in younger patients. We therefore used the NCCN NHL Outcomes Database to compare R-HyperCVAD, R-CHOP followed by HDT/ASCR and R-CHOP alone as first-line therapy. Our endpoints were progression-free survival (PFS) and overall survival (OS). Methods:The NCCN Non-Hodgkin's Lymphoma Outcomes Database is a prospective cohort study collecting comprehensive clinical, treatment, and outcome data for patients seen at 7 participating NCCN centers. Overall, 229 patients <65 years old with newly diagnosed MCL presented at NCCN institutions between August 2000 and February 2009. Patients were excluded if they (1) were enrolled in clinical trial (n=27), (2) did not receive Rituximab therapy (n=27), (3) did not receive either R-HyperCVAD or R-CHOP induction therapy (n=10), or (4) received both R-CHOP and R-HyperCVAD as induction (n=9). Induction therapy was determined as the initial chemo-immunotherapy received within 180 days of diagnosis. HDT/ASCR consolidation was defined as a transplant after achieving remission. In the R-CHOP+ HDT/ASCR group, ASCR was initiated within 100 days of induction therapy for 90% of patients. The maximum time from induction to ASCR was 172 days. In total, 156 patients were included in the final analysis. Median follow-up was 30 months. Results:Overall, 28 (18%) patients received R-CHOP alone, 29 (19%) received R-CHOP+HDT/ASCR, and 99 (63%) received R-HyperCVAD. No significant differences were observed between therapy groups with regards to co-morbidity (p=0.419), ECOG performance status (p=0.216), B symptoms (p=0.685), bulky disease (p=0.647), IPI risk group (p=0.247), or bone marrow involvement (p=0.651). No difference in PFS (p=0.546) was observed between the R-HyperCVAD and R-CHOP+HDT/ASCR arm (figure 1a). R-CHOP without consolidation had significantly poorer PFS than both R-HyperCVAD (p=0.001) and R-CHOP+HDT/ASCR (p=0.001). No significant differences in OS were observed between the three groups. However, there was a strong trend favoring R-HyperCVAD over R-CHOP (p=0.082, figure 1b). Conclusion:R-CHOP was inferior to both R-HyperCVAD and R-CHOP+HDT/ASCR, which had equal PFS and OS in patients with de novo mantle cell lymphoma. Even with these aggressive induction regimens in younger patient populations, the median PFS in these cohorts was only 3 years. Future trials should focus on incorporating novel agents rather than comparing efficacy of current suboptimal regimens. [Display omitted] Disclosures:Czuczman:NCCN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Nademanee:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Blayney:American Society of Clinical Oncology: Membership on an entity's Board of Directors or advisory committees; BlueCross Blue Shield of Michigan: Research Funding; NCCN: Honoraria; University of Michigan Health System: Employment. Friedberg:Genentech: Membership on an entity's Board of Directors or advisory committees.

Concordance with NCCN Colorectal Cancer Guidelines and ASCO/NCCN Quality Measures: An NCCN Institutional Analysis

The National Comprehensive Cancer Network (NCCN) Outcomes Database was created to assess concordance to evidence- and consensus-based guidelines and to measure adherence to quality measures on an ongoing basis. The Colorectal Cancer Database began in 2005 as a collaboration among 8 NCCN centers. Newly diagnosed colon and rectal cancer patients presenting to 1 of 8 NCCN centers between September 1, 2005, and May 21, 2008, were eligible for analysis of concordance with NCCN treatment guidelines for colorectal cancer and with a set of quality metrics jointly developed by ASCO and NCCN in 2007. Adherence rates were determined for each metric. Center-specific rates were benchmarked against mean concordance rates for all participating centers. A total of 3443 patients were evaluable. Mean concordance rates with NCCN colorectal cancer guidelines and ASCO/NCCN quality measures were generally high ( >or= 90%). However, relatively low mean concordance rates were noted for adjuvant chemotherapy treatment recommendations within 9 months of diagnosis of stage II to III rectal cancer (81%), and neoadjuvant chemoradiation in clinical T4 rectal primaries (83%). These low rates of concordance seemed to be consistent across centers. Adherence to guidelines and quality measures is generally high at institutions participating in the NCCN colorectal cancer database. Lack of documentation, patient refusal, delayed treatment initiation, and lack of consensus about whether treatment was essential were the primary reasons for nonconcordance. Measurement of concordance and the reasons for nonconcordance enable participating centers to understand and improve their care delivery systems.

Factors Associated With Sphincter-Preserving Surgery for Rectal Cancer at National Comprehensive Cancer Network Centers

To determine rate and predictors of sphincter-preserving surgery (SPS) for rectal cancer patients treated at specialty institutions. SPS has been considered a surrogate for surgical quality, and sphincter preservation is tremendously important to patients. Evidence of association between case volume and SPS rate has prompted recommendations that all rectal cancer patients undergo surgery at specialty institutions. However, rates of SPS, and the factors associated with ability to perform SPS, have not been well-characterized. A prospective registry of all colorectal cancer patients treated at 7 National Comprehensive Cancer Network institutions was used to identify patients with clinical stage I-III rectal cancer undergoing surgery (n = 674) between September 2005 and October 2007. Patient, tumor and treatment factors were abstracted; patients' clinical characteristics with and without SPS were compared using descriptive statistics and multivariable logistic regression. Of 674 identified patients (median age, 58.2; 60% male), 520 (77%) had SPS. Of these, 240 had low anterior resection with coloanal anastomosis, 268 low anterior resection without coloanal anastomosis; 12 had other SPS procedures. Sixty-two percent had a temporary diverting stoma. On multivariable analyses, independent predictors of SPS included younger age at diagnosis, proximal location in the rectum, nonfixed tumor, and institution. SPS rates at National Comprehensive Cancer Network institutions exceed those seen in population-based samples and clinical trials. In addition to expected variation in SPS rates based on patient and tumor characteristics, we identified variation among institutions. Although the optimal rate of SPS remains unknown, this provides areas for further research and potential performance improvement.

Quality of breast cancer care in NCCN centers as assessed by the ASCO/NCCN quality measures: Overall performance and reasons for nonconcordance

6506 Background: To assess the quality of breast cancer care in the National Comprehensive Cancer Network (NCCN), we compared practice against the ASCO/NCCN quality measures (QM). Methods: Using the NCCN Outcomes Database, we studied the care of women with newly diagnosed stage I-III breast cancer treated at 8 NCCN centers in 2003–6 to determine the proportion whose care was consistent with the 3 QMs (tamoxifen or anastrozole within 1 year of diagnosis for HR+ &gt;1 cm tumors [HT]; post- lumpectomy radiation within 1 year of diagnosis for women &lt;70 yo [RT]; and chemotherapy within 120 days of diagnosis of HR- &gt;1 cm tumors for women &lt;70 yo). Based on chart review, reasons for non-concordant care were classified as: 1) treatment recommended, but declined; 2) MD recommended against treatment; 3) non-recommended treatment administered; or 4) system problem (referral to the relevant specialist not documented or specialist not seen, delayed treatment initiation, or no relevant documentation in the chart). Results: 5,175 women were analyzable on at least one QM. Overall, treatment was consistent with the QM for 6,628/7,265 (91%) of the unique patient-recommendation pairs. Non-concordant care was received by 11% of patients eligible for the HT QM, 5% for the RT QM, and 13% for the chemotherapy QM. The reasons for non-concordance are shown in the table. Conclusions: Overall, breast cancer care in the NCCN is highly concordant with the ASCO/NCCN quality measures. System problems rather than patient refusal or physician recommendations account for the majority of care that deviates from the QM recommendations. This suggests that quality improvement targeting systems rather than physicians would be especially efficient and effective. [Table: see text] No significant financial relationships to disclose.

The impact of obesity on adherence to the National Comprehensive Cancer Network (NCCN) guidelines recommending chemotherapy for patients with operable breast cancer

6517 Background: Obesity (measured using body mass index [BMI]) is regarded as a prognostic factor for worse breast cancer survival. We hypothesized that obesity may influence adherence to NCCN guidelines recommending chemotherapy for patients with operable breast cancer at NCCN centers. Methods: We identified women &lt; 70 years diagnosed with stage I, II, or III breast cancer from 1997 to 2006 at 8 NCCN centers for whom guidelines recommended chemotherapy. Body mass index was assessed in categories (&lt;25 kg/m2 [normal], 25 to &lt;30 kg/m2 [overweight], 30 to 39kg/m2 [obese], ≥40 kg/m2 [morbidly obese]) and in 5 kg/m2 increments. Multivariable logistic regression analysis adjusting for center, age at diagnosis, ethnicity, comorbidity score, and guideline was used to examine the association between BMI at diagnosis and non-receipt of chemotherapy. Results: 9,389 women were eligible for the study: 38% normal weight; 30% overweight; 23% obese; 5% morbidly obese; and 4% unknown. In multivariable analysis with BMI as a categorical variable, there was no association between weight status and non-receipt of chemotherapy (p = 0.35). When BMI was assessed in 5kg/m2 increments, weight status was a statistically significant predictor of non-receipt of chemotherapy (p = 0.02), but the odd ratios exceeded 1.0 only for BMIs ≥42.6kg/m2. Other patient-related factors associated with non-receipt of chemotherapy included older age at diagnosis (p &lt; 0.01), presence of comorbidities (p &lt; 0.01) and center (p &lt; 0.01). Conclusions: Overall, the quality of breast cancer care as measured by adherence to NCCN guidelines recommending chemotherapy was not affected by patient overweight or obese status. Chemotherapy use was lower among patients with extreme morbid obesity, which may represent appropriate clinical decision-making. Evaluating factors that may contribute to worse prognosis among obese patients is essential for individualizing care and improving breast cancer outcome. No significant financial relationships to disclose.

Identifying high-priority quality measures for breast cancer quality improvement using data from a nationally representative sample

6507 Background: We previously developed a simple, data-based strategy for selecting high-priority quality measures, and applied it to practice performance data from eight National Comprehensive Cancer Network (NCCN) centers to identify high-priority measures for breast cancer care. We now seek to evaluate the generalizability of these results by identifying which measures rank highly when practice performance data from a nationally representative sample, rather than a select group of cancer centers, are used. Methods: Using SEER-Medicare data, we assessed practice performance for 9933 women 65–70 years old diagnosed 1998–2002 with non-metastatic invasive breast cancer. For each quality measure, we determined the number of eligible patients, the number who did not receive recommended therapy, and the overall and target (goal) concordance values. We entered these data into a previously described algorithm to derive a numerical prioritization score for each measure. Spearman correlations were used to analyze comparisons between datasets. Results: We were able to evaluate practice performance relative to most (18/30; 60%) of the measures included in our original NCCN analysis. The absence of oral hormone therapy and DCIS pathology data in SEER-Medicare precluded assessments of quality relative to the remaining measures. The highest-ranking measures recommended chemotherapy for hormone-receptor positive tumors &gt;1 cm, axillary node surgery and radiation after lumpectomy for stage I-II cancer, and no radiation after mastectomy for node-negative cancer &lt;5 cm. Excluding hormone therapy and DCIS measures, the 6 highest-ranking measures in the SEER-Medicare and NCCN analyses were identical. Correlation between the prioritization scores for the 18 measures common to both datasets was 0.74. Conclusions: While SEER-Medicare data only include patients &gt;65 and NCCN data only represent select institutions, information from both can be used to identify high-priority quality measures. That the same measures rank highly in both analyses suggests these are comprehensive, generalizable, policy ready national standards, and that this is a valid method for identifying high-priority quality measures. No significant financial relationships to disclose.

Comparison of Referring and Final Pathology for Patients With Non-Hodgkin's Lymphoma in the National Comprehensive Cancer Network

Before the implementation of the WHO lymphoma classification system, disagreement about pathologic diagnosis was common. We sought to estimate the impact of expert review in the modern era by comparing final pathologic diagnoses at five comprehensive cancer centers with diagnoses assigned at referring centers. Patients in the National Comprehensive Cancer Network (NCCN) non-Hodgkin's lymphoma (NHL) database with a documented pathologic diagnosis before presentation and a final pathologic diagnosis of any of five common B-cell NHLs were eligible. After central review of discordant cases, we estimated the rate of pathologic concordance, then investigated the etiology of discordance as well its potential impact on prognosis and treatment. The overall pathologic discordance rate was 6% (43 of 731 patients; 95% CI, 4% to 8%). For the majority of cases in which the referring diagnosis was apparently final, no additional studies were conducted at the NCCN center, and the change in diagnosis reflected a different interpretation of existing data. Concordance was highest for diffuse large B-cell lymphoma (95%) and follicular lymphoma (FL; grades 1, 2, and not otherwise specified, 95%) and lowest for grade 3 FL (88%). Of the 43 pathologically discordant cases, 81% (35 patients) might have experienced a change in treatment as a result of the pathologic reclassification. In the era of the WHO lymphoma classification system, the majority of common B-cell NHLs diagnosed in the community were unchanged by second opinion review by an expert hematopathologist. However, for one patient in 20, there was a discordance in diagnosis that could have altered therapy.