National Comprehensive Cancer Network Centers Research Articles

Understanding the Impact of Belzutifan on Treatment Strategies for Patients with VHL.

Belzutifan was recently approved for the management of Von Hippel–Lindau disease (VHL). Given the morbidity of recurrent treatment, systemic therapy to reduce or eliminate the need for surgery has been long-awaited. Herein, we sought to gain insight about future utilization by surveying VHL kidney cancer experts in the United States. A survey developed by members of the VHL Alliance (VHLA) Clinical Advisory Council was distributed to kidney cancer providers at VHLA and National Comprehensive Cancer Network (NCCN) centers. Surveys were administered on a secure web-based platform. A total of 60 respondents from 29 institutions participated. Urologists (50%) and medical oncologists (43%) represented the majority of participants. The majority (98%) of respondents anticipated that belzutifan’s approval would significantly change the current treatment landscape. Most reported that therapy should be continuous (76%). There was a difference in willingness to prescribe belzutifan by specialty (38% of urologists vs 91% of medical oncologists (P = 0.02)). In individuals with renal tumors <3 cm, 36% would still recommend surveillance, while 36% would initiate belzutifan to prevent growth. In those with multifocal renal lesions and growth of a solitary tumor on belzutifan, 50% would proceed with only treatment of that site. In conclusion, VHL kidney cancer specialists anticipate a paradigm shift with the approval of belzutifan. Provider roles may change with movement away from surgical management. Opinions on treatment indications, such as when to initiate therapy and how to best salvage, vary widely and therefore collaborative efforts among experts may assist in the development of new clinical guidelines.

Financial payments from the pharmaceutical industry to U.S. cancer centers, 2014-2019.

1582 Background: Payments from the pharmaceutical industry to US health care providers were made public through Open Payments in 2013. Since then, industry payments to individual physicians have been studied extensively, but payments to hospitals remain uncharacterized. The goal of this study was to examine trends in industry payments to US cancer centers. Methods: We identified all US cancer centers that were National Comprehensive Cancer Network (NCCN) members or were National Cancer Institute (NCI) comprehensive cancer center as of 2019. Each institution was manually mapped to Open Payments, which contains industry payment data. Where applicable, subsidiary hospitals were included with the parent center. Among the NCCN centers, we used National Plan and Provider Enumeration System data to identify medical oncologists practicing there. Oncologists were linked to Open Payments by name and address. We analyzed “research payments” (RP), which include payments related to preclinical and clinical research, and “general payments” (GP), which include non-research-related payments in categories such as speaker fees, consulting fees, meals, grants, charitable contributions, and licensing fees. We ascertained public research support from NIH data, and included all research project grants. We used correlation analysis and linear regression models to assess the association between industry payments to a cancer center and to oncologists practicing at that center. All dollar values were inflation-adjusted to 2019 dollars using the Consumer Price Index for medical care from the US Bureau of Labor Statistics. Results: Overall industry RP to US cancer centers increased from $527 million in 2014 to $653 million in 2019, while GP increased from $346 million to $786 million. NCI research funding increased from $1,397 million in 2014 to $1,583 million in 2019 (13.3% increase) while overall industry payments (RP+GP) increased from $873 million to $1,439 million (64.8% increase). Industry payments were highest as a portion of total income (industry + NCI) at MD Anderson (64.2%) and lowest at St. Jude (0.1%). Among NCCN institutions, industry payments to cancer centers and the oncologists practicing at those centers were correlated (coefficient = 0.382). A $1,000 increase in GP to a cancer center from a given pharmaceutical company was associated with a $1.00 ($0.61 - $1.30) increase in GP from that company to oncologists at that cancer center. Conclusions: From 2014-2019, cancer center funding from industry sources grew quickly, driven by an increase in non-research payments, and now approaches the amount of public research funding cancer centers receive. Cancer center acceptance of industry payments is associated with increased industry payments to its employed physicians, which are known to sway prescribing practices. These trends raise concerns regarding the ability of these institutions to fulfill their public missions.

MP24-02 SURVEY BASED STUDY OF EMERGING MANAGEMENT STRATEGIES FOR VHL

You have accessJournal of UrologyCME1 May 2022MP24-02 SURVEY BASED STUDY OF EMERGING MANAGEMENT STRATEGIES FOR VHL Neal Patel, Aileen Arvelo, Gennady Bratslavsky, Chandra Clark, Othon Iliopoulos, Eric Jonasch, Sandy Liu, Joshua Mann, Peter Muraki, and Brian Shuch Neal PatelNeal Patel More articles by this author , Aileen ArveloAileen Arvelo More articles by this author , Gennady BratslavskyGennady Bratslavsky More articles by this author , Chandra ClarkChandra Clark More articles by this author , Othon IliopoulosOthon Iliopoulos More articles by this author , Eric JonaschEric Jonasch More articles by this author , Sandy LiuSandy Liu More articles by this author , Joshua MannJoshua Mann More articles by this author , Peter MurakiPeter Muraki More articles by this author , and Brian ShuchBrian Shuch More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002563.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Belzutifan was recently FDA approved for the management of Von Hippel-Lindau syndrome (VHL). Given the disease complexity and morbidity of recurrent surgery, a well-tolerated systemic agent has been long-awaited. Balancing benefit with chronic usage and toxicity must be considered. To gain insight in future usage, a survey was provided to VHL kidney cancer experts in the United States. METHODS: A survey was developed by members of the VHL Family Alliance Advisory Council. The survey was distributed to practitioners involved in the care of VHL kidney cancer patients at designated VHL Alliance Care Centers and National Comprehensive Cancer Network centers. Center contacts were asked to distribute the survey amongst kidney cancer specialists who would be involved in VHL kidney cancer care. Surveys were anonymous and hosted on a secure, web-based platform. VHL practitioners were asked about the feasibility of using belzutifan, which specialty should administer, clinical indications for renal and non-renal manifestations, and optimal duration of therapy. Descriptive statistics were performed and Pearson chi-square analyses to evaluate differences between groups. RESULTS: A total of 59 respondents from 30 institutions participated. Urologists (51%) and medical oncologists (42%) represented the majority of participants. The majority (98%) of respondents anticipated that belzutifan’s approval would significantly change the current kidney cancer treatment landscape and therapy should be continuous (76%). 43% of urologists planned to prescribe belzitufan compared to 84% of medical oncologists (p=0.006). Only 9% of medical oncologists believed that urologists should be involved in belzutifan administration as opposed to 38% of urologist (p=0.015). In individuals with renal tumors <3 cm with low anticipated surgical morbidity, only 36% would continue the prior treatment paradigm of surveillance then surgery while 36% would initiate belzutifan to prevent growth. In those with multifocal disease with growth of a solitary lesion while on belzutifan, 50% would proceed with isolated treatment of that site. CONCLUSIONS: Most VHL kidney cancer specialists anticipate a paradigm shift in the field with the approval of belzutifan. Provider roles may change with movement away from local treatment. Opinions on which specialists should administer belzutifan differ by specialty. Treatment indications on topics such as when to initiate therapy and how to best salvage vary widely. Collaborative efforts amongst experts to accumulate additional clinical data will help guide a new era of VHL management. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e392 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neal Patel More articles by this author Aileen Arvelo More articles by this author Gennady Bratslavsky More articles by this author Chandra Clark More articles by this author Othon Iliopoulos More articles by this author Eric Jonasch More articles by this author Sandy Liu More articles by this author Joshua Mann More articles by this author Peter Muraki More articles by this author Brian Shuch More articles by this author Expand All Advertisement PDF DownloadLoading ...

Minimally invasive hysterectomy surgery rates for endometrial cancer performed at National Comprehensive Cancer Network (NCCN) Centers

ObjectivesMinimally invasive surgery (MIS) is a quality measure for endometrial cancer (EC) established by the Society of Gynecologic Oncology and the American College of Surgeons. Our study objective was to assess the proportion of EC cases performed by MIS at National Comprehensive Cancer Network (NCCN) centers and evaluate perioperative outcomes. MethodsA retrospective cohort study of women who underwent surgical treatment for EC from 2013 to 2014 was conducted at four NCCN centers. Multivariable mixed logistic regression models analyzed factors associated with failure to perform MIS and perioperative complications. ResultsIn total 1621 patients were evaluated; 86.5% underwent MIS (robotic-assisted 72.5%, laparoscopic 20.9%, vaginal 6.6%). On multivariable analysis, factors associated with failure to undergo MIS were uterine size >12cm (Odds Ratio [OR]: 0.17, 95% CI 0.03–0.9), stage III (OR: 0.16, 95% CI 0.05–0.49) and IV disease (OR: 0.07, 95% CI 0.02–0.22). For stage I/II disease, complications occurred in 5.1% of MIS and 21.7% of laparotomy cases (p<0.01). Laparotomy was associated with increases in any complication (OR: 6.0, 95% CI 3.3–10.8), gastrointestinal (OR: 7.2, 95% CI 2.6–19.5), wound (OR: 3.7, 95% CI 1.5–9.2), respiratory (OR 37.5, 95% CI 3.9–358.0), VTE (OR 10.5, 95% CI 1.3–82.8) and 30-day readmission (OR: 2.6, 95% CI 1.4–4.9) compared to MIS. ConclusionsAt NCCN-designated centers, the MIS hysterectomy rate in EC is higher than the published national average, with low perioperative complications. Previously identified disparities of age, race, and BMI were not observed. A proposed MIS hysterectomy benchmark of >80% in EC care is feasible when performed at high volume centers.

Trends in intensity modulated radiation therapy use for locally advanced rectal cancer at National Comprehensive Cancer Network centers

PurposeIntensity modulated radiation therapy (IMRT) has been rapidly incorporated into clinical practice because of its technological advantages over 3-dimensional conformal radiation therapy (CRT). We characterized trends in IMRT utilization in trimodality treatment of locally advanced rectal cancer at National Comprehensive Cancer Network cancer centers between 2005 and 2011. Methods and materialsUsing the prospective National Comprehensive Cancer Network Colorectal Cancer Database, we determined treatment patterns for 976 patients with stage II-III rectal cancer who received pelvic radiation therapy at contributing centers between 2005 and 2011. Multivariable logistic regression was used to identify factors associated with IMRT versus 3-dimensional CRT. Radiation therapy compliance and time to completion were used to compare acute toxicity. ResultsA total of 947 patients (97%) received 3-dimensional CRT (80%) or IMRT (17%). Ninety-eight percent of these patients received radiation therapy preoperatively, and 81% underwent definitive resection. IMRT use increased from <13% pre-2009 to >30% in 2010 and thereafter, with significant variability among institutions (range, 0%-43%). Other factors associated with IMRT use included age ≥65 years, dose >50.4 Gy, African-American race, and no transabdominal surgery. Rates of and time to radiation therapy completion were similar between the groups. ConclusionsAlthough most patients with stage II-III rectal cancer at queried National Cancer Institute–designated cancer centers between 2005 and 2011 received 3-dimensional CRT, significant and increasing numbers received IMRT. IMRT utilization is highly variable among institutions and not uniform among sociodemographic groups but may be more consistently embraced in specific clinical settings. Given this trend, comparative-effectiveness research is needed to evaluate the benefits of IMRT for rectal cancer.

High Rates of Minimally Invasive Hysterectomy Surgery for Endometrial Cancer at National Comprehensive Cancer Network Centers

High Rates of Minimally Invasive Hysterectomy Surgery for Endometrial Cancer at National Comprehensive Cancer Network Centers

Subtype-Dependent Relationship Between Young Age at Diagnosis and Breast Cancer Survival.

Young women are at increased risk for developing more aggressive subtypes of breast cancer. Although previous studies have shown a higher risk of breast cancer recurrence and death among young women with early-stage breast cancer, they have not adequately addressed the role of tumor subtype in outcomes. We examined data from women with newly diagnosed stage I to III breast cancer presenting to one of eight National Comprehensive Cancer Network centers between January 2000 and December 2007. Multivariable Cox proportional hazards models were used to assess the relationship between age and breast cancer-specific survival. A total of 17,575 women with stage I to III breast cancer were eligible for analysis, among whom 1,916 were ≤ 40 years of age at diagnosis. Median follow-up time was 6.4 years. In a multivariable Cox proportional hazards model controlling for sociodemographic, disease, and treatment characteristics, women ≤ 40 years of age at diagnosis had greater breast cancer mortality (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.7). In stratified analyses, age ≤ 40 years was associated with statistically significant increases in risk of breast cancer death among women with luminal A (HR, 2.1; 95% CI, 1.4 to 3.2) and luminal B (HR 1.4; 95% CI, 1.1 to 1.9) tumors, with borderline significance among women with triple-negative tumors (HR, 1.4; 95% CI, 1.0 to 1.8) but not among those with human epidermal growth factor receptor 2 subtypes (HR, 1.2; 95% CI, 0.8 to 1.9). In an additional model controlling for detection method, young age was associated with significantly increased risk of breast cancer death only among women with luminal A tumors. The effect of age on survival of women with early breast cancer seems to vary by breast cancer subtype. Young age seems to be particularly prognostic in women with luminal breast cancers.

Clinical significance of prospectively assigned Gleason tertiary pattern 4 in contemporary Gleason score 3+3=6 prostate cancer.

To determine the oncologic impact of prospectively assigned tertiary pattern 4 in contemporary Gleason score (GS) 3 + 3 = 6 radical prostatectomy (RP) specimens. Oncologic outcomes were retrospectively reviewed for 720 consecutive patients from a single National Comprehensive Cancer Network (NCCN) center with at least 6 months follow-up after RP for GS3 + 3 = 6 (GS6, N = 222), GS6 with tertiary pattern 4 (GS6t4, N = 62), or GS3 + 4 = 7 (N = 436) prostate cancer, as prospectively graded since 2006 using the 2005 International Society of Urologic Pathologists criteria. Preoperative NCCN risk category, RP pathology, progression-free survival (PFS) and metastasis-free survival (MFS) were compared among the GS6, GS6t4, and GS3 + 4 = 7 groups using χ(2) , Kaplan-Meier, and log-rank analyses. The incidence of low NCCN preoperative risk classification for GS6t4 patients (63%) was less than that for GS6 patients (77%) while greater than that for GS3 + 4 = 7 patients (30%, P < 0.001). GS6t4 patients had RP pathologic features which were intermediate in risk between that of GS6 and GS3 + 4 = 7 based on extraprostatic extension (27% vs. 6% vs. 31%, respectively, P < 0.001) and mean percentage of prostate gland involvement (13% vs. 10% vs. 16%, respectively, P < 0.001). With a mean overall follow-up of 42 months, PFS for GS6t4 patients (5-year 85%) was intermediate between that of GS6 (5-year 93%) and GS3 + 4 = 7 (5-year 76%) patients (P < 0.001). The 5-year MFS rate was 100% for GS6 and GS6t4 patients compared to 97% for GS3 + 4 = 7 patients (P = 0.07). This study provides the longest follow-up to date for RP patients with prospectively assigned GS6t4 and supports a risk for adverse RP pathology and postoperative disease progression that is intermediate between GS6 and GS3 + 4 = 7. Whether a tertiary pattern 4 in GS6 disease increases the risk of metastasis is uncertain and requires longer term study. Given favorable oncologic outcomes, less stringent postoperative surveillance for both GS6 and GS6t4 patients may be warranted.

Trends in the use of mastectomy in women with small node-negative breast cancer treated at US academic centers

Breast-conserving surgery (BCS) provides equivalent survival outcomes to unilateral mastectomy. There is no survival advantage to bilateral mastectomy in average risk breast cancer. Among a cohort of breast cancer patients expected to be candidates for BCS, we examined choice of surgery and factors associated with it. A prospective cohort study of unilateral clinical Stage I breast cancer patients treated at National Comprehensive Cancer Network centers from 2000 to 2009 was performed. The proportion of patients who initially underwent mastectomy versus BCS and time to definitive surgery and chemotherapy were examined. Of 10,249 patients, 23% underwent mastectomy as an initial surgery. No decline in the use of mastectomy as initial surgery was found. There was significant institutional variation, with rates of initial mastectomy ranging from 14 to 30% (adjusted odds ratio: 0.42-1.38). Tumor characteristics were associated with surgical option, but with small absolute differences. Of those who received initial mastectomy, 22% had bilateral mastectomy, with an increase over time (2000:13% vs. 2009:30%) and substantial institutional variation (11-34%). Women treated with initial mastectomy had longer median times from diagnosis to complete definitive surgery (6 vs. 4weeks) and to start of adjuvant chemotherapy (12 vs. 11weeks). Among Stage I breast cancer, the overall use of mastectomy did not change significantly over 10years; however, an increasing proportion of women with unilateral cancer had bilateral mastectomy, and there was wide variation in type of surgery by institution. Further studies to assess reasons for the observed wide variation are warranted.

Minimally Invasive Approaches to Rectal Cancer and Diverticulitis

Several advances have occurred in the field of colorectal surgery over the past 25 years, but 3 areas of noticeable progress relate to appreciating an anatomical operative approach to rectal cancer, understanding the natural course of diverticular disease, and adopting minimally invasive strategies for large bowel disorders such as colon cancer and ulcerative colitis.1,2 The high local recurrence rates customarily accepted after curative resection of rectal cancer were challenged when an association between the circumferential resection margin (CRM) and local recurrence was recognized. In the current era, careful sharp dissection within the anatomical planes leads to excision of an intact mesorectum with uninvolved margins and local recurrence rates as low as 5%.3 Similarly, recent evidence refutes historical dogma that maintained 2 episodes of uncomplicated diverticulitis warranted an elective operation, and peritonitis secondary to complicated disease requires a Hartmann procedure (ie, resection of perforated sigmoid colon, closure of distal bowel, and creation of colostomy). Surgeons now commonly counsel against an elective colectomy for recurrent uncomplicated diverticulitis and often perform urgent resection with diverted anastomosis for complicated disease with peritonitis.4 Just as knowledge has evolved, so has technology. More than half of elective operations performed for colorectal cancer at National Comprehensive Cancer Network centers from 20105 and for diverticulitis in the Nationwide Inpatient Sample database from 20096 were minimally invasive in their approach. In this issue of JAMA, 3 clinical trials7-9 focus on outcomes associated with minimally invasive operations for colorectal disorders. The studies by Fleshman et al7 and Stevenson et al8 describe results from randomized, multicenter clinical trials from North America (American College of Surgeons Oncology Group [ACOSOG] Z6051 trial) and Australasia (Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial [AlaCaRT]), respectively, investigating the noninferiority of minimally invasive compared with open pelvic dissection for patients with rectal cancer. In both studies, only surgeons accredited after video review of relevant operations were allowed to participate, and the primary outcome was defined as the adequacy of surgical dissection as assessed by completeness of the total mesorectal excision (TME), uninvolved CRM, and uninvolved distal resection margin. The North American study included patients (N = 486) with clinical stage II or III rectal cancer treated with neoadjuvant therapy followed by minimally invasive (n = 240) or open (n = 222) proctectomy.7 The Australasian study enrolled patients (N = 475) with clinical stage I-III rectal cancer who underwent laparoscopic (n = 238) or open (n = 235) pelvic dissection; 50% received preoperative radiotherapy.8 The technical quality of surgery in both trials was high as demonstrated by few laparoscopic conversions, high sphincter preservation rates, and low rates of anastomotic leakage and other complications in these study groups that included high-risk overweight patients, the majority of whom were male. Likewise, the composite pathologic success rate based on meeting all 3 surgical dissection criteria was very high in the North American (84%) and Australasian (85%) trials. However, in both studies, the adequacy of surgical dissection tended to be lower in theminimally invasive group compared with the open resection group despite comparable low rates of distal margin involvement. The ACOSOG Z6051 trial reported an adequate composite surgical dissection in 82% of patients undergoing minimally invasive surgery and 87% undergoing open proctectomy (difference, −5.3%; 1-sided 95% CI, −10.8% to , P for noninferiority = .41). This difference did not meet the prespecified noninferiority margin of 6%. The ALaCaRT trial found the laparoscopic and open success rates to be 82% and 89% (difference, −7.0%; 1-sided 95% CI of −12.4% to ; P for noninferiority = .38). Similarly, this difference did not meet the prespecified noninferiority margin of 8%. Earlier randomized, multicenter trials from South Korea (COREAN trial)10 and Europe (COLOR II trial)11,12 included patients undergoing laparoscopic or open proctectomy for clinical stage II-III rectal cancer after neoadjuvant chemoradiotherapy and stage I-III rectal cancer, respectively. The COREAN trial demonstrated a complete or nearly complete TME in 92% and 88% (P = .55) of patients undergoing laparoscopic and open proctectomy, respectively, and an uninvolved CRM (>1 mm) in 97% and 96% (P = .77) of cases, respectively.10 The 3-year local recurrence rates were comparable at 2.6% for laparoscopic and 4.9% for open surgery, with similar disease-free and overall survival rates. Similarly, the COLOR II trial found a complete TME in 88% of laparoscopic and 92% of open resection cases (P = .25), an Related articles pages 1346, 1356 and 1364 Opinion

Use and Effectiveness of Intraperitoneal Chemotherapy for Treatment of Ovarian Cancer.

A 2006 randomized trial demonstrated a 16-month survival benefit with intraperitoneal and intravenous (IP/IV) chemotherapy administered to patients who had ovarian cancer, compared with IV chemotherapy alone, but more treatment-related toxicities. The objective of this study was to examine the use and effectiveness of IP/IV chemotherapy in clinical practice. Prospective cohort study of 823 women with stage III, optimally cytoreduced ovarian cancer diagnosed at six National Comprehensive Cancer Network institutions. We examined IP/IV chemotherapy use in all patients diagnosed between 2003 and 2012 (N = 823), and overall survival and treatment-related toxicities with Cox regression and logistic regression, respectively, in a propensity score-matched sample (n = 402) of patients diagnosed from 2006 to 2012, excluding trial participants, to minimize selection bias. Use of IP/IV chemotherapy increased from 0% to 33% between 2003 and 2006, increased to 50% from 2007 to 2008, and plateaued thereafter. Between 2006 and 2012, adoption of IP/IV chemotherapy varied by institution from 4% to 67% (P < .001) and 43% of patients received modified IP/IV regimens at treatment initiation. In the propensity score-matched sample, IP/IV chemotherapy was associated with significantly improved overall survival (3-year overall survival, 81% v 71%; hazard ratio, 0.68; 95% CI, 0.47 to 0.99), compared with IV chemotherapy, but also more frequent alterations in chemotherapy delivery route (adjusted rates discontinuation or change, 20.4% v 10.0%; adjusted odds ratio, 2.83; 95% CI, 1.47 to 5.47). Although the use of IP/IV chemotherapy increased significantly at National Comprehensive Cancer Network centers between 2003 and 2012, fewer than 50% of eligible patients received it. Increasing IP/IV chemotherapy use in clinical practice may be an important and underused strategy to improve ovarian cancer outcomes.

Racial and Ethnic Differences in Breast Cancer Survival: Mediating Effect of Tumor Characteristics and Sociodemographic and Treatment Factors

To evaluate the relationship between race/ethnicity and breast cancer-specific survival according to subtype and explore mediating factors. Participants were women presenting with stage I to III breast cancer between January 2000 and December 2007 at National Comprehensive Cancer Network centers with survival follow-up through December 2009. Cox proportional hazards regression was used to compare breast cancer-specific survival among Asians (n = 533), Hispanics (n = 1,122), and blacks (n = 1,345) with that among whites (n = 14,268), overall and stratified by subtype (luminal A like, luminal B like, human epidermal growth factor receptor 2 type, and triple negative). Model estimates were used to derive mediation proportion and 95% CI for selected risk factors. In multivariable adjusted models, overall, blacks had 21% higher risk of breast cancer-specific death (hazard ratio [HR], 1.21; 95% CI, 1.00 to 1.45). For estrogen receptor-positive tumors, black and white survival differences were greatest within 2 years of diagnosis (years 0 to 2: HR, 2.65; 95% CI, 1.34 to 5.24; year 2 to end of follow-up: HR, 1.50; 95% CI, 1.12 to 2.00). Blacks were 76% and 56% more likely to die as a result of luminal A-like and luminal B-like tumors, respectively. No disparities were observed for triple-negative or human epidermal growth factor receptor 2-type tumors. Asians and Hispanics were less likely to die as a result of breast cancer compared with whites (Asians: HR, 0.56; 95% CI, 0.37 to 0.85; Hispanics: HR, 0.74; 95% CI, 0.58 to 0.95). For blacks, tumor characteristics and stage at diagnosis were significant disparity mediators. Body mass index was an important mediator for blacks and Asians. Racial disparities in breast cancer survival vary by tumor subtype. Interventions are needed to reduce disparities, particularly in the first 2 years after diagnosis among black women with estrogen receptor-positive tumors.

Abstract P2-13-03: Variation in the use of mastectomy (MAST) in women with small node negative breast cancer (BC) treated at US academic institutions

Abstract Background: More than two decades ago several trials have shown equivalent survival between breast conserving surgery (BCS) and MAST. Among a contemporary cohort of patients (pts) with Stage I BC who would be expected to be candidates for BCS; we examined the initial choice of surgery and factors associated with it. Pts and methods: Prospective cohort study including pts with clinical Stage I BC treated at a National Comprehensive Cancer Network center that participated in the BC outcomes database from 2000-09. Descriptive analyses were performed examining the proportion of pts who initially underwent MAST vs BCS. Factors associated with initial surgery were analyzed using multivariable logistic regression. Results: Of 10,249 pts with clinical Stage I BC, 2,361(23%) underwent MAST as the initial surgery and 7,888 (77%) BCS. Of those, 8% were ultimately converted to MAST. The median time from diagnosis to initial surgery was longer among the MAST group (4 vs. 6 weeks). Patient, tumor, care and institutional factors were associated with higher rates of initial MAST: 30% of pts with &amp;lt;50 years of age had a MAST vs. 17% of those ≥70; 41% of pts with body mass index (BMI) &amp;lt; 18.5 kg/m2 (underweight) had a MAST vs. 20% of those with a BMI &amp;gt;30 kg/m2 (obese). There was significant institutional variation, with rates of initial MAST ranging from 14-30%. The use of preoperative magnetic resonance imaging (MRI) was associated with a higher rate of initial MAST (32% vs.22%). Differences by tumor subtype were observed, 38% of pts with HER2+/HR- tumors had initial MAST vs. 22-28% among other subtypes. In the multivariate model, age, BMI, comorbidity, income, center, stage, tumor subtype, grade, histology and preoperative MRI were associated with the choice of initial surgery. Multivariate logistic model to investigate factors associated with initial MAST MAST vs BCS OR95%CIPAge &amp;lt;0.01&amp;lt;501 50-590.70.6 - 0.8 60-690.70.6 - 0.8 70+0.60.5 - 0.7 BMI (kg/m2) &amp;lt;0.01&amp;lt;18.51.81.3 - 2.6 18.5-&amp;lt;251 25-&amp;lt;300.80.7 - 0.9 ≥300.70.6 - 0.8 Unknown0.80.6 - 1.0 Comorbidity 0.0501 1+1.11.0 - 1.3 Race 0.8Non Hispanic white1 Non Hispanic black10.8-1.2 Hispanic10.8-1.3 Other1.10.9-1.4 Insurance 0.16Manged care/ Indemnity1 Medicare10.9-1.2 Self-pay/Medicaid1.31-1.6 Other10.6-1.6 Median Household income 0.021 (low)1 20.90.8-1.1 30.90.8-1.1 40.90.8-1.0 5 (high)0.80.6-0.9 Year of diagnosis11-10.35Center &amp;lt;0.01A1 B0.90.7-1.1 C0.70.6-0.9 D1.41.1-1.7 E0.40.3-0.6 F0.80.6-1.1 G1.31-1.6 H0.60.4-0.8 Clinical Stage &amp;lt;0.01T1a1 T1b0.80.6-0.9 T1c10.8-1.2 T1NOS1.10.9-1.4 Tumor Subtype &amp;lt;0.01HER2+HR+1 HER2+HR-1.51.1-1.9 HER2-HR+0.90.7-1.0 HER-HR-0.70.6-0.9 Grade &amp;lt;0.01Low Intermediate1 High1.21.1-1.4 Histology Ductal1 &amp;lt;0.01Lobular1.41.2-1.7 Mixed1.31.1-1.5 Other0.70.5-0.8 Preoperative MRI No1 &amp;lt;0.01Yes1.81.6-2.1 Conclusions: Among a cohort of pts with small node negative BC, 23% elected to have MAST with significant variation associated with choice of treatment, while some of this variation is likely appropriate and clinically indicated, further studies to assess pt understanding of the tradeoffs between BCS and MAST is warranted. These findings need to be considered in light of the increasing number of pts who are choosing MAST/bilateral MAST. Citation Format: Ines Vaz Luis, Melissa E Hughes, Angel Cronin, Hope S Rugo, Stephen B Edge, Beverly Moy, Richard Theriault, Michael J Hassett, Eric P Winer, Nancy U Lin. Variation in the use of mastectomy (MAST) in women with small node negative breast cancer (BC) treated at US academic institutions [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-03.

Variation in type of adjuvant chemotherapy received among patients with stage I breast cancer: A multi-institutional study.

Among patients with stage I breast cancer, there is significant uncertainty concerning the optimal threshold at which to consider chemotherapy, and when considered, there is controversy regarding whether to consider non-intensive versus intensive regimens. The authors examined the types and costs of adjuvant chemotherapy received among patients with stage I breast cancer. The current study was a prospective cohort study including patients with stage I breast cancer who were treated at a National Comprehensive Cancer Network center from 2000 through 2009. Stage was defined according to the version of the American Joint Committee on Cancer Staging Manual applicable at the time of diagnosis. Stratifying by human epidermal growth factor receptor 2 (HER2), the authors examined the percentage of patients receiving intensive versus non-intensive chemotherapy regimens and the factors associated with type of chemotherapy administered using multivariable logistic regression. Costs of the most common regimens were estimated. Of 8907 patients, 33% received adjuvant chemotherapy. Among those individuals, there was an increase in the use of intensive chemotherapy within the last decade, from 31% in 2000 through 2005 to 63% in 2008 through 2009 (including an increase in the use of the combination of docetaxel, carboplatin, and trastuzumab) among patients with HER2-positive disease and from 15% in 2000 through 2005 to 41% in 2008 through 2009 among patients with HER2-negative disease (32% of patients with hormone receptor-positive and 59% of patients with triple-negative disease). Among patients treated with non-intensive regimens, there was an increase in the use of the combination of docetaxel and cyclophosphamide noted, with a decrease in the use of the doxorubicin and cyclophosphamide combination. The choice of regimen varied significantly by institution. The major drivers of cost variation were the incorporation of biologics (eg, trastuzumab) and growth factors, with significant variation even within non-intensive and intensive regimens. Over time, there was an increase in use of intensive regimens among Stage I breast cancer, with striking institutional and cost variations.

Incidence of minimally invasive colorectal cancer surgery at National Comprehensive Cancer Network centers.

Laparoscopic colectomy has been shown to have equivalent oncologic outcomes to open colectomy for the management of colon cancer, but its adoption nationally has been slow. This study investigates the prevalence and factors associated with laparoscopic colorectal resection at National Comprehensive Cancer Network (NCCN) centers. Data on patients undergoing surgery for colon and rectal cancer at NCCN centers from 2005 to 2010 were obtained from chart review of medical records for the NCCN Outcomes Project and included information on socioeconomic status, insurance coverage, comorbidity, and physician-reported Eastern Cooperative Oncology Group (ECOG) performance status. Associations between receipt of minimally invasive surgery and patient and clinical variables were analyzed with univariate and multivariable logistic regression. All statistical tests were two-sided. A total of 4032 patients, diagnosed between September 2005 and December 2010, underwent elective colon or rectal resection for cancer at NCCN centers. Median age of colon cancer patients was 62.6 years, and 49% were men. The percent of colon cancer patients treated with minimally invasive surgery (MIS) increased from 35% in 2006 to 51% in 2010 across all centers but varied statistically significantly between centers. On multivariable analysis, factors associated with minimally invasive surgery for colon cancer patients who had surgery at an NCCN institution were older age (P = .02), male sex (P = .006), fewer comorbidities (P ≤ .001), lower final T-stage (P < .001), median household income greater than or equal to $80000 (P < .001), ECOG performance status = 0 (P = .02), and NCCN institution (P ≤ .001). The use of MIS increased at NCCN centers. However, there was statistically significant variation in adoption of MIS technique among centers.

High Body Mass Index (BMI) in North American Elderly Diffuse Large B-Cell Lymphoma (DLBCL) Patients Treated with Rituximab (R)-CHOP Compensates for Negative Impact of Male Gender

Background: Recent reports from prospective clinical trials of R-containing chemotherapy in DLBCL patients suggest that gender, weight and/or BMI influence clinical outcomes. Pharmacokinetic studies by the German High Grade Lymphoma Study Group have shown that R clearance is relatively slow in elderly women compared to men, leading to higher levels and prolonged exposure and hence better clinical outcomes in elderly females. Specifically, it has been suggested that elderly men are underdosed, based on faster R clearance (Muller et al., 2012; Pfreundschuh et al., 2014). Regarding BMI as a predictor of clinical outcome, analysis of the US Veterans Administrative database showed an association between increased BMI and improved survival in DLBCL patients (Carson et al., 2012), while the ECOG clinical trial (E4494) for elderly DLBCL patients failed to reveal a significant association of BMI with clinical outcomes, or a gender difference related to BMI in failure-free survival (Hong et al., 2014). To further investigate these associations, we studied the effect of gender, BMI as well as body surface area (BSA, the actual dosing parameter), and potential interactions among these factors on long-term clinical outcomes for elderly DLBCL patients in the National Comprehensive Cancer Network (NCCN) non-Hodgkin lymphoma database.Methods:De novo DLBCL patients with age > 60 yrs. were identified from the NCCN adult DLBCL cohort. Patients were diagnosed between June 2000 and December 2010. All received R as part of first-line therapy. Outcomes evaluated included progression free survival (PFS) and overall survival (OS) at 3 years based on patient gender, age and BMI/ BSA at presentation. Gender was stratified based on BMI (<=18.5, >18.5-25, >25) or BSA (<=2, >2), and Kaplan-Meier estimates were calculated. Associations with disease progression and survival were additionally adjusted for the International Prognostic Index (IPI) in the multivariable Cox regression analyses.Results: Of the 1,386 DLBCL patients who received R, 627 were elderly with age >60 yrs. The majority of elderly men were either overweight or large: only 13% had BMI <=25 and only 26% had BSA <=2. Elderly men (n=325, 52%) experienced worse PFS (3 yr-Hazard Ratio, HR 1.5, 95% CI: 1.1-2.1, p=0.02) and OS (3 yr-HR 1.6, 1.1-2.4, p=0.01) compared to elderly women. Of note, the poor risk associated with male gender was associated with patients over 60, but not the younger cohort (3 yr-PFS, HR 1.3, 0.9-1.9, p=0.12). The benefit associated with female gender in the elderly cohort decreased with increases in BMI and BSA (Figure). There was a benefit associated with female gender when compared to male gender in the BMI (<=25) (log rank, p<0.01) and BSA <=2 (p=0.04) strata, but not among patients with high BMI (>25) or BSA (>2). In multivariable analysis, low or normal BMI as compared to high BMI was independently associated with poor outcomes (3-yr PFS, HR: 1.6, 1.1-2.2, p<0.01) after adjusting for gender. There was a trend suggesting that BSA <=2 correlated with worse 3-yr PFS in the elderly group adjusting for gender (3 yr-HR 1.4, 0.9-2.0, p=0.12). The HR estimates remained largely unchanged after adjusting for IPI. Notably, higher BMI was not associated with more favorable prognostic clinical factors.Conclusions: Our results, derived from analysis of unselected patients with DLBCL treated with R-containing chemotherapy at major NCCN centers, confirmed an age-dependent disadvantage to male gender in treatment outcomes. The magnitude of this negative effect diminished with higher levels of BMI and BSA, with the greatest negative impact occurring in elderly men with BMI <=25 or BSA <=2. Our findings support efforts to optimize R dosing, especially in the elderly male subset with BMI <=25 or BSA <=2. Future prospective trials should factor size and gender into the study design and analysis. Our results support the ongoing German randomized trial to evaluate enhanced rituximab dosing for older male patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of guideline changes on use or omission of radiation in the elderly with early breast cancer: practice patterns at National Comprehensive Cancer Network institutions.

Breast radiation therapy (RT) is a care standard after breast-conservation surgery that improves local control and survival in women. In 2004, a phase III trial demonstrated radiation after breast-conservation surgery provided no survival and limited local control benefit to women aged 70 years and older with stage I, estrogen receptor-positive cancers who receive endocrine therapy. This led to breast-conservation surgery and endocrine therapy alone being incorporated as a category I option in the National Comprehensive Cancer Network (NCCN) Guidelines for older women in 2004. We examined factors associated with change in radiation use in elderly patients at 13 NCCN centers. We identified women treated at NCCN centers meeting age and stage criteria during 2000 to 2009. Factors considered a priori potentially associated with RT use were evaluated in univariate and multivariable models, including year of diagnosis, tumor and patient characteristics, axillary surgery, and treating institution. Date of diagnosis was classified as 2000 to 2004 vs 2005 to 2009, reflecting when guidelines changed. Among 1,292 eligible cases, 78% received RT. In multivariable analysis, diagnosis after 2004 (p = 0.0003), older age (p < 0.0001), higher comorbidity score (p = 0.0006), smaller tumors (p = 0.0146), and omission of axillary surgery (p < 0.0001) predicted RT omission. Ninety-four percent of women aged 70 to 74 years received RT in 2000, compared with 88% in 2009. For the same times and age 80 years and older, RT use was 80% vs 41%. Finally, RT use was associated with treating institution (p < 0.0001). After guideline changes for RT use in older women, NCCN centers demonstrated wide variation in implementing change. This suggests other factors are also influencing guideline uptake.

Effect of intraperitoneal chemotherapy on survival for ovarian cancer in clinical practice and frequency of use.

5576 Background: In 2006 the National Cancer Institute (NCI) issued a rare clinical alert recommending intraperitoneal chemotherapy (IP) to treat ovarian cancer after GOG-172, a randomized clinical trial comparing IP and intravenous chemotherapy (IV), demonstrated a 16-month survival advantage with IP. The aims of this study were to determine: (1) changes in IP utilization over time, (2) factors associated with adoption of IP therapy, and (3) the impact of IP on survival. Methods: Prospective cohort study of women with stage III, optimally-cytoreduced ovarian cancer treated at National Comprehensive Cancer Network (NCCN) institutions. Trends were evaluated in 823 patients between 2003-2012. In 603 patients, diagnosed after 2006, multivariable logistic regression and propensity-score analyses were used to examine factors associated with receipt of IP therapy and associations between treatment modality, adverse events, and overall survival. Results: IP utilization rose from 0% to 33% between 2003-2006, increased to 50% in 2007-2008, and decreased to 43% during 2009-2012. At treatment initiation 43% of patients received modified IP regimens, 29% received the GOG 172 regimen, and 28% received IP on a clinical trial. In adjusted analyses, younger age, fewer comorbid conditions, and clinical trial enrollment were associated with IP therapy (all P≤0.01). NCCN center was independently associated with receipt of IP; the adjusted proportion of patients receiving IP varied by site between 16% and 71% (P<0.001). After propensity-score weighted adjustment, patients receiving IP were more likely to switch to IV due to toxicity (AOR=2.01, 95% CI=1.30-3.12) compared with IV. Adjusted 5-year overall survival rates were 57% for IP vs. 44% for IV (hazard ratio=0.69, 95% CI=0.50-0.94). Conclusions: The use of IP therapy increased significantly over the past decade at NCCN centers. However, recently only a minority of eligible patients have received it. Despite frequent modifications, IP chemotherapy is associated with significantly improved survival in clinical practice. Future studies should examine whether site-specific variations in IP utilization reflect patients’ informed treatment preferences.

Emerging trends in type of chemotherapy (CT) received among patients (pts) with stage I breast cancer (BC).

522 Background: We examined time trends of CT used and associations with pts characteristics in Stage I BC. Methods: Prospective cohort studyincluding pts with Stage I BC treated at a National Comprehensive Cancer Network center from 2000-09. We examined the proportion of pts receiving intensive vs. non-intensive CT over time.We defined an intensive regimen as: a combination of anthracyclines and taxanes (e.g. ACT ± H) or a combination of carboplatin and docetaxel (e.g. TCH), and non-intensive as: anthracycline-based (e.g. AC), taxane-based (e.g. TC) or similar. We evaluated factors associated with type of CT using multivariable logistic regression. Analyses were stratified by HER2 receptor status. Results: Of 8,907 pts, 33% received adjuvant CT. There was a dramatic increase of intensive CT: among HER2+ pts from 31% in 2000-05 to 63% in 2008-09 (including an increase in the use of TCH) and among HER2- from 15% in 2000-05 to 41% in 2008-09. Among non-intensive regimens there was an increase in the use of ...

Comparison of referring and final pathology for patients with T‐cell lymphoma in the National Comprehensive Cancer Network

T-cell lymphomas (TCLs) are uncommon in the United States. The accurate diagnosis of TCL is challenging and requires morphologic interpretation, immunophenotyping, and molecular techniques. The authors compared pathologic diagnoses at referring centers with diagnoses from expert hematopathology review to determine concordance rates and to characterize the usefulness of second-opinion pathology review for TCL. Patients in the National Comprehensive Cancer Network non-Hodgkin lymphoma database with peripheral TCL, not otherwise specified (PTCL-NOS), angioimmunoblastic TCL (AITL), and anaplastic lymphoma kinase (ALK)-positive and ALK-negative anaplastic large cell lymphoma (ALCL) were eligible if they had prior tissue specimens examined at a referring institution. Pathologic concordance was evaluated using available pathology and diagnostic testing reports and provider progress notes. The etiology of discordance and the potential impact on treatment were examined. Among 131 eligible patients, 57 (44%) had concordant results, totaling 64% of the 89 patients who were referred with a final diagnosis. Thirty-two patients (24%) had discordant results, representing 36% of those who were referred with a final diagnosis. The rates of discordance among patients with of PTCL-NOS, AITL, ALK-negative ALCL, and ALK-positive ALCL were 19%, 33%, 34%, and 6%, respectively. In 14 patients (44% of discordant results), pathologic reclassification could have resulted in a different therapeutic strategy. Forty-two patients (32%) were referred for classification with a provisional diagnosis. In a large cohort of patients with TCL who were referred to National Comprehensive Cancer Network centers, the likelihood of a concordant final diagnosis at a referring institution was low. As current and future therapies target TCL subsets, these data suggest that patients with suspected TCLs would benefit from evaluation by an expert hematopathologist.