Leveraging an Informatics Approach to Identify an Unmet Clinical Need for BRCA1/2 Testing Among Patients With Ovarian Cancer.

PURPOSE: Although BRCA1/2 testing in ovarian cancer improves outcomes, it is vastly underutilized. Scalable approaches are urgently needed to improve genomically guided care. METHODS: We developed a Natural Language Processing (NLP) pipeline to extract electronic medical record information to identify recipients of BRCA testing. We applied the NLP pipeline to assess testing status in 308 patients with ovarian cancer receiving care at a National Cancer Institute Comprehensive Cancer Center (main campus [MC] and five affiliated clinical network sites [CNS]) from 2017 to 2019. We compared characteristics between (1) patients who had/had not received testing and (2) testing utilization by site. RESULTS: We found high uptake of BRCA testing (approximately 78%) from 2017 to 2019 with no significant differences between the MC and CNS. We observed an increase in testing over time (67%-85%), higher uptake of testing among younger patients (mean age tested = 61 years v untested = 65 years, P = .01), and higher testing among Hispanic (84%) compared with White, Non-Hispanic (78%), and Asian (75%) patients (P = .006). Documentation of referral for an internal genetics consultation for BRCA pathogenic variant carriers was higher at the MC compared with the CNS (94% v 31%). CONCLUSION: We were able to successfully use a novel NLP pipeline to assess use of BRCA testing among patients with ovarian cancer. Despite relatively high levels of BRCA testing at our institution, 22% of patients had no documentation of genetic testing and documentation of referral to genetics among BRCA carriers in the CNS was low. Given success of the NLP pipeline, such an informatics-based approach holds promise as a scalable solution to identify gaps in genetic testing to ensure optimal treatment interventions in a timely manner.

Outcomes of secondary cytoreductive surgery for patients with platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Most women with advanced epithelial ovarian cancer develop recurrent disease, despite maximal surgical cytoreduction and adjuvant platinum-based chemotherapy. In observational studies, secondary cytoreductive surgery has been associated with improved survival; however its use is controversial, because there are concerns that the improved outcomes may reflect selection bias rather than the superiority of secondary surgery. OBJECTIVE: To compare the overall survival of women with platinum-sensitive recurrent ovarian cancer treated at National Cancer Institute-designated cancer centers who receive secondary surgery vs chemotherapy. STUDY DESIGN: This retrospective cohort study included women from 6 National Cancer Institute-designated cancer centers diagnosed with platinum-sensitive recurrent ovarian cancer between January 1, 2004, and December 31, 2011. The primary outcome was overall survival. Propensity score matching was used to compare similar women who received secondary surgery vs chemotherapy. Additional analyses examined how these findings may be influenced by the prevalence of unobserved confounders at the time of recurrence. RESULTS: Among 626 women, 146 (23%) received secondary surgery and 480 (77%) received chemotherapy. In adjusted analyses, patients who received secondary surgery were younger (P = 0.001), had earlier-stage disease at diagnosis (P = 0.002), and had longer disease-free intervals (P < 0.001) compared with those receiving chemotherapy. In the propensity score-matched groups (n = 244 patients), the median overall survival was 54 months in patients who received secondary surgery and 33 months in those treated with chemotherapy (P < 0.001). Among patients who received secondary surgery, 102 (70%) achieved optimal secondary cytoreduction. There were no significant differences in complication rates between the 2 groups. In sensitivity analyses, the survival advantage associated with secondary surgery could be explained by the presence of more multifocal recurrences (if 4.3 times more common), ascites (if 2.7 times more common), or carcinomatosis (if 2.1 times more common) among patients who received chemotherapy instead of secondary surgery. CONCLUSION: Patients with platinum-sensitive recurrent ovarian cancer who received secondary surgery had favorable surgical characteristics and were likely to have minimal residual disease following secondary surgery. These patients had a superior median overall survival compared with patients who received chemotherapy, although unmeasured confounders may explain this observed difference.

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

PURPOSE: Intensity 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 MATERIALS: Using 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. RESULTS: A 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. CONCLUSIONS: Although 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.

Clinical risk score to predict likelihood of recurrence after ductal carcinoma in situ treated with breast-conserving surgery.

PURPOSE: A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score to provide individualized information about IBTR risk to guide treatment decisions. METHODS: Data from 2762 patients treated with BCS for DCIS at centers within the National Comprehensive Cancer Network (NCCN) were used to identify statistically significant non-treatment-related predictors for 5-year IBTR. Factors most associated with IBTR were estrogen-receptor status of the DCIS, presence of comedo necrosis, and patient age at diagnosis. These three parameters were used to create a point-based risk score. Discrimination of this score was assessed in a separate DCIS population of 301 women (100 with IBTR and 200 without) from Kaiser Permanente Northern California (KPNC). RESULTS: Using NCCN data, the 5-year likelihood of IBTR without adjuvant therapy was 9% (95% CI 5-12%), 23% (95% CI 13-32%), and 51% (95% CI 26-75%) in the low, intermediate, and high-risk groups, respectively. Addition of the risk score to a model including only treatment improved the C-statistic from 0.69 to 0.74 (improvement of 0.05). Cross-validation of the score resulted in a C-statistic of 0.76. The score had a c-statistic of 0.67 using the KPNC data, revealing that it discriminated well. CONCLUSIONS: This simple, no-cost risk score may be used by patients and physicians to facilitate preference-based decision-making about DCIS management informed by a more accurate understanding of risks.

Acceptance of adjuvant chemotherapy recommendations in early-stage hormone-positive breast cancer.

BACKGROUND: The role of systemic chemotherapy in early-stage, estrogen receptor (ER)-positive, and Her2-negative breast cancer remains an area of active investigation. The decision to recommend chemotherapy is multifactorial, and some patients decline recommended chemotherapy. We sought to identify patient factors leading to refusal of adjuvant therapy. MATERIALS AND METHODS: Data were collected from National Comprehensive Cancer Network Outcomes database and used to identify patients with primary, unilateral, T1-T2, N0, ER+, Her2-disease diagnosed from 2005-2011. Patient and clinical characteristics were analyzed for associations with physician recommendation for chemotherapy and patient acceptance of chemotherapy. A logistic regression model was used to identify patient and tumor characteristics associated with recommendation for and acceptance of chemotherapy. RESULTS: A total of 329 patients were identified. Chemotherapy was recommended in 191 patients (58.1%) and not in 138 (41.9%). Young age (odds ratio [OR]: 3.9, 95% confidence interval [CI]: 1.2-12.7), large tumor size (6.69, 95% CI: 3.31-13.5), and high Oncotype DX scores (11.2, 95% CI: 4.5-27.9) were more likely to receive a recommendation. About 71 patients (37.1%) refused chemotherapy. Patients younger than age 50 (20.9, 95% CI: 2.5-172.0), larger tumor size (3.4, 95% CI: 1.3-8.7), Oncotype DX score > 31 (31.3, 95% CI: 3.3-295.0), privately insured (8.2, 95% CI: 1.9-34.7), and Hispanic ethnicity (5.2, 95% CI: 1.6-16.8) were more likely to accept chemotherapy. CONCLUSIONS: Physician recommendations for adjuvant chemotherapy for early-stage ER + breast cancer varied by commonly considered factors. Patient acceptance varied by similar factors but was also influenced by race and insurance status. This may be explained by cultural or social factors not well understood or not overcome by physician guidance.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Variation in Definitive Therapy for Localized Non-Small Cell Lung Cancer Among National Comprehensive Cancer Network Institutions.

PURPOSE: This study determined practice patterns in the staging and treatment of patients with stage I non-small cell lung cancer (NSCLC) among National Comprehensive Cancer Network (NCCN) member institutions. Secondary aims were to determine trends in the use of definitive therapy, predictors of treatment type, and acute adverse events associated with primary modalities of treatment. METHODS AND MATERIALS: Data from the National Comprehensive Cancer Network Oncology Outcomes Database from 2007 to 2011 for US patients with stage I NSCLC were used. Main outcome measures included patterns of care, predictors of treatment, acute morbidity, and acute mortality. RESULTS: Seventy-nine percent of patients received surgery, 16% received definitive radiation therapy (RT), and 3% were not treated. Seventy-four percent of the RT patients received stereotactic body RT (SBRT), and the remainder received nonstereotactic RT (NSRT). Among participating NCCN member institutions, the number of surgeries-to-RT course ratios varied between 1.6 and 34.7 (P<.01), and the SBRT-to-NSRT ratio varied between 0 and 13 (P=.01). Significant variations were also observed in staging practices, with brain imaging 0.33 (0.25-0.43) times as likely and mediastinoscopy 31.26 (21.84-44.76) times more likely for surgical patients than for RT patients. Toxicity rates for surgical and for SBRT patients were similar, although the rates were double for NSRT patients. CONCLUSIONS: The variations in treatment observed among NCCN institutions reflects the lack of level I evidence directing the use of surgery or SBRT for stage I NSCLC. In this setting, research of patient and physician preferences may help to guide future decision making.

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

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

PURPOSE: To evaluate the relationship between race/ethnicity and breast cancer-specific survival according to subtype and explore mediating factors. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: The use of MIS increased at NCCN centers. However, there was statistically significant variation in adoption of MIS technique among centers.

Radiation for diffuse large B-cell lymphoma in the rituximab era: analysis of the National Comprehensive Cancer Network lymphoma outcomes project.

BACKGROUND: The role of consolidation radiotherapy was examined for patients with diffuse large B-cell lymphoma who were treated at institutions of the National Comprehensive Cancer Network during the rituximab era. METHODS: Failure-free survival (FFS) and overall survival (OS) were analyzed in terms of patient and treatment characteristics. Potential associations were investigated with univariate and multivariate survival analysis and matched pair analysis. RESULTS: There were 841 patients, and most (710 or 84%) received 6 to 8 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); 293 (35%) received consolidation radiation therapy (RT). Failure occurred for 181 patients: 126 patients (70%) who did not receive RT and 55 patients (30%) who did. At 5 years, both OS and FFS rates were better for patients who had received RT versus those who did not (OS, 91% vs 83% [P = .01]; FFS, 83% vs 76% [P = .05]). A matched pair analysis (217 pairs matched by age, stage, International Prognostic Index [IPI] score, B symptoms, disease bulk, and response to chemotherapy) showed that the receipt of RT improved OS (hazard ratio [HR], 0.53 [P = .07]) and FFS (HR, 0.77 [P = .34]) for patients with stage III/IV disease, but too few events took place among those with stage I/II disease for meaningful comparisons (HR for OS, 0.94 [P = .89]; HR for FFS, 1.81 [P = .15]). A multivariate analysis suggested that the IPI score and the response to chemotherapy had the greatest influence on outcomes. CONCLUSIONS: There was a trend of higher OS and FFS rates for patients who had received consolidation RT after R-CHOP (especially for patients with stage III/IV disease), but the difference did not reach statistical significance.

Socioeconomic and clinical factors are key to uncovering disparity in accrual onto therapeutic trials for breast cancer.

To monitor and address disparity in accrual, patient participation in cancer clinical trials is routinely summarized by race/ethnicity. To investigate whether confounding obscures racial/ethnic disparity in participation, all women with breast cancer treated by medical oncologists at City of Hope Comprehensive Cancer Center from 2004 through 2009 were classified by birthplace and self-reported race/ethnicity, and followed for accrual onto therapeutic trials through 2010. Undetectable on univariate analysis, significantly reduced participation by subjects of African, Asian, Eastern European, Latin American, and Middle Eastern ancestries was revealed after accounting for age, socioeconomic factors, tumor and oncologist characteristics, and intrapractice clustering of patients.

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.

BACKGROUND: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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.

Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. METHODS: Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. RESULTS: There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). CONCLUSIONS: TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era.

The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with aggressive non-Hodgkin lymphoma (NHL) for the past 20 years. Using raw clinical data from the National Comprehensive Cancer Network (NCCN) database collected during the rituximab era, we built an enhanced IPI with the goal of improving risk stratification. Clinical features from 1650 adults with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed from 2000-2010 at 7 NCCN cancer centers were assessed for their prognostic significance, with statistical efforts to further refine the categorization of age and normalized LDH. Five predictors (age, lactate dehydrogenase (LDH), sites of involvement, Ann Arbor stage, ECOG performance status) were identified and a maximum of 8 points assigned. Four risk groups were formed: low (0-1), low-intermediate (2-3), high-intermediate (4-5), and high (6-8). Compared with the IPI, the NCCN-IPI better discriminated low- and high-risk subgroups (5-year overall survival [OS]: 96% vs 33%) than the IPI (5 year OS: 90% vs 54%), respectively. When validated using an independent cohort from the British Columbia Cancer Agency (n = 1138), it also demonstrated enhanced discrimination for both low- and high-risk patients. The NCCN-IPI is easy to apply and more powerful than the IPI for predicting survival in the rituximab era.

Stem cell transplantation for follicular lymphoma relapsed/refractory after prior rituximab: a comprehensive analysis from the NCCN lymphoma outcomes project.

BACKGROUND: Stem cell transplant (SCT)-related outcomes and prognostication for relapsed/refractory follicular lymphoma (FL) are not well-defined in the post-rituximab era. METHODS: Through the National Comprehensive Cancer Network (NCCN) lymphoma outcomes study, 184 patients with relapsed/refractory FL who underwent autologous SCT (autoSCT) or allogenic SCT (alloSCT) following disease relapse after prior rituximab-based therapy were examined. RESULTS: Patients who underwent autoSCT (N=136) were older compared with patients who underwent alloSCT (N=48) (54 versus 51 years, respectively, P=.01) and more frequently had grade 3 FL (35% versus 8%, respectively, P=.006). Patients who underwent alloSCT received more prior therapies (4 versus 3, respectively, P<.0001) and more often had resistant disease at SCT (19% versus 6%, respectively, P=.008). Cumulative 100-day nonrelapse mortality (NRM) for autoSCT and alloSCT were 1% and 6%, respectively (P<.0001), whereas 3-year NRM rates were 3% versus 24%, respectively (P<.0001). For autoSCT and alloSCT, cumulative rates of relapse, progression, and/or transformation were 32% versus 16%, respectively (P=.03), whereas 3-year overall survival rates were 87% versus 61% (P<.0001); there were no differences in failure-free survival. AlloSCT was associated with increased risk of death on multivariate analysis (hazard ratio=2.77, 95% confidence interval=1.46-5.26, P=.002). This finding persisted on propensity scoring/matching. Multivariate analysis for autoSCT patients identified age>60 years and>3 prior therapies as adverse factors. Furthermore, a survival model was created for the autoSCT cohort based on number of factors present (0, 1, 2); 3-year failure-free survival was 72%, 47%, and 20%, respectively (P=.0003), and 3-year overall survival was 96%, 82%, and 62%, respectively (P<.0001). CONCLUSIONS: AutoSCT remains an effective therapy for patients with FL. For alloSCT, continued strategies to reduce NRM are needed.

Patterns of use of 18-fluoro-2-deoxy-D-glucose positron emission tomography for initial staging of grade 1-2 follicular lymphoma and its impact on initial treatment strategy in the National Comprehensive Cancer Network Non-Hodgkin Lymphoma Outcomes database.

We describe the patterns of use of 18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for the initial staging of patients with newly diagnosed grade 1-2 follicular lymphoma (FL) and its potential impact on treatment. Data were obtained from the National Comprehensive Cancer Network Non-Hodgkin Lymphoma Outcomes database. Patients who presented between 1 January 2001 and 30 September 2009 with newly diagnosed grade 1-2 FL, with at least 6 months of follow-up, were included. We identified 953 eligible patients and 532 (56%) underwent FDG-PET as part of initial staging. Among patients who underwent FDG-PET for initial staging, 438 (82%) received early treatment compared to 259 (61.5%) of those staged without FDG-PET (p < 0.0001). Of all patients with stage I FL (n = 100), 47% were treated with radiotherapy (RT) alone, and the choice of initial treatment strategy for stage I FL did not vary significantly by use of FDG-PET (p = 0.22). The use of FDG-PET for staging of FL is widespread and is associated with a greater proportion of patients receiving early therapy. Given the widespread use and high cost of FDG-PET, its clinical utility in stage I FL should be further evaluated.

Smoking status and survival in the national comprehensive cancer network non-small cell lung cancer cohort.

BACKGROUND: The objectives of this study were to evaluate survival among current smokers, former smokers, and never smokers who are diagnosed with non-small cell lung cancer (NSCLC). METHODS: The study included patients who participated in the National Comprehensive Cancer Network's NSCLC Database Project. Current, former, and never smokers were compared with respect to overall survival by fitting Cox regression models. RESULTS: Data from 4200 patients were examined, including 618 never smokers, 1483 current smokers, 380 former smokers who quit 1 to 12 months before diagnosis, and 1719 former smokers who quit >12 months before diagnosis. Among patients with stage I, II, and III disease, only never smokers had better survival than current smokers (hazard ratio, 0.47 [95% confidence interval, 0.26-0.85] vs 0.51 [95% confidence interval, 0.38-0.68], respectively). Among patients with stage IV disease, the impact of smoking depended on age: Among younger patients (aged ≤55 years), being a never smoker and a former smoker for ≥12 months increased survival. After age 85 years, smoking status did not have a significant impact on overall survival. CONCLUSIONS: Patients who were smoking at the time of diagnosis had worse survival compared with never smokers. Among younger patients with stage IV disease, current smokers also had worse survival compared with former smokers who quit >12 months before diagnosis. It is likely that tumor biology plays a major role in the differences observed; however, to improve survival, it is prudent to encourage all smokers to quit smoking if they are diagnosed with NSCLC.

Postoperative adjuvant chemotherapy use in patients with stage II/III rectal cancer treated with neoadjuvant therapy: a national comprehensive cancer network analysis.

PURPOSE: Practice guidelines recommend that patients who receive neoadjuvant chemotherapy and radiation for locally advanced rectal cancer complete postoperative adjuvant systemic chemotherapy, irrespective of tumor downstaging. PATIENTS AND METHODS: The National Comprehensive Cancer Network (NCCN) Colorectal Cancer Database tracks longitudinal care for patients treated at eight specialty cancer centers across the United States and was used to evaluate how frequently patients with rectal cancer who were treated with neoadjuvant chemotherapy also received postoperative systemic chemotherapy. Patient and tumor characteristics were examined in a multivariable logistic regression model. RESULTS: Between September 2005 and December 2010, 2,073 patients with stage II/III rectal cancer were enrolled in the database. Of these, 1,193 patients receiving neoadjuvant chemoradiotherapy were in the analysis, including 203 patients not receiving any adjuvant chemotherapy. For those seen by a medical oncologist, the most frequent reason chemotherapy was not recommended was comorbid illness (25 of 50, 50%); the most frequent reason chemotherapy was not received even though it was recommended or discussed was patient refusal (54 of 74, 73%). After controlling for NCCN Cancer Center and clinical TNM stage in a multivariable logistic model, factors significantly associated with not receiving adjuvant chemotherapy were age, Eastern Cooperative Oncology Group performance status ≥ 1, on Medicaid or indigent compared with private insurance, complete pathologic response, presence of re-operation/wound infection, and no closure of ileostomy/colostomy. CONCLUSION: Even at specialty cancer centers, a sizeable minority of patients with rectal cancer treated with curative-intent neoadjuvant chemoradiotherapy do not complete postoperative chemotherapy. Strategies to facilitate the ability to complete this third and final component of curative intent treatment are necessary.