tbuckley/cabot-search huggingface dataset:
Do cancer centers need to assess quality and outcomes? Introducing a customized ACS-NSQIP for oncology (Onc-NSQIP).
Authors: K. Y. Bilimoria, X. Wang, M. E. Cohen, B. L. Hall, K. Richards, R. P. Merkow, P. W. Pisters, C. Y. Ko
Journal: Journal of Clinical Oncology (2011)

475 Background: To identify quality improvement opportunities, hospitals can use ACS NSQIP to compare their risk-adjusted performance to other hospitals. However, Cancer Centers have few opportunities to compare their outcomes to similar hospitals for oncologic operations. Our objective was to develop an oncology-specific version of ACS NSQIP (Onc-NSQIP) and determine whether it could be useful for Cancer Centers. Methods: From ACS-NSQIP (2006-2009), patients undergoing major colorectal (n=34,858; 221 hospitals) and pancreatic (n=7,667; 65 hospitals) as well as esophageal, gastric, and soft tissue operations for malignancy were identified. Risk-adjusted postoperative outcomes were assessed with regression models adjusting for demographics, comorbidities, and operative procedure. Relative rankings of NCI-designated Comprehensive Cancer Centers in ACS NSQIP among the other ACS NSQIP hospitals were compared. Results: Cancer Center outcomes varied widely for colorectal and pancreas. For overall colorectal morbidity, Cancer Centers were ranked in the top third (n=4), middle third (n=7), and bottom third (n=10). For colorectal 30-day mortality, Cancer Centers were ranked in the top (n=14), middle (n=3), and bottom third (n=4). For overall pancreatic morbidity, Cancer Centers were ranked in the top (n=5), middle (n=7), and bottom third (n=7). For pancreatic 30-day mortality, Cancer Centers were ranked in the top (n=5), middle (n=6), and bottom third (n=8). Similar results were observed for colorectal and pancreas for DVT/PE, SSI, reoperation, and length of stay. Onc-NSQIP models were comparable to standard ACS NSQIP models. At least some Cancer Centers were statistical outliers for most outcomes (P&lt;0.05). Results were similar for other malignancies. Conclusions: Cancer Center outcomes varied as much as other ACS NSQIP hospitals, demonstrating need for quality assessment. Without standardized risk-adjusted outcomes comparisons, Cancer Centers cannot accurately assess their outcomes to identify quality improvement targets. ACS NSQIP's new platform allows customization so hospitals can compare surgical oncology-specific risk-adjusted processes and outcomes. No significant financial relationships to disclose.
Germline TP53 mutations in women with very early onset breast cancer (BR)
Authors: S. Masciari, L. Harris, K. Branda, A. Petkovska, J. Paez, D. Haber, L. Digianni, W. Sellers, F. Li, J. Garber
Journal: Journal of Clinical Oncology (2005)

1015 Background: Women with Li-Fraumeni syndrome (LFS) have a 49% risk of cancer by age 30, most of which is BR. In small series of women with early BR, prevalence of germline TP53 mutation is 1% (age <40) or 4% (age <30), most with personal or family history suggesting LFS. If true prevalence were higher, clinical testing for TP53 mutations might be useful, as carriers are advised to avoid nonessential radiation due to 2nd cancer risk. Among women tested in our cancer genetics program, age at BR diagnosis was 33 years in female members of 38 TP53 mutation kindreds versus 41 yrs (p<0.0001) in 186 women with BRCA1 and 45 yrs (p<0.0001) in 65 women with BRCA2 mutations. Methods: The prevalence of germline TP53 mutations among women diagnosed with BR age ≤33 years was assessed. DNA was extracted from 165 cell lines from a population-based series of women with BR age ≤33 years in Connecticut and from whole blood from 45 similar women from the Dana-Farber/Harvard Cancer Center SPORE bank. Family history data came from questionnaires and could not be confirmed under the protocols. None met strict criteria for LFS, but 9 had histories consistent with Li-Fraumeni-Like (LFL) syndrome (see Table). TP53 analysis utilized high through-put techniques. Results: 3 germline mutations were identified in the cohort [prevalence 1.4%, 95% CI 0.3 to 4.1]. Among probands 1 had a mother with BR at 40, 1 a mother with BR at 59 and maternal grandmother with colon >70; the third had no family cancer history. There were no mutations among the 9 women with LFL. BRCA1/2 analysis results on the cohort will be available for ASCO. Conclusion: Routine screening for germline TP53 mutations in women with BR at unusually young ages will have a low yield in otherwise unselected patients. These data are consistent with Lallo et al, Lancet 2003. No significant financial relationships to disclose.
Mature long-term outcome using a continuous 50-Gy shrinking field chemoradiation schedule for squamous cell carcinoma of the anus.
Authors: R. Cooper, K. Spindler, R. Prestwich, P. Byrnes, D. Sebag-Montefiore
Journal: Journal of Clinical Oncology (2011)

4096 Background: Chemoradiotherapy (CRT) is the standard of care for anal cancer, but radiotherapy techniques and use of chemotherapy varies. We undertook a retrospective study of an unselected population based experience of anal cancer referred from within the Yorkshire Cancer Network (2.6 million) over a period of 11 years. We analysed the pattern of care and outcome of concurrent CRT using a shrinking field continuous radiotherapy technique, which helped the design of the chemoradiation schedule used in the UK ACT 2 trial. Methods: Between 1996 and 2007 303 patients were referred for treatment at St. James Institute of Oncology, Leeds, UK. Treatment was conducted under the care of two nonsurgical oncologists. Patients whose treatment intent was curative for SCC of the anus using a standard local protocol were identified and included in this analysis. Treatment comprised of 50 Gy in 25 fractions as a continuous two-phase shrinking field technique with mitomycin C day 1 and 5-fluorouracil week day1-4 and 29-32. Results: A total of 167 (55%) patients were selected for curative treatment with the 50Gy protocol. At a median follow-up of 57 months (range 1.5-175) 103 patients were alive, and 31 had died from anal cancer (19%). The overall 5-year survival (OS) and cancer specific survival (SSC) were 72% and 80%, respectively. The loco-regional failure (LRF) was 20% (35/167) including 16 patients with local only, 18 local and distant and 12 patients with distal failure alone (incomplete data n=1). Only 2 local failures occurred >24 months after completing CRT. Salvage surgery was performed in 54% (19/35) of local failures and 5 were still alive without evidence of disease at time of analysis. The median OS in the group of patients with LRF was 15.6 months (95% CI 12.1-20.3). Cox regression analysis revealed that T stage as an independent prognostic influence on OS, SSC and LRF. Conclusions: These mature results confirm excellent long term control and survival with a continuous shrinking field CRT schedule using 50Gy, a single dose of MMC and 5FU. The results of this approach used in a routine site specialised clinical practice are comparable with those observed in the UK ACT2 trial.
Outcomes in stage I non-small cell lung cancer following the introduction of stereotactic body radiotherapy in Alberta, Canada.
Authors: Marc Kerba, Zsolt Gabos, Sunita Ghosh, Hongwei Liu, Harold Y. Lau, Barbara Roberts
Journal: Journal of Clinical Oncology (2014)

306 Background: Stereotactic body radiotherapy (SBRT) is a treatment option for patients with Stage I (T1-T2N0M0) NSCLC (non-small cell lung cancer) who decline surgery or are medically inoperable. Case series suggest superior outcomes with lung SBRT compared to conventional radiotherapy and high local control rates. The primary study objective was to describe population outcomes in the initial management of stage 1 NSCLC patients including treatment utilization rates and survival. Methods: Clinical records of patients diagnosed with Stage 1 NSCLC who attended any SBRT clinic in Alberta between 2005 and 2011 were examined with REB approval. These cases were linked to the Alberta Cancer Registry and Provincial Health Administration databases. Clinical, treatment, pre-diagnosis 3M Aggregate Clinical Risk Grouping (ACRG3) scores as a proxy for prevailing patient comorbidity and health services characteristics pertaining to all cases of stage 1 NSCLC between 2005 and 2011 were determined. A cox regression model was constructed to examine the influence of these factors and their interactions on cancer outcomes. Results: 2,146 patients were diagnosed with stage 1 NSCLC. Median patient age was 72 and overall 43.0% of cases had a 1 year pre-treatment ACRG3 score of 10-49. Observed treatment utilization rates; surgery 63.4% (95%CI: 61.4-65.4), conventional RT 9.0% (7.9-10.3%), SBRT 3.6% (2.8-4.4%), chemotherapy 0.8% (0.5-1.4%) and no treatment 23.2% (21.4-25.0%). Median survival ranged from 69.6 months for surgery to 17.0 months if no active treatment was delivered. SBRT had survival outcomes superior to conventional radiotherapy: median survival of 39.4 vs. 23.5 months (p&lt;0.001), despite more patients 69.9% vs 63.0% having an ACRG3-1y of 50 or higher. On multivariate analysis, while accounting for all modeled variables including ACRG3 pre-treatment and compared to patients receiving no active treatment, primary surgical intervention HR= 0.23 (95%C.I.:0.18-0.28) and SBRT HR=0.33 (0.21-0.51) remained most strongly associated with survival.No significant variable interactions (p&lt;0.05) between treatment modality, patient age, pathology diagnosis and ACRG3 scores were demonstrated to impact on survival outcomes. Conclusions: Surgery for Stage I NSCLC patients is associated with the best overall survival. SBRT patients have improved survival over conventional radiotherapy. Improvements in population level outcomes may result from an increased utilization of SBRT in the non-surgical management of stage I lung cancer.
Barriers to traditional palliative care for stage IV breast cancer patients, 2003-2012.
Authors: Runhua Shi, Jay M. Marion, Zhenzhen Shi, Richie R Diaz, Glenn Morris Mills
Journal: Journal of Clinical Oncology (2015)

120 Background: Multiple factors may impact ability of patients with Stage IV breast cancer to access traditional palliative care (PC), which centers on disease-altering procedures such as surgery, radiation therapy, and chemotherapy. To further investigate barriers to accessing PC, the National Cancer Data Base data from 2003-2012 was analyzed. Methods: Data was analyzed from 55,490 patients diagnosed with Stage IV breast cancer registered in the National Cancer Data Base. The outcome variable was patient use of PC. The predictor variables included sex, age, race, Charlson Comorbidity index, insurance status, income, education, year diagnosed, distance travelled, facility type, diagnosing/treating facility, and diagnosis to treatment interval. Univariate analysis was used to determine the prevalence of palliative care according to predictor variables. Multivariate Logistic regression was used to investigate the effect of each predictor variable on patient use of PC while adjusting for all other predictive factors. Results: Of the 55,490 Stage IV breast cancer patients analyzed, 17.38% received palliative care. Radiation therapy (8.76%) and chemotherapy, hormone, and other systemic treatments (4.51%) contributed to the bulk of PC. In multivariate analysis, after adjustment for all other predictor variables, race, income, education, distance travelled, and diagnosis to treatment interval were each shown to significantly predict use of PC. Black and Asian patients were 11.4% and 26.1% less likely to use PC than their white peers. Lower zipcode income, higher zipcode education, and shorter distance travelled were predictors of increased PC use. Shorter diagnosis to treatment interval was a predictor of increased PC use; compared to patients with a 31+ day interval, those with a 0-7 day interval were 67.71% more likely to receive PC and 8-31 day interval, 37%. Conclusions: Using univariate and multivariate analysis, we identified factors that may act as barriers to access traditional palliative care for patients diagnosed with Stage IV breast cancer. We observed that race, income, education, distance travelled, and diagnosis to treatment interval significantly predicted the use of palliative care.
AlphaB-crystallin (aBC) expression in breast cancer brain metastases (BM) and primary breast cancer (pBC) with eventual BM and association with outcome.
Authors: B. Adamo, A. M. Deal, C. Livasy, E. Burrows, K. Fritchie, K. L. Blackwell, E. P. Hamilton, J. Geradts, L. Thorne, A. Ugolkov, C. R. Miller, M. G. Ewend, L. A. Carey, C. M. Perou, V. L. Cryns, C. K. Anders
Journal: Journal of Clinical Oncology (2011)

2041 Background: aBC, a small heat shock protein, is commonly expressed in basal BC and predicts poor survival in BC patients (pts). aBC has been associated with the development of BM within basal BC. We evaluated the expression of aBC in BM and pBC with eventual BM and its association with survival. Methods: Under IRB approval (UNC/Duke), we established a clinically-annotated biobank from 78 pts: 51 BM and 38 pBC with eventual BM (11 were matched BC and BM pairs); 59 pts had complete treatment (tx) data. IHC subtype was assigned for BM and pBC: HR+ (hormone receptor)/HER2-, triple-negative (TN; ER-/PR-/HER2-), and HR+or-/HER2+. aBC expression was based on % of positively stained tumor cells: negative (0%), weak (<30%) and strong positive (≥30%). Overall survival (OS) and survival after BM were evaluated by the Kaplan-Meier method (log-rank test). Results: Median age was 50 yrs (26-84). 67% were Caucasian, 32% African American. 90% received systemic tx for metastatic BC, of which 67% followed BM. 90% received local tx (resection and/or radiation) for BM. There was no difference in receipt of local or systemic tx by aBC. Subtype for pBC (n=36) was 31% (HR+/HER2-), 42% (TN), and 28% (HR+or-/HER2+); for BM (n=42) 33%, 43% and 24%, respectively. aBC was expressed in 37% (14/38) of pBC and 47% (24/51) of BM. Concordance of aBC expression between pBC and BM was 55% (6/11). Gain of aBC expression (4/11) was more common in BM than loss (1/11). aBC was more commonly expressed in TNBC (pBC 73%; BM 67%) compared to HR+/HER2- (pBC 9%; 29% BM) or HR+or-/HER2+ (pBC 0%; 30% BM). OS and survival after BM differed by subtype (all p<0.02); pts with TNBC experienced the poorest outcome. OS and survival after BM was inferior for all pts (n=38) and those with TNBC (n=15) whose pBC expressed aBC (Table). aBC expression within BM was not prognostic (p>0.05). Conclusions: aBC expression in BM and pBC with eventual BM is frequent and associated with TNBC. Among pts with BM, expression of aBC in the pBC predicts for inferior OS and survival after BM even among poor prognosis pts with TNBC BM. pBC aBC+ aBC- P value TNBC aBC+ TNBC aBC- P value OS (yrs) 1.4 4.7 0.0002 1.4 4.7 0.01 Survival after BCBM (yrs) 0.13 0.91 0.001 0.14 1.5 0.02
The valuation of [18F]FETNIM PET/CT imaging for detecting tumor hypoxia in non-small cell lung cancer
Authors: M. Hu, J. M. Yu, X. Sun, W. Zhao, G. Yang, D. Mu, S. Zhao, X. Xu, S. Yuan
Journal: Journal of Clinical Oncology (2008)

7504 Background: Hypoxia is known to be an important prognostic factor for long-term survival and local tumor control in non- small cell lung cancer (NSCLC), fluorine-18 fluoroerythronitroimidazole [18F]FETNIM is a nitroimidazole compound that is a new PET tracer for imaging tumor hypoxia. Quantitative analysis of [18F]FETNIM uptake may provide prognostic information and a means to target specifically tumor cells resistant to conventional treatment. Methods: A total of 19 patients with newly diagnosed NSCLC underwent [18F]FETNIM PET/CT imaging before surgery. PET/CT imaging was performed at 120 min after each radiotracer injection. For semi-quantitative analysis, the maximum standardized uptake value (SUVmax) was obtained by drawing regions of interest (ROI) on the PET images for tumor tissues. The tumor volume was calculated by CT. Hypoxia related markers hypoxia-inducible factors-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF) and glucose transporter type 1 (GLUT-1) was estimated in tissue specimens by immunohistochemistry. Immunohistochemical findings were correlat- ed with SUVmax. Results: A median of SUVmax for tumor tissues of 1.70 (2.23±1.58, range: 0.97–7.4) was observed. The SUVmax of [18F] FETNIM PET/CT for tumor tissues was significantly higher than that for normal lung tissues of the opposite side (2.23±1.58 vs 0.70±0.35; t=4.103, P=0.001) and significantly correlated with tumor volumes (78.03±48.70cm3) (r=0.878, P<0.001). Furthermore, the most discriminative cut-off point was found at an SUVmax of 0.97. A significant correlation was observed between SUVmax and HIF-1alpha (r=0.82; P<0.001), GLUT1 (r=0.69; P<0.001), VEGF (r=0.73; P<0.001). Conclusions: This study shows that the SUVmax is associated with the expression of HIF-1alpha, GLUT1 and VEGF, it provides evidence that the uptake of [18F]FETNIM in NSCLC correlates with the oxygenation status in tumors. [18F]FETNIM PET/CT may be useful in clinical trials in which novel therapeutic agent targeting tumor hypoxia is evaluated. No significant financial relationships to disclose.
An assessment of neoadjuvant therapy for breast cancer and treatment wait times at the BC Cancer Agency Vancouver.
Authors: Rachel Adilman, Robyn Leonard, Zia Poonja, Christine E. Simmons
Journal: Journal of Clinical Oncology (2014)

140 Background: Neoadjuvant therapy (NAT) is widely considered to be the standard of care for patients diagnosed with locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). NAT is also considered in patients with more aggressive subtypes (Her2+ or triple negative cancers). However, it remains unclear which patients are being considered for NAT, which patients are indeed receiving NAT, and how long the current wait times for chemotherapy and hormone therapy are in this patient population. This study was designed to characterize the breast cancer patients being referred to the BC Cancer Agency (BCCA) Vancouver’s NAT clinic, and to determine the average wait times for chemotherapy and hormone therapy in these patients. Methods: Between May 13th, 2013 and June 3rd, 2014, a total of 160 potential NAT candidates were seen at the BCCA Vancouver NAT clinic. Breast cancer characteristics and wait times for these patients were assessed prospectively using a secure database. Results: Of these 160 patients, 119 (74%) actually received NAT; 76.7% of these were deemed LABC patients (clinical stage IIB or III), and 6% were “window of opportunity” (WOP) patients (those considered for NAT due to long surgical wait times). NAT patient receptor status differed significantly from the receptor statuses of patients who did not receive NAT (p=0.006), with Her2+ and triple negative breast cancer patients being most likely to receive NAT. Seventy-eight percent of ER+Her2+, 86% of ER-Her2+, 67% of ER+Her2-, and 80% of triple negative patients received NAT. A total of 4 patients (2.5%) presented in clinic with metastatic disease and thus were not considered for NAT. The average wait time between when a patient was referred to the BCCA and when they commenced chemotherapy was 18.1 days (median: 16), while the average wait time to receive hormone therapy alone was 12.3 days (median: 10). Conclusions: These findings suggest a need to expedite screening and care for these high-risk breast cancer patients in order to characterize and treat the disease neoadjuvantly before it has metastasized. Strategies to reduce wait times in this breast cancer population are being further assessed.
The association of pretreatment (pre-tx) neutrophil to lymphocyte ratio (NLR) with outcome of sunitinib tx in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: P. Huang, M. A. Carducci, M. A. Eisenberger, R. Pili, J. J. Kim, E. S. Antonarakis, H. J. Hammers, D. Keizman
Journal: Journal of Clinical Oncology (2011)

4621 Background: Sunitinib is a standard tx for mRCC. The NLR, an index of systemic inflammation, is associated with recurrence of non mRCC and poor prognosis in several types of cancer. We set out to assess the association between pre-tx NLR and outcome of sunitinib tx in pts with mRCC. Methods: We performed a retrospective study of an unselected cohort of pts with mRCC, who were treated with 50 mg of oral sunitinib in cycles of 4 weeks followed by 2 weeks of rest. We analyzed the pre-tx NLR (calculated by dividing the neutrophil count value by the number of lymphocytes) and potential factors associated with outcome such as age, past nephrectomy, RCC histology (clear cell vs non clear cell), time from diagnosis to tx, ≥ 2 metastatic sites, ECOG performance status, anemia, corrected calcium > 10 mg/dL, platelets count, prior cytokines/ targeted tx, sunitinib induced hypertension, % pts that had dose reduction/tx interruption, and mean dose/cycle. Progression free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method. Multivariate analyses using Cox Regression model were performed to determine their independent effect. A survival tree analysis was used to find the best NLR cut-off value. Results: Between 2004-2011, 133 pts with mRCC were treated with sunitinib. Excluded from the analysis were pts without available data on pretx NLR, those with baseline comorbidity such as CLL, and recent (≤1 month) health event (infection, surgery) or tx (steroids, radiation, cytokines) known to be associated with a change of blood counts. 109 pts were included in the analysis. 57 (53%) had an elevated NLR (>3) at baseline. Factors associated with PFS were NLR ≤ 3 (HR 0.38, p= 0.009, median PFS 4 vs 15 months in pts with baseline NLR >3 vs ≤ 3), past nephrectomy (HR 0.38, p= 0.049) and non clear cell histology (HR 1.5, p=0.0260). NLR ≤ 3 was associated with OS (HR 0.3, p=0.007, median 14 months vs not reached with a median followup time of 35 months). Conclusions: In patients with mRCC treated with sunitinib, pretx NLR may predict progression free survival and overall survival. Whether this is specific to sunitinib or generalizable to other TKIs is not known.
Human antibody conjugates of potential utility for prostate cancer therapy: A comparison of MGBA conjugates with antibodies targeting a cell surface target (prostate-specific membrane antigen) and an extracellular matrix target (Mindin/RG-1)
Authors: Chin Pan, Jonathan Terrett, Chetana Rao, Colin Chong, Rory Dai, Eilene Kwok, Mary Huber, Liang Chen, Alan Zhang, Sufi Bilal, Charlie Cong, Rangan Vangipuram, David Passmore, Shrikant Deshpande, Sanjeev Gangwar, Pina Cardarelli, David King
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

4062 

Human antibodies have been generated to two tumor-associated antigens of potential interest in prostate cancer. Both of these targets are highly expressed in prostate cancer, but with different distribution patterns. Prostate-specific membrane antigen (PSMA) has been highly validated as an antigen up-regulated on the surface of prostate cancer cells, whereas mindin/RG-1 is an extracellular protein believed to be retained within the extracellular matrix of human prostate tumors and their metastases (Parry et al. , 2005, Cancer Res. 65, 8397-8405). High affinity human antibodies to both proteins have been isolated from transgenic mice, and conjugates linked to synthetic DNA minor-groove binding alkylating (MGBA) agents have been prepared. Anti-PSMA antibody internalizes rapidly into LNCaP cells, but anti-mindin/RG-1 does not internalize in in vitro assays as expected. The two conjugates have been compared in vivo in two different subcutaneous xenograft models, one using LNCaP cells and the other using a co-culture of LNCaP with stromal cells. Data is complicated by the secretion of some mindin/RG-1 by LNCaP cells themselves, however, the anti-mindin/RG-1 conjugate clearly shows improved efficacy in the animal model including stromal cells. The anti-PSMA conjugate shows efficacy in both models, although is active at lower doses in the absence of the stromal cell component. Alternative animal model studies are ongoing in attempts to further understand the differences achieved in anti-tumor response by the two approaches.