tbuckley/cabot-search huggingface dataset:
A national evaluation of response and factors affecting response to neoadjuvant therapy in breast and rectal cancer.
Authors: S. B. Edge, D. Gress, D. P. Winchester, A. Stewart
Journal: Journal of Clinical Oncology (2011)

6091 Background: Neoadjuvant therapy (NAT) in breast (BC) and rectal cancer (RC) improves outcome and response to NAT is a prognostic factor. National use and response to NAT data outside clinical trials have not been reported because the cancer registry system does not record post-NAT “y” TNM stage. This study evaluated a modified registry system to collect pre-NAT and post-NAT “y” stage and define response rate and factors affecting NAT response. Methods: 1,173 hospitals with Commission on Cancer accredited programs reporting to the National Cancer Data Base (NCDB) used a modification of the Collaborative Stage Data Collection System to collect pre-NAT clinical stage and post-NAT pathologic stage (NAT chemotherapy for BC and radiation for RC) from random cases in 2007 selected from each hospital by the NCDB. Pathologic complete response (pCR) was defined as no tumor at the primary site or in lymph nodes after NAT. Factors affecting pCR were examined by logistic regression. Results: The study included 3,985 BC and 2,455 RC, comprising 44% of BC and 73% of RC treated by NAT in the NCDB. pCR occurred in 11.3% of BC and 11.2% of RC cases. Factors independently associated with pCR in BC were negative hormone receptors and clinically negative nodes before NAT; and in RC were resection of 5 or fewer lymph nodes, and treatment at NCI-designated cancer centers. Conclusions: A modified registry data system allows identification of response to NAT. Nationwide rates of pCR in BC and RC showed pCR were lower than reported in clinical trials. Key factors associated with pCR in BC were negative hormone receptors and clinically negative nodes, and in RC limited node resection and treatment at NCI-designated centers. Cancer type Factor Category Number cases Odds ratio (95% CI) for pCR Breast Hormone receptors Positive 1,245 Referent Negative 869 2.29 (1.86-3.34) Pre-NAT clinical node status Positive 1,301 Referent Negative 813 1.56 (1.19-2.04) Rectal Number of lymph nodes resected 1-5 194 Referent 6-10 327 0.46 (0.28–0.74) 11-15 236 0.19 (0.10-0.37) > 16 224 0.26 (0.14–0.48) Cancer program type Community 161 Referent Comprehensive Community 490 1.70 (0.89–3.27) Teaching 256 1.27 (0.60–2.67) NCI-designated 74 6.39 (2.84-14.40)
The association of<i> JAK2</i> polymorphisms with prognosis in castration-resistant prostate cancer (CRPC).
Authors: Ben Yiming Zhang, Shaun M. Riska, Douglas W. Mahoney, James Robert Cerhan, Brian Addis Costello, Roxana Stefania Dronca, Fernando Quevedo, Henry C. Pitot, Manish Kohli
Journal: Journal of Clinical Oncology (2016)

313 Background: We evaluated variation in candidate genes implicated in either initiation or progression of prostate cancer with survival in CRPC stage. Methods: Germline DNA was extracted from peripheral blood mononuclear cells of CRPC patients enrolled in a clinically annotated registry. Fourteen candidate genes were tagged using single nucleotide polymorphisms (SNPs) from HapMap with minor allele frequency of &gt; 5%. The primary endpoint was overall survival (OS), defined as time from development of CRPC to death. Principal component analysis was used for gene levels tests of significance. For SNP level results the per allele hazard ratios (HR) and 95% confidence intervals (CI) under the additive allele model using Cox regression adjusted for age at CRCP and Gleason score (GS) were used. Results: Two hundred and forty five CRPC patients who met the criteria of having adequate DNA were genotyped (14 genes, 84 SNPs). The median age of the cohort was 69 years (range 43-93). The GS distribution was 55% with GS≥8, 32% with GS = 7 and 13% with GS &lt; 7 or unknown. Median time from castration resistance to death for the cohort was 2.67 years (IQ range: 1.6-4.07, 144 deaths). At the gene level JAK2 was detected to be associated with OS. Six of 18 JAK2 SNPs were associated with OS after adjustment for age and GS as well as pruning of SNPs in high linkage disequilibrium with each other (see table). In our multivariate model including age, GS, rs2149556, and rs4372063, the adjusted HRs for rs2149556 and rs4372063 were 0.67 (95% CI 0.38-1.18) and 2.17 (95% CI 1.25-3.76), respectively. The protective effect of rs2149556 appears after adjusting for the presence of minor alleles for rs4372063 in this dataset. Conclusions: Germline variation in the JAK2gene is associated with survival in CRPC stage and warrants further validation as a potential prognostic biomarker. [Table: see text]
Treatment of small node-negative HER2+ invasive breast carcinomas: Forty-month update of the joint Aerio/Remagus study.
Authors: J. Wassermann, L. Albiges, M. J. Rodrigues, E. Brain, S. Delaloge, J. Guinebretiere, M. C. Mathieu, E. Guillot, A. Vincent-Salomon, P. H. Cottu
Journal: Journal of Clinical Oncology (2011)

557 Background: Trials have shown benefit of adjuvant trastuzumab (TZM) for N+ or supra-centrimetric HER2+ breast carcinomas. Methods: Retrospective multicenter series from 2000 to 2008 of infra-centimetric HER2+ invasive breast carcinomas (InfraHER2) non metastatic. Tumors with ≥80% of carcinoma in situ, multifocal and metastatic tumors were excluded. Results: 97 cases have been evaluated. Median age was 55 years (24 to 87 years). 67% were discovered by systematic breast cancer screening with no significative difference between T1a and T1b (79% vs 64%, Fisher’s exact test p=0.23). Median size was 8 mm (range, 2 to 10 mm), 22 were T1a, 75 tumors were T1b. Fifty-one tumors (53%) exhibited significant HR expression. All patients had surgery. 57% (n=55) had a sentinel lymph node procedure. 68% (n=66) had a local irradiation and 44 patients (71% of those who had undergone breast conservative surgery) a tumor bed boost. 42/51 HR+ patients received hormonotherapy (82%): 21 received aromatase inhibitors (AI) upfront or sequential, 9 received tamoxifen (TAM) alone, 11 received LHRH agonists alone or in combination with TAM or AI. 43% (n=42) had chemotherapy (CT), (Anthracycline alone for 20 cases, taxane for 2 cases, sequential A/T for 19 cases and concurrent for 1 case) almost all (37) were associated to TZM. In three cases, TZM was administered without chemotherapy. Decision of adjuvant CT was associated (all p<0.05) with hormonal receptors (HR) negative status, Elston-Ellis grade (EE) 2/3 and high mitotic index (MI) while patients with HR+/low MI tumors were rarely treated (p<0.001). With a 41 months median follow-up, there was no invasive recurrence in TZM group and 8 of the 56 patients treated without TZM had a recurrent invasive disease including three fatal. Difference in recurrence between TZM treated patients and others was statistically significant (40-months Kaplan-Meier cumulative risk: 100% vs 89%; log-rank p=0.02). Conclusions: In our practice N- InfraHER2 tumors may have a significant risk of recurrence which could be avoided by chemo-trastuzumab-based adjuvant treatment. Patients with N- InfraHER2 tumors should be included in HER2-targeted adjuvant trials.
A novel pathology-based preoperative risk score to predict distant and locoregional residual disease and survival for incidentally discovered gallbladder cancer: A 10-institution study from the US Extrahepatic Biliary Malignancy Consortium.
Authors: Cecilia Grace Ethun, Lauren McLendon Postlewait, Timothy M. Pawlik, Stefan Buettner, George A. Poultsides, Thuy Tran, Kamran Idrees, Chelsea A Isom, Ryan C. Fields, Linda Jin, Sharon M. Weber, Ahmed I. Salem, Charles Raben Scoggins, Perry Shen, Harveshp Mogal, Carl Richard Schmidt, Eliza W Beal, Ioannis Hatzaras, Rivfka Shenoy, Shishir Kumar Maithel
Journal: Journal of Clinical Oncology (2016)

202 Background: T-stage alone is currently used to guide treatment for incidentally discovered gallbladder cancer. We aimed to develop a more robust predictive model for discovering distant or locoregional residual disease at the time of re-resection. Methods: All patients with incidentally discovered gallbladder cancer who underwent re-resection at 10 institutions from 2000-2015 were included. We utilized routine pathology data from initial cholecystectomy to create a gallbladder cancer predictive risk score (GBRS) for finding distant or locoregional residual disease at re-resection and predicting overall survival (OS). Results: Of 449pts with gallbladder cancer, 262 (58%) were incidentally discovered and underwent attempted re-resection. Advanced T-stage, grade, and lymphovascular (LVI) and perineural (PNI) invasion were all associated with increased rates of distant and locoregional residual disease, and decreased OS. Each pathologic characteristic was assigned a value (T1a: 0, T1b: 1, T2: 2, T3/4: 3; well diff: 1, mod diff: 2, poor diff: 3; LVI neg: 1, LVI pos: 2; PNI neg: 1, PNI pos: 2), which were added for a total GBRS score ranging from 3-10. The scores were then separated into 3 risk groups (Low: 3-4; Intermediate: 5-7; High: 8-10). Each progressive GBRS group was associated with an increased risk of finding distant and isolated locoregional residual disease at the time of re-resection, and was associated with reduced median OS (Table). Conclusions: By accounting for pathologic variations within each T-stage, this novel predictive risk-score redistributes T1b, T2, and T3 disease across separate risk-groups and more accurately identifies patients with incidentally discovered gallbladder cancer at risk for distant and locoregional residual disease, and decreased long-term survival. This score may help to better optimize treatment strategy for patients with incidentally discovered gallbladder cancer. [Table: see text]
Activity of a novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 to enhance antitumor activities of gemcitabine and EMAP II in pancreatic cancer.
Authors: N. Awasthi, P. L. Yen, M. A. Schwarz, R. Schwarz
Journal: Journal of Clinical Oncology (2011)

255 Background: Gemcitabine (Gem, G) has limited benefits as single agent or in combination for pancreatic ductal adenocarcinomas (PDACs). The phosphatidylinositol-3-kinase (PI3K)/AKT and mammalian target of rapamycin (mTOR) signaling pathways are frequently dysregulated in diverse human cancers including PDAC. NVP-BEZ235 (BEZ, B) is a novel dual PI3K/mTOR inhibitor that has been shown to have antitumor activity in multiple tumor types. Endothelial monocyte activating polypeptide II (EMAP, E) is an antiendothelial and antiangiogenic agent that enhances Gem and docetaxel activity in PDAC. We tested the combination benefits of BEZ and Gem in addition to EMAP in experimental PDAC. Methods: In vitro cell proliferation and protein expression were analyzed by WST-1 assay and Western blotting. In vivo animal survival experiments were performed in NOD-SCID PDAC xenografts. Results: Cultured cells of PDAC (AsPC-1), endothelial (HUVECs), and fibroblast origin (WI-38) all expressed AKT and mTOR protein. BEZ inhibited in vitro cell proliferation of AsPC-1 and HUVECs cells, with some additive effects in combination with Gem or EMAP, after 72 hours of incubation. In AsPC-1, treatment of BEZ (100 nM), Gem (100 nM) and EMAP (1 μM) caused 34, -7, -16, 62, 51, 3, and 59 percent inhibition in proliferation in the B, G, E, B+G, B+E, G+E and B+G+E groups. In HUVECs, percent inhibition in proliferation was 35, 33, 15, 55, 35, 31 and 53 in the B, G, E, B+G, B+E, G+E and B+G+E groups, respectively. Compared to controls (median survival: 16 days), an animal survival increase after BEZ and EMAP therapy alone (both 21 days) and Gem therapy alone (28 d) was observed. Further increases in survival occurred in combination therapy groups B+G (30 d, p=0.007), B+E (27 d, p=0.02), G+E (31 d, p=0.001) and B+G+E (33 d, p=0.004). Conclusions: Bez has experimental PDAC antitumor activity in vitro and in vivo that is further enhanced by combination of Gem and EMAP. These findings demonstrate advantages of combination therapy strategies targeting multiple pathways in pancreatic cancer treatment. No significant financial relationships to disclose.
Patterns of lymphatic metastases in upper tract urothelial carcinoma: Experience from three comprehensive cancer centers.
Authors: Surena F. Matin, Patrick Espiritu, Jonathan A. Coleman, John P. Sfakianos, Philippe E. Spiess
Journal: Journal of Clinical Oncology (2015)

349 Background: Data on patterns of lymph node metastasis (LNM) for upper tract urothelial carcinoma (UTUC) is sparse despite its critical relevance for staging and therapeutic potential, with only 1 prior study detailing patterns of spread in 23 pathologically confirmed cases (Kondo T et al, Urol. 2007). Methods: We retrospectively identified and reviewed patients with pTany N+ M0 UTUC at 3 comprehensive cancer centers which routinely perform template-based dissections for UTUC. Anatomic locations of the primary tumor and positive lymph nodes based on the pathological specimens were analyzed, and maps of the location and incidence of LNM constructed. Results: A total of 92 patients with pN+ UTUC were identified, 63 of whom had renal pelvis (n=43) or proximal ureteral (n=20) tumors. LNM from left renal pelvis tumors occurred to the hilar (29.4%), pre- and para-aortic (50.0%) regions, with secondary spread to suprarenal (1.8%), interaortocaval (5.9%), and common iliac (2.9%) regions. LNM from right renal pelvic tumors occurred to the hilar (24.1%), pre- and para-caval (38.0%), retrocaval (13.8%), and inter-aortocaval (24.1%) areas. Left proximal ureteral tumors primarily had LNM to the hilar (46.1%), para-aortic (46.1%), and retro-aortic (7.7%) regions. Right proximal ureteral tumors had LNM to the hilar (36.4%), paracaval (54.5%), and retrocaval (9.1%) regions. A significant difference in survival was noted with patients who had organ confined tumor (p = 0.002) and a lymph node density of less than 25% (p = 0.005). The 1, 2, and 5-year cancer-specific survival rates of the overall cohort were 69%, 49%, and 27%, respectively. Conclusions: Our multi-institutional study provides data regarding the primary landing zones for LNM in renal pelvis and proximal ureter UTUC as well as guidance for developing anatomic dissection templates for prospective studies in UTUC incorporating surgical methodologies as a variable.
Physician’s awareness and practices toward colorectal cancer screening guidelines.
Authors: Sowjanya Kanna, Asif Ali, Kiran Anna, Thimmaiah Theethira Ganapathi, Raja Shekhar Reddy Sappati Biyyani, Kevin D Mullen
Journal: Journal of Clinical Oncology (2012)

431 Background: Colorectal cancer (CRC) is the second most common cancer with an estimated incidence of 72,090 men and 70,480 women and a cause specific mortality of 51,370 in 2010. Despite promotion of CRC screening by various professional societies ACG /AGA and USPSTF, there seems to be an under utilization of screening colonoscopy for unclear reasons. We aimed to study the awareness of physicians towards CRC screening across various levels of training in different specialities. Methods: A survey questionnaire of 16 questions, assessing awareness of CRC screening guidelines was provided to 100 physicians in our academic medical center who are at various levels of training in Primary Care Group (PCG comprising residents, attending physicians in Internal Medicine and Family Medicine) and Specialty Group (SG comprising fellows, attending physicians in Gastroenterology). Results: Out of 100 questionnaires, we received 59 responses (50 PCG and 9 SG) which are included in the results. About 54% of the study group followed CRC guidelines (32% USPSTF CRC screening guidelines compared to 22 % ACG/AGA guidelines) and 46% did not. All the physicians who did not follow the guidelines belonged to the PCG. Most common screening modality chosen was colonoscopy alone (46% PCG and 100% SG), followed by colonoscopy with FOBT (36% PCG), FOBT (12% PCG) and 3% PCG answered barium enema along with FOBT/ sigmoidoscopy. A 100% response from both SG and PCG was obtained for commencing screening colonoscopy at 50 years of age but only 27% of the PCG compared to 80% SG were aware of the screening cessation guidelines. Interestingly a vast majority of the study group (88%) text messaging as a better way of reminder to improve compliance compared to phone calls and postal letters. About 72% of the respondents themselves would want colonoscopy as screening modality compared to 17% for FOBT and 7% for sigmoidoscopy. An overwhelming majority of the study group (80% of both PCG and SG) felt the need for continued education in regards to guidelines for screening in didactic sessions. Conclusions: Despite clear guidelines for screening colonoscopy, we found a significant lack of awareness amongst PCG compared to SG, and our study emphasizes the need for continued education.
An analysis of the effect of stage at diagnosis of bowel cancer on survival: Findings from the South Australian Clinical Registry (SACR) for metastatic colorectal cancer (mCRC).
Authors: K. Jain, T. J. Price, C. Beeke, R. Padbury, G. P. Young, D. Roder, A. R. Townsend, S. Bishnoi, C. S. Karapetis
Journal: Journal of Clinical Oncology (2011)

3628 Background: Stage at diagnosis of CRC strongly correlates with prognosis. The impact of initial stage on outcome after development of metastatic (met) disease is not entirely clear. Methods: The SACR for mCRC collects data for mCRC patients (pts) diagnosed after Feb 1, 2006. Pts were grouped depending on stage at initial diagnosis to compare outcomes between metachronous and synchronous mCRC. Results: 1,878 mCRC pts are currently in the database. Median age was 73 yrs (range 17-105 yrs) with male preponderance (57%). Majority of pts had synchronous met disease (1206 pts; 64.2%) while the rest had St III (383; 20.4%), St II (n=254; 13.5%) and St I (n=24; 1.2%) disease at their initial diagnosis. Liver was the single most common met site (39%). Tumour grade was equally distributed by stage. Of the metachronous group, 61% pts had colon as primary site. St I, II and III was uniformly distributed among pts with colon or rectal metachronous mCRC. Median time to recurrence (TTR) was longer for St I pts as compared to St II pts (3.94 yrs vs. 2.0 yrs; p=0.04) and this trend was sustained between St II and St III pts (2.0 yrs vs. 1.52 yrs; p<0.001) as well. For stage III pts, the median TTR was similar for pts receiving neo-adjuvant or adjuvant treatment in comparison to those who had surgery alone (1.62 yrs v 1.38 yrs; p=0.59). 63% pts with metachronous mCRC from St I disease are still alive whereas the median survival was similar in pts with remaining metachronous and synchronous mCRC (St II – 1.36yrs, St III – 1.30 yrs, St IV – 1.22 yrs). Conclusions: In a large population based registry we found that pts presenting with St I CRC have a longer time to recurrence and a longer survival from time of recurrence as compared to pts presenting with St II, St III CRC, and synchronous mCRC. There was no difference observed in TTR or survival after recurrence when comparing stage II and III CRC and this was not affected by adjuvant chemotherapy use. mCRC pts initially presenting with stage II and III CRC had similar survival to those presenting with synchronous mCRC. Our findings are limited by the small number of patients that develop mCRC after an initial diagnosis of stage I CRC.
Long-term survival rates of older breast cancer patients: Population-based estimates over three decades.
Authors: B. Kanapuru, A. Jemal, C. S. Hesdorffer, W. B. Ershler, J. W. Yates
Journal: Journal of Clinical Oncology (2011)

9051 Background: Significant progress has been made in the treatment of breast cancer. However, the impact of these treatments on survival in older patients with breast cancer is not clear. Methods: We used data from the Surveillance, Epidemiology, and End Results database to determine relative survival of older patients with breast cancer. We compared trends in survival between 1977-86, 1987-96 and 1997-2006 in patients 65-74, 75-84 and 85+ years of age. Survival rates were calculated for up to 9 years after diagnosis. Results: Between 1977-86 and 1997-2006, 1 year survival increased from 94.9% to 97.9%, 93.6% to 96.7% and 88.5% to 93.5% in the 65-74, 75-84, and 85+ age groups, respectively. Survival gains increased with each year in all three age groups with the greatest improvement observed at 9 years of follow up. Smaller differences were seen between 1987-96 and 1997-2006. Although the ‘oldest old’ (85+ years) had the lowest survival rates, improvement in overall survival was greatest in this age group. Conclusions: Relative survival for older patients has increased considerably in the interval between 1977 and 2006, with the largest improvement seen in those 85 years and older. These results likely indicate that the benefit from advances in therapy and supportive care also extends to older patients with breast cancer including the ‘oldest old’. This may have significant relevance in terms of defining management strategies for the treatment of older breast cancer patients particularly at a time when rationing of health care is under consideration. Relative survival rates for breast cancer. Calendar period Time since diagnosis (Years) Age group (years) 1977 to 1986 Survival % (SE) 1987 to 1996 Survival % (SE) 1997 to 2006 Survival % (SE) 1 5-74 94.9 (0.4) 97.1 (0.2) 97.9 (0.2) 75-84 93.6 (0.6) 96.3 (0.4) 96.7 (0.4) 85+ 88.5 (1.4) 92.8 (1.0) 93.5 (1.0) 5 65-74 78.8 (0.6) 87.7 (0.6) 91.4 (0.6) 75-84 77.0 (1.2) 86.9 (0.8) 91.8 (1.0) 85+ 67.7 (2.9) 80.3 (2.6) 85.0 (3.0) 9 65-74 68.4 (0.8) 81.9 (0.7) 87.3 (1.2) 75-84 67.6 (1.6)* 81.5 (1.4)* 89.7 (2.2)* 85+ 54.4 (4.6)* 68.2 (4.4) 78.4 (8.6) * Relative survival increased from a prior interval and has been adjusted. Abbreviation: SE, standard error to estimate 95% confidence interval.