tbuckley/cabot-search huggingface dataset:
Effect of adjuvant trastuzumab on locoregional recurrence in human epidermal growth factor receptor 2-positive breast cancer treated with post-mastectomy radiation therapy.
Authors: Ryan Michael Lanning, Nadeem Riaz, Monica Morrow, Tracy-Ann Moo, Mahmoud El-Tamer, Kate Krause, Yu Chen, Xin Pei, Simon N. Powell, Alice Y. Ho
Journal: Journal of Clinical Oncology (2013)

61 Background: HER2 overexpression is associated with an increased risk of LRR after mastectomy in the era prior to the use of adjuvant trastuzumab. The purpose of this study was to examine the effect of adjuvant trastuzumab on rates of LRR and whether this effect varied with the use of PMRT. Methods: From our institutional database, 474 women with Stage I-III HER2+ invasive breast cancer treated with mastectomy +/- adjuvant therapy from 1999-2007 were identified. Those patients lost to follow-up, treated with lapatinib, or diagnosed between 5/2004 to 5/2005 (when trastuzumab prescribing practices varied) were excluded; leaving 395 in the final study population. Two cohorts were compared: 139 women who received trastuzumab (5/2005-12/2007) and 256 women who did not (prior to 5/2005). Competing risks analyses were used to estimate cumulative incidence of LRR. Competing risks regression was used to evaluate the association between treatment factors and LRR. To minimize lead-time bias, patient data was censored at 5 years after mastectomy in both groups. Results: There were 18 LRRs in the entire cohort (16 no trastuzumab, 2 trastuzumab). Women in the no trastuzumab group were less likely to be node positive, receive chemotherapy or PMRT (all p&lt;0.001). The hazard ratio for LRR was 0.218in the trastuzumab group (p= 0.04, 95% C.I. 0.05-0.94) with a 5-year risk of LRR of 1.5% in the trastuzumab versus 6.6% in the no trastuzumab group. After adjusting for PMRT and chemotherapy receipt, trastuzumab trended towards significance in decreasing LRR (p= 0.063). On subset analysis of 139 women who received PMRT, trastuzumab significantly reduced LRR (7.3% no trastuzumab, 0% trastuzumab, p=0.025). Among those who did not receive PMRT (256), trastuzumab did not significantly decrease LRR (6.3% no trastuzumab, 2.9 % trastuzumab, p=0.28). Conclusions: Adjuvant trastuzumab significantly reduced LRR in women with HER2+ breast cancer who received PMRT. A trend toward decreased LRR was observed in the entire population, but did not reach statistical significance, suggesting that the benefit is greater in HER2+ patients receiving multimodality therapy.
Primary appendiceal mucinous adenocarcinoma in two first-degree relatives: Case report and retrospective chart review.
Authors: A. R. Racek, K. G. Rabe, M. J. Wick, A. Psychogios, N. M. Lindor
Journal: Journal of Clinical Oncology (2011)

397 Background: Carcinomas of the appendix are exceedingly rare tumors and have an annual age-adjusted incidence of around 0.4 cases per 100,000. Appendiceal adenocarcinoma accounts for &lt;0.5% of all gastrointestinal neoplasms and, of these, mucinous adenocarcinomas account for the majority. Published accounts of familial instances of primary appendiceal tumors are strikingly rare. Methods: We report two siblings who both developed primary mucinous adenocarcinomas. A genetics evaluation was conducted to determine if there was a recognizable underlying single gene disorder: no DNA mismatch repair defect was evident and no other diagnosis was apparent. A review of appendiceal cancers seen at Mayo Clinic from l997 to the present was conducted to search for additional familial cases. Results: Among 316 cases of primary appendiceal cancer of any histologic type, this sib pair was the only family reporting a second affected family member. Conclusions: The occurrence of appendiceal cancer in siblings may represent a random occurrence. Adenocarcinomas of the most common type of appendiceal cancer and occur at older ages than other histologic subtypes. A strikingly rare predisposition syndrome cannot be ruled out. [Table: see text] No significant financial relationships to disclose.
Skin toxicity and treatment compliance of first-line cetuximab with irinotecan, oxaliplatin, and fluoropyrimidines-based chemotherapy in metastatic colorectal cancer (mCRC): The preliminary analysis of observer study.
Authors: Carmine Pinto, Gerardo Rosati, Ivan Lolli, Enzo Ruggeri, Libero Ciuffreda, Daris Ferrari, Francesca Di Fabio, Silvana Chiara, Paolo Tralongo, Giovanni Paolo Ianniello, Antonio Frassoldati, Salvatore Tumolo, Francesco DI Costanzo
Journal: Journal of Clinical Oncology (2013)

530 Background: The ObservEr study evaluated the quality of life (QoL), skin toxicity control and treatment compliance of cetuximab plus first-line chemotherapy in a general cohort of patients with mCRC. Methods: ObservEr is a non interventional, observational, multicenter, prospective study. The primary end point is the evaluation of change in QoL during the period in which a first line treatment chemotherapy is given, with specific focus on the impact of the dermatological toxicity of this treatment. Data on QoL (Dermatology Life Quality Index/DLQI and EORTC QLQ C30) is assessed at baseline weekly for the first 8 weeks of treatment. Results: Between April 2011 and September 2012, the expected 210 patients (pts) were enrolled in 31 Italian centers. This preliminary analysis includes 112 pts enrolled to until April 2012. Pt characteristics were: 77(68.7%) males, 35(31.3%) females; median age 70 years (44-80 years); PS ECOG-0 86(76.8%), ECOG-1 36(23.2%); potentially resectable liver metastasis 32(28.6%); chemotherapy regimen FOLFIRI 55(49.1%), XELIRI 13(11.6%), FOLFOX 22(19.6%), XELOX 10(8.9%), irinotecan 4(3.6%), 5FU/AF (de Gramont) 2(1.8%), others 6(5.4%). The interval time between request and result of KRAS test was 10 days (7-16 days). Prophylactic skin toxicity with vitamin K1 cream was performed in 79(70.5%) pts, and reactive skin toxicity treatment included vitamin K1 cream in 32(28.6%). Grade 1-3 skin toxicity was observed in 87(77.7%) pts, and grade 3 in 10(8.9%). No significant difference in grade 3 skin toxicity was detected between males vs females (10.4 vs 5.7%; p=0.722), age &lt;60 vs ≥60 years (9.7 vs 8.6%; p=1.000), and prophylactic vs reactive treatment (7.6 vs 12.5%; p=0.470). Cetuximab temporary and permanent discontinuation relation to skin toxicity was observed in 15(13.4%) and 2(1.8%) pts, respectively. Conclusions: This results suggest that the introduction of K1 cream in the prophylactic or reactive treatment reduce the incidence of grade 3 skin toxicity with improvement of cetuximab compliance. The results of QoL will be available for the 2013 ASCO GI Meeting. Clinical trial information: ID239.
Breast cancer stem cells mutations: A new understanding of intratumoral heterogeneity.
Authors: Cory Donovan, Amy Skinner, Rodney F. Pommier, Jennifer L. Alabran, Patrick Muller, Nicole Gordon, John T. Vetto, Arpana Naik, SuEllen Pommier
Journal: Journal of Clinical Oncology (2013)

25 Background: Breast cancer has long been recognized as a heterogeneous disease. This has profound implications for diagnosis, treatment and disease recurrence. Oncogenic mutations have been identified in breast cancer cells with stem-like and progenitor properties (BCSC). We have previously reported that BCSC mutations correlated with axillary lymph node metastases. This was even more significant when micrometastatic disease was included. Our hypothesis is that tumor heterogeneity extends to the genetics of BCSC, and that BCSC mutations are better predictors of lymph node status than whole tumor genetics. Methods: BCSC from fresh tissue specimens were matched to their whole tumor specimens. BCSC and whole tumor DNA were sent for PCR-based mutation analysis. Patient data was collected by chart review. Results: Twenty-eight matched BCSC and whole tumor samples were analyzed. PI3K/Akt signaling mutations in PIK3CA, AKT1, HRAS, and MET were identified in BCSC from 10 tumors. In 4 of these, mutations were also identified in the corresponding whole tumor specimens. In 4 patients, mutations were identified in whole tumor samples only. Fourteen tumors had no mutations. Tumor stage, grade, receptor status, and age did not correlate with tumor or BCSC mutation status. In contrast to BCSC mutations, mutation status of the whole tumor did not correlate with micro or macro metastatic disease in the lymph node (p = 0.92). Conclusions: Mutations in BCSC are more predictive of lymph node metastases than mutations identified in the tumors. Thus, PI3K/Akt pathway mutations in tumor precursor cells may have a stronger influence on tumor metastatic potential than mutations identified in whole tumor samples. Whole tumors and BCSC populations demonstrate significant heterogeneity, as mutations identified in BCSC and tumors were not always concordant. Rare BCSC populations must be tested separately as they provide crucial prognostic and treatment information in conjunction with whole tumor genetic analyses.
Safety and efficacy of bevacizumab and systemic therapy in metastatic colorectal cancer (mCRC) patients with peritoneal disease in the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) database.
Authors: Aflah Roohullah, Hui-li Wong, Katrin Marie Sjoquist, Kathryn Maree Field, Ben Tran, Jeremy David Shapiro, Joseph James McKendrick, Desmond Yip, Louise M. Nott, Peter Gibbs, Lorraine A. Chantrill
Journal: Journal of Clinical Oncology (2014)

569 Background: Patients (pts) with peritoneal metastases from CRC are considered a poor prognostic group. Data on safety and efficacy of systemic chemotherapy and bevacizumab (BEV) in these pts are limited. Of particular concern peritoneal disease has been reported to increase the risk of GI perforation in pts treated with BEV. Methods: TRACC is a prospective, multisite, mCRC registry with data collection ongoing at 14 Australian hospitals since July 2009. Data related to baseline demographics, treatment and outcomes were extracted and differences between pts with and without peritoneal disease were examined. Results: 1,012 pts were identified, median age 68 years (range 19-97), 179 (17.7%) had peritoneal disease at diagnosis; median follow up was 20.9 months (m). In pts with peritoneal disease there were a higher proportion of pts with poor ECOG (2-4) 30.2% vs. 17.1% p = 0.0002; colon primary 87.7% vs. 66.7% p &lt; 0.0001; and multiple disease sites p &lt; 0.0001. A similar proportion received chemotherapy in the peritoneal group 136/179 (76.0%) compared to the non-peritoneal group 619/833 (74.3%). In the peritoneal group 90/136 (66.2%) received BEV. For patients with peritoneal disease the addition of BEV to chemotherapy was associated with an improved PFS 8.6m vs. 5.1m (HR = 0.62 95%CI 0.40-0.96 p = 0.034) and OS 18.7m vs. 12.1m (HR = 0.59 95%CI 0.36-0.96 p = 0.032) compared to chemotherapy alone. On univariate analysis the proportional benefit from the addition of BEV was similar to the non-peritoneal group. GI perforation was not increased in BEV-treated pts with peritoneal disease 2/90 (2.2%) vs. 8/332 (2.4%) without peritoneal disease, p = 1.000. Conclusions: In routine clinical practice, clinicians appear comfortable prescribing BEV in the presence of peritoneal disease. The addition of BEV to chemotherapy in these pts appears to be safe, with no apparent excess risk of GI perforation, and is associated with an improved PFS and OS. Multivariate analyses are planned.
Regional patterns and time trends in breast cancer mortality among women in China.
Authors: Y. Zheng, C. Wu, W. Dong, F. Wu
Journal: Journal of Clinical Oncology (2011)

e12016 Background: Breast cancer is one of the leading causes of death in China. There is limited information available from large population-based cancer registries to describe the variability in breast cancer mortality in women by region and over time. Methods: The number of deaths and number of women at risk were obtained from the Third National Mortality Retrospective Sampling Survey (2004-2005). A total of 69 690 241 person-years (py) were accumulated in this study. The time trends in mortality during 1973 to 2005 were assessed using data from this survey as well as two previous surveys known as the First Survey in 1973-1975 and the Second Survey in 1990-1992. These surveys are broadly considered representative of the population in China. Results: The crude mortality rate among female breast cancer patients in China in 2004-2005 was 5.90 per 100 000 py (4112/69 690 241). This ranked the sixth most common cancer death in women, and accounted for 5.90% (4112/69 667) of all female cancer deaths. The crude mortality rates among female breast cancer patients were 6.86/100 000 py (1777/25 900 856) in Eastern China, 5.91/100 000 py (1431/24 225 738) in Central China and 4.62/100 000 py (904/19 563 647) in Western China. The age-standardized mortality rate in urban areas (4.91/100 000 py, 1899 deaths) was 1.44 fold higher than that in rural areas (3.42/100 000 py, 2213 deaths). The crude mortality doubled from 2.95/100 000 py in 1973-1975. The age-standardized mortality rate increased from 1.09/100 000 py in 1973-1975 to 3.97/100 000 py in 2004-2005. Conclusions: The mortality rate of female breast cancer in urban areas was higher than in rural areas. The mortality rate was highest in the Eastern region of China, followed by the Central then the Western regions. Breast cancer mortality in women increased substantially in China between 1973 & 2005.
Outcomes in cancer patients (pts) admitted to a surgical (SICU) or medical ICU (MICU) compared to a newly opened cancer specific ICU (HICU).
Authors: David D. Stenehjem, Meredith Bannon, Jonathan Boltax
Journal: Journal of Clinical Oncology (2014)

279 Background: The University of Utah opened a cancer specific ICU (HICU) in 2011 admitting medical and surgical cancer pts. Prior to this, medical cancer pts were admitted to the MICU while the SICU admitted both and medical and surgical pts. The primary objective of this study was to compare the quality metrics of mortality and length of stay (LOS). Methods: Pts with a cancer diagnosis and admitted to the MICU or SICU from 2009-2011 or the HICU from 2011-2013 were evaluated. Pts were stratified by ICU type and the HICU was also analyzed by excluding post-operative pts (HICU-MED). Survival from admission, hospital and ICU mortality, and LOS was assessed. Results: A total of 1,375 pts were included with 259 (19%), 416 (30%), and 700 (51%) pts admitted to the MICU, SICU, and HICU, respectively. The median age was 62 years (range 18-91 years) and 57% (n = 787) were male; no significant differences in age (p = 0.1975) and sex (p = 0.7681) were observed between ICU’s. Cancer classification was oncology (65%, n = 888), hematology (32%, n = 435), and BMT (4%, n = 52). Of all pts admitted to the HICU, 44% (n = 308) were post-operative and excluded from HICU-MED (n = 392). See table for survival and LOS comparisons. Conclusions: No differences in overall survival and hospital morality (ICU and out-of-ICU) were observed comparing pts admitted to the HICU vs SICU and HICU-MED vs MICU. ICU-free days were significantly shorter resulting in shorter hospitalizations for the HICU vs SICU, which may have contributed to the reduced 30-day mortality in pts admitted to the HICU. [Table: see text]
Combination of oral capecitabine and vinorelbine in metastatic breast cancer: A retrospective analysis of activity and tolerability profile.
Authors: C. Arcanà, M. C. Ingemi, H. J. Soto Parra, M. Iorfida, P. Spadaro
Journal: Journal of Clinical Oncology (2011)

e11049 Background: The purpose of this study was to retrospectively analyze toxicity profile and activity of an all-oral combination schedule of capecitabine (Cape) and vinorelbine (VNR) in metastatic breast cancer (MBC) patients (pts). Methods: All 60 pts treated had a histological confirmed diagnosis of breast cancer (BC). Each 3-week cycle of treatment consisted of 500 mg/m2 cape twice daily (2 weeks on, 1 week off), and 60 mg/m2 VNR on days 1 and 8. Results: From June 2007 to December 2010 we treated 60 MBC pts. Median age was 49 years (range 33-73). 42 pts (70%) had a performance status (PS) ECOG 0; 12 pts (20%) PS 1, 6 pts (10%) PS 2. 12 pts (20%) had metastatic disease at time of diagnosis. 52 (86,5%) expressed estrogenic receptor (ER); 10 pts (16,6%) had a HER2-positive disease; 38 (63,3%) HER-2 negative; 4 pts (6,66%) had a triple negative disease. 38 pts (63,3%) received adjuvant (adj) hormonal therapies (HT); 44 pts (73,3%) adj/neoadj chemotherapy (CT). Median time to recurrence was 37 months (range 5-192). 12 pts (20%) received Cape + VNR as first metastatic line treatment. 56 pts (93,3%) had more than one metastatic site involved (range 2-4). 42 pts (70%) had bone metastases (mts); 34 (56,6%) hepatic mts; 30 (50%) mts to lung; 18 pts (30%) nodal mts; 8 (13,3%) pleural effusion; 6 (10%) skin mts; 6 (10%) brain mts. Median number of cycles administered was 6 (range 3-16). Tolerability: 36 pts (59,7%) referred nausea G1; 14 pts (23,2%) had vomiting G1; 28 pts (46,5%) reported asthenia G1-G2; 22 pts (36,5%) diarrhea. We observed neutropenia G1-G2 in 24 pts (39,8%) (1 (1,6%) requiring treatment discontinuation) and 1 (1,6%) alopecia G1. 50 pts (83,3%) were evaluable for response. We had an objective response rate of 60% (ORR) following RECIST criteria: 3 (6%) complete responses (CR) and 27 (54%) stable diseases (SD). We observed 20 (40%) progression diseases (PD). After a median follow-up of 20 months (range 4-42), median progression free survival (PFS) was 10 months (range 3-20) and median overall survival (OS) was 55 months (range 20-116). Conclusions: Oral combination of Cape and VNR is a well-tolerated regimen and has an activity profile in pre-treated MBC pts.
Dendrogenin_A : A Natural Liver X Receptor Modulator for the Treatment of Acute Myeloid Leukemia
Authors: Christian Recher, Marion David, Philippe de Medina, Cécile Bize, Nizar Serhan, Michael R Paillasse, Estelle Saland, Emmanuel Noguer, Julia Cherier, Cécile Demur, Clément Larrue, Fabienne de Toni, François Vergez, Jean-emmanuel Sarry, Sandrine Silvente-Poirot, Marc Poirot
Journal: Blood (2014)
The clinicopathological characteristics of understaging and overstaging of the preoperative assessment for gastric cancer by endoscopic ultrasonography and computed tomography.
Authors: Ae-Ra Lee, Dong Ho Lee, Jae Jin Hwang, Cheol Min Shin, Hyuk Yoon, Young Soo Park, Nayoung Kim
Journal: Journal of Clinical Oncology (2015)

34 Background: Despite the development of EUS and CT technology, there are no clinically relevant imaging tools to detect accurate preoperative staging such as lymph node (LN) metastases. The aim of this study was to elucidate of the clinicopathological characteristics of understaging and overstaging of the preoperative assessment for the gastric cancer by EUS and CT. Methods: In total, 180 patients who underwent EUS and CT, followed by gastrectomy at Bundang Hospital, Seoul National University, from July 2012 to June 2014, were analyzed. The results from the preoperative EUS and CT were compared to the postoperative pathological findings. Results: For T staging, a total of 180 patients who underwent CT and EUS have been recruited and 99 patients with visualized primary lesions on CT were analyzed. For N staging, 180 patients who underwent EUS and CT were analyzed. The overall accuracy of EUS and CT for T staging was 63.7% and 69%, respectively. The overall accuracy for N staging was 74.3% and 69.6%, respectively. Compared with variables of under and over staging group with accurate staging group, Accuracy of T staging for lesions at the cardia (36.4% vs. 63.6%, P = 0.021), advanced gastric cancer group (55% vs. 90.9%, P = 0.005) and advanced T stage group (24.4% vs. 5.2 %, P = 0.001) was higher than that non-cardia lesions and EGC group. Ulcerative lesion (38.5% vs. 61.5%, P &lt; 0.001) and histologically undifferentiated type (3.8% vs. 93.8%, P = 0.002) had significantly lower accuracy in N staging than non-ulcerative lesions and the differentiated cancer. Conclusions: Caution is required in interpreting the T staging of the advanced T stage (T3 and T4) lesions, lesions at the cardia and advanced gastric cancer lesions. The ulcerative and undifferentiated lesions needed careful interpretation for N staging. However, there seemed to be no significant differences of clinicopathological characteristics between EUS and CT. The accuracy of CT was close to that of EUS and both modalities were useful and complementary for the locoregional staging of gastric cancer.
A phase I/II study of safety and efficacy of orteronel (TAK-700), an oral, investigational, nonsteroidal 17,20-lyase inhibitor, with docetaxel and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC): Updated phase II results.
Authors: Daniel Petrylak, Jitendra G. Gandhi, William R. Clark, Elisabeth I. Heath, Jianqing Lin, William K. Oh, David B. Agus, Bradley Curtis Carthon, Susan Moran, Ning Kong, Ajit Suri, Michael Bargfrede, Glenn Liu
Journal: Journal of Clinical Oncology (2013)

59 Background: Orteronel is an investigational non-steroidal, selective inhibitor of 17,20-lyase, a key enzyme in the production of steroidal hormones. DP is currently an approved therapy in mCRPC; this phase 1/2 study examined orteronel + DP in men with mCRPC. Methods: Castrate men (testosterone [T] &lt;50 ng/dL) with mCRPC, no prior chemotherapy and no ketoconazole/abiraterone received orteronel (400 mg BID) + D (75 mg/m 2 q3w) + P (5 mg BID). The primary phase 2 objectives were tolerability, PK, serum PSA declines, and best PSA response. Secondary objectives included time to progression of PSA ± radiographic disease, response by RECIST 1.1. Results: At data cutoff (July 23, 2012), 24 men had been treated and 12 remained on study: median age was 66 yrs (n=24, range 53–87), ECOG PS 0/1 (88%/13%). At baseline, median PSA was 46 ng/mL (4.5–813) and T was 6.8 ng/dL (2.6–13.8). 9 men discontinued due to AEs (the most common was fatigue [13%]). All men reported at least 1 Gr ≥3 AE (23 were drug-related). Drug-related Gr ≥3 AEs ≥10% were neutropenia (38%); WBC decreased (25%); fatigue (21%); decreased neutrophil count (17%); blood alkaline phosphatase increased, and leukopenia (each 13%). The most common drug-related SAE was dehydration (13%). There were 2 on-study deaths, due to disease progression and respiratory distress, both considered unrelated to treatment. At 3 mo, PSA response was evaluable in 18 men; PSA30/50/90 rates were 83%/72%/28%. Best PSA decline (median) was -76% (n=23; -99 to +144%). Median T at 3 mo decreased to ≤0.2 ng/dL (0.3–10.6). Response was evaluable in 9 men; 5 achieved a PR; ORR was 56% (n=9; 80% CI: 30, 79). Median time to PSA progression was 6.1 mo (95% CI: 4.6, not reached); median time to radiologic progression was not reached. The C max of orteronel + DP was similar to that of DP alone with no evidence of DDI. Conclusions: Orteronel 400 mg BID + DP appears tolerable and shows androgen-lowering activity, and strong PSA and partial tumor response in mCRPC. There was no evidence of DDI between orteronel and DP. Updated data, including a detailed PK analysis, will be presented. Clinical trial information: NCT01084655.