tbuckley/cabot-search huggingface dataset:
Frequency and distribution of HER2 overexpression in advanced malignancies.
Authors: R. Ashfaq, D. Arguello, R. A. Feldman, G. Basu, D. Loesch, A. Kemkes
Journal: Journal of Clinical Oncology (2011)

e21153 Background: Testing for HER2 has revolutionized the management of breast cancer and, now, gastro-esophageal junction cancer. The purpose of this study was to capture the relative frequency and distribution of HER2 overexpression in other cancers. Methods: In a cohort of 11,223 patient samples, HER2 was assayed by immunohistochemistry using the Ventana HER2 (4B5) antibody. Slides were then read by pathologists using the cutoff of (>=3+ and >=30% as positive) for HER2. In this same cohort, 2,246 patient samples underwent HER2 by FISH testing using Abbott’s Pathvysion HER2 assay. FISH analysis was interpreted by a cytogeneticist based on ASCO/CAP guidelines for breast cancer. Prior to the analysis, 4,116 patient samples were excluded secondary to an unknown tumor lineage or other lineage rarely seen in our laboratory. In all, twenty-seven tumor lineages comprising 7,107 patient specimens were analyzed. Results: Our preliminary observations indicated that the frequency of HER2 by IHC is highest in breast carcinoma (68.6%), colorectal adenocarcinoma (7.2%), ovarian surface epithelial carcinoma (5.4%), gastroesophageal adenocarcinoma (4.5%), non-small cell lung cancer (3.1 %), pancreatic adenocarcinoma (1.3%) and gastric adenocarcinoma (1.3%) In these same lineages, frequency of HER2 by FISH is highest in breast carcinoma (46.0%) followed by surface epithelial ovarian carcinoma (12.7%), non-small cell lung cancer (8.3 %), gastroesophageal adenocarcinoma (6.7%), gastric adenocarcinoma (4.8%), pancreatic adenocarcinoma (4.0%), colorectal adenocarcinoma (3.2%). Distributional differences in IHC versus FISH results were analyzed by Pearson’s chi-square (x2) test, with statistical significance (p<0.05) achieved in breast carcinoma, gastric adenocarcinoma, gastroesophageal adenocarcinoma and surface epithelial ovarian carcinoma. Conclusions: To our knowledge, this is the first study involving a large patient pool with advanced malignancies in which HER2 status was investigated in a single clinical laboratory with standardized IHC and FISH. This study shows that HER2 is frequently expressed in other cancer types, which merits the inclusion of therapeutic strategies using HER2-targeted therapy in such tumors.
Clinical benefit (CB) of high-dose interleukin-2 (HD IL-2) in clear cell (cc) metastatic renal cell carcinoma (mRCC).
Authors: Neeraj Agarwal, Kinjal Parikh, Srinivas Kiran Tantravahi, Hilda Crispin, Joan Van Atta, Julia Anne Batten, Daniel Sageser, Wolfram E. Samlowski, Kenneth F. Grossmann, Junfeng Wang, David D. Stenehjem
Journal: Journal of Clinical Oncology (2014)

461 Background: HD IL-2, an immunotherapy, is a standard of care for a select group of patients (pts) with mRCC. Generally objective response (OR) rates, i.e. complete response (CR) + partial response (PR), of 16-20% are discussed with pts, but not disease stabilization (SD). Recent data suggest that cancer immunotherapy may improve survival without inducing OR. Thus, treatment with HD IL-2 may provide survival benefit to an additional group of pts not experiencing OR, but only SD as the best response. Here we report CB ( OR+SD), and specifically report outcomes of cc mRCC pts experiencing SD as the best response, on treatment with HD IL-2. Methods: All sequential cc mRCC pts treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000-2012 were included. Pts were evaluated for best response, progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS). Two practitioners independently reviewed HD IL-2 response with discrepancies adjudicated by a third reviewer. Results: 85 pts, 79% male, were identified with a median age of 56 (range 32-76) years. Pts belonged to the following MSKCC risk categories: 11 (13%) good, 70 (82%) intermediate, and 4 (5%) poor risk. A CR was identified in 9 (11%), PR in 5 (6%), SD in 26 (31%), progressive disease (PD) in 38 (45%), and unknown/not evaluable (NE) in 7 (8%) pts; yielding a clinical benefit in 40 (47%) pts. The median PFS, TNT, and OS in these individual groups of pts are compared in the table. Conclusions: A clinical benefit of HD IL-2 was achieved in nearly half of all clear cell mRCC pts. OS was not significantly different in OR and SD groups. Even though OR favorably determine outcomes, SD is also an important response criterion, and may be discussed during counseling pts for treatment with HD IL-2. [Table: see text]
Aromatase localization in human endometrial carcinoma: The potential effects of arcinoma-stromal cell Interactions
Authors: N. Takahashi, H. Utsunomiya, R. Kobayashi, M. Matsumoto, K. Yoshinaga, S. Nagase, T. Takano, H. Niikura, K. Ito, N. Yaegashi
Journal: Journal of Clinical Oncology (2008)

16598 Background: Estrogens play important roles in the growth and invasion of human endometrial and breast carcinomas. Aromatase is considered a key enzyme in intratumoral estrogen production through conversion of serum androgens in endometrial carcinoma tissue. However, routine evaluation methods for detection of intratumoral aromatase expression in clinical specimens have not been established. This study examined localization of aromatase. Because it has not been reported whether factors released from human intratumoral stromal cells affect aromatase expression of endometrial carcinoma or parenchymal cells, we looked for possible effects of isolated stromal cells from endometrial carcinoma tissue on aromatase enzymatic activity in endometrial carcinoma cell lines. Methods: A total of six endometrial carcinoma specimens were obtained from Japanese patients. We examined intratumoral localization of aromatase in human endometrial carcinoma using Laser capture dissection/quantitative RT-PCR and immunohistochemistry. Secondly, we examined possible effects of isolated stromal cells from endometrial carcinoma tissues on aromatase enzymatic activity in endometrial carcinoma cell lines. For physical separation of stromal cells and carcinoma cell lines, transwell cultures were established. The cells were cultured in transwell chambers in the absence or presence of stromal cells for 24 hrs. After cultivation, carcinoma and stromal cells were separated and each component was examined via aromatization assay. Results: Aromatase mRNA and protein were detected in stromal cells from human endometrial carcinoma tissues. Aromatase activity was detected in endometrial carcinoma cell lines although levels were lower than those of tumor stromal cells. Aromatase activity in stromal cells was significantly increased by co-culture with endometrial carcinoma cells compared with monoculture. Conclusions: The co-culture system used in our study could provide important information with regard to evaluation of intratumoral carcinoma-stromal cell interactions in aromatase production. These results might provide important information for achieving better clinical responses to aromatase inhibitors in patients with endometrial carcinoma. No significant financial relationships to disclose.
Follow-up data from a phase II study of adjuvant S-1/cisplatin chemotherapy followed by S-1 based chemoradiotherapy for advanced gastric cancer.
Authors: Hyun-Jeong Shim, Woo Kyun Bae, Jun-Eul Hwang, Young-Kyu Park, Seong-Yeop Ryu, Taek-Keun Nam, Ik-Joo Chung, Sang-Hee Cho
Journal: Journal of Clinical Oncology (2016)

116 Background: Surgery is the only possible curative treatment for gastric cancer. However, the high recurrence rate makes gastric cancer difficult to cure by surgery alone. The present study was conducted to evaluate the clinical outcomes and toxicity of adjuvant treatment, including S-1/cisplatin chemotherapy followed by radiotherapy with concurrent S-1. Methods: Patients with radically D2-resected adenocarcinoma of the stomach of stage IB–IV (M0) were eligible. Patients were treated with S-1 (40–60 mg depending on the patient’s body surface area) twice daily for 3 weeks and cisplatin (60 mg/m²) intravenously on day 1 every 5 weeks. Patients received CRT (45 Gy of radiation at 1.8 Gy/day, 5 days per week, for 5 weeks with the same dose of S-1 during radiation) followed by two additional cycles of S-1/cisplatin. The primary endpoint was the 3-year disease-free survival (DFS) rate; the secondary endpoints were the 3-year overall survival rate and toxicities. Results: Until May 2012, 46 patients were enrolled, and 34 (73.9%) completed the planned treatment. The median age was 53 years (range: 31–69 years), and the numbers of patients with stage IB, II, III and IV disease were 0, 17, 25 and 4, respectively. Grade 3–4 toxicities were as follows: neutropenia (28.2%), nausea (17.4%), vomiting (8.7%) and anorexia (15.2%). At the time of analysis, after a median follow-up period of 56.5 months (3.03–74.0 months), 16 recurrence events and 15 deaths were reported. The estimated 3-year DFS and survival rates were 65.2% and 76.1%, respectively. The most common site of recurrence was the peritoneum (n = 12). Conclusions: The results of this phase II study show that intensified adjuvant treatment with S-1/cisplatin chemotherapy and S-1-based chemoradiotherapy was effective in reducing disease recurrence. A randomized trial is needed to evaluate the role of the addition of radiation to chemotherapy in adjuvant treatment for gastric cancer. Clinical trial information: NCT01824004.
Weekly cisplatin-epirubicin-paclitaxel with G-CSF support (PET) vs. triweekly epirubicin-paclitaxel (ET) in metastatic breast cancer (MBC). Final results of the 9908 SICOG trial
Authors: G. Frasci, G. D’Aiuto, P. Comella, A. Siani, R. Thomas, G. Botti, F. Avino, G. Iodice, T. Petrosino, G. Comella
Journal: Journal of Clinical Oncology (2005)

580 Background: The present study was aimed at comparing the antitumor activity of 12 weekly PET cycles with that of 6 triweekly ET cycles in MBC patients. Methods: Women with MBC, aging < 70 years, with ECOG P.S. 0–2 were randomized to receive 12 weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2, paclitaxel 120 mg/m2 with G-CSF d 3–5 each week, or 6 cycles of epirubicin 90 mg/m2, paclitaxel 175 mg/m2 every 3 weeks. Time to Treatment Failure was the main end-point. One-hundred and twenty pts. per arm were planned. An interim analysis focusing on TTF was planned on the first 60 pts./arm enrolled, according to the Schaid’s design. A minimum follow-up of 6 months from the last pt. enrolled was required. Early stopping rules: p > 0.32 or p< 0.01. Results: The planned interim analysis was performed on May the 1st 2004, when 60 pts. in each arm had a minimum potential follow-up of 6 months. Overall 145 patients had been recruited at that time (PET=72; ET=73). Overall 96 failures had occurred among the 120 analysed pts. (PET=51 ET=45). Median TTF being 11.7 and 12.3 months in PET and ET respectively (p=0.66). 55 deaths had occurred (PET=24 ET=31), MST being 46 and 36 months for PET and ET arm respectively (p=0.37). Responses were as follows: PET: 11 CRs, 34 PRs for an ORR of 75%; ET: 8 CRs, 20 PRs, for an ORR of 47% (p=0.001) Anaemia, mucositis, peripheral neuropathy, and gastrointestinal toxicity were substantially more frequent in the PET arm. On October 15° a further analysis including all 145 enrolled pts. has been performed. Median TTFs were 11.7 and 12.6 months for PET and ET, respectively. Conclusions: PET weekly regimen is superior to standard ET in terms of ORR in MBC patients. However, Time to Treatment Failure, which was the main end-point of the present study, was superimposible in the two arms. In view of that, the accrual has been stopped and the null hypothesis accepted. No significant financial relationships to disclose.
Pathologic findings in additional prostatic and periprostatic tissue removed during radical prostatectomy.
Authors: Henry Chen, Richard J. Kahnoski, Brian R. Lane
Journal: Journal of Clinical Oncology (2013)

172 Background: Additional prostatic and periprostatic tissue (PPT) can be removed during radical prostatectomy (RP) when there is concern for incomplete removal of the entire prostate gland or residual extraprostatic extension of cancer. The presence of cancer in PPT during RP is largely unknown. We analyzed the rate of positive PPT findings during RP in a community-based health system to determine the yield of PPT resection to inform future clinical practice. Methods: Retrospective review of pathology reports from 976patients undergoing RP between 1998-2011 was performed. Demographic and pathologic data were collected in an IRB-approved database. Results: Of 976 RP, 267 patients (27%) had PPT excised (median: 1, range: 1-4). Median PSA was 5.0 (IQR: 3.9-7), clinical stage was T1c in 69%, and biopsy Gleason score was 6 or lower in 39%, 7 in 52% and 8 or higher in 9%. Pathologic stage was pT2 in 85%, T3 in 13%, and LN positive in 2.6%. Among 177 bladder neck biopsies, 31% contained benign prostate and 3.4% (n=6) had adenocarcinoma. Of 37 urethral biopsies, 46% contained benign prostate and 16% (n=6) had adenocarcinoma. Of 21 prostatic apical excisions, 86% contained benign prostate and 14% (n=3) contained adenocarcinoma. Of 35 excisions of suspected residual (or fragmented) prostate (posterior-lateral, median, base, capsule, pedicle), 94% contained prostate and 0% contained adenocarcinoma. No prostate tissue or cancer was present in 15 samples labeled as “periprostatic fat” and 9 “neurovascular bundle”. Conclusions: Complete excision of adenocarcinoma during RP remains the primary surgical objective. Clinical suspicion of incomplete excision of benign or cancer-containing prostate tissue may lead to removal of additional PPT samples. In this single-center study, prostate tissue was present in 45% of such samples overall, supporting this practice. However, cancer is rarely present in such samples (5.6% of cases with PPT removed, 1.5% of RP overall), with apical/urethral regions appearing to be at highest risk (~15% of samples).
Development of a multidisciplinary program for evaluation and treatment of pancreatic cancer in a community healthcare system.
Authors: Robert C. Hermann, Scott Early, Sachin Goel, Justin Hart, Magali Huertas, Chad Khulman, Leigh Webb, Barbara J Wilson, Sahir Shroff
Journal: Journal of Clinical Oncology (2016)

303 Background: The incidence and mortality of pancreas cancer is rising in the United States. Only patients who are able to have complete (R0) resection have the potential of cure. Optimal surgical outcomes are influenced by local center volume and multidisciplinary support. We describe the development of a multidisciplinary approach to the evaluation and treatment of pancreas cancer in a community health care system. Methods: This project was initiated by the WellStar Cancer Program, encompassing 5 hospitals. An Institutional Guideline was developed, based upon NCCN, with refinements related to local capabilities and preferences. The Guideline emphasized the review of cases at a weekly tumor board for multidisciplinary coordination of care. Standards for staging evaluations, medical imaging, chemotherapy choices, radiation therapy, and surgical approach were included. A GI Nurse Navigator attended the conferences and assisted in the coordination of care. Specific outcomes were tracked by the Nurse Navigator and the Cancer Registry. Here we describe the program impact related to staging, treatment, nurse navigation, volume and outcomes during the 2011-2014 development phase of the program. Results: A total of 308 cases of pancreas cancer were captured by the registry in 2011-2014. 131 were diagnosed with stage IV disease and offered palliative therapy. 30 Stage I and 139 Stage II-III underwent staging evaluation and consideration of multidisciplinary care, summarized in the table below, and compared to a baseline registry cohort of the 4 preceding years. Conclusions: The development of a Multidisciplinary Team approach to pancreas cancer within a 5 hospital community system has led to improvement in treatment outcomes, including R0 resection rate. Full 2-year results to be updated at the meeting. [Table: see text]
Tolerability of and biochemical control of permanent Pd-103 brachytherapy followed by external beam radiotherapy for localized prostate adenocarcinoma.
Authors: Samuel M. Richter, Paul D. Aridgides, Oleg Shapiro, Jesse N. Aronowitz, Jeffrey Bogart
Journal: Journal of Clinical Oncology (2012)

245 Background: The optimal sequencing of brachytherapy and external radiotherapy (EBRT) for patients receiving combined therapy for localized prostate cancer has not been established, and in this series we report our experience of patients treated with brachytherapy followed by EBRT. Methods: Retrospective review of patients treated with combined Pd-103 brachytherapy and EBRT with minimum of 2 years of follow-up. Variables assessed included T stage, Gleason score, pre-treatment PSA, use of androgen suppression (ADT), EBRT dose and brachytherapy dose. Biochemical failure was defined as a PSA rise of ≥ 2 ng/mL above nadir. Results: 87 patients received Pd-103 brachytherapy (median 80 Gy) followed by EBRT (median 45 Gy). Median age was 65 years (49–80). By risk groupings (Zelefsky) 26.4% of patients were low risk, 47.1% were intermediate risk, and 26.4% were high risk. Most low risk patients had either perineural invasion or ≥ 50% involved biopsy cores. Neoadjuvant and concurrent ADT was given in 21% of patients. With a median follow-up of 56 months (range 24 to 113), there were 4 failures (all in the intermediate or high risk group), with an overall 5-year biochemical failure free survival (BFFS) of 91.8%. 2 patients had documented distant failures, while none of the presumed local failures had a positive biopsy. There was no statistical difference in BFFS based on risk group, T stage, Gleason score, initial PSA, or ADT use. The median PSA nadir was 0.1 and occurred at a median of 30 months from brachytherapy. A nadir of ≤ 0.5 was seen in 87% of patients and was associated with improved 5-year BFFS (100% vs 22%, p&lt;.0001). The median time to PSA nadir for patients &lt; 60 years was 34.5 months compared to 26.5 months in patients ≥ 60 (p=.036). Overall, treatment was well-tolerated with no cases of late Grade ≥ 2 rectal or urinary toxicity reported. Conclusions: Excellent long-term disease control and low morbidity was observed for patients with localized prostate adenocarcinoma treated with interstitial brachytherapy followed by EBRT. Future prospective research assessing the relative therapeutic ratio of alternate sequencing approaches would appear warranted.
A novel staging system for disease-specific survival in patients with breast cancer treated with surgery as the first intervention.
Authors: M. Yi, E. A. Mittendorf, T. A. Buchholz, A. A. Sahin, H. M. Kuerer, S. Luo, K. Y. Bilimoria, J. Crow, J. N. Cormier, A. M. Gonzalez-Angulo, A. Buzdar, G. N. Hortobagyi, K. Hunt
Journal: Journal of Clinical Oncology (2011)

92 Background: American Joint Committee on Cancer (AJCC) staging of breast cancer is used to determine prognosis, yet survival of patients within each stage shows wide variation and remains unpredictable. We hypothesized that differences in underlying biology might influence some of this variation and that the addition of biologic markers to current AJCC staging parameters would improve predictions of prognosis. Methods: We identified an initial cohort of 3,728 patients at our center who underwent surgery as the first intervention between 1997 and 2006. We used a Cox proportional hazards model, with backward stepwise exclusion of factors and stratified on pathologic stage (PS), to test the added significance of modified Black’s nuclear grade (G), the presence of lymphovascular invasion (L), estrogen receptor status (E), progesterone receptor status (P), or combined ER and PR status (EP), or combined receptor subtype (ER+PR+HER2 [M]). We assigned values 0-2 to these disease-specific survival (DSS)–associated factors and then used different combinations to assess different staging systems. Surveillance Epidemiology and End Results (SEER) data was used as the external cohort (n=26,711) to validate the scoring system. Results: Median follow-up time for the initial cohort was 6.5 years, and the 5-year DSS rate was 97.4%. Six different staging systems were used to predict 5-year patient outcomes: PS, PS+G, PS+GL, PS+EG, PS+GEP, and PS+GM. We compared 5-year DSS rates, Akaike’s information criterion (AIC) and Harrell’s concordance index (C-index) for each staging system. We found that the PS+GEP staging system was most precise with lowest AIC (1927.3) and had the highest C-index (0.80). The ability of the PS+GEP system to stratify outcomes was confirmed in the internal bootstrapping samples and the external validation cohort. Conclusions: Our results validate a new staging system that incorporates tumor grade, ER and PR status into current AJCC staging for breast cancer. We recommend that biologic markers be incorporated into revised versions of the AJCC staging system for patients undergoing surgery as their first intervention.
Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury
Authors: Yan Xie, Benjamin Bowe, Tingting Li, Hong Xian, Yan Yan, Ziyad Al-Aly
Journal: Kidney International (2017)

Proton pump inhibitor (PPI) use is associated with an increased risk of acute kidney injury (AKI), incident chronic kidney disease (CKD), and progression to end-stage renal disease (ESRD). PPI-associated CKD is presumed to be mediated by intervening AKI. However, whether PPI use is associated with an increased risk of chronic renal outcomes in the absence of intervening AKI is unknown. To evaluate this we used the Department of Veterans Affairs national databases to build a cohort of 144,032 incident users of acid suppression therapy that included 125,596 PPI and 18,436 Histamine H2 receptor antagonist (H2 blockers) consumers. Over 5 years of follow-up in survival models, cohort participants were censored at the time of AKI occurrence. Compared with incident users of H2 blockers, incident users of PPIs had an increased risk of an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73m2 (hazard ratio 1.19; 95% confidence interval 1.15-1.24), incident CKD (1.26; 1.20-1.33), eGFR decline over 30% (1.22; 1.16-1.28), and ESRD or eGFR decline over 50% (1.30; 1.15-1.48). Results were consistent in models that excluded participants with AKI either before chronic renal outcomes, during the time in the cohort, or before cohort entry. The proportion of PPI effect mediated by AKI was 44.7%, 45.47%, 46.00%, and 46.72% for incident eGFR under 60 ml/min/1.73m2, incident CKD, eGFR decline over 30%, and ESRD or over 50% decline in eGFR, respectively. Thus, PPI use is associated with increased risk of chronic renal outcomes in the absence of intervening AKI. Hence, reliance on antecedent AKI as warning sign to guard against the risk of CKD among PPI users is not sufficient as a sole mitigation strategy.