tbuckley/cabot-search huggingface dataset:
Phase II trial of combination therapy with intravenous carboplatin (C) and oral everolimus (EVE) and prednisone (P) in docetaxel-pretreated (DP) metastatic castrate-resistant prostate cancer (mCRPC): A Prostate Cancer Clinical Trial Consortium study.
Authors: Muthu Kumaran Veeraputhiran, Daniel H. Shevrin, Lance K. Heilbrun, Daryn Smith, Jing Li, Brenda Dickow, Elisabeth I. Heath, Ulka N. Vaishampayan
Journal: Journal of Clinical Oncology (2013)

156 Background: Platinum based therapies have demonstrated efficacy in DP mCRPC. EVE demonstrated preclinical efficacy in chemotherapy resistant prostate cancer models. Clinical synergy was noted between C and EVE, hence a phase II trial of the combination was conducted. Methods: Primary endpoint was time to progression (TTP). Progression was defined per RECIST criteria for measurable disease (MD), or skeletal event, or &gt; 2 new areas of bone metastases. DP mCRPC patients with adequate renal and liver function, and performance status of 0 or 1 were eligible. Intravenous C at target AUC of 5 on day 1, and oral EVE 5mg once daily and P 5mg twice daily were administered in 21 day cycles. PSA was assessed every 21 days and radiologic response was assessed every 3 cycles. Secondary endpoints included overall survival (OS), correlation of TTP and PSA response, with markers such as phopho mTOR, pAKT, p70S6 and circulating tumor cells (CTC). Results: 26 patients (pts) enrolled, including 8 African Americans, and accrual is complete. Median age was 69 years (range 54-86). Median pretherapy PSA was 190 ng/ml (range 13 - 2174). 18 pts (69%) had bone pain. Gleason score was &gt; 8 in 18 pts. 19 pts had measurable disease of which 15 had MD progression, 18 had bone scan progression, and 2 had PSA-only progression. 124 cycles have been administered; median 3 cycles (range 1 - 16). The predominant grade 3 or 4 toxicities were thrombocytopenia in 8 pts, pulmonary embolism in 2 and neutropenia in 3. No treatment related deaths occurred. Of 26 pts who are response evaluable, 4 (15%) had a &gt; 30% PSA decline and 1 had a &gt;90% PSA decline. Of 19 pts with MD, 8 had stable disease and no objective responses were observed. The median TTP and OS were 2.5 months (90% CI: 1.8 - 4.3), and 12.5 months (90% CI: 6.7 - 16.1), respectively. Correlative studies including pharmacokinetic and pharmacodynamic evaluations are ongoing, and will be reported. Conclusions: The combination was tolerable but revealed modest clinical efficacy. Biomarker evaluation may help identify a subset likely to benefit from mTOR inhibition strategy in mCRPC. Clinical trial information: NCT01051570.
Induction erlotinib or gemcitabine/carboplatin factorial assignment therapy in stage IIIA-N2 non-small cell lung cancer.
Authors: W. Zhong, X. Yang, R. Liao, Q. Nie, S. Dong, J. Su, X. Zhang, Q. Zhou, J. Yang, Y. L. Wu
Journal: Journal of Clinical Oncology (2011)

e17512 Background: Stage IIIA-N2 NSCLC represents a heterogeneous group of patients with ipsilateral mediastinal lymph nodes involvement. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) may provide dramatic responses in patients with non-small cell lung cancer (NSCLC) carrying EGFR mutations. The purpose of this study is to evaluate the role of induction EGFR-TKI therapy in IIIA-N2 NSCLC. Methods: A Phase II trial conferring induction erlotinib therapy is currently recruiting participants (NCT00600587). Patients with resectable NSCLC of stage IIIA-N2 were assigned to either induction erlotinib arm or induction gemcitabine/carboplatin (GC) arm based on the EGFR mutations analysis. Results: From January 2008 till now, 21 patients with IIIA-N2 NSCLC diagnosed by mediastinoscopy or PET/CT have been enrolled. Ten cases with EGFR mutation were assigned to the erlotinib arm, while 11 cases harboring wild-type EGFR received the GC regimen. In the erlotinib arm, one case suffered from postoperative bleeding, and another case suffered from acute radiotherapy-induced pneumonitis which led to death. In the GC arm, three cases suffered from grade IV thrombocytopenia, among which two cases received transfusion. In the 19 cases with full data up till now, the response rates were 66.7% (6/9) for the erlotinib arm and 40% (4/10) for the GC arm (P=0.31). The pathological N2 complete response rates were 22.2% (2/9) for the erlotinib arm and 30% (3/10) for the GC arm (P=1.0). Five cases received complete resection in the erlotinib arm, while 6 cases received complete resection in the GC arm. In the erlotinib arm, the most common failure model after initial therapy was distant metastases (5/7), especially brain metastases (3/7). The median progression free survival time was 236 days for the erlotinib arm and 271 days for the GC arm (P=0.27). In addition, two cases in the erlotinib arm got partial response to gefitinib therapy after progression to erlotinib induction therapy and the following complete resection. Conclusions: Induction erlotinib therapy in IIIA-N2 NSCLC with EGFR activating mutation is a promising strategy. Brain metastases were major failure model.
Effect of adjuvant chemotherapy (CRx) on the cognitive function of older patients (pts) with breast cancer (BC): Results from a prospective study
Authors: A. Hurria, C. Rosen, E. Zuckerman, J. Holland, K. Panageas, M. Witmer, W. van Gorp, L. Norton, C. Hudis
Journal: Journal of Clinical Oncology (2005)

8204 Background: Data suggests a possible impact of adjuvant (adj) CRx for BC on cognitive function but an effect in pts ≥ age 65 has not been previously reported. Methods: 31 pts ≥ age 65 with stage I-III BC enrolled in an IRB-approved prospective protocol that examined the impact of adj CRx on cognition & functional status. Inclusion criteria: age ≥ 65, stage I-III BC, & receipt of adj CRx at MSKCC [CMF (cyclophosphamide 600mg/m2 IV, methotrexate 40mg/m2 IV, 5-fluorouracil 600mg/m2 IV q3 wk x 8) or an anthracycline-based regimen: AC (doxorubicin 60mg/m2, cyclophosphamide 600mg/m2 q3 wk x 4), AC-T (AC followed by Paclitaxel 175mg/m2 IV q3 wk x 4), or AC-T-H (AC-T followed by trastuzumab 2mg/kg q 1wk x 52 on another study)] with dose modifications per cause. Exclusion criteria: prior BC, CRx, or CNS XRT. Neuropsych & functional status tests were performed pre- & 6 months (mo) post-CRx. 27 are evaluable: 3 refused post test & 1 is still on-study. Mean age 71 (range 65–84), stages are: I (41%), IIA (37%), IIB (15%), IIIA (4%), IIIC (4%). CRx was CMF (70%), AC (7%), AC-T (19%), AC-T-H (4%). The following domains were examined: attention, language, verbal & visual memory, spatial, psychomotor, & executive functions. Results: The # of scores 2SD below the norm were calculated for each pt pre- & 6 mo post-CRx: 13 (48%) had no change, 11 (41%) worsened, & 3 (11%) improved [p=0.05] Table 1 summarizes the incidence of cognitive impairment, defined as 1 SD decline pre- to 6 mo post-CRx in ≥ 2 domains. Pre & 6 mo post-Crx functional status scores were unchanged: ADL (p=0.18), IADL (p=0.61), or KPS (p=0.16). Conclusions: This pilot study suggests a possible impact of adjuvant BC CRx on older women’s cognitive function without an associated functional status decline; however, subtle changes in function wouldn’t be captured by these scales. Further prospective study is needed to confirm these observations & identify any subgroups possibly at special risk. No significant financial relationships to disclose.
Uracil-tegafur (UFT) based radiochemotherapy in adjuvant treatment of resected high risk gastric cancer
Authors: C. Gemici, O. Demir, T. Salepci, M. Gumus, A. Mayadagli, O. O. Seseogullari
Journal: Journal of Clinical Oncology (2005)

4175 Background: Adjuvant radiochemotherapy using bolus 5-FU has been recently established as the standard treatment of resected gastric cancer (Macdonald et al. Proc ASCO 2000, NEJM 2001). One major concern regarding this treatment protocol was the frequency of grade 3 and 4 toxicities seen in 41% and 32% of the cases respectively. Only 64% of the patients completed the planned treatment. Hematologic toxicity was predominantly observed followed by gastrointestinal toxic effects. This study evaluates the feasibility and toxicity of combined modality treatment using UFT instead of bolus 5-FU. Methods: 37, T3/T4 or N+ resected gastric cancer patients were treated in a manner similar to the Macdonald regimen with UFT instead of bolus 5-FU. Patients received UFT, 300 mg/m2, divided in two daily doses on days 1–15 of a 21-day cycle or on days 1–21 of a 28-day cycle, 1–3 cycles before and 1–2 cycles after radiotherapy. During radiotherapy, patients received UFT, 300 mg/m2 in two daily doses for five days from Monday to Friday starting on the first day, ending on the last day of radiation. Radiotherapy was administered with AP/PA fields to the tumor bed and regional nodes with 6 or 15-MV photons, by 2 Gy fractions/day, 5 days/week to a total dose of 46 Gy. Results: Grade 3 and 4 toxicity occurred in 38% and in 14% of the cases respectively. Gastrointestinal toxic effects predominated, comprising 89% of all grade 3 and 4 toxicities; nausea/vomiting 47%, esophagitis 16%, anorexia 16%, diarrhea 11%. Neutropenia being the only hematologic toxicity was observed in 2 patients (11%). Among 37 patients, 7 didn’t complete the planned treatment due to the toxicity (19%). Conclusions: Although bolus 5-FU based adjuvant radiochemotherapy improved the survival in high risk gastric cancer, it caused significant toxicity. Bolus 5-FU is not the optimal chemotherapeutic agent when combined with radiation with respect to efficacy and toxicity. UFT acting like infusional 5-FU may improve these parameters. This UFT based adjuvant radiochemotherapy protocol not only changed the toxicity profile of the treatment but also resulted in less acute grade 3 and 4 toxicity and in less treatment discontinuation when compared with the Macdonald protocol. No significant financial relationships to disclose.
Lineage Instruction by Oncogenic Tyrosine Kinase Fusions.
Authors: Hirokazu Shigematsu, Shin-ichi Mizuno, Hiromi Iwasaki, Yojiro Arinobu, Hidetoshi Ozawa, David W. Sternberg, Brian Huntly, D. Gary Gilliland, Koichi Akashi
Journal: Blood (2005)
Gleason pattern 5 as a pathologic predictor of recurrence, development of metastasis, and prostate cancer-specific death for patients receiving salvage radiation therapy following radical prostatectomy.
Authors: William C. Jackson, Skyler B. Johnson, Corey Foster, Darren Li, Benjamin Foster, Yeohan Song, Howard Mark Sandler, Ganesh S. Palapattu, Priya Kunju, Rohit Mehra, Daniel A. Hamstra, Felix Yi-Chung Feng
Journal: Journal of Clinical Oncology (2013)

151 Background: The presence of primary, secondary, and tertiary Gleason pattern 5 (GP5) in prostate cancer has been shown to predict outcomes and improve risk stratification following radical prostatectomy (RP) and external beam radiation therapy (EBRT). However, the predictive value of GP5 has not been assessed in salvage EBRT (SRT) for a rising PSA after RP. We sought to assess the prognostic capability of the presence of GP5 in this setting. Methods: 575 patients who received SRT at a single institution for biochemical recurrence after RP were retrospectively reviewed in an IRB approved analysis. We assessed the impact of GP5 on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) using Kaplan-Meier and Cox Proportional Hazards models. Results: Median follow up was 56.7 months post SRT. On pathologic evaluation, 563 patients had a documented Gleason score (GS). 60 patients (10.7%) had primary, secondary, or tertiary GP5. GP5 was the strongest pathologic predictor of DM (p&lt;0.01 HR: 1.9 [95%CI: 1.3-2.9]) and PCSM (p&lt;0.01 HR: 4.0 [95%CI: 2.1-7.7]) on univariate analysis. The presence of GP5 was a better predictor of BF, DM, PCSM, and OS than stratification by GS8-10. Patients with GP5 had clinically worse outcomes than GS8 patients without GP5. There was no difference in outcome between primary, secondary, and tertiary GP5. On multivariate analysis, GP5 was the strongest pathologic predictor of BF (p&lt;0.01 HR: 2.7 [95%CI: 1.6-4.5]), DM (p&lt;0.01 HR: 11.2 [95%CI: 3.9-32.2]), and PCSM (p&lt;0.01 HR: 6.0 [95%CI: 1.8-19.6]). Conclusions: In SRT, where pathologic factors including extra-capsular extension, seminal vesicle invasion, and margin status are known, the presence of GP5 is the strongest pathologic predictor of BF, DM, and PCSM. Traditional GS risk stratification fails to fully utilize the prognostic capabilities of individual GP’s for SRT patients following RP. Intensification of treatment regimens, such as early use of androgen deprivation therapy or adjuvant radiation, may be appropriate for patients with GP5 in this setting.
Patterns and predictors of chemotherapy and trastuzumab use for early-stage breast cancer in Kaiser Permanente Northern California, 2004-2007.
Authors: Allison W. Kurian, Daphne Lichtensztajn, Theresa H.M. Keegan, Rita W. Leung, Sarah J. Shema, Dawn L. Hershman, Lawrence H. Kushi, Laurel A. Habel, Tatjana Kolevska, Bette Jane Caan, Scarlett Lin Gomez
Journal: Journal of Clinical Oncology (2012)

256 Background: Chemotherapy regimens for early-stage breast cancer have been extensively tested by randomized clinical trials, and specified by evidence based-practice guidelines. However, little is known about the translation of trial results and guidelines to oncology practice. Methods: We extracted individual-level data on chemotherapy administration from the electronic medical records of Kaiser Permanente Northern California (KPNC), a pre-paid integrated health-care delivery system serving 29% of the local population. We linked data to the California Cancer Registry, incorporating demographic and tumor factors, and performed multivariable logistic regression analyses on the receipt of specific chemotherapy regimens. Results: We identified 6,178 women diagnosed with stage I to III breast cancer at KPNC during 2004 to 2007; 2,735 (44.3%) received at least one chemotherapy infusion at KPNC within 18 months of diagnosis. Factors associated with receiving chemotherapy, and specifically receiving anthracyclines, taxanes, and/or trastuzumab, included young age, large tumor size, involved lymph nodes, hormone receptor-negative or HER2/neu-positive tumors, and high tumor grade; comorbid conditions were inversely associated with chemotherapy use (heart disease for anthracyclines, neuropathy for taxanes). We observed less chemotherapy use by unmarried women, less anthracycline and taxane use by low-socioeconomic status (SES) non-Hispanic whites, and more anthracycline use by high-SES Asian/Pacific Islanders (versus high-SES non-Hispanic whites). Concordance with relevant measures of the American Society of Clinical Oncology Quality Oncology Practice Initiative (QOPI) was highest among younger women with larger, higher grade tumors. Conclusions: In this health care organization with essentially equal access, we discovered that chemotherapy use was concordant with practice guidelines, yet may vary according to socio-demographic factors. These findings may inform efforts to optimize treatment, and guide studies of quality in breast cancer care.
Evaluation of the pathologic features of positive lymph nodes in the mesorectum after short-term preoperative chemoradiotherapy.
Authors: Naohito Beppu, Hidenori Yanagi, Hiroshi Doi, Norihiko Kamikonya, Yasuhiro Inoue, Naohiro Tomita, Naoki Yamanaka
Journal: Journal of Clinical Oncology (2013)

571 Background: The purpose of this study was to investigate the relationship between the pathological degeneration of primary tumor and positive lymph nodes (LNs) after preoperative chemoradiotherapy for rectal cancer. Methods: We analyzed the resected specimens from 53 patients (pts) with ypN+ rectal cancer received curative resection after chemoradiotherapy (25 Gy/10 fr/5 days+S-1 80 mg/m 2 ×10 days).The primary tumor regression was assessed using the tumor regression grade (TRG 0 to 4) according to Dworak classification. 144 positive LNs in the mesorectum were measured and were assessed using the LN regression grade (LRG) as follows; LRG 1 =minor to moderate regression, LRG 2 =major regression, and LRG 3 =total regression. To confirm apoptosis, the LNs with LRG 2 or 3 were stained by TUNEL method. Furthermore, we examined the relationship among the size of LNs, the TRG, and the LRG. Results: The TRG 1, 2, and 3 was found in 24 pts, 15 pts, and 14 pts, respectively. In addition, there were no pts with TRG 0 or 4. The LRG 1, 2, and 3 was found in 74 LNs, 48 LNs, and 22 LNs, respectively. 14 in 15 LNs equal to or greater than 10 mm (≥10mm) showed the LRG 1.Whereas, in 129 LNs less than 10 mm (&lt;10mm), the proportion of the LRG 2 or 3 in pts with each TRG was 33.8 % (26/77), 69.0 % (20/29), and 100 % (23/23) in the TRG 1, 2, and 3 respectively. Conclusions: 1) Larger LNs (≥10 mm) seemed to be radioresistant. 2) A good correlation of the response to chemoradiation between the primary tumor and LNs were observed in smaller LNs (&lt; 10 mm). 3) Primary tumor with the TRG 3 can predict the efficacy of preoperative chemoradiotherapy for the positive LNs in the pts with rectal cancer.
Quality control (QC) tissue array for the prospective rvaluation of translational research projects. A program of the EORTC GI and RGB Groups
Authors: M. P. Lutz, C. Belluco, C. Julié, D. Aust, B. Nordlinger, C.-H. Köhne, E. van Cutsem, N. Brünner
Journal: Journal of Clinical Oncology (2005)

9600 Background: Translational research often correlates immunohistochemistry (IHC) on archival tissue with clinical information. However, IHC is not standardized and quality control is not yet widely established. Important parameters which can not be controlled are the fixation time and tissue heterogeneity. Therefore, a tissue array was designed to evaluate the suitability of a given antigen/antibody test before use in clinical trials. Methods: A 216 spot tissue array was designed using paraffin-embedded tissue from 14 colorectal cancers. Immediately after surgery, specimen from tumor rim or tumor center were formalin-fixed individually over night, for > 24 h, or for > 48 h, respectively. After evaluation by H&E staining, three cores from each specimen were assembled in a tissue array, i.e. 18 cores per tumor. Sections were distributed to 6 laboratories for IHC each using one or more of the commercial antibodies for p53, Ki67, CEA, CK20, Cox2 in routine staining protocols, or for 3 experimental antigens. Blinded reading of immunoreaction was performed by the investigators using a 3-step visual grading scale and by a central laboratory before unblinding of allocation. Results: In all laboratories, IHC was successful using the commercial antibodies. IHC with the experimental antigens failed due to high background or inconsistent staining. The staining pattern varied considerably between cores from individual specimen (e.g. Ki67: from 10–90% pos. nuclei; CEA: 50–100% pos. cells, CK20: 10–60% pos. cells) with moderate differences for staining intensity (variation from weak to moderate or moderate to strong). If average staining intensity or staining pattern for the three cores per location were calculated, there was no difference between tumor center and rim (p ≥0.62 in paired t-tests for all comparisons). Most importantly, fixation time had no impact on the expression levels of the five antigens (p values from 0.12 to 0.93). Conclusions: This QC tissue array is a useful tool to ensure the reliability of a given antibody and staining procedure before its use in translational research in multicenter clinical trials. No significant financial relationships to disclose.
Risk Adapted BEACOPP Regimen Based on Early Scintigraphy Can Reduce the Cumulative Dose of Chemotherapy for Standard and High Risk Hodgkin Lymphoma (HD) with No Impairment of Outcome.
Authors: Eldad J. Dann, Rachel Bar Shalom, Nissim Haim, Ada Tamir, Menachem Ben Shachar, Irit Avivi, Tsila Zuckerman, Mark Kirschbaum, Odelia Goor, Diana Libster, Jacob M. Rowe, Ron Apelbaum
Journal: Blood (2005)
Effect of national recommendations on hepatitis B virus screening in a large U.S. cancer center.
Authors: Jessica Hwang, Michael Fisch, Anna Lok, Hong Zhang, John Vierling, Maria Suarez-Almazor
Journal: Journal of Clinical Oncology (2012)

175 Background: National organizations recommend screening for hepatitis B virus (HBV) before chemotherapy but differ regarding which patients should be screened. We aimed to determine changes in screening rates at a cancer center after national recommendations were published between 2008 and 2010. Methods: We conducted a retrospective cohort study of HBV screening in cancer patients registered 1/2004 through 4/2011. Screening was defined as HBsAg and anti-HBc tests ordered around initial chemotherapy. We compared screening rates for 3 periods: before publication recommendations, during the period of publication of CDC, NCCN, AASLD, IOM, and ASCO recommendations, and after publication of recommendations. Logistic regression models were used to identify predictors of screening. Results: Of 139,981 new patients, 18,688 received chemotherapy, and 3,020 (16.2%) were screened. HBV screening rates increased over the 3 periods (14.8%, 18.2%, 19.9%; p&lt;0.0001), but &lt;19% of patients with HBV risk factors were screened. Among patients with hematologic malignancies, over 66% were screened during the entire study period, and odds of screening nearly doubled after publication of recommendations (p&lt;0.0001). Less than 4% of patients with solid tumors were screened during the entire study period despite 70% increase in odds of screening after recommendations (p=0.003). Other predictors of screening included younger age, planned rituximab therapy, and known risk factors for HBV infection. Conclusions: HBV screening increased after publication of national recommendations, yet most patients with solid tumors or HBV risk factors remained unscreened. Efforts are needed to increase awareness of the importance of HBV screening prior to chemotherapy and antiviral prophylaxis to prevent HBV reactivation.
Determination of breast density by bioimpedance.
Authors: Karina Bukhanov, Joel S. Ironstone, Cindy Basso, Tina Bilodeau
Journal: Journal of Clinical Oncology (2012)

56 Background: Mammographic breast density is a significant risk factor for breast cancer. Women with extremely dense breasts are at 4-to-6 times the risk of developing breast cancer than women with primarily fatty breast tissue. Electrical Breast Densitometry (EBD) is a new technique that assesses breast density. EBD is non-ionizing, fast, has low cost per test ($20-$30) and may help in breast cancer risk assessment in the primary care setting. Methods: This study evaluated the feasibility of the EBD in an IRB-approved pilot study of 20 patients. The study used a custom-made self-adhesive electrode (SenoSENSE Medical Systems, Toronto, Canada) interfaced to an off-the-shelf impedance meter (Bodystat 1500, Bodystat, Isle of Man, UK) with a customized cable. On the same day as the subject’s scheduled mammogram, impedance measurements were acquired for each breast. Mammogram densities were scored by a trained radiologist using standard BiRADS breast density categories 1 to 4. Results: A high correlation coefficient was observed (Pearson correlation coefficient &gt;0.80) between breast density determined by the EBD and the BiRADS breast density score. In addition a statistically significant difference was observed between dense categories (BiRADS 3,4) and fatty categories (BiRADS 1,2) (p&lt;0.01), as well as between extremely dense breasts (BiRADS 4) and all other categories (p&lt;0.01). Very high correlation (Pearson correlation coefficient &gt;0.95) was observed between EBD measurements on the left and right breasts. Previous studies have reported a left/right correlation of 0.89 for blinded mammography readers. Conclusions: These results suggests that the EBD measure may be less variable than mammographic estimates of density. The results of the study suggest that Electrical Breast Densitometry is a promising technique for the assessment of breast density and the ability to aid in evaluation of breast cancer risk. It can be reasonably deployed at primary care facilities.