tbuckley/cabot-search huggingface dataset:
Role of intraoperative imprint cytology for evaluation of surgical margins in breast cancer: A prospective controlled study of about 400 lumpectomies
Authors: F. D’Halluin, P. Tas, S. Rouquette, C. Bendavid, H. Mesbah
Journal: Journal of Clinical Oncology (2008)

11592 Background: To assess the efficacy of intraoperative imprint cytology (IIC) in conservative surgery for early-stage breast cancer. Methods: This is a prospective controlled study led at the Comprehensive Cancer Center of Rennes, France. We reviewed a total of 736 patients who underwent lumpectomy for unifocal breast cancer from January 2004 to December 2005: 400 procedures were finally included. After a standardized surgical procedure, the lumpectomy specimens were intraoperatively oriented by the surgeon and were submitted fresh to pathology for cytologic assessment. The IIC consisted of touching the four faces of interest (superior, inferior, and laterals) onto the glass slide for a cytologic examination. Results: A total of 1,665 separate margins were analyzed. The correlation between IIC and permanent sections was 91.5%. Sensitivity was 88.6%, and specificity was 92.2%. Positive predictive value was 73.6%, and negative predictive value was and 97%. The rate of false positives was significantly increased when the technique used more than four apposition slides (p=0.0019), and when fibrocystic lesions were identified in the lumpectomy (p<0.001). The ductal carcinoma in situ was statistically over-represented among the false negatives (p<0.005), above all when its size was ≥ 30 mm (p<0.005). The intraoperative reexcisions not requested by the pathologist in case of ICC negative were tumor free in 93.9% of cases; conversely there was 71.2% residual tumor when the pathologist requested these reexcisions. The global rate of postoperative reexcisions was 13.25% and IIC avoided a second intervention for 47 patients on the 400 treated (11.75%). Conclusions: Intraoperative imprint cytology is a rapid, simple, reliable and cost-effective method to analyse the margin status of lumpectomy in patient undergoing breast conservative surgery. This technique allows a survey of the entire surface area of the lumpectomy specimen. This method is enable to reduce the number of second operative procedures especially when there is no fibrocystic changes in the breast tissue around the tumor, and when the in situ component of the tumor is limited. No significant financial relationships to disclose.
Should Hematopoietic Stem Cell Transplantation in First Complete Remission Be Restricted to High-Risk Patients in Childhood Acute Myeloid Leukemia?.
Authors: Hideki Muramatsu, Nobuhiro Nishio, Asahito Hama, Hiroshi Yagasaki, Yoshiyuki Takahashi, Sayoko Doisaki, Nobuhiro Watanabe, Kimikazu Matsumoto, Koji Kato, Seiji Kojima
Journal: Blood (2007)
Novel copper complexes with potent/synergistic antitumor activity in vivo and promising clinical activity.
Authors: A. Prokop, S. Zadolinnaya, A. Abduvaliev, C. Frias, K. Hagenow, A. Voigt, V. Tatarskiy
Journal: Journal of Clinical Oncology (2011)

e13518 Background: The role of copper in cancer has been subject of intense investigations. Methods: In the current study, we investigated the anticancer properties of novel copper complexes in vitro in various cell lines (e.g., BJAB, Nalm-6, K562) determining DNA fragmentation, proliferation, mitochondrial membrane potential and calcium concentration. Furthermore, the in vivo efficacy of novel copper complexes in different syngenic (B16 melanoma, sarcoma 180, renal cancer RENCA) and xenograft (BJAB lymphoma) tumor models was investigated. Results: The novel copper complexes showed strong apoptotic and anti-proliferative effects in vitro. In comparison with standard cytotoxic drugs an at least two-fold increase in DNA fragmentation on primary human leukemia cells was observed. Synergistic effects up to +129% in lymphoma cells and potent activity in cell lines resistant towards standard cytotoxic drugs (vincristin, daunorubicin and doxorubicin) in cells of leukemia (Nalm-6) and lymphoma (BJAB) was demonstrated. The compounds target the mitonchdrial cyclosporine A-sensitive channels triggering the intrinsic apoptosis pathway. In the syngenic models (B16 melanoma, sarcoma 180) and in a lymphoma xenograft model a significant reduction of tumor weight/volume of 60-90% was shown. Significant anti-metastatic and anti-angiogenic activity was observed in the RENCA model. In investigator-initiated trials 43 patients with a variety of solid and hematological diagnoses (stage IV) were treated orally. Tumor regression of more than 50% was observed in more than 50% of the cases without causing severe side effects. Conclusions: The in vitro and in vivo data as well as the clinical cases and the safety profile position the novel copper complexes as exciting new cancer therapeutics.
The prognostic significance of apoptosis-related biological markers in Chinese gastric cancer patients.
Authors: X. Liu, Y. Xu, Z. Long, H. Zhu, Y. Wang
Journal: Journal of Clinical Oncology (2011)

108 Background: The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as P21, P27, P53, Bcl-2, Bax, and c-myc, and clinicopathological features and their prognostic value. Methods: From January 1996 to December 2007, 4,426 patients had undergone gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 501 patients, the expression levels of P21, P27, P53, Bcl-2, Bax, and c-myc were examined by immunohistochemistry. The prognostic value of biological markers and the correlation between biological markers and other clinicopathological factors were investigated. Results: There were 339 males and 162 females (2.09:1) with a mean age of 57. The percentages of positive expression of P21, P27, P53, Bcl-2, Bax, and c-myc were 73%, 25%, 65%, 22%, 43%, and 58%, respectively. There was a strong correlation between P21, P53, Bax, and c-myc expression (p = 0.00). There was significant association between P27, Bcl-2, and Bax expression (p &lt; 0.05). The P21 expression correlated with male (p = 0.00), histological grade (p = 0.00), Borrmann type (p = 0.02), tumor location (p = 0.01); the P53 expression with histological grade (p = 0.01); Bcl-2 expression with pathological stage (p = 0.01); Bax expression with male (p = 0.02), histological grade (p = 0.01), Borrmann type (p = 0.01), tumor location (p = 0.00), lymph node metastasis (p = 0.03), pathological stage (p = 0.01); c-myc expression with Borrmann type (p = 0.00). Bcl-2 expression was related with good survival in univariate analysis (p = 0.01). Multivariate analysis showed that Bcl-2 expression and pathological stage were defined as independent prognostic factors for gastric cancers. There was significant differences of overall 5-year survival rates according to Bcl-2 expression or not in stage III (p = 0.00). Conclusions: The expressionof Bcl-2 was an independent prognostic factor for Chinese patients with gastric cancer; it might be a candidate for the gastric cancer staging system. No significant financial relationships to disclose.
Developing a comprehensive smoking cessation program in patients with lung cancer: The role of social smoking environments.
Authors: Lawson Eng, Jie Su, Xin Qiu, Prakruthi R. Palepu, Henrique Hon, Ehab Fadhel, Luke Harland, Anthony La Delfa, Steven Habbous, Aidin Kashigar, Sinead Cuffe, Natasha B. Leighl, Andrew Pierre, Peter Selby, David P. Goldstein, Geoffrey Liu, Wei Xu
Journal: Journal of Clinical Oncology (2012)

75 Background: Smoking during cancer treatment negatively impacts outcome, survival, and quality of life. Social smoking environments (SSEs) (i.e., smoking in household, peers, and spouse) influence cessation rates in non-cancer patients, but are understudied in cancer patients. Methods: Lung cancer patients, recruited from Princess Margaret Hospital (2006-2012) were given baseline and follow-up questionnaires (median of 2 years apart) evaluating changes in smoking habits and SSEs. Multivariate logistic regression and Cox-proportional hazard models evaluated the association of socio-demographics, clinicopathological and SSE factors with smoking cessation and time to quitting, respectively. Results: 721 patients completed both questionnaires. Of the 261 current smokers at diagnosis, 180 (69%) had quit by follow-up. Among 318 ex-smokers, 5 re-started smoking after diagnosis. All of the 140 never smokers remained non-smoking. Home smoke exposure (OR=9.4; 95% CI: 3.4-26.2; p=2.0 x 10E-5), spousal smoking (OR=4.7, 95% CI:1.7-12.6; p=3.0 x 10E-3) and peer smoking (OR=2.6; 95% CI:1.1-6.1; p=0.03) were each associated with reduced cessation, adjusted for a base multivariate model that included education and past history of depression. Individuals with no SSE factors had a much higher chance of quitting smoking when compared to patients with multiple areas of SSEs (0 vs. 3, OR=16.4; 95% CI: 4.1-66.7; p=7.3 x 10E-5). Similar results were seen when using time-to-quitting as the outcome (0 vs 3, OR=4.4, 95% CI=1.4-14.1, p=0.01). Time to quitting analysis found that 60% of patients with at least one SSE who did quit, did so within 6 months of diagnosis. Subgroup analysis revealed similar associations in early- and late-stage patient groups. Conclusions: SSE is a key factor in smoking cessation, where household smoke exposures reduces the chance of quitting up to 9-fold. SSEs should be a key consideration when developing smoking cessation programs in lung cancer patients, as part of quality improvement strategies. Approaches incorporating household members or spouses into the smoking cessation intervention, around the time of diagnosis, should be researched further. GL and WX are co-senior authors.
Effect of dose intensification (DI) of octreotide-LAR (O-LAR) among symptomatic patients with neuroendocrine tumors (NETs).
Authors: Khalid S. Al Efraij, Mohammed A Aljama, Hagen F. Kennecke
Journal: Journal of Clinical Oncology (2014)

299 Background: O-LAR 20 to 30 mg IM monthly (qM) is approved for the management of symptomatic NETs. While higher doses are sometimes used for improved symptom control, the benefit of this is not well described. The objectives of the study were to evaluate pre-DI and post-DI symptom, biomarker and tumor size among patients who received O-LAR 40-60 mg qM. Methods: With approval of the BC Cancer Agency research ethics committee the charts of all referred patients with NETs who received O-LAR 40-60 mg qM between 2005 and 2001 were reviewed. Symptom severity was graded on a 4 point scale and any post-increase improvement from grade 2,3 or 4 to 1 or no symptoms was classified an improvement. Pre-DI Chromogranin A (CGA) and 24-hour urine 5-HIAA were compared with the median of 3 post-DI levels and a 10% decrease was classified as a decrease. Results: A total of 37 patients received DI therapy with 40 mg (36), 50 mg (3), and 60 mg (16), for a total of 55 DI events. Median age was 60 and 49, 19, 32% had a tumor of small bowel, pancreas, other, respectively. Post-DI CGA and 5 HIAA levels decreased in 31% (15/49) and 23 % of patients (8/35) respectively. Symptom improvement post DI was observed in 62% (13/21) with diarrhea, 76% (13/17) with flushing, 53% (8/15) with abdominal pain. Post DI, no decreases in tumor size were observed, 29% (14/49) had radiological stable disease and the remainder had progressive tumors. Conclusions: O-LAR 40-60 mg qM was associated with improved symptom control among NET patients with refractory secretory symptoms. CGA and 5-HIAA levels varied in response to DI and were not accurate indicators of symptom control. There was no evidence of tumor regression with O-LAR DI. [Table: see text]
Distance-to-care: Stage at diagnosis for New Mexico (NM) residents with colorectal cancer (CRC).
Authors: Meredith C. Mason, Andrew Bruner, Angela W. Meisner, Katherine T. Morris, Itzhak Nir, Ashwani Rajput, Charles Wiggins
Journal: Journal of Clinical Oncology (2012)

421 Background: CRC is a leading cause of morbidity and mortality among NM’s American Indians, Hispanics, and non-Hispanic whites. Previous studies have shown that rural residents are more likely than urban dwellers to be diagnosed with late stage disease. Geographically New Mexico is the 5 th largest state with a population of 2 million, many of whom reside in rural regions. This study was designed to characterize the association between distance-to-care and stage of disease at diagnosis in NM. Methods: The population-based NM Tumor Registry was used to identify records for all incident cases of CRC between 2001-2008. Latitude and longitude were determined for the place of residence for cancer cases and for the facility where each case was diagnosed. The “Great Circles” algorithm was used to estimate the distance from place of residence to the diagnosing facility. The percentage of cases diagnosed with early stage vs. other stages (i.e., regional, distant, and unknown stages-combined) was assessed by quartile of distance-to-care with the use of the chi-squared test for trend. Multiple logistic regression was used to characterize the association between stage and quartile of distance-to-care while controlling for other factors know to be associated with stage at diagnosis. Results: Analysis was based on 6,291 incident cases of CRC that were diagnosed among NM residents. Latitude and longitude for both place of residence at diagnosis and location of diagnosing facility were available for 4,385 (69.7%) of all incident cases. The percentage of cases diagnosed at early stage was inversely related to the distance between the place of residence at diagnosis and the facility where the cancer was diagnosed, as follows: 41.4% of cases in Quartile 1 (shortest distance-to-care); 39.9% in Quartile 2; 37.8% in Quartile 3; and 35.3% in Quartile 4 (p=0.002).By multiple logistic regression, distance-to-care was a significant predictor of stage at diagnosis after adjustment of sex, age and race/ethnicity. Conclusions: Rural residents of NM who must travel relatively long distances to receive medical care are at increased risk of being diagnosed at late stage colorectal cancer.
Upfront bevacizumab with temozolomide or with temozolomide and irinotecan for unresectable or multifocal glioblastoma.
Authors: E. Lou, D. A. Reardon, K. Peters, A. Desjardins, J. E. Herndon, A. D. Coan, S. G. Turner, A. L. Sumrall, L. Bailey, H. S. Friedman, J. J. Vredenburgh
Journal: Journal of Clinical Oncology (2011)

2055 Background: Patients with unresectable or multifocal glioblastomas (GBs) have a poor prognosis with median survival of 6-10 months. Given the angiogenic phenotype of GB, we conducted two phase II trials of upfront 5-day temozolomide (TMZ) and Bevacizumab (BV) with or without Irinotecan in patients with newly diagnosed unresectable or multifocal GB. Methods: Before radiation, patients received up to 4 cycles of temozolomide at 200 mg/m2/d days 1-5 and BV at 10 mg/kg on days 1 and 15 in each 28-day cycle. In the second trial, Irinotecan was added on days 1 and 15 at 125 mg/M2 for patients not on an enzyme-inducing anti-epileptic drug (EIAED), or 340 mg/M2 for patients on an EIAED. An MRI was performed monthly and therapy continued as long as there was no tumor progression, grade 4 non-hematologic toxicity, or recurrent grade 4 hematologic toxicity after dose reduction. The primary endpoint was tumor response using the RANO criteria. Results: In the initial trial of TMZ and BV, 41 patients were enrolled from 10/07 to 9/08. MRI’s were available from 31 patients. There were 8 (25.8%) partial responses, 19 (61.3 %) patients with stable disease, and 4 (12.9 %) had disease progression. 19 of the 41 patients enrolled completed four cycles without tumor progression. The regimen was tolerable, with three grade 4 hematologic toxicities. There were 3 venous thromboembolic complications. There were 2 CNS hemorrhages. The median PFS was 5.2 mos (3.2, 9.0 months) and the median OS was 11.7 months (7.1, 15.6 months). In the second trial, Irinotecan was added to TMZ and BV and 41 patients were enrolled between 12/09 and 11/10. The partial response rate was 41%, 44% had stable disease and 15% had progression. 16 of 41 patients completed four cycles without tumor progression. There were 4 patients with grade 4 hematologic toxicity, 7 patients with venous thromboembolic complications and 1 with CNS hemorrhage. The median PFS was 6.7 months (2.0, 10.5 months) and median OS was 10.5 months (7.2, ND months). Conclusions: Upfront TMZ and BV was well tolerated. Adding Irinotecan to TMZ and BV does not appear to improve survival. Upfront therapy for unresectable or multifocal GB is an excellent platform to determine clinical activity.
Efficacy and Safety of Lenalidomide in the Treatment of Multiple Myeloma (MM) Patients: a Preliminary Report of Polish Myeloma Group
Authors: Lidia Usnarska-Zubkiewicz, Jakub Debski, Aleksandra Butrym, Wojciech Legiec, Anna Dmoszynska, Beata Stella-Holowiecka, Jan Maciej Zaucha, Marcin Rymko, Tigran Torosian, Kazimierz Kuliczkowski
Journal: Blood (2011)
Tumor profiling of 1189 geriatric breast tumors.
Authors: Joanne Xiu, Sandeep K. Reddy, Paula Raffin Pohlmann
Journal: Journal of Clinical Oncology (2015)

116 Background: Breast cancer (BC) is a disease of aging and the number of geriatric patients is rising in the US. However, this group of patients is often excluded from clinical trials and under-represented in biomarker literature, complicating treatment selection strategies. Methods: BC tumors referred to Caris Life Sciences (Phoenix, AZ) between 2009 and 2015 were tested with a combination of immunohistochemistry (IHC), fluorescent/chromogenic in-situ hybridization (ISH) and sequencing (Next-generation and Sanger). De-identified biomarker data were analyzed. Results: A total of 1189 tumors collected from BC patients (M = 21/F = 1168) aged ≥ 70 (range: 70-97, average 75.6) were analyzed (breast biopsy n = 512; metastatic site n = 677). Of the 1088 tumors with available IHCs of ER, PR and IHC and/or ISH of HER2, 613 (56%) were HR+/HER2-, 72 (7%) were HR+/HER2+, 346 (32%) were TNBC and 57 (5%) were HR-/HER2+. Overall, 39 of 47 genes sequenced carried mutations with frequencies ranging from 0.2% to 37%. Highest mutation rates were seen in PIK3CA (37%), TP53 (37%), BRCA2 (12%), PTEN (5.8%), AKT1 (4.2%), cMET (3.9%), ERBB2 (3.5%), BRCA1 (3.3%) and ATM (3.2%). Among 13 patients with ERBB2 mutation, 3 had it amplified. PD-L1 expression on tumor cells was seen in 13% and PD-1 expression on tumor-infiltrating lymphocytes in 46%, with TNBC subtype showing the highest expression: 20% and 60%, respectively. In addition, TOPO1, TLE3, AR, TOP2A, SPARC were overexpressed in 61%, 58%, 55%, 51%, 37% of tumors, respectively, suggesting potential sensitivity to irinotecan, taxanes, anthracyclines and nab-paclitaxel. TS, RRM1 and ERCC1 were under-expressed in 69%, 69% and 53%, respectively, suggesting potential sensitivity to fluoropyrimidines, gemcitabine and platinums. A comparison with 7531 tumors from patients younger than 70, as well as description of abnormalities per molecular subtype of BC will be presented. Conclusions: Using multiple testing technologies, potentially targetable biomarker aberrations were identified in a large cohort of geriatric tumors. Our study provides key elements for the design of clinical trials focusing on geriatric patient population.
Performance characteristics and validation of automated tumor-infiltrating lymphocyte counting.
Authors: C. C. Hoyt, I. S. Hagemann, A. R. Hagemann, L. Wang, E. Hung, K. Lane, G. Coukos, M. D. Feldman
Journal: Journal of Clinical Oncology (2011)

10562 Background: In many cancers, intratumoral infiltration lymphocytes (TILs), as assessed in FFPE tissue sections, indicate levels of tumor immunogenicity, and are a strong predictor of overall and progression-free survival. Potentially, tests that characterize TIL phenotype, location, and density in tumor and surrounding stroma could aid the selection of immunotherapy and define targets for individualized treatment. However, TIL assessment today, based on human visual perception, is prone to error, due to complicated tissue architectures, ambiguous histology revealed through hematoxylin counterstain, and other human factors. In this study, we investigate computer-aided histologic event counting, using as our sample use-case counting lymphocytes in serous ovarian carcinoma specimens. We compare results to visual assessment. Methods: Sections of a tissue microarray (TMA) containing 618 ovarian cancer histocores were stained with anti-CD3 antibody to identify T lymphocytes. For manual scoring, a trained pathologist rated lymphocyte density on a semi-quantitative scale of 0 to 3. For automated scoring, TMA slides were scanned using a multispectral imaging system. A machine-learning algorithm was trained to segment tumor from stroma. Parameters for identifying lymphocytes were refined. Results: The machine learning algorithm determined tumor TIL density for 70% of cores and stromal TIL density for 42%. With triplicate representation of each tumor on the array, 93% of tumors had at least one core informative for intratumoral TILs, and 71% had at least one core informative for stromal TILs. There was a significant strong positive correlation between total manual and machine counts (r=0.6581, p<0.0001 by Spearman's nonparametric test). Conclusions: Results indicate machine scoring can meaningfully capture TIL status of tumors and yield quantitative, normalized feature count using consistent rules. Furthermore, combining machine scoring with multispectral, multi-analyte imaging enables TIL phenotyping (e.g., CD3+/ CD8+/FoxP3+). These findings help validate automated lymphocyte counting as a method in translational research utilizing TMAs.