tbuckley/cabot-search huggingface dataset:
Comparing prognosis estimates of patients with cancer and their oncologists.
Authors: Ryan D. Gentzler, Walter K Kraft, Benjamin E Leiby, Joanne E. Filicko-O'Hara
Journal: Journal of Clinical Oncology (2012)

e16548 Background: Authors have reported a discrepancy between patient (pt) and physician survival estimates in pts with advanced malignancies. Methods: Oncology pts receiving chemotherapy at Thomas Jefferson University Hospital were assessed for their prognosis estimates. Matched surveys were given to their oncologists. The primary outcome was the level of agreement between pt and physician survival estimates. Prognosis estimates were obtained by three categorical responses: &lt; 1 year, 1–5 years, or &gt; 5 years. Pt prognosis estimates were categorized as pessimistic, concordant, or optimistic in relation to physician estimates, and differences between pt and physician estimates were evaluated using a two-sided Stuart-Maxwell test. Secondary outcomes assessed pt perceptions related to prognosis. Results: 51 pts completed surveys, and 29 of 51 matching physician responses were obtained for the primary analysis. 1 pt was deemed ineligible. 14 (48.2%) pts were optimistic, 14 (48.2%) were concordant, and only 1 (3.4%) was pessimistic. These results demonstrate asymmetric responses for the categorical variables, and pts were more likely to be optimistic when compared to physicians’ estimates (p=0.006). Of the 50 pts completing the survey, only 44% (22) based their survival estimate on information received from their oncologist, while others listed themselves (18%, 9) or hope (6%, 3) as the source of information. The majority of pts (86%, 43) use the internet to learn about their cancer, but only 8% (4) identified the internet as their information source for choosing a prognosis estimate. A discrepancy between pts’ beliefs about curability also exists. 5 of the 20 (25%) pts who believed their disease is curable had metastatic lung, breast, or neuroendocrine pancreatic cancer. Conclusions: The findings of this study demonstrate that pts estimate longer survival when compared to physician estimates. Other results of the survey also shed light on where pts obtain information pertaining to their cancer diagnosis and pts’ beliefs about the curability of their disease. This data highlights a need for a multicenter survey to validate these conclusions and the creation of teaching tools to help pts better understand their disease and prognosis.
Pre-treatment Near-Infrared Spectral Tomography (NIRST) to predict pathologic complete response to neoadjuvant chemotherapy (NAC) in women with locally advanced breast cancer (LABC).
Authors: Peter Kaufman, Shudong Jiang, Roberta diFlorio-Alexander, Jiang Gui, Brian W. Pogue, Keith D. Paulsen
Journal: Journal of Clinical Oncology (2015)

1047 Background: NIRST has a potential role for easily integrated monitoring and prediction of therapeutic response in women with LABC undergoing NAC. It captures biophysical changes in tissue occurring in the vascular as well as intra- and extra-cellular matrix compartments. Methods: 42 Women with LABC receiving NAC were enrolled in this pilot study to evaluate the role of NIRST, undergoing NIRST before, during, and after NAC. The NIRST imaging technology uses low intensity NIR light at 6 wavelengths (658-849nm) to assess total hemoglobin concentration (HbT), blood oxygen saturation (StO2), and water, at different time points. To normalize subject-specific variations of absolute HbT, StO2, and water in the tumor region, the ratios of these parameters to that of the baseline contralateral breast were used, to test the ability to differentiate patients having a pathologic complete response (pCR) versus lack of pCR. Additionally, whether the pre-treatment Dynamic Contrast MRI (CE-MRI) will improve the pre-treatment predication power was tested. A two-sample t-test was used to determine p-values for difference in mean between pCR and non pCR groups and Area Under the Receiver Operating Characteristic curve (AUC) was obtained to illustrate graphically. Results: The best NIRST predictor was tumor HbT change during the first cycle of NAC. The p-value and AUC were 0.001 and 1.0 between subjects with pCR and non pCR, respectively. A statistically-significant separation of Pre-TX HbTbetween subjects with pCR and non pCR (p-value < 0.01, AUC = 0.92) was also found, suggesting that NIRST has the potential to differentiate between groups before NAC has begun. Additionally, by adding the delayed signal intensity enhancement of breast in pretreatment staging CE-MRI (relative to the contralateral breast), the AUC of differentiating pCR from non pCR can be raised to 0.94. Conclusions: HbT change subsequent to the first cycle of NAC and Pre-TX HbT correlate to response to NAC and may be predictive of pCR. These biomarker data could lead to image-based surrogates for pCR, and thus accelerate the validation of optimal NAC regimens.
Prognostic significance of tumor suppressor gene maspin in pulmonary adenocarcinoma
Authors: N. Ohike, M. Nakashima, A. Shiokawa, T. Morohoshi, N. Maass, Y. Miki, K. Nagasaki
Journal: Journal of Clinical Oncology (2004)

7162 Background Maspin is a unique member of the serine protease inhibitor family with tumor suppressive potential in breast and prostate cancer. Recent studies have shown that loss of maspin expression correlates with progression and metastasis of tumors and poor prognoses for patients with several types of cancers. Paradoxically, maspin expression has been reported in ovarian and pancreatic cancers. However, the presence of maspin expression in pulmonary cancers has not been evaluated. In this study, we evaluated maspin expression in pulmonary adenocarcinoma in relation to a number of clinicopathological features. MethodsMaspin expression was examined immunohistochemically in a series of 78 pulmonary adenocarcinomas. ResultsThirty-seven (47%) showed distinct maspin expression (maspin-positive group) and 41 (53%) did not (maspin-negative group). In the surrounding pulmonary tissues, alveolar epithelial cells lacked maspin expression, but maspin staining was usually present in bronchial basal cells and occasionally present in surface bronchial epithelial cells. Maspin expression was not associated significantly with most clinicopathological variables including sex, age, tumor size, primary tumor, lymph node metastasis, visceral pleural invasion, pulmonary metastasis, stage grouping and p53 expression. However, the maspin-positive group had a better 5-year survival rate (62%) than did the negative group (42%). The difference in the 5-year survival rate was more significant in stage II-IV patients (maspin-positive group, 53%; -negative group, 16%, p = 0.049). Conclusions Our data indicate that maspin has prognostic significance for pulmonary adenocarcinoma. A better understanding of the role of maspin in tumor suppression may be helpful for development of novel chemotherapies for patients with this deadly tumor. No significant financial relationships to disclose.
The changing pattern of lung cancer: A 30-year experience at a single university hospital in Brazil.
Authors: Eloa Pereira Brabo, Vinicius Siqueira Tavares Meira Silva, Matheus Herculano Assis Teixeira, Ronir Raggio Luiz, Marcos Eduardo Machado Paschoal
Journal: Journal of Clinical Oncology (2015)

e12608 Background: Lung cancer is the second most common cancer and the leading cause of cancer death in Brazilian men. During the last decades changes in the frequency of adenocarcinoma, female gender and never smokers had increased. The aim of our study was to assess if these changes also happened in our Brazilian single Institution population of lung cancer patients (LCP), during a thirty-year period. Methods: We retrospectively reviewed the records of LCP attending the thoracic oncology unit of a University Hospital from 1980 to 2009. The observed changes were analyzed using the Chi-square and Mann-Whitney tests for categorical and quantitative variables, respectively. Time was stratified in five-year periods for analysis purpose. Results: Records from 1.635 patients were reviewed. The median age was 63 years (range 15-90). Female gender, adenocarcinoma subtype, older age (> 70 years) and never smoker proportions increased. Otherwise SCLC type, localized stages (stages I and II for NSCLC and limited disease for SCLC) and the number of cigarettes smoked decreased over time; the values are displayed in the table below. Conclusions: The changes observed in gender, adenocarcinoma subtype, older age patients, SCLC and never smokers performed as expected according to many previous reports. The decrease in limited stages cases probably reflects changes in the local referrals of our Institution in this time period. The decrease in the smoking status measured by the pack-years tool in our study correlates with the decrease in cigarette consumption that occurred in Brazil in the same time period. Time in 5-years periods Variables 80-84 85-89 90-94 95-99 00-04 05-09 p value Female * 0 13 25 29 31 41 0.00 > 70 y * 24 18 19 25 30 34 0.00 Adenocarcinoma *# 33 30 34 39 52 64 0.00 Never smokers * 7 8 8 9 8 15 0.03 SCLC* 14 18 16 12 13 11 0.01 Localized stages *à 27 25 24 26 19 15 0.01 Pack-years 73 66 61 61 58 59 0.00 * - Expressed as % # - Considering NSCLC patients only à - Stages I and II for NSCLC and limited disease for SCLC
Prospective evaluation of RRM1 as a predictor of response to gemcitabine/carboplatin (GC) in non-small cell lung cancer (NSCLC)
Authors: G. Bepler, A. Sharma, H. Greenberg, A. Cantor, X. Li, T. Hazelton, F. Walsh, G. Simon
Journal: Journal of Clinical Oncology (2006)

7054 Background: RRM1 is the regulatory subunit of ribonucleotide reductase. It is a molecular target of G. RRM1 increases upon continuous exposure of cell lines to G. Preliminary data suggest improved survival for patients with low as opposed to high tumoral expression of RRM1 when treated with G-based chemotherapy. Methods: We determined the efficacy of G and C as induction therapy in patients with locally advanced NSCLC. Trial eligibility included measurable disease, no prior chemotherapy or RT, PS 0–1, and no weight loss. Patients were staged with CT, PET, and brain MRI. GC consisted of two 28-day cycles of G, 1,000 mg/m 2 d1&amp;8 and C, AUC 5 d 1. Unidimensional tumor measurements were obtained before and after GC. The study required tumor collection prior to therapy by core needle biopsy. Specimens were frozen in LN. Tumor cells were collected by LCM. Real-time quantitative RT-PCR gene analysis was performed in triplicate per sample for RRM1 and 18SrRNA. Results: Between 11/03 and 7/05, 30 eligible patients were enrolled, and the required tumor biopsies were obtained in all. In one patient, a pneumothorax developed that required chest tube placement. Disease response ranged from a 9% increase to a 100% decrease. 14/26 had SD, 11/26 PR, and 1/26 CR. The patients’ age was 47- 87 years; 12 were women; 13 had IIIA and 13 IIIB; 10 had sq, 7 ad, and 9 LC or NOS NSCLC. RRM1 expression ranged from 0.18 to 129.3. There was a significant (p = 0.014) inverse correlation (r = −0.474) between RRM1 expression and disease response. When grouping patients into those with response (CR/PR) and without response (SD), RRM1 expression was significantly (p = 0.027) associated with response. No significant association was found between RRM1 expression and other parameters. Conclusions: In a prospective clinical trial intratumoral RRM1 expression was significantly and inversely correlated with disease response to gemcitabine and carboplatin. These results strongly suggest that tumoral RRM1 expression is a major predictor of disease response to gemcitabine-based chemotherapy. No significant financial relationships to disclose.
Genetic Polymorphisms Identify the Likelihood of Bone Disease in Myeloma: Correlations with Myeloma Cell DKK1 Expression and High Risk Gene Signatures.
Authors: Brian G.M. Durie, Brian Van Ness, Christine Ramos, Owen Stephens, Majda Haznadar, Antje Hoering, Jeff Haessler, Michael S. Katz, Gregory R. Mundy, Robert A. Kyle, Gareth J. Morgan, John Crowley, Bart Barlogie, John Shaughnessy
Journal: Blood (2007)
Hereditary implications of somatic tumor testing.
Authors: Pauline Funchain, Davendra Sohal, Alok A. Khorana, Jame Abraham, Nathan A. Pennell, Brian I. Rini, Robert Dreicer, Brian James Bolwell, Charis Eng
Journal: Journal of Clinical Oncology (2015)

1523 Background: Approximately 5-10% of all cancers are due to hereditary causes. Panel testing for somatic alterations to identify therapeutic targets has gained widespread use. Germline (heritable) implications from such testing have not yet been explored. In a prospective cohort study of patients who underwent tumor profiling by next generation sequencing (NGS), we determined the prevalence of potentially germline (PG) alterations and the frequency of referral to genetics professionals. Methods: We prospectively accrued 250 patients to an IRB-approved protocol to undergo commercial tumor genomic profiling. Inclusion criteria included pathologic diagnosis of select solid tumor malignancies without a known curative option, age ≥ 18 years, and ECOG PS 0-2. Tumor samples underwent targeted NGS through the FoundationOne panel (Cambridge, MA). Genes captured by this test were classified as PG if the gene is known to cause hereditary predisposition to cancer and has available CAP/CLIA-certified germline testing. Results: Of 315 genes tested by tumor genomic sequencing, 41 genes were classified as PG. Alterations were found in 23 PG genes. Of 222 patients with resulted tumor sequencing, 179 (81%) were found to harbor >1 PG alteration. After exclusion of TP53, APC, and CDKN2Aalterations, frequently somatically mutated in tumors, 91 (41%) were found to harbor any PG alteration. 34 patients harbored >1 hit in a single PG gene (e.g. "double mutants"). When considering the mean number of PG alterations found per patient, the top 4 cancer types were glioblastoma, colorectal, bladder, and breast. In this series of 222, 23 (10%) were evaluated by genetics professionals: 3 genetics referrals were a direct result of somatic panel testing, resulting in 1 (33%) previously unknown germline mutation. Germline testing has been completed in 19 patients, and revealed 4 germline mutations and 4 variants of unknown significance. Allelic fractions derived from tumor genomic profiling for these confirmed germline variants ranged between 35-72% (mean: 51%). Conclusions: Somatic screening of tumors has germline implications. Tumor and germline testing are not equivalent, and should be done separately. More extensive data are necessary to determine guidelines for genetics referrals.
Older patient participation in SWOG lung cancer trials: Comparative analysis from 1993 to 2008.
Authors: Paul Joseph Hesketh, Mary Weber Redman, Joseph M Unger, James Moon, David R. Gandara
Journal: Journal of Clinical Oncology (2012)

7570 Background: In 1999, SWOG published a study demonstrating the underrepresentation of patients 65 years and older on clinical trials (Hutchins NEJM). A second report published in 2006 demonstrated increasing proportions of patients &gt; 65 years (31% 1997-2000; 38% 2001-2003) being enrolled into SWOG trials (Unger JCO). Older patient enrollment was still disproportionately low compared to the US cancer population. The current analysis focuses on patients with lung cancer from 1993-2008. Methods: The proportions of enrollment onto SWOG lung cancer treatment trials by age (65-69, 70-79, ≥80 years) and gender were computed for 4-year time intervals between 1993 and 2008; corresponding rates in the US were derived from US Census and National Cancer Institute SEER data. Proportions in the SWOG trials were compared to the SEER proportions using a 1-sample binomial test of proportions. Time trends within SWOG were evaluated using linear regression. Results: The proportion of patients 65-69 was significantly higher than the US population between 1993 and 2004, but was not significantly different after 2004. Proportions of patients on SWOG trials 70-79 years old and ≥ 80 were significantly smaller than the US population. Females were underrepresented from 1993-2004. Between 2005 and 2008 female enrollment was not significantly different from the US population. Conclusions: Currently, the proportion of patients 65-69 years of age and of female gender enrolled in SWOG trials is representative of the general lung cancer population. Although some progress has been made in increasing trial participation of patients &gt; 70, enrollment remains disproportionately low. The disparity is most evident in patients &gt; 80. Continued efforts are needed to increase older patient participation in lung cancer trials. Supported in part by PHS Cooperative Agreement grants awarded by the National Cancer Institute: DHHS, CA32102 and CA38926. [Table: see text]
Risk after local excision alone for DCIS patients.
Authors: Eileen Rakovitch, Sharon Nofech-Mozes, Wedad Hanna, Frederick L. Baehner, Refik Saskin, Steven M. Butler, Alan Tuck, Sandip Sengupta, Leela Elavathil, Prashant A Jani, Michel Bonin, Martin Chang, Susan Robertson, Elzbieta Slodkowska, Cindy H Fong, Joseph Michael Anderson, Farid Jamshidian, Diana B. Cherbavaz, Steven Shak, Lawrence Frank Paszat
Journal: Journal of Clinical Oncology (2015)

1013 Background: The DCIS Score (DS) was validated as a predictor of ipsilateral breast recurrence (IBR; DCIS or invasive) in E5194 pts tx by breast-conserving surgery (BCS) w/o RT. The Ontario population-based study of 3,320 pts w/ DCIS from 1994 to 2003 (Rakovitch, 2013) tested the DS as a predictor of IBR risk in a broader, more contemporary population of pts tx w/ BCS alone - w/ & w/o clear margins (CM). Methods: DS was obtained per E5194. The pre-specified 1o objective was to determine the relationship (HR/50 units) between the risk of an IBR and the continuous DS (using Cox models) in pts tx w/ BCS alone w/ ER+ DCIS and CM (no ink on tumor). The association between the continuous DS in all pts with BCS alone w/ & w/o CM was explored. Results: 1,751 pt blocks were collected; 718 had BCS alone (571 w/ CM). Median f/u was 9.4 yrs. Among 718 pts w/ BCS alone, 136 had an IBR (DCIS, N=57; invasive, N=80). Among 571 pts w/ CM, 100 had IBR (DCIS, N=44; invasive, N=57). In the 1oanalysis, among pts tx by BCS alone w/ CM the continuous DS was significantly associated with IBR in ER+ pts (HR 2.26; 95%CI 1.41,3.59; P=0.001) and in all pts (HR 2.15; 95%CI 1.43,3.22;P=<0.001). DS was associated w/ invasive IBR (HR 1.78; 95%CI 1.03,3.05;P=0.04). In multivariable analysis for IBR, the HR/50 units for the DS among pts tx w/BCS alone w/ CM was 1.68 (95%CI 1.08,2.62; P=0.022) adjusting for multifocality, tumor size, subtype, and age. Among all 718 pts tx by BCS alone w/ and w/o CM, the DS was associated w/ IBR, and the HR/50 units for the DS was 2.04 (95%CI 1.39,2.98; P=<0.001) adjusting for multifocality, size, subtype, and age. Conclusions: The DS quantifies IBR risk for DCIS pts tx by BCS w/ or w/o CM. Integrating the DS with established risk factors can more accurately identify DCIS pts tx with BCS alone with low (<10%) or high (>25%) 10yr average IBR risk. 10 yr KM IBR rate (95%CI). DS Risk Group CM CM & unifocal DCIS All pts regardless of margin status Positive or uncertain margins N N N N Low (<39) 355 12.7% (9.5%, 16.9%) 298 9.7% (6.8%, 13.8%) 450 13.6% (10.6%, 17.3%) 95 16.8% (10.4%, 26.3%) Int (39-54) 95 33.0% (23.6%, 44.8%) 72 27.1% (17.7%, 40.2%) 118 32.4% (24.0%, 42.8%) 23 29.5% (14.4%, 54.4%) High (≥55) 121 27.8% (20.0%, 37.8%) 87 27.0% (18.2%, 38.9%) 150 31.6% (24.2%, 40.6%) 29 47.8% (30.4%, 68.8%) Log rank P-value 571 <0.001 457 <0.001 718 <0.001 147 0.004
Examining the influence of incidentally using ACEI on survival outcomes in stage III non-small cell lung cancer patients treated with definitive radiotherapy.
Authors: Hongmei Wang, Zhongxing X. Liao, Yan Zhuang, Lawrence B. Levy, Ting Xu, Daniel Richard Gomez
Journal: Journal of Clinical Oncology (2013)

7521 Background: The influence of angiotensin-converting enzyme inhibitors (ACEIs) on tumor progression is controversial, with some reports showing an antitumor mechanism and others demonstrating an increased risk of progression while on these agents. Our aim was to better elucidate the effect of ACEIs on locally advanced non-small cell lung cancer (NSCLC) outcomes in the setting of conflicting prior results. Methods: We retrospectively reviewed 673 patients with stage III NSCLC who received definitive radiotherapy +/- chemotherapy. Cox proportional hazard models were utilized to determine the association between ACEI intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Results: Univariate analysis showed an increased hazard of LRP among patients who used ACEI. After adjusting for multiple variables, ACEI use remained significant. No association was found regarding DMFS, DFS, or OS (Table). Conclusions: The use of ACEI was associated with an increased risk of locoregional progression in this population of patients. These findings provide implications for continuing this treatment through radiation therapy, if further validated through prospective studies. [Table: see text]
Optimized biodegradable polymeric reservoir-mediated local and sustained co-delivery of dendritic cells and oncolytic adenovirus co-expressing IL-12 and GM-CSF for cancer immunotherapy
Authors: Eonju Oh, Jung-Eun Oh, JinWoo Hong, YoonHo Chung, Yunki Lee, Ki Dong Park, Sungwan Kim, Chae-Ok Yun
Journal: Journal of Controlled Release (2017)