tbuckley/cabot-search huggingface dataset:
P53 is an independent predictor of tumor recurrence and progression after nephrectomy for patients with localized Renal Cell Carcinoma: Implications for surveillance and adjuvant clinical trials
Authors: O. Shvarts, D. Seligson, J. Lam, T. Shi, S. Horvath, R. Figlin, A. Belldegrun, A. Pantuck
Journal: Journal of Clinical Oncology (2004)

4546 Background: We attempted to determine which clinical and molecular variables can best predict cancer recurrence following nephrectomy for localized Renal Cell Carcinoma(RCC) Methods: From a custom kidney cancer tissue microarray containing tumor specimens from 366 patients, 193 patients who underwent nephrectomy for localized RCC at UCLA between 1989 and 2000 were identified. The array was then analyzed by immunohistochemistry for CAIX, CAXII, Ki67, Gelsolin, p53, EpCAM, pTEN, and Vimentin . The medical records of these patients were then reviewed for clinical data including age, sex, TNM stage, tumor size, nuclear grade, ECOG performance status(ps), recurrence status(both local and metastatic) and, when applicable, time to recurrence. Univariate and multivariate analyses were conducted to determine independent clinical and molecular predictors of tumor recurrences. Optimal cutoff values for significant molecular markers were evaluated. Results: Fifteen percent of the patients recurred following nephrectomy. Univariate analysis demonstrated tumor size, T stage, grade, ECOG ps, Ki67, EpCAM, and p53 to have an impact on recurrence(p<0.05). However, multivariate analysis demonstrated that the only independent predictors were T stage(p=0.018),ECOG(p=0.004), and p53(p=0.003). An optimal cutoff value for p53 mean staining was determined to be 20% of cells. Patients with localized tumors demonstrating mean p53 staining values above and below this cutoff demonstrated recurrence rates of 35.7% and 13.4%, respectively(p=0.018, RR= 3.28). Conclusions: P53 is the only independent molecular predictor of tumor recurrence for patients undergoing treatment for localized RCC, successfully identifying a subset of patients with a significantly higher probability of recurrence that could derive the greatest benefit from more stringent post surgical surveillance and from adjuvant clinical trials. No significant financial relationships to disclose.
Ideal breast volume resection during wide local excision: Is it ∏ in the sky?
Authors: Dearbhla Hillick, Eoghan Shanley, Aslam Mohd Noor, Alison Johnston, Michael Sugrue
Journal: Journal of Clinical Oncology (2014)

91 Background: Despite advances in imaging and pre-operative work-up, there is significant variability in breast volume excision, margin positivity and re-excision rates in wide local excision (WLE) surgery. Suggested ideal resection volumes and benchmarks for maximal % breast volume excision have been suggested (Krekel N, Zonderhuis B, Muller S et al (2011). Excessive Resections in Breast Conserving Surgery A Retrospective Multicentre Study. The Breast Journal 17 (6): 602-609). This study assessed whether there was much difference between actual and expected breast specimen volumes, allowing for tumour size variation. Methods: A retrospective review was undertaken of symptomatic patients undergoing WLE in a single breast surgeon’s practice between May 2011 and May 2013 at a designated breast cancer centre. Patients with DCIS were not included. Modified Krekel optimal resection volumes (ORV) [4/3 π (r+1.0cm) 3 ] were estimated to include 1.0cm, 1.5cm and 2.0cm macroscopic margins. Breast volume was calculated using Katariya and Kalbhen mammographic formulae. Excess resection was defined as the difference between total specimen and optimal specimen volume. Results: 50 consecutive patients, mean age 63 years (range 38-88), mean BMI 28.1 ±4.8, mean tumour size 24.0 ±11.5cm 3 were studied. Of the 50 patients 44/50 (88%) had a palpable tumour. 52% had T2 tumours, 68% had associated DCIS and 32% were node positive. Mean specimen weight was 78.6g ±1. Mean optimal and actual breast resection volumes were 42.6 ±37.3 cm 3 and 160 ±102.4 cm 3 ; 6/50 had positive margins leading to re-excision in 4. The mean breast and specimen resection volumes were 815 ±327.4cm 3 and 225 ±153.8 cm 3 resulting in a mean percentage breast volume excision of 19.3 ±99%. Potential excess resection in 48/50 patients with a mean excess resection volume of 182.7 ±145 cm 3 . Conclusions: This study identified the opportunity to improve consistency in the volume of breast resected. Determining ideal volume resection should be part of patient surgical oncological planning.
High insulin-like growth factor 1 receptor (IGF1R) expression is associated with poor survival in surgically treated non-small cell lung cancer (NSCLC) patients (pts)
Authors: D. T. Merrick, R. Dziadziuszko, B. Szostakiewicz, A. Szymanowska, W. Rzyman, E. Jassem, J. Jassem, W. A. Franklin, P. A. Bunn, F. R. Hirsch
Journal: Journal of Clinical Oncology (2007)

7550 Background: IGF1R represents a novel molecular target in NSCLC. We aimed to evaluate the association between IGF1R expression, clinical characteristics and survival in operable NSCLC pts. Methods: 184 consecutive surgically treated pts (median follow up of 32 months [range: 13–51 months]) were included in the study. There were 23% females, 55% pts with squamous cell carcinoma, 28% with adenocarcinoma, 3% with large cell carcinoma, 13% with mixed carcinoma and 1% with other types, 5% were never-smokers. Median age was 64 years (range: 37–85 years). Pathological stage I was diagnosed in 41%, stage II –22%, stage III –33% and stage IV –4% pts. Induction or adjuvant treatment was not routinely used. IGF1R was evaluated in tissue microarray by immunohistochemistry and scored by two observers according to H-score, taking into account proportion of cells with positive staining times staining intensity (scale 0–400). Results: IGF1R IHC expression was low in analyzed samples (median H-score 20, range: 0–223). Higher IGF1R score was observed in adenocarcinomas vs. squamous-cell carcinomas (p=0.02) and never-smokers vs. smokers (p=0.02). IGF1R score did not depend on stage (p=0.98) and sex (p=0.83). When analyzed as a continuous variable, IGF1R score tended to associate with worse survival in the entire cohort (p=0.10), and was significantly associated with inferior survival in patients with complete (R0) resections (p=0.04). When categorized with cut-off point of 50 (30% of patients positive), IGF1R expression was again associated with poor survival (p=0.05). This association was confined to pathological stage I (hazard ratio, HR=3.07; 95% confidence interval, CI=1.41–6.70, p=0.005) vs. all other stages (HR=1.03; 95% CI=0.63–1.70, p=0.90), and to patients with adenocarcinoma histology (HR=2.67; 95%CI=1.17–6.70, p=0.02 vs. all other histologies (HR=1.28; 95%CI=0.79–2.11, p=0.32). Conclusion: In this cohort of operable NSCLC pts, high IGF1R expression was associated with never-smoking history, adenocarcinoma histology, and poor survival, particularly in stage I disease and in patients with adenocarcinoma. These results support involvement of IGF pathway in the progression of early-stage NSCLC. No significant financial relationships to disclose.
Axillary ultrasonographic criteria to predict chemotherapy response in breast cancer patients receiving neoadjuvant chemotherapy.
Authors: Koun Joy Yoo, Sun Mi Kim, Sung-Won Kim, So Yeon Park, Seung-Hee Choi, Jieun Lee, Mi Jung Jang, Bo La Yun
Journal: Journal of Clinical Oncology (2014)

48 Background: The purpose of the study is to evaluate ultrasonographic criteria to predict response of axillary LNs in patients with breast cancer receiving neoadjuvant chemotherapy. Methods: We retrospectively reviewed data of 402 patients who underwent neoadjuvant chemotherapy from August 2003 to December 2012. Of these, 202 breast cancers in 199 patients (bilateral in 2 patients) in whom axillary LN metastasis was confirmed using axillary ultrasonography (US) and US-guided fine-needle aspiration biopsy (FNAB) were included in the study. US evaluation was done for the long and short axes, and cortical thickening before and after chemotherapy. The ratio of decreased long and short axes and cortical thickening on prechemotherapy US was also calculated. Statistical analysis with receiver operating characteristic (ROC) curve was used to determine the valuable ultrasonographic criteria for predicting pathologic complete remission (CR) using Medicalc program. Results: Final pathologic diagnoses of LNs were yNo in 57, yN1 in 76, yN2 in 50 and yN3 in 19 cases. The mean size of LNs were 1.8cm in long axis, 1.0cm in short axis and 0.9cm in cortical thickening on prechemotherapy US and 1.1cm in long axis, 0.6 cm in short axis and 0.4 cm in cortical thickening on postchemotherapy US. The area under the ROC curve (AUC) was 0.578 for cortex thickening, 0.523 for the long axis, and 0.523 for the short axis of LN on postchemotherapy US. The AUC was 0.643 for the decreased cortex thickening ratio, 0.585 for the long axis ratio, and 0.585 for the short axis ratio. The most significant criteria was decreased cortex thickening ratio to the long and short axes (p &lt; 0.05). The sensitivity and specificity of the decreased cortex thickening ratio for predicting CR were 43.7% and 80.7%, respectively, with a 0.5 cut off value. Conclusions: The most significant criteria for predicting CR was decreased cortex thickening ratio to the long and short axes. It is applicable for selecting sentinel LN biopsy candidates from among breast cancer patients who have undergone neoadjuvant therapy.
Climate Change and Collective Violence
Authors: Barry S. Levy, Victor W. Sidel, Jonathan A. Patz
Journal: Annual Review of Public Health (2017)

Climate change is causing increases in temperature, changes in precipitation and extreme weather events, sea-level rise, and other environmental impacts. It is also causing or contributing to heat-related disorders, respiratory and allergic disorders, infectious diseases, malnutrition due to food insecurity, and mental health disorders. In addition, increasing evidence indicates that climate change is causally associated with collective violence, generally in combination with other causal factors. Increased temperatures and extremes of precipitation with their associated consequences, including resultant scarcity of cropland and other key environmental resources, are major pathways by which climate change leads to collective violence. Public health professionals can help prevent collective violence due to climate change (a) by supporting mitigation measures to reduce greenhouse gas emissions, (b) by promoting adaptation measures to address the consequences of climate change and to improve community resilience, and
Molecular markers of the mTOR pathway activation in human tumors: A baseline analysis
Authors: F. Rojo, C. Iglesias, J. Tabernero, J. Jimenez, S. Rodriguez, J. Bellmunt, S. Ramon, J. Baselga
Journal: Journal of Clinical Oncology (2004)

9524 Background: Activation of the PI3-K/Akt/mTOR signal transduction pathway contributes to the development and progression of tumors by prevention of apoptosis and deregulation of the cell cycle. Dissecting the molecular events of this pathway may provide instrumental knowledge with implications for the development of PI3K/Akt/mTOR inhibitors and multi-signalling inhibitory strategies. Methods: We have analysed 121 paraffin-embedded human malignant tumors: 25 gastric, 25 colon, 23 breast, 19 prostate, 19 glioblastoma and 10 pancreas, with a complete immunohistochemistry profile including multiple phosphorylated (p) downstream proteins: pAkt, p4EBP1, pp70S6K and pS6K. The levels of expression were evaluated as percentage and intensity of stained cells (Hscore). Results: Globally, there was a significant correlation between the levels of pAkt, p4EBP1, pp70S6K and pS6K (Spearman's test, p<0.001). pAkt expression was consistently high in all tumor types whereas the downstream effectors presented higher expression in pancreatic, breast, prostatic and glioblastoma than in gastric and colon tumors (table). pAkt and downstream effectors were mainly detected in the infiltrating edge of the tumor. Interestingly, pAkt and downstream effectors where highly expressed in the poor-differentiated areas of the tumor whereas in the well-differentiated areas only pAkt was highly expressed. Conclusions: Detection of p molecules of the Akt/mTOR pathway is feasible in a variety of tumor types. As new agents targeting the PI3-K/Akt/mTOR pathway are entering in the clinic, our findings suggest that the level of in vivo activation of these downstream proteins could be used to establish correlations with response. Pharmacodynamic studies aimed to determine the degree of inhibition of this pathway in the tumor might be relevant to establish the optimal biological dose of these compounds. No significant financial relationships to disclose.
Steroids and immunosuppressive agents potentiate the cytotoxicity of the EGFR inhibitor erlotinib (E) in human skin keratinocytes whereas Vit K3 exerts a protective effect: Implications for the management of the skin rash
Authors: R. Perez-Soler, Y. Zou, T. Li, Y. Ling
Journal: Journal of Clinical Oncology (2007)

9124 Background: Skin toxicity secondary to EGFR inhibitors is treated symptomatically with topical and systemic combinations of steroids, antibiotics, antihistamines, and immunosuppressive agents with variable and often unsatisfactory results. Vit K3 prevents EGFR inhibition induced by E and cetuximab in human A431 tumor cells, probably through an effect on the phosphatase (Perez-Soler, ASCO 2006). We studied the cytotoxic effects of different agents used to treat the EGFR inhibitor-mediated skin rash on human immortalized skin keratinocytes exposed to the EGFR inhibitor E as well as the potential protective effect of Vit K3. Methods: The cytotoxicity of E in the presence of non cytotoxic concentrations of hydrocortisone, minocycline, cyclosporine-A, diphenhydramine, and Vit K3 was assessed by MTT assay in human HaCat cells, a cell line derived from human basal epidermal cells. Results: E cytotoxicity was enhanced by 2–5 fold by cyclosporine A and hydrocortisone, not affected by minocycline and diphenhydramine, and reduced by 5-fold by Vit K3. Vit K3 25–50 μM induced EGFR activation and prevented E's inhibitory effect on EGFR. Conclusions: Steroids and immunosuppressive agents may potentiate the cytotoxic effect of anti-EGFR agents in the skin, thus providing a possible explanation for the erratic and mixed therapeutic results often observed with the use of these agents. Vit K3 was the only agent capable of abrogating the cytotoxic effect of E in this clinically relevant model of normal human skin. A topical formulation of Vit K3 is undergoing preclinical evaluation. Supported by NCI CA 91784 and 113630 and a grant from Hana Biosciences. No significant financial relationships to disclose.
The importance of vascular invasion (vi) in women with breast cancer (bc) and between 1 and 3 positive nodes: Analysis of 272 patients
Authors: E. Fiorio, A. Auriemma, M. Mandarà, A. Caldara, A. Mercanti, M. Pavarana, R. Micciolo, G. Cetto, A. Molino
Journal: Journal of Clinical Oncology (2006)

20062 Background: Node positivity and the number of positive nodes are the most important prognostic factors in BC, and affected patients usually have a worse OS. The presence of VI in primary BC is a prognostic factor correlated with a high risk of metastatic spread whose importance led to it being included in the new classification proposed at the VII St. Gallen Consensus Conference. Methods: We studied VI in 272 pts with invasive BC and 1–3 positive nodes in order to evaluate its importance, and correlate it with the pathological, biological and clinical factors of T (1,2,3,4), diameter (0–10 mm, 11–20 mm, 21–50 mm, ≥50 mm), grading (G1, G2, G3), ER and PgR (positive vs negative), Ki-67 proliferative index (low 0–10%; intermediate 11–25%; high 26–100%), c-erbB2 (positive vs negative), age at diagnosis (≤49, 50–65, ≥65 years), type of diagnosis (asymptomatic vs symptomatic) and type of surgery (conservative vs mastectomy). The data were analysed using the chi-squared test. Results: Unlike those without VI, the tumours with node involvement (N+ 1–3) and VI correlated with poor prognostic factors: they were larger (pT2: 62.5% vs 37.5%; p = 0.001), had higher grades (G2: 50.7% vs 49.3%; G3: 72.2% vs 27.8%; p = 0.0004), and were more likely to be ER- (75.6% vs 24.4%; p = 0.004) and c-erbB2+ (50.6% vs 49.4%; p = 0.06). The patients were younger at diagnosis (63% vs 37% aged ≤49 years; p = 0.01) and more likely to have a symptomatic diagnosis (61% vs 39%; p = 0.001). No association with PgR was found. Conclusion: Our results show that primary BC with N+ 1–3 and VI+ correlates with poorer prognostic factors (diameter &gt;20 mm, G2/G3, ER-, c-erbB2+, younger age and symptomatic diagnosis). These correlations are in accordance with the new classification proposed at the VII St. Gallen Consensus Conference concerning high-risk pts with early BC. As these pts are at high risk of recurrence after good local surgery, it is important to offer them adequate adjuvant therapy as a reasonable treatment opinion on the basis of their endocrinal responsiveness. No significant financial relationships to disclose.
Ethnic differences in outcome from resected gastric adenocarcinoma in the United States: Improved survival in Asian Americans
Authors: A. Artinyan, P. A. Soriano, J. D. Ellenhorn, J. Kim
Journal: Journal of Clinical Oncology (2008)

4540 Background: Reported survival from gastric cancer has been consistently higher in Asian nations than in the United States (US). This survival advantage has been attributed to disparate surgical technique with resultant stage migration, and/or tumor biology. We assessed gastric cancer outcomes in the US to evaluate surgical technique as a potential source of disparity. Methods: Patients with resected, localized gastric adenocarcinoma diagnosed between 1988–2004 were identified from the US Surveillance, Epidemiology, and End Results (SEER) registry. Survival differences between Asians (n=4,446) and Whites (n=15,870) were compared using the Kaplan-Meier method. Multivariate Cox regression analysis was used to determine differences in survival by race, controlling for clinicopathologic factors. Results: Asians had a higher proportion of distal gastric tumors compared to White patients (92% vs. 68%, p<0.001) and a greater number of examined lymph nodes (14.9 vs. 10.9, p<0.001). Overall, Asians had significantly better survival than Whites [median survival (MS) 36 vs. 23 mo., p<0.001]. On stratified analysis, the survival difference between Asians and Whites was greatest for distal gastric cancers (MS 38 vs. 24 mo., respectively; p<0.001); the difference in outcome for proximal lesions was significant, albeit small (MS 22 vs. 21 mo., respectively; p = 0.02). A significant survival advantage for Asians was observed in each of stages I-III disease (all p<0.001) but not stage IV disease (p=0.14). On multivariate analysis, controlling individually for T-stage, total number of examined and positive lymph nodes, and other clinical factors, Asian race remained a significant predictor of improved survival (HR 0.83, 95% CI 0.79–0.87; p<0.001). Conclusion: Asian Americans with resected, localized gastric adenocarcinoma have significantly better survival compared to Whites independent of disease stage and number of harvested lymph nodes. In this US population, improved survival in Asian Americans appears unrelated to surgical technique. Given these findings, the survival disparity between Asian vs. Western populations may be the result of other factors including tumor biology. No significant financial relationships to disclose.
Tumor markers of prognosis.
Authors: R C Leonard
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.7.1102 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2045851 Tumor markers of prognosis. R C LeonardxR C LeonardSearch for articles by this author https://doi.org/10.1200/JCO.1991.9.7.1102 First Page PDF © 1991 by American Society of Clinical Oncology
Body mass index (BMI) and obesity as a predictor of clinical outcome in patients with Hodgkin's lymphoma treated with AVBD.
Authors: R. Patil, F. J. Hernandez-Ilizaliturri, A. Elefante, M. S. Czuczman
Journal: Journal of Clinical Oncology (2010)

8063 Background: BMI and obesity have been associated with altered pharmacokinetics (PK)/ pharmacodynamics (PKD) or poorer clinical outcome in several solid tumor malignancies. The impact of BMI or obesity in the outcome of HL patients and how it relates to other prognostic indicators is largely unknown. We retrospectively investigated the effects of BMI on complete response rate (CRR), progression free survival (PFS) and overall survival (OS) in HL patients treated with AVBD at RPCI. Methods: HL patients were identified using the tumor registry and pharmacy database at our institution. Only patients treated between 2000 and 2009 with complete demographic, clinical (including weight and height) and pharmacological data were included in the analysis. Patients were divided based on their BMI into normal (BMI ≤24.9) vs. overweight (BMI ≥25) or normal vs. obese (BMI≥30). Differences in CRR, PFS and OSS were compared based on BMI category. Results: A total of 137 patients (76% Nodular sclerosis subtype) were included in the study. Median age was 33 yrs (F/M: 57/80). According to BMI, 48 were normal, 43 overweight, and 46 obese. Males were more likely to have BMI ≥25 (P=0.028). No differences in stage, B-symptoms, or bulky disease were seen between subgroups. The CRR to AVBD was 80.3% and did not correlate with BMI. Relapsed/refractory disease was observed in 23.4% of the pts. The PFS was lower in patients with BMI ≥ 25 than in normal weight patients (P=0.016). There was no significant difference in the OS between the BMI subgroups. Additional 100 pts have been identified and the cohort will be expanded. Conclusions: Our preliminary data suggests that BMI may be a predictor of PFS in patients with HL receiving standard doses of ABVD. It is possible that the PK or PKD of ABVD may be altered by patient's BMI leading to sub-therapeutic doses in the tumor bed and relapsed/refractory disease. The incorporation of PKD modeling into the multidisciplinary treatment of malignancies may improve clinical outcomes, including for HL patients. No significant financial relationships to disclose.