tbuckley/cabot-search huggingface dataset:
Opportunities for better management of cancer in patients receiving chemotherapy at Aurora Health Care (AHC), a large integrated health system in eastern Wisconsin.
Authors: Paragkumar R. Amin, Jacob C. Frick, Marija Bjegovich-Weidman, Dorry Mitchell, Jessica Tougas
Journal: Journal of Clinical Oncology (2012)

110 Background: Cancer patients, especially those on chemotherapy, have complex medical histories. They experience a variety of medical problems from their cancer and treatments. This quality improvement study is designed to collect information about chemotherapy related emergency department (ED) visits to estimate ED utilization rates, recognize patterns and evaluate other confounders. The goal is to assess and reduce ED use at AHC through improved care management. Methods: The one-year data analysis includes any patient who received chemotherapy in an outpatient care setting and had a visit to the ED within 60 days of treatment. Chemotherapy was defined by designated CPT codes combined with a primary cancer diagnosis. Every ED visit was matched to all available chemotherapy visits for each patient, retaining the chemotherapy visit nearest in chronology prior to the ED visit. Data Exclusions: (a) Patients who received chemotherapy outside AHC, and then accessed an AHC ED; (b) Patients who received inpatient chemotherapy. Results: There were 28,738 chemotherapy encounters for 4,264 unique patients system-wide. AHC EDs saw 1,669 visits for 1,048 unique patients within 60 days of chemotherapy (24.6%). The top three cancer diagnoses were 21% thoracic; 21% GI; and 16% lymph/hematopoietic. Of the 1,669 ED visits, 35% occurred within seven days and 77% within 30 days of treatment. Almost half (45.6%) of the ED visits occurred during normal office hours. No significant variation was noted by day of week. An initial focus was on the tertiary center which represented 318 (20%) of the 1,669 ED visits. The most common diagnoses for an ED visit were pain (17%) and deconditioning (17%), followed by infection (11%) and respiratory symptoms (11%). Conclusions: This study documents the ED utilization by AHC chemotherapy patients. Unexpectedly, ED use occurred frequently during normal office hours. Most visits were represented by a limited number of cancer diagnoses and presenting complaints. Intervention is planned to reduce ED use after chemotherapy at AHC through improved patient education and by shifting these visits to less expensive venues when possible.
Angiogenic markers during bevacizumab-based treatment in metastatic renal cell carcinoma (RCC).
Authors: Tanya B. Dorff, Jeff Longmate, Susan G. Groshen, Walter Michael Stadler, Mayer N. Fishman, Ulka N. Vaishampayan, Jacek K. Pinski, Sumanta K. Pal, James Hu, David I. Quinn, Primo Lara
Journal: Journal of Clinical Oncology (2016)

522 Background: Targeting the vascular endothelial growth factor (VEGF) pathway delays progression in mRCC, however innate and acquired resistance limit success. CD105 (endoglin) is a TGFb family receptor which is upregulated after VEGF inhibition, possibly mediating resistance. We studied serum CD105 and TGFb at baseline and after treatment, and tissue levels of TGFbR1 &amp; 2 plus AVCRL, to discover biomarkers for treatment response as part of a randomized trial of bevacizumab (Bev) +/- the anti-endoglin antibody TRC105. Clinical data from the trial were presented at ASCO 2015 (Dorff et al, abstr 4542). Methods: Serum was collected at baseline and before cycles 2&amp;4. ELISA was performed using kits from Abcam. Changes from baseline were evaluated and compared overall and between arms using a general linear mixed effects model. Immunohistochemistry was performed on paraffin embedded tissue samples using antibodies from R&amp;D systems; tissue and baseline ELISA data were evaluated for association with PFS using Kaplan-Meier analysis and the logrank test. Results: 54 subjects (24 on Bev and 28 on Bev+TRC105) had at least one analyzed serum sample; 14 and 19 respectively had both baseline and cycle 2 samples. Mean CD105 was 82.8 (95%CI 64.6, 106.2) at baseline and 59.0 (95%CI 43.2, 80.7) at cycle 2; for 16 patients with cycle 4 data the mean was 39.8, significantly lower than baseline (p = 0.024), but not different between treatment arms. Cycle 2 TGFb levels were not different from baseline (p = 0.66) or between arms (p = 0.17). Baseline serum TGFb below the median ( &lt; 10.6) was associated with higher likelihood of PFS at 12 and 24 weeks; (0.78 vs 0.3 and 0.49 vs 0.19, respectively, p = 0.022); baseline CD105 was not (p = 0.83). Tissue was available for 29 subjects. No tissue markers (TGFbR1 &amp;2 or AVCRL) were associated with longer PFS except, in exploratory analysis, higher TGFbR2 staining in patients treated with TRC105 (p = 0.017). Conclusions: No pharmacodynamics markers for TRC105 therapy were identified. Lower baseline serum TGFb levels may be prognostic of PFS during Bev therapy, supporting the notion that this pathway contributes to resistance. Better PFS in TRC105-treated patients with higher tissue TGFbR2 expression warrants further study. Clinical trial information: NCT01727089.
Gallium Scan after the second and fourth chemotherapy cycle predicts clinical outcomes in aggressive non-Hodgkin’s lymphomas
Authors: J. Dang, B. Pro, J. Romaguera, L. Fayad
Journal: Journal of Clinical Oncology (2005)

6576 Background: Gallium scintigraphy has been used to assess response to treatment in patients receiving chemotherapy for non-Hodgkin’s lymphoma (NHL). Methods: From 1992 to 1996, 190 newly diagnosed patients with aggressive NHL were treated with frontline chemotherapy. All patients had positive baseline gallium scans (Ga-67). They received gallium scans after cycle 2 (n=139), cycle 4 (n=113), and cycle 6 (n=24). Results: A retrospective analyis shows that patients whose gallium scan remained positive after two courses of chemotherapy had a shorter median overall survival (OS) of 23 months in contrast to those whose gallium scan turned negative (median OS= 107 months; p=0.00434). Similarly, Ga-67 positivity predicted a shorter disease-free survival (DFS) (median DFS 6.6 months vs. 106 months; p=0.00279). After four courses, persistent Ga-67 positivity also correlated with a shorter median OS (Ga-67 positive 14.6 months vs. Ga-67 negative 102.5 months, p=0.00092) and a shorter median DFS (Ga-67 positive 6.2 months vs. Ga-67 negative 90 months, p=0.00006). The status of the last gallium scan performed (after course 2, 4, or 6) also showed these differences in median OS (Ga-67 positive 18 months vs. Ga-67 negative 111 months; p=.00017) and median DFS (Ga-67 positive 6 months vs. Ga-67 negative 107 months, p=00001). By Cox regression analysis, the results of a gallium scan after the second, fourth, and sixth course of chemotherapy was independent of the MD Anderson Tumor Score and the International Prognostic Index (IPI) in predicting poor outcomes in aggressive NHL. Conclusion: A positive gallium scan at mid-cycle of chemotherapy treatment identifies a group of patients with a strong likelihood for early disease relapse and poor overall survival. This test can identify patients whose disease has intrinsic resistance to frontline treatment and may benefit from a change to more aggressive or novel therapies. No significant financial relationships to disclose.
Ambulatory Blood Pressure Monitoring in Multiple Myeloma Patients Treated with VAD Protocol.
Authors: Angelika Pyszel, Monika Biedron, Rafal Poreba, Tomasz Wrobel, Grzegorz Mazur, Andrzej Szuba, Wojciech Kucharski, Maciej Podgorski, Kazimierz Kuliczkowski, Ryszard Andrzejak
Journal: Blood (2005)
The pattern of chemokine receptors expressed by tumor cells predicts the site of metastatic relapse in patients with axillary node positive breast cancer
Authors: F. Andre, N. Cabioglu, H. Assi, J. C. Sabourin, S. Delaloge, A. Sahin, J. C. Soria, M. Cristofanilli
Journal: Journal of Clinical Oncology (2005)

9501 Background: Some types of tumors present an organ-specific pattern of metastases. Although studies performed in animal models present strong evidence for a role of chemokine receptors in this phenomenon, there is no clinical study that specifically correlates the pattern of chemokine receptor expression with the site of metastases. In the present study, we have looked at the correlation between the chemokine receptors expressed by primary tumor cells and the site of metastatic relapse in patients with T1–3N+M0 breast cancer. Methods: CX3CR1, CXCR4, CCR6 and CCR7 expressions were evaluated by immunohistochemistry on primary tumors obtained from 142 patients with T1–3N+M0 breast cancer. These patients were included in a prospective trial between 1972 and 1979. None of the patients received adjuvant chemotherapy. Results: CX3CR1, CXCR4, CCR6, CCR7 expressions were found in 59 (43%), 42 (31%), 45 (34%) and 93 (66%) patients respectively. The expression of chemokine receptors did not correlate with any clinical characteristics, except a higher rate of very young patients (<35 year) in the CXCR4+ subgroup (14% vs 4%, p=0.04). After a median follow-up of 25 years, 75 patients (53%) have presented a metastatic relapse. The expression of chemokine receptors did not predict the metastasis-free survival, nor the overall survival. On the other hand, the pattern of chemokine receptor expression predicted the site of metastatic relapse. CX3CR1 staining predicted the occurence of brain metastases (14% vs 1%, p=0.004). CXCR4 staining predicted the occurrence of liver metastases (38% vs 14%, p=0.001) and lung metastases (28% vs 16%, p=0.05). CCR7 predicted the occurrence of skin metastases (11% vs 0%, p=0.03) and CCR6 predicted the occurrence of malignant pleural effusion (24% vs 10%, p=0.04). Conclusion: The study shows that the pattern of chemokine receptors expressed by tumor cells predicts the site of metastatic relapse in patients with T1–3N+M0 breast cancer. This study, in line with data obtained in animal models, may suggest in a clinical model that the chemokine receptor family could be the biological support of the << seed and soil >> theory. No significant financial relationships to disclose.
The REQUITE Project: Validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality of life in cancer survivors.
Authors: Riccardo Valdagni, Anusha Appanvel, Akke Botma, Adam Webb, David Azria, Tom Burr, Jenny Chang-Claude, Susan Davidson, Rebecca M. Elliot, Sara Gutierrez-Enríquez, Kerstie Johnson, Philippe Lambin, Tiziana Rancati, Barry Rosenstein, Dirk De Ruysscher, Chris Talbot, Hubert Thierens, Ana Vega, Frederik Wenz, Catharine West
Journal: Journal of Clinical Oncology (2016)

85 Background: To present the REQUITE project (Validating Predictive Models and Biomarkers of Radiotherapy (RT) toxicity to reduce side-effects and improve quality-of-life in cancer survivors) and first results on the enrollment and acute toxicity (tox) of prostate cancer (Pca) patients (pts). Methods: The European Union funded REQUITE project involves centers in Europe and the USA. The main objectives of the project are to: carry out a multicentre, cohort study collecting blood samples, standardized epidemiology and treatment data, longitudinal side-effect and quality of life data (before and after treatment, years 1 and 2); produce a centralized database and biobank of DNA for 5,300 patients; validate clinical/dosimetric predictors of RT tox and incorporate biomarker data. The project focuses on cancers of the breast, lung and prostate. For PCa the primary endpoint is rectal bleeding at 2 years. Results: A centralized database was established for data collection, including storage of complete dosimetric information in DICOM RT format. Enrollment started in April 2014 and will end in August 2018. In the first 16 months 909 PCa pts were enrolled: 10% low risk, 33% intermediate and 57% high risk. 63% pts received exclusive RT (neoadjuvant hormone therapy in 62%) and 37% post-prostatectomy; 97% external beam RT (prescription doses: 60-85Gy, 2Gy equivalent, alpha/beta=3Gy), while 3% received brachytherapy. Data on acute tox at RT end (measured by CTCAE 4.03) are available for 496 pts. 79 G2-G3 GI tox were reported, with proctitis and diarrhea having the higher prevalence (45 and 30 events respectively). 74 pts exhibited G2-G3 GU tox, with 34 pts reporting multiple symptoms and frequency and urgency having the higher prevalence (43 and 30 events respectively, 25 pts both). Conclusions: REQUITE is proving the feasibility of a prospective standardized collection of epidemiological/clinical/dosimetric/toxicity data coupled to centralized storing of biological material. Meanwhile a large database is being created, which will be of value also for future research in the field of radioinduced side effects. REQUITE is funded by a European Union FP7 grant (601826).
Diagnostic Criteria for Hematopoietic Stem Cell Transplantation-Associated Microangiopathy (TAM): Results of a Consensus Process by an International Working Group.
Authors: Tapani Ruutu, G. Barosi, R. J. Benjamin, R. E. Clark, J. N. George, A. Gratwohl, E. Holler, M. Iacobelli, K. Kentouche, B. Lämmle, J. L. Moake, P. Richardson, G. Socié, Z. Zeigler, D. Niederwieser, T. Barbui
Journal: Blood (2005)
Level of arterial ligation in sigmoid colon and rectal cancer surgery.
Authors: Koji Yasuda
Journal: Journal of Clinical Oncology (2013)

358 Background: Curative resection of sigmoid colon and rectal cancer includes "high tie" of the inferior mesenteric artery (IMA). However, IMA ligation compromises blood flow to the anastomosis, which may increase the leakage rate and it is unclear whether this confers a survival advantage. Accodingly, IMA may be ligated at a point just below the origin of the left colic artery (LCA) ("low tie"), with lymph node (LN) dissection around IMA. No study has investigated the detailed prognostic results between "high tie" and "low tie, with LN dissection around IMA". The aim of this study was to assess the utility of "low tie, with LN dissection around IMA" on survival in patients with sigmoid colon or rectal cancer. Methods: A total of 268 sigmoid colon or rectal cancer patients who underwent curative operation from 1998 to 2007 were enrolled in this study. The patient's medical records were reviewed to obtain information about operative method, the number of LN dissection, the number of metastatic LN, the site of metastatic LN, recurrence pattern, complication. Overall survival and relapse-free survival were calculated using the Kaplan-Meier method, with differences assessed using logrank test. Results: We divided all patients into three groups according to the ligation level of IMA. 41 patients were ligated at the level of IMA root (Group A: "high tie"). 164 patients were ligated just caudally to the origin of the LCA ("low tie"), with LN dissection around IMA. 63 patients were ligated at the level of superior rectal artery just caudally to the sigmoid artery. The significant difference was not observed in a complication rate in three groups. The significant difference was not observed in the survival rate and the relapse-free survival rate according to each stage in group A and group B either. Also, the significant difference was not observed in the survival rate and the relapse-free survival rate in node-positive cases in group A and group B. Conclusions: "Low tie,with lymph node dissection aroud IMA" is anatomically less invasive and is not inferior to the ligation in the IMA root ("hige tie") in prognostic point.
Population-based identification and characterization study of patients at-risk for hereditary breast cancer in in Southern Brazil: Preliminary results
Authors: P. Ashton-Prolla, E. I. Palmero, L. Schuler-Faccini, R. Giugliani, L. Kalakun, S. L. Cossio, I. P. Ewald, M. Caleffi
Journal: Journal of Clinical Oncology (2005)

9664 Background: Hereditary breast cancer (HBC) accounts for only 5–10% of all breast cancer cases (BC) in most populations. In Rio Grande do Sul (RS), BC is the first cause of all deaths in young women (30–49 years). This study will examine the contribution of genetic risk factors to this observation. Methods: A target sample of all 10,000 women residing in a specific area of Porto Alegre will be characterized for HBC risk factors. Results: Currently, 2500 of these women were recruited and submitted to an HBC risk-questionnaire to assess presence of: a) 1st degree relative with BC and/or OC; b) male relative with BC; c) relative with BC under age 50; d) 2 or more relatives with BC and/or OC; e) relative with bilateral BC; f) relative with both breast and ovarian cancer. Sixteen percent of these women reported at least one of these risk factors and were called for a genetic evaluation. Of these, 118 families were evaluated so far. Regarding specific risk factors, 43% reported at least one 1st degree relative with BC and/or OC; 50% at least one relative with BC before age 50, and 6% at least one relative with bilateral BC. The average lifetime risk of breast cancer for these patients by the Gail and Claus models was 11,34% and 13,73% respectively. The estimated average mutation probability in these genes was 11,77% and 28/118 families (23%) had a >20% chance of carrying a mutation. When criteria for other breast cancer predisposition syndromes was analysed, we found that 6/118 (5%) families fulfilled criteria for the Li-Fraumeni-like syndrome. Finally we compared the lifetime risk estimates for BC obrtained during the initial visit with that obtained after confirmation of family history with medical records. Risk was stratified in three categories: low (< 10%), medium (10–30%), and high (> 30%). In an initial evaluation, risk was as follows: low 63,25%, medium 26,5% and high in 10,25%; after confirmation of family history, these figures were 78,55%, 10,53% and 10,53%, respectively. There was concordance in initial and final risk estimates in 87% of patients. Conclusions: Results of this study will influence the delineation of specific BC prevention strategies for the local community. No significant financial relationships to disclose.
Liver metastases as predictors of outcome in renal cell carcinoma (RCC) patients (pts) treated with first-line sunitinib (SU) and sorafenib (SO).
Authors: Paolo Grassi, Elena Verzoni, Luca Porcu, Isabella Testa, Roberto Iacovelli, Enrico Garanzini, Roberto Salvioni, Filippo G. De Braud, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2014)

536 Background: The predictive role of metastatic sites in RCC pts treated with tyrosine kinase inhibitors (TKIs) is unclear. Aim of this study was to investigate whether first line SU and SO was associated to metastatic sites in terms of progression-free survival (PFS) and overall survival (OS). Methods: A retrospective cohort of consecutive metastatic RCC (mRCC) pts treated with TKIs at Istituto Nazionale Tumori of Milan was analyzed. All pts received at least one targeted therapy including: SO, SU, bevacizumab plus interferon-alfa, pazopanib or temsirolimus. The product limit method was used to estimate survival functions and Cox regression to estimate hazard ratios (HRs) and to test statistical interaction between sub-groups identified by different metastatic sites. Results: 358 mRCC pts receiving first line TKIs between January 2005 and October 2012 were evaluated. Overall 206 pts (58%) received SO while 103 pts (29%) SU. Median duration of treatment for SU and SO groups was 16 (95%CI 12.0-20.1) and 9 months (mo) respectively (95%CI 7.0-12.0). After a median follow-up of 56.1 mo (range: 1.0-93.2) median OS for SO group was 19.9 mo (95%CI 16.0-25.1) while OS for SU group was not yet defined. Noteworthy 142 pts (69%) treated with SO received SU at disease progression (PD) while 36 pts (35%) received SO at SU failure. A statistically significant interaction between first line treatment and metastatic sites was found for the liver site in terms of PFS and OS (PFS p=0.034; OS p=0.004). SU was associated with a 18% [95%CI (-37%)- 123%] higher risk of PD as compared to SO in pts with liver mets while pts without liver mets showed a 46% [95%CI (-61%)-(-24%)] decreased risk of PD as compared to SO. SU was associated with a 40% [95%CI (-32%)-187%] higher risk of death as compared to SO in pts with liver mets while pts without liver mets showed a 62% [95%CI (-76%)-(-40%)] decreased risk of death as compared to SO. The predictive role of liver mets was confirmed introducing the Motzer score (PFS p=0.084; OS p=0.009). Conclusions: mRCC pts with liver mets treated with first line SO showed a better outcome as compared to SU while pts without liver mets treated with first line SO showed a worse outcome as compared to SU.
Loss of the mismatch repair protein MSH6 in glioblastomas recurrent after temozolomide
Authors: Daniel Cahill, Linsey Reavie, Candice Romany, David Louis
Journal: Cancer Research (2007)

1974  Glioblastomas are treated by surgical resection followed with radiotherapy (XRT) and the alkylating chemotherapeutic agent temozolomide (TMZ). Recently, inactivating mutations in the mismatch repair (MMR) gene MSH6 were identified in two glioblastomas recurrent post-TMZ. Since MMR pathway inactivation is a known mediator of alkylator resistance in vitro, these findings suggested MSH6 inactivation was causally linked to these two recurrences. However, the extent of involvement of MSH6 in glioblastoma is unknown. We sought to determine the overall frequency and clinical relevance of MSH6 alterations in glioblastomas. The MSH6 gene was sequenced in pre-treatment and recurrent glioblastomas. MSH6 mutation was not observed in any pre-treatment glioblastoma, while a significant subset of recurrent cases had somatic mutations. MSH6 and MGMT immunohistochemistry was systematically scored in a second panel of clinically well-characterized glioblastomas. MSH6 protein expression was detected in all pre-treatment cases examined but, notably, expression was lost in significant subset of recurrences from matched post-XRT+TMZ cases. Loss of MSH6 was not associated with MGMT status. We conclude that loss of MSH6 occurs in post-XRT+TMZ glioblastoma recurrences, mirroring the MMR pathway inactivation observed during in vitro emergence of alkylator resistance. MSH6 deficiency may therefore contribute to the progression of recurrent glioblastomas during TMZ treatment.