tbuckley/cabot-search huggingface dataset:
The role of cytoreductive nephrectomy in elderly patients with metastatic renal cell carcinoma in an era of targeted therapy.
Authors: Dipesh Uprety, Amir Bista, Yazhini Vallatharasu, David E. Marinier
Journal: Journal of Clinical Oncology (2017)

499 Background: The role of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) has not been clearly understood after the approval of new targeted therapies, particularly in an elderly population. We therefore conducted this study to evaluate survival difference (CN vs. no CN) among elderly patients with mRCC in targeted era. To limit the heterogeneity in use of targeted agents we define targeted era as February 2006 to December 2011, as sunitinib got FDA approval for use in RCC in January 2006. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER-18) database to identify elderly (≥ 65 years) patients with mRCC, as first primary malignancy, who were diagnosed between February 2006 and 2011. Kaplan-Meier curve and log rank test were used to compare overall survival (OS) and cancer-specific survival (CSS) between patients receiving CN and not receiving CN. Cox proportional hazard model was used for multivariate analysis. Results: Out of 3,365 patients, 1088 (32.3%) received CN. There was a significant survival benefit for those who received CN vs. those who did not (Median OS: 22 months vs. 5 months, p&lt; 0.001; Median CSS: 25 months vs. 6 months, p&lt;0.001). After adjusting for age, sex, race, T-stage, N-stage, histology types, and year of diagnosis, patient receiving CN had significantly better 3-year OS and 3-year CSS compared to patients not receiving CN with HR of 0.37, 95% CI of 0.34 to 0.41; p&lt;0.001 and HR of 0.37, 95% CI of 0.34 to 0.42, p &lt;0.001 respectively. Among patients who received CN, younger age at diagnosis, other races (other than Caucasian and African American), and N0 stage were found to be independent factors predicting better survival. Conclusions: SEER database lacks individual patient’s information. One may argue that the non-surgical group may have larger proportion of patients with poor performance status. Despite this limitation, our study showed that CN has significant survival benefit and should be a serious consideration in elderly patients if they have good performance status.
Defects within the Myeloid Derived Supressor Cells (MDSCS) Compartment may Facilitate Aberrant Immune Responses in Systemic Lupus Erythematosus (SLE)
Authors: K Vlachou, A Fanouriakis, M Glymenaki, M Ioannou, V Mastorodemos, P Verginis, D Boumpas
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> There is a currently unmet need to define the mechanisms involved in the homeostatic control of the immune response in autoimmune diseases. MDSCs (characterised in mice as CD11b+Gr1+ and in humans as CD14-HLA-DR<sub>low</sub>CD15+CD33+) represent a heterogeneous population of myeloid precursors of macrophages, dendritic cells and granulocytes with a distinct regulatory role in suppressing T-cell responses. We sought to delineate the role of these cells both in murine and human lupus. <h3>Materials and methods</h3> We used the lupus prone (NZB x NZW) F1 female mice [3 months old, pre-SLE (n=6) and 6-8 months old, SLE mice (n=6)]. C57BL/6 (B6) female mice [3 mo (n=2) or 6 mo (n=6)] were used as controls. B6 mice immunised with myelin peptide in adjuvant (Experimental Autoimmune Encephalomyelitis) were used as a disease control. Cells were isolated from the bone marrow and spleen of the indicated groups and were stained with fluorescent-conjugated antibodies. Cells were stained for the aforementioned markers and for 7AAD. Analysis was performed in humans as well, using samples from SLE patients (n=18), healthy controls (n=20) and multiple sclerosis (MS) patients (n=31) as disease control. The phenotype and enumeration of cell populations were performed by flow cytometry. <h3>Results</h3> Compared to healthy B6 mice, splenic MDSCs of pre-SLE F1 animals were decreased both in frequency and absolute numbers (*p=0.012), indicating a defect in the MDSC compartment in F1 lupus mice. MDSCs were significantly expanded in the spleen of F1 diseased animals compared to healthy F1 controls (*p=0.017) albeit at significantly lower levels compared to mice with EAE (***p&lt;0.0001). In humans, subjects with active lupus (n=8) exhibited higher numbers of MDSCs in the peripheral blood compared to inactive patients (n=10) and healthy controls, but at lower levels compared to patients with active MS (n=14). Ongoing experiments using in vivo transfer of murine MDSCs address their potential to halt renal disease progression and the cells/molecules involved. <h3>Conclusions</h3> Together these data suggest defective MDSC accumulation and/or expansion in the periphery in lupus which may contribute to the immune deregulation observed in this disease. Identification of the cell subsets and the molecules involved may provide additional therapeutic targets for the restoration of immune tolerance in lupus.
Effect of five years of imatinib on cure for patients with advanced GIST: Updated survival results from the prospective randomized phase III BFR14 trial.
Authors: François Bertucci, Isabelle Laure Ray-Coquard, Binh Bui Nguyen, Antoine Adenis, Maria Rios, Florence Duffaud, Didier Cupissol, Christine Chevreau, Emmanuelle Bompas, Julien Domont, Sylvie Chabaud, David Pérol, Jean-Yves Blay, Axel Le Cesne
Journal: Journal of Clinical Oncology (2012)

10095 Background: We previously demonstrated that interruption of imatinib (IM) after 1, 3, and 5 yrs in responding patients (pts) with advanced GIST is associated with rapid relapse but reintroduction of IM allowed tumor control in almost all pts. Here, we examined the outcome of patients randomized in the interruption arm (I arm), and notably the characteristics of those not yet progressing. Methods: This prospective multicenter BFR14 study was initiated in June 2002 and closed for inclusion in July 2009. Seventy-one non-progressing patients were randomized in the I arm after 1 (N=32), 3 (N=25) and 5 years (N=14) of IM 400 mg/day. IM (same dose) was reintroduced in case of progressive disease (PD). Results: The median follow-up (FU) from randomization was 74, 48 and 22 months for pts randomized at 1, 3 and 5 yrs of IM treatment respectively. Updated survival data (January 2012) are summarized in the table. Out of the 3 pts not progressing in the I arm at 1 yr, 1 pt had refused to stop IM and 1 pt had a localized GIST with small residual disease at inclusion. Out of the 3 pts not progressing in the I arm at 3 yrs, 1 pt had refused to stop IM and 2 pts were included after complete resection of both primary tumor and metastases with a small residual disease. The FU of pts randomized at 5 yrs was short but out of the 5 non progressive pts, 2 are considered in PD on functional imaging (January 2012), 2 had a locally advanced GIST subsequently operated during IM and before randomization, and 1 had no target lesion at inclusion (resection of synchronous metastases). Conclusions: All but one pts with residual masses under IM and randomized in the I arm have relapsed. Six out of 7 patients not yet progressing in the I arm had reached complete remission following surgery at inclusion or before randomization (initial resection/debulking of metastases). [Table: see text]
The association of epidermal growth factor receptor (<i>EGFR</i>) polymorphisms and clinicopathological factors with skin rash on gefitinib use
Authors: C. Huang, C. Yang, K. Yeh, F. Hu, Z. Lin, J. Wan, L. Tseng, C. Yu, A. Cheng
Journal: Journal of Clinical Oncology (2007)

18118 Background: Skin rash is the most common toxicity of EGFR-targeted therapy. Skin rash of EGFR inhibitor is associated with longer survival or tumor response. However, the clinical and genetic factors associated with this skin rash are not well understood. Methods: Fifty-two non-small-cell lung cancer patients enrolled in a prospective clinical trial of first-line gefitinib treatment were genotyped for EGFR intron 1 CA repeat polymorphism (CAn) and single nucleotide polymorphisms at promoters G-216T, C-191A, and R521K. Grade 2 to 3 skin rash within 4 weeks of treatment (early G2/3 rash) was correlated with the genotype and clinicopathological features of the patients by multivariate logistic regression. Results: Seventeen patients (32.7%) developed early G2/3 rash. In multivariate logistic regression analysis, only the CAn genotype was associated with early G2/3 rash and the effect was modified by patient age. Early G2/3 rash developed in 21% of patients with homozygous long allele (19 to 22 repeats, L) genotype (4/19), 31% of heterozygous short allele (15 to 18 repeats, S) / L genotype (8/26), and 71% of S/S genotype (5/7), respectively. The median ages of patients with early G2/3 rash and patients without early G2/3 rash were 57 years (range: 39–77) and 69 years (range: 43–86), respectively. The estimated logarithm of odds ratio (ln OR) for early G2/3 rash, as compared to S/S genotype, for S/L genotype was -0.038 multiplied by patient age (P = 0.011); and the ln OR for L/L genotype was -0.050 multiplied by patient age (P = 0.004). Fifty patients were evaluable for response. In logistic regression analysis, early G2/3 rash correlated with tumor response (P = 0.027). However, the CAn genotype was not significantly correlated with tumor response (P = 0.43). Conclusions: Homozygous short allele of EGFR CAn is more likely to develop skin rashes on gefitinib treatment. Genotyping of EGFR CAn appears to be a useful predictive marker for development of skin rashes on gefitinib use. [Table: see text]
Isolation of circulating tumor cells using a novel EMT-based capture method.
Authors: Rhonda Lynn Bitting, Rengasamy Boominathan, Chandra Rao, Elizabeth Embree, Daniel J. George, Mark C. Connelly, Gabor Kemeny, Mariano Garcia-Blanco, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2012)

10533 Background: Circulating tumor cells (CTCs) have potential prognostic, predictive and surrogate implications in oncology. In patients with metastatic castration-resistant prostate cancer (CRPC) and breast cancer (BC), we have shown that CTCs isolated using epithelial cell adhesion molecule (EpCAM) ferromagnetic capture express mesenchymal markers, including N- and O-cadherin, suggesting phenotypic plasticity and the presence of epithelial-mesenchymal transitions (EMT). Therefore, we postulate that during metastasis, tumor cells exist as a spectrum of epithelial to mesenchymal phenotypes and may not be captured with existing EpCAM-based CTC technology. The goal of this study is to identify CTCs in CRPC and BC patients using a novel mesenchymal-based capture method. Methods: In patients with advanced CRPC and BC, two EDTA and one CellSave tube of blood are collected. Using the CellSearch system (Veridex, USA), CTCs are captured with either anti-N-cadherin (N-cad) or anti-O-cadherin (O-cad) ferrofluid and detected cells (events) are defined as beta-catenin and DAPI positive, CD45 negative intact cells. We evaluated the performance of these EMT-based ferrofluids in healthy volunteers, control cells, and in a pilot study of patients with CRPC, and compared enumeration of cells using novel vs. standard EpCAM-based capture methods. Results: In healthy volunteers, rare events were detected using the novel capture methods. In CRPC patients, O-cad capture detected more events in 3 of 5 subjects than EpCAM-based capture, and the majority of captured cells were cytokeratin negative. See table below. Conclusions: These preliminary results suggest that a novel CTC phenotype exists in CRPC based on EMT properties, particularly overexpression of O-cadherin. Further characterization of these cells from patients with advanced PC, BC, and other solid tumors will provide insight into EMT and metastasis biology. [Table: see text]
Development of follow up recommendations for completely resected gastroenteropancreatic neuroendocrine tumours (GEP-NETS): Practice Survey of Commonwealth Neuroendocrine Tumour Collaboration (CommNETS) in conjunction with North American Neuroendocrine Tumour Society (NANETS).
Authors: Simron Singh, David Lok Hang Chan, Lesley Moody, Sarah Carsley, David C. Metz, Jonathan R. Strosberg, Eva Segelov
Journal: Journal of Clinical Oncology (2017)

224 Background: Published guidelines for follow up after R0 resection of GEP-NETS are complex and emphasize closer surveillance in the first 3 years, as per other GI malignancies. NETS have a different pattern and timescale of recurrence, hence require more practical and tailored follow up. Aim: To examine real world follow up practices compared to published guidelines for follow up of patients with GEP-NETs. Methods: A detailed electronic cross-sectional survey was developed and distributed to members of the CommNETS Collaboration (Australia, NZ, Canada) and NANETs. Questions addressed demographics, knowledge and use of current guidelines and follow up practices relating to various prognostic factors. Descriptive statistics were obtained for all responses, stratified by country, patient volume and specialty. Results: There were 163 respondents: Australia: 59; NZ: 25; Canada: 46; US: 33. 50% were Medical Oncologists; 23% Surgeons; 13% Nuclear Medicine; 14% other. 38% of respondents were “very familiar” with NCCN NET guidelines; 33% with ENETS, 17% with ESMO, however only 15%, 27% and 10% found them “very useful”, respectively. 63% reported not using guidelines at their institution. Ranking of prognostic factors (top 5, decreasing order): grade, Ki67/mitotic count, T stage, N stage and site of origin. Follow up in 1st 2 years was most commonly every 6 months (62%); in years 3-5 every 12 months (59%) and &gt; 5 years, 12 months (41%). Follow up patterns did not differ significantly by patient volume. The commonest investigations were CT scans (66%) and CgA (86%). When poor prognostic factors were introduced, increased visits and tests were recommended. Conclusions: This large international survey yields detailed information, highlighting variation in current follow up practices not well addressed by current guidelines. This forms a strong basis for the upcoming CommNETS/NANETS consensus meeting, which aims to produce user friendly, practical guidelines tailored to the expected pattern of recurrence in patients with NETs.
Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma.
Authors: Thomas Powles, Peter H. O'Donnell, Christophe Massard, Hendrik-Tobias Arkenau, Terence W. Friedlander, Chris Hoimes, Jae-Lyun Lee, Michael Ong, Srikala S. Sridhar, Nicholas J. Vogelzang, Mayer N. Fishman, Jingsong Zhang, Sandy Srinivas, Jigar Parikh, Joyce Antal, Xiaoping Jin, Ashok Kumar Gupta, Noah M. Hahn
Journal: Journal of Clinical Oncology (2017)

286 Background: Anti-PD-L1 immunotherapy has shown promising clinical activity in urothelial carcinoma (UC). We report on a planned update of efficacy and follow-up in patients (pts) receiving durvalumab for the treatment of locally advanced or metastatic UC. Methods: Pts received durvalumab 10 mg/kg Q2W up to 12 months (mo), unacceptable toxicity or confirmed progressive disease. Tumor PD-L1 expression was assessed using the validated Ventana SP263 assay (PD-L1 high = TC ≥ 25% or IC ≥ 25%). Primary endpoints were confirmed ORR by RECIST v1.1 with blinded independent central review (BICR) and safety. Duration of response (DoR) and overall survival (OS) were key secondary endpoints. Results: As of July 24, 2016 (data cutoff [DCO]), the primary efficacy population included 103 pts who were followed for at least 13 weeks (median duration of follow up 7.3 mo); 37% had ≥ 2 prior regimens; 97% had prior platinum treatment; 95% had visceral metastases; and 49% had liver metastases at baseline. As of the DCO, 21 pts (20.4%) had a confirmed response per BICR (including 5 pts [4.9%] with a complete response) and an additional 3 pts had an unconfirmed response. Responses were seen in both PD-L1 high and PD-L1 low/negative subgroups (Table). Responses occurred early (median time to response 1.4 mo) and were durable. Median DoR has not been reached. Of the 21 confirmed responders, 18 pts had an ongoing response, 16 pts had DoR ≥ 6 mo and 7 pts had DoR ≥ 9 mo. Treatment-related Grade 3/4 AE rates were low (5.2%; as treated population, n = 191); Grade 3/4 immune-mediated AEs (imAEs) occurred in 3 pts, and 1 pt discontinued treatment due to an imAE of acute kidney injury. Conclusions: Durvalumab administered at 10 mg/kg Q2W showed clinical activity and an excellent safety profile in pts with locally advanced or metastatic UC. Clinical trial information: NCT01693562. [Table: see text]
Impact of antiangiogenic treatments on exhausted PD-1<sup>+</sup> T lymphocytes in colorectal cancer.
Authors: Simon Pernot, Magali Terme, Elie Marcheteau, Thibault Voron, Orianne Colussi, Eric Tartour, Julien Taïeb
Journal: Journal of Clinical Oncology (2013)

e22121 Background: Tumors develop immunosuppressive mechanisms to escape the immune system. Among these mechanisms, T lymphocytes can express inhibitory molecules such as Program Death-1 (PD-1) protein which impair their activation and their effector functions. Multi-target anti-angiogenic tyrosine kinase inhibitors (TKI) that are routinely used as first- or second-line treatment of cancer patients, have been shown to modulate immunosuppressive mechanisms especially regulatory T cells. However, the role of specific VEGF/VEGFR blockade on PD-1 expression by T lymphocytes has not been studied. Methods: PD-1 expression on T lymphocytes has been analyzed by flow cytometry in a mouse model of colorectal cancer (CT26) treated by anti-angiogenic molecules targeting the VEGF-A/VEGFR axis and in the peripheral blood of metastatic colorectal cancer patients. Results: Sunitinib that directly targets VEGFR, PDGFR, c-kit, but also anti-VEGF-A antibody (the mouse orthologue of bevacizumab) decrease PD-1 expression on T lymphocytes infiltrating the tumors. Interestingly, anti-angiogenic treatments decrease the percentage of lymphocytes expressing not only PD-1 but also Tim-3 suggesting that the most exhausted T cells are targeted by anti-angiogenic treatments. Administration of masitinib, a TKI acting on KIT, PDGFR and FAK but not on the VEGF/VEGF-R pathway, was not able to modulate PD-1 expression on T cells. Finally, anti-VEGF-A treatment (bevacizumab) associated with chemotherapy decreases the proportion of PD-1 + CD4 + T cells in the peripheral blood of metastatic colorectal cancer patients. Conclusions: These results show that anti-angiogenic treatments targeting VEGFA/VEGFR decrease PD-1-expressing T lymphocytes in colorectal cancer. These results suggest that VEGF-A could be involved in PD-1 expression and maybe in the induction of T lymphocyte exhaustion in colorectal cancer. We and others have shown that anti-angiogenic molecules could modulate other immunosuppressive populations such as regulatory T cells and myeloid suppressive cells, anti-angiogenic molecules might be efficiently associated with immunotherapeutic strategies in colorectal cancer.
Patterns of follow-up in oncologic care across Canada.
Authors: Allison Y. Ye, Winson Y. Cheung, Karen Goddard, Robert Anton Olson
Journal: Journal of Clinical Oncology (2013)

e20589 Background: With continual advancements in cancer care, improved outcomes and increasing survivor populations, cancer survivorship has become an important area of research. Methods: A 35-question electronic survey was sent to physician members of the Canadian Association of Radiation Oncologists. Based on their scope of practice, respondents were presented with brief clinical scenarios pertaining to various survivor populations. A subsequent series of questions were posed to determine routine follow-up practices. Results: In total, 111 radiation oncologists (RO) responded (44% response rate); 29% were female, 43% were in practice less than 10 years, and most regions of Canada were well represented. Most worked in centers staffed by more than 10 oncologists (69%), and saw more than 200 new patient consults per year (78%). 10% would not follow patients routinely, mainly in cases involving breast or prostate survivors. 73% of such patients (73%) would be followed by their primary care providers (PCP) whereas ROs would follow their CNS, GI, HN and GYNE patients. Lack of resources (55%) and a belief that follow-up by PCPs is equally effective (55%) were the top two reasons for not following patients. Treatment toxicity (92%) and the possibility of salvage or palliative treatment (86%) were the two most common reasons for routine follow-up. The majority (55%) of ROs follow patients for &lt; 5 years, with 36% following for 5-10 years, and a minority (9%) following for longer than 10 years. 54% would not change the frequency of their follow-up, but 39% would decrease and only 7% would make no change. Workload and lack of resources were major barriers to follow-up, but in addition, many felt that follow-up by FPs or Advanced Practice Nurses could be equally effective. Some felt this would require additional training and more guidelines to make this effective. Conclusions: The majority of ROs follow their patients, especially when salvage treatment is possible. A significant portion would decrease their follow-up in frequency because of workload burden, resource limitations and a belief that there can or should be increased involvement from FPs and other allied health care providers.
Definitive surgical salvage treatment for recurrent colon cancer.
Authors: Christina Edwards Bailey, Chung-Yuan Hu, Y. Nancy You, Amanda Cuddy, Joe Spencer Liles, George J. Chang
Journal: Journal of Clinical Oncology (2015)

e14704 Background: Approximately 10 to 50% of patients who undergo curative resection of colon cancer will develop recurrent disease. Post-treatment surveillance may improve the early detection of recurrent disease, but little is known about subsequent treatment and treatment eligibility for recurrent disease. The primary aim of this study is to characterize patients who underwent surgical salvage for recurrent colon cancer within an elderly population based dataset. Methods: A retrospective cohort study of patients > 66 years old with stage I-III colon cancer that underwent surgical resection in the Surveillance, Epidemiology, and End Results-Medicare linked database (1992-2008) was performed. We reviewed all claims during the surveillance period for systemic chemotherapy for presumed recurrence. The surveillance period began 3 months after surgical resection +/- adjuvant chemotherapy. Definitive surgical salvage treatment (DT) was defined as liver or lung resection during the surveillance period. Patient, tumor, and treatment characteristics were analyzed using multivariate logistic regression. Results: Of 65,112 patients who underwent colon cancer resection, 7,787 received systemic chemotherapy during the surveillance period. Within this group, 557 (7.15%) patients underwent at least 1 DT which consisted of 372 (66.8%) liver resections and 185 (33.2%) lung resections. The mean time to DT was 2.34 (STD 1.99) years. The cumulative incidence rates of DT for years 1 to 5 was 1.8%, 3.9%, 5.6%, 7.1%, and 8.1% respectively. The incidence rate was 4 per 100,000 person years. After adjusting for patient and treatment factors, patients who underwent DT were more likely to be younger, married, have a more recent year of diagnosis, present with low grade tumors, and receive adjuvant chemotherapy compared to patients who did not undergo DT. Conclusions: Few elderly patients received chemotherapy and underwent DT for presumed recurrent disease. Age, marital status, year of diagnosis, tumor grade, and adjuvant chemotherapy were key determinants of DT. These factors should be considered during surveillance of patients after curative resection.