tbuckley/cabot-search huggingface dataset:
T cell infiltration in matched renal biopsy (bx) and nephrectomy (nx) samples in renal cell carcinoma (RCC).
Authors: Haris Zahoor, Paul G Pavicic, Christopher Przybycin, Paul Elson, C. Marcela Diaz-Montero, James Finke, Patricia A. Rayman, Timothy D. Gilligan, Petros Grivas, Moshe Chaim Ornstein, Jorge A. Garcia, Brian I. Rini
Journal: Journal of Clinical Oncology (2017)

472 Background: T cell infiltration in tumors has been investigated as a biomarker of response to checkpoint inhibitors. A neo-adjuvant trial of checkpoint inhibition in locally-advanced RCC is ongoing at Cleveland Clinic, where T cell infiltration in pre-treatment renal mass bx will be compared to post-treatment nx specimens. However, there are no data regarding the association of T cell infiltration in matched bx and nx samples without intervening treatment. Understanding this association will enable further study of this potential biomarker in future neo-adjuvant studies. Methods: Matched bx and nx samples (without intervening systemic therapy) were identified from patients with non-metastatic RCC. Demographic and pathological data were collected from chart review. Selected tissue sections from bx and nx samples of each patient were reviewed, and marked for tumor and intra-tumoral lymphocytes by the pathologist. Immunohistochemistry (IHC) was utilized to stain these selected tissue sections for T cell markers (CD3, CD4 and CD8). Intra-tumoral T cells were then quantified in the pre-marked tissue sections as counts per total tumor area surveyed, using Image-Pro Plus (Media Cybernetics, Inc.). Spearman correlation (ρ) was used to measure the strength of association of T cell infiltration between matched samples. Results: 30 matched pairs were investigated. The median interval between bx and nx was 2.8 (0.2-87.7) months. Clear cell was the most common histology (29/30; 97%). 15/30 (50%) had grade 3-4 tumors, 2/19 (11%) patients had sarcomatoid features, 7/25 (29%) had necrosis, and 8/28 (29%) had lymphovascular invasion. We found a positive correlation between the frequencies of CD8 + T cells between matched bx and nx samples (ρ= 0.39; p=0.03). CD3 + and CD4 + T cells did not show significant correlation. (Table) Conclusions: Bx material can be used to accurately assess the degree of CD8 + T cell infiltration in RCC. [Table: see text]
Meta-analysis of neo-adjuvant androgen deprivation therapy (AD) in localised prostate cancer
Authors: S. Kumar, C. Harrison, M. Shelley, M. Mason
Journal: Journal of Clinical Oncology (2006)

4643 Background: AD before primary therapy, either prostatectomy (P) or radiotherapy (RT) is increasingly used in routine practice. Clinical trials of surgical series have shown an improvement in pathological variables but with limited survival data. A few RT studies have shown a clinical benefit. We performed a systematic review and meta-analysis to assess the true impact of NA treatment. Methods: Data from published clinical trials of patients with non-metastatic PC were extracted for quality, and included design, participants and comparisons and meta-analysis was performed for comparable data. The primary endpoint was overall survival (OS) and secondary endpoints included disease-specific, disease-free survival (DFS) and disease recurrence rates. Analysis was performed using Revman 4.2.8. For dichotomous data the odds ratio was calculated with 95% confidence interval (CI) and the results were tested for homogeneity at a significance level of p &lt; 0.1. A fixed effects model was used if there was no evidence of heterogeneity between studies. Results: AD before P led to a significant reduction in disease recurrence (number (n) of patients 973 in 3 trials-overall odds ratio OR 0.74; 95% CI 0.55–1.0; p = 0.05). In addition there was a significant reduction of positive surgical margins (n 1802 in 8 trials-OR 0.34; 95% CI 0.27–0.42; p &lt; 0.00001).There were no comparable data for pooled analysis of DFS or OS. The use of AD before RT resulted in a significant improvement in disease-specific survival (n 1082 in 3 trials-OR 1.37; 95% CI 1.06–1.77; p =0.02) and DFS (n 991 in 2 trials-OR 1.86; 95% CI 1.93–2.40; p &lt; 0.00001). The data for biochemical DFS was heterogenous due to differences in definition of PSA recurrence but the overall effect was highly significant in favour of AD (n 1097 in 3 trials-OR 1.93; 95% CI 1.45–2.56 p &lt; 0.00001). There was a trend to improvement of OS at 1, 2 and 5 years, not statistically significant. Conclusions: Despite a significant improvement in pathological variables with AD before surgery, available evidence is limited regarding a survival benefit which requires prolonged follow-up of patients. In selected patients undergoing RT, the addition of AD results in improved disease specific survival and DFS, likely improvement of biochemical DFS and trend to improvement in OS. No significant financial relationships to disclose.
The surgical Apgar score is an independent prognostic factor in patients with pancreatic cancer undergoing pancreaticoduodenectomy followed by adjuvant chemotherapy.
Authors: Yosuke Atsumi, Toru Aoyama, Keisuke Kazama, Masaaki Murakawa, Manabu Shiozawa, Satoshi Kobayashi, Makoto Ueno, Manabu Morimoto, Norio Yukawa, Takashi Oshima, Takaki Yoshikawa, Yasushi Rino, Munetaka Masuda, Soichiro Morinaga
Journal: Journal of Clinical Oncology (2017)

472 Background: We investigated the impact of the surgical Apgar score (SAS) on survival in patients with pancreatic cancer and recurrence after curative surgery followed by adjuvant chemotherapy. Methods: This study included 103 patients who underwent curative surgery for pancreatic cancer between 2005 and 2014. Patients with a SAS of 0-4 were classified into the low SAS group, while those with a SAS of 5-10 were classified into the high SAS group. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Results: The OS rates at 3 and 5 years after surgery were 23.0% and 14.4%, respectively, in the low SAS group and 32.3% and 21.4%, respectively, in the high SAS group, which was a statistically significant difference (p = 0.039). The RFS rates at 3 and 5 years after surgery were 13.1% and 13.1 %, respectively, in the low SAS group and 21.4% and 19.2%, respectively, in the high SAS group, which was a marginally significant difference (p = 0.100). Multivariate analysis demonstrated that the SAS was a significant independent risk factor for OS and a marginally significant risk factor for RFS. Conclusions: The SAS was a risk factor for OS in patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer. The surgical procedure, perioperative care and surgical strategy should be carefully planned to improve survival.
Adverse prognostic impact of heterogeneous <i>HER2</i> gene amplification in patients with esophageal adenocarcinoma (EAC).
Authors: Harry H. Yoon, Qian Shi, William R. Sukov, Christopher A. Sattler, Anne E. Wiktor, Tsung-Teh Wu, Robert B. Diasio, Robert B. Jenkins, Frank A. Sinicrope
Journal: Journal of Clinical Oncology (2012)

4009 Background: HER2 expression in upper digestive cancer is reported to be heterogeneous, which substantially affects interpretation of HER2 positivity in the clinic. Yet the frequency and prognostic impact of HER2 genetic heterogeneity and polysomy 17 (poly17) are unknown in EAC. Methods: HER2 amplification (fluorescence in situ hybridization) and protein expression were examined in untreated surgical EAC specimens (N = 661) at Mayo Clinic. HER2 genetic heterogeneity was defined per ASCO/CAP as amplification (HER2/CEP17 ratio ≥ 2) in 5-50% of cancer cells; poly17 refers to ≥ 3 copies of chromosome 17. Most tumors were T 3-4 (68%) or lymph node (LN)-positive (73%). Cox models were used to assess disease-specific (DSS) and overall survival (OS). Results: HER2 amplification was detected in 117 of 661 EACs (18%), of which 20 (17%) showed HER2 heterogeneity. HER2 heterogeneous tumors had a significantly higher frequency of poly17 and high tumor grade. HER2 heterogeneity by amplification vs expression were correlated. Since heterogeneity was limited to HER2-amplified tumors, survival analysis was stratified by amplification status. In multivariable analysis, only HER2 heterogeneity and metastatic LN number were prognostic (Table). Conclusions: Among HER2 amplified EACs, 17% show HER2 heterogeneity, which is associated with increased poly17 and independently predicts 2-fold higher risk of cancer-specific death. Among HER2-nonamplified cases, poly17 is independently associated with worse survival. These novel findings demonstrate aggressive subgroups in HER2-amplified and -nonamplified EACs that have important implications for HER2 analysis and evaluation of benefit from HER2 targeted therapy. [Table: see text]
Cancer pain management practices and their impact on quality of life for Asian cancer patients.
Authors: Yong-Chul Kim, Hanlim Moon, Jin Seok Ahn, Maria Minerva P. Calimag, Ta-Chung Chao, Kok Yuen Ho, Lye Mun Tho, Zhong-Jun Xia, Lois Ward
Journal: Journal of Clinical Oncology (2015)

6531 Background: In order to implement more effective policies for cancer pain management, a better understanding of current practices and their effects on patients are needed. The ACHEON study was a survey-based investigation of the impact of cancer pain and management practices on patients’ quality of life in 10 Asian countries. Methods: Patients experiencing cancer pain were randomly surveyed in 10 Asian countries with a 33-item questionnaire assessing attitudes and perceptions towards cancer pain management. Patients aged ≥ 18 years with a documented history of cancer pain in the preceding month were selected. Results: Of the 1,190 patients (median age; 53, male/female 805/385) surveyed, 1,026 reported moderate-to-severe pain (median duration, 12 months). The attribution of the pain was 53% from cancer, 18% from cancer-related therapy and 29% from mixed sources. 1,056 (90%) patients were treated for their cancer pain and only 308 patients were receiving opioids, to their knowledge. Patients agreed that their pain affected activities of daily living (86%), sleeping patterns (87%), concentration and focus (92%), as well as causing too much reliance on other people (67%), while only a small proportion reported having a good quality of life (34%). Only 22% of patients were employed, and 44% of those had been absent from work for more than 7 days over the past 3 months due to their cancer pain. It was reported that 42% of the patients who were unemployed had stopped working due to cancer pain. Conclusions: The ACHEON study results show that cancer pain significantly affects multiple aspects of quality of life for patients. The development of more effective management practices for cancer pain will require collaborative efforts from institutional, social and regulatory parties.
Development of a novel patient-derived preclinical model from malignant effusions in patients with tyrosine kinase inhibitor resistant clear cell renal cell carcinoma.
Authors: Jung Hun Kang, Mi Hwa Heo, Hee Kyung Kim, Jinhyun Cho, Youjin Kim, Hansang Lee, Sang-Cheol Lee, Se Hoon Park
Journal: Journal of Clinical Oncology (2017)

445 Background: Although targeting angiogenesis with tyrosine kinase inhibitors (TKIs) has become standard of care in the treatment of clear cell renal cell carcinoma (RCC), resistance mechanism are not fully understood and there is a need to develop new therapeutic options overcoming them. Methods: To develop a preclinical model that predicts clinical activity of novel agents.We established patient-derived cell (PDC) and xenograft (PDX) models from malignant effusions (n = 15) or surgical specimen (n = 4).Genomic features of the PDX model were compared with those of the primary tumor. Drug effects of cell viability were then tested with PDC and PDX models. Results: Successful PDCs, defined as cells that maintained growth following 2 passages, were established in 5 of 15 malignant effusions and 1 of 4 surgical specimens. One PDC, clinically refractory to TKIs, was implanted and engrafted in mice resulting in a comparable histology to the primary tumor. The PDC-PDX model also showed similar genomic features when tested using targeted sequencing of cancer-related genes. When we examined the drug effects of the PDX model, the tumor cells showed resistance to TKIs and everolimus in vitro. Conclusions: The results suggest that the PDC-PDX preclinical model we developed using malignant effusions can be a useful preclinical model to interrogate sensitivity to targeted agents based on genomic alterations. We show that novel preclinical models are developed using malignant effusions derived from patients with kidney cancer. The preclinical models can be used to test anti-tumor activity of novel therapeutics. The preclinical model we developed can be used to interrogate sensitivity to targeted agents based on genomic alterations. The PDC model from malignant effusions of patients was successfully converted to a PDX model, and represents an important and feasible platform for future cancer research.
Anaplastic gliomas at first recurrence: Outcome analysis.
Authors: Enrico Franceschi, Marco Bartolotti, Patrizia Dall'Occa, Rosalba Poggi, Stefania Bartolini, Monica Di Battista, Gianluca Marucci, Mario Ermani, Alba Ariela Brandes
Journal: Journal of Clinical Oncology (2012)

2061 Background: Although anaplastic gliomas show a more favorable response to postsurgical therapy than glioblastoma, when recurs, salvage therapies offer only temporary benefit. Moreover, due to the rarity of these entities, no study exists to evaluate the clinical outcomes of anaplastic gliomas at first recurrence. Methods: A retrospective analysis was made using a database on 249 anaplastic glioma patients (pts) followed prospectively between 01/2000 and 12/2011. Eligibility criteria: age ≥18 years; PS 0-2; histological diagnosis at first surgery of anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and anaplastic oligoastrocytoma (AOA); first recurrence after postsurgical treatments. Results: 163 pts (recurrent AA:52%, AOA:23%, AO: 25%, mean age: 45 years, range: 21–74) were enrolled. 1p deletion and MGMT methylation were found in 23% and 56% of evaluable specimens, respectively. At time progression, second surgery was performed in 51 pts (31%). Chemotherapy was delivered in 128 pts: temozolomide in 96 pts (75%), PCV regimen in 11 pts (9%), and other cytotoxic treatments in 21 pts (16%). Median PFS was 7.1 months (95% CI: 5.8–8.5), being PFS-6 57.8% (95%CI: 49.8%–65.8%), mOS: 18.3 months (95% CI: 13.9–22.8) and OS-12: 63% (95%CI: 55.4%-70.6%). 1p status was not significantly associated with PFS and OS measured from first recurrence to second progression or death, respectively (p=0.12 and p=0.08). In the Cox proportional hazard model, PFS at recurrence was significantly correlated with OS measured at the first disease recurrence (p&lt;0.00001). Conclusions: our data represent the largest series that evaluated the outcome of anaplastic gliomas at first recurrence. In this setting, PFS should be considered as a worthy endpoint, being significantly correlated with OS.
CUSUM analysis of mortality following esophagectomy to allow for identification and intervention of quality problems.
Authors: Patrick James McLaren, Kyle D Hart, James P. Dolan, John G. Hunter
Journal: Journal of Clinical Oncology (2017)

203 Background: CUSUM analysis is an analytic tool for monitoring institutional quality and clinical outcomes. CUSUM is a summative plot of an event that occurs over time. The slope that is generated can be used to determine rates of occurrence and deviations from an accepted rate. CUSUM can be used to monitor mortality rates following esophagectomy. Methods: A single institution prospectively maintained esophageal disease registry was used to construct CUSUM plots for in-hospital and 30-day mortality. All patients undergoing esophagectomy with reconstruction from 1995-2015 were included for analysis. Time points that deviated from an accepted mortality rate of 5% were evaluated for cause analysis. Results: From 1995-2015, 485 esophagectomies were performed with a cumulative in-hospital mortality rate of 4.7%. In 2008 our institution shifted to a primarily minimally invasive approach. Prior to March 2008 in-hospital mortality was 7.4%. After this time, in-hospital mortality was 2.1%, corresponding with a decreased slope of the CUSUM plot. A second period was investigated from September 2012-October 2012. Eight esophagostomies were performed with 3 deaths for a 37.5% mortality rate. All 3 patients were deaths related to ARDS and multisystem organ failure; this prompted an institutional epidemiologic investigation, as well as review of our enhanced esophageal recovery pathway. Since this time frame in-hospital mortality has been 1%. Conclusions: CUSUM analysis offers a useful observational tool to monitor institutional quality following esophagectomy. Investigations into mortality can identify quality problems and can lead to implementation of improved process measures that may lead to improved future outcomes.
Above-label doses of octreotide-LAR in patients with metastatic small-intestinal carcinoid tumors.
Authors: Jill M. Weber, Max Feldman, Larry Kvols, Jonathan R. Strosberg
Journal: Journal of Clinical Oncology (2012)

e14579 Background: Octreotide LAR is indicated for treatment of the malignant carcinoid syndrome, and has been studied at doses of 10-30mg intramuscularly every 4 weeks. It has also been proven to delay time to progression of metastatic midgut carcinoid tumors at a dose of 30mg every 4 weeks. In clinical practice, higher doses are often prescribed for patients who experience refractory carcinoid syndrome (flushing and/or diarrhea) or tumor growth while on the maximal labeled dose. We performed a retrospective, longitudinal review of octreotide LAR administration at a tertiary institution to determine the frequency of ‘above-label’ dosing and outcomes. Methods: A retrospective chart-review was performed using a database of patients with metastatic small-bowel carcinoid tumors treated at the Moffitt Cancer Center between the years 2000 and 2010. Data included the maximal dose of octreotide LAR administered, reasons for change in dose or frequency (above the labeled dose of 30mg every 4 weeks), and clinical responses to dose change. Results: 337 patients were considered evaluable, among whom 99 patients (27%) underwent at least one increase in dose or frequency of octreotide-LAR above the standard labeled dose. The most common maximal doses were 40mg every 4 weeks (37 patients), 60mg every 4 weeks (34 patients), and 30mg every 3 weeks (17 patients). The indications for dose increase were worsening carcinoid syndrome (60 patients), radiographic progression (33 patients) and rising urine 5-HIAA (6 patients). Among patients whose doses were increased for refractory carcinoid syndrome, 62% experienced improvement in diarrhea and 56% experienced improvement in flushing. Conclusions: In clinical practice, octreotide LAR is commonly prescribed in doses or schedules above the labled dose and frequency. Patients with refractory carcinoid syndrome appear to experience a clinical benefit from the change. Prospective data is needed to evaluate this strategy.
Cancer survivors’ experiences with insurance, employment and personal finances: Results from a multi-site study.
Authors: Larissa Nekhlyudov, Rod Walker, Rebecca Ziebell, Borsika Rabin, Stephanie Nutt, Jessica Chubak
Journal: Journal of Clinical Oncology (2015)

9574 Background: Prior studies have shown that cancer has significant implications for survivors’ insurance coverage, employment and financial status. We aimed to examine whether these implications may differ for survivors depending on the type of cancer experienced. Methods: Using the Cancer Survivorship Supplement of the Medical Expenditures Panel Survey, we surveyed a cohort of cancer survivors enrolled in one of three health plans in Massachusetts, Colorado and Washington State in 2013. We stratified our sample to include those diagnosed with breast, colorectal, lung, and prostate cancers and melanoma between 2003 and 2008. Results: Of the 615 eligible respondents, 590 reported having had insurance at some point during/since their diagnosis, and few of those reported coverage barriers in seeing doctors or facilities of their choice. About half (n = 334) of the respondents reported having been employed at some time during/since their cancer; of those, approximately 25% reported they or their spouses remained at their jobs due to concerns about losing insurance, with no significant differences observed by cancer type. Further, of those employed, the majority (63%) reported making changes in their jobs (e.g., taking extended time off, working part time) or career choices due to cancer. These changes were more common among those with lung (80%), colorectal (74%) and breast cancer (68%) compared to prostate cancer (53%) and melanoma (38%) (p < 0.001). Additionally, 42% reported that cancer interfered with their physical and/or mental tasks at work or reduced their productivity. These limitations were again more common among lung, colorectal, and breast cancer survivors (p = 0.001). Of all survivors, approximately 15% reported financial hardships due to their cancer; most often among those with lung (23%) and breast cancer (22%) (p < 0.001). Conclusions: In this insured population, few experienced restrictions with their cancer care coverage, though maintaining coverage often drove employment decision making. Having cancer was associated with significant impact on survivors’ work schedules, job productivity and personal finances, particularly among those with lung, breast and colorectal cancer.