tbuckley/cabot-search huggingface dataset:
Incidence of minimally invasive colorectal cancer (CRC) surgery in patients treated at NCCN institutions
Authors: M. Weiser, D. Romanus, A. terVeer, A. Rajput, J. Skibber, C. Earle, S. Shibata, E. Martin, P. Engstrom, D. Schrag
Journal: Journal of Clinical Oncology (2007)

6575 Background: In May 2004 the Clinical Outcomes of Surgical Therapy Study Group published the results of the North American randomized trial demonstrating that oncologic outcome is similar for laparoscopic assisted and open surgery for CRC. This and other studies have shown quicker recovery with laparoscopic CRC surgery including earlier resolution of postoperative ileus, less discomfort, and earlier discharge from the hospital. The extent to which surgeons have adopted the minimally invasive surgical (MIS) approach in CRC is unknown. Methods: Using the NCCN Colon/Rectal Cancer Outcomes Project Database, 715 patients were identified who underwent CRC resection in 2005–6. The distribution of lesions included right colon (39%), left colon (31%), and rectum (30%). The incidence of MIS for CRC and clinicopathologic features associated with this approach were analyzed by logistic regression; results are reported as odd ratio (OR) with 95% confidence intervals (CI), and significance defined at p&lt;0.05 level. Results: A total of 167 (23%) patients underwent MIS colorectal surgery (laparoscopy in 98% and robotic in 2%). Conversion to open surgery was noted in 33 cases (20%). Surgery was performed in outside institutions in 21% of cases prior to patients presenting to NCCN institutions for further treatment. The MIS approach was more common in colon than rectal cancer (30% vs.12%, OR 2.96, CI 1.94–4.51, p&lt;0.0001). Within the colon cancer cohort, right sided lesions were more likely to be approached with MIS techniques rather than left sided lesions (32% vs. 25%; OR 1.42, CI 1.96–2.21, p&lt;0.0001). Stage I tumors were also more likely to be managed with the less invasive approach: Stage I-41%; II-20%; III-21%; IV-19% (Stage I vs. IV, OR=3.00, CI 1.74–5.16 p&lt;0.0001). No differences in surgical approach were noted based on age, gender, race, Charlson comorbidity score, insurance type, or location of surgery (NCCN vs outside facility). Conclusion: The majority of CRC surgery for patients presenting to NCCN institutions is performed by open techniques. Right sided and early stage CRCs were more likely treated with MIS, possibly related to the less demanding nature of the procedure. The adoption of MIS is expected to rise as surgeons become trained in MIS techniques for CRC. No significant financial relationships to disclose.
Are cells from a snowman realistic? Cryopreserved tissues as a source for single-cell RNA-sequencing experiments
Authors: Felipe A. Vieira Braga, Sarah A. Teichmann, Michael J. T. Stubbington
Journal: Genome biology (2017)

A recently published study in Genome Biology shows that cells isolated from cryopreserved tissues are a reliable source of genetic material for single-cell RNA-sequencing experiments. Please see related Method article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1171-9
Quantitative measurement of HER2 levels by multiplexed mass spectrometry to predict survival in gastric cancer patients treated with trastuzumab.
Authors: Chan-Young Ock, Eunkyung An, Do-Youn Oh, Tae-Yong Kim, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Wei-Li Liao, Fabiola Cecchi, Adele Blackler, Sheeno P Thyparambil, William Arthur Hoos, Woo Ho Kim, Jon Burrows, Todd A. Hembrough, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2015)

4050 Background: Trastuzumab-based chemotherapy is standard treatment for HER2-positive advanced gastric cancer (AGC). Although increased HER2 gene amplification by fluorescent in situ hybridization (FISH) has been correlated with sensitivity to trastuzumab, the predictive value of HER2 protein expression levels for trastuzumab sensitivity has not been reported. In this work, we quantitate levels of HER2 using a mass spectrometry-based assay and identify a cutoff for HER2 protein levels that is predictive of enhanced response to trastuzumab. Methods: A multiplexed, selected reaction monitoring (SRM) mass spectrometry assay was used to determine the absolute level of the HER2 protein in patient tumors. HER2 immunohistochemistry (IHC) status, HER2/CEP17 ratio, HER2 gene copy number, and HER2 protein levels were compared in 249 AGC tumors, 95 of which were treated with trastuzumab. Overall survival (OS) in the trastuzumab cohort was correlated with HER2 protein levels and a predictive cutoff was determined by the lowest p value of log rank test. Results: While HER2 protein quantitation by mass spectrometry positively correlated with both FISH and IHC, a wide range of HER2 protein levels was observed in tumors classified as HER2-positive by conventional methods. Ninety five trastuzumab treated patients were stratified into two groups based on HER2 protein level: HER2 high expressers and HER2 moderate expressers. Patients classified as HER2 high expressers (n = 48), with HER2 levels above 2383 amol/ug, had twice the overall survival (OS) of patients (n = 47) classified as moderate expressers (OS: 35.0 vs. 17.5 months, HR 0.5, p= 0.007). Conclusions: We used a non-antibody based assay to quantify absolute levels of HER2 protein in samples from AGC patients. We found high variability in HER2 expression within a patient population that had been classified as 3+ by IHC. High levels of HER2 correlated with increased overall survival following trastuzumab. This study demonstrates the HER2 measurement by SRM could guide physicians in their patient's selection for trastuzumab-based chemotherapy.
Efficacy of i.v. and oral ibandronate in bone metastases breast cancer patients and some clinical aspects of bisphosphonates studies: Clinical experience of one trial center
Authors: M. Lichinitser, N. N. Semenov
Journal: Journal of Clinical Oncology (2007)

1096 Background: Ibandronate is the only bisphosphonate that has both i.v. and oral formulation. Previously similar effectiveness of 6 mg i.v. and 50 mg oral Ibandronate compared with placebo in breast cancer metastatic bone disease was demonstrated. Methods: Due to similar inc/excl criteria in both (MF 4265 and MF4414–34) trials, we directly compare frequency of pathological fractures, hypercalcemia and osteolisys markers dynamics for patients, who received ibandronate 6 mg i.v. monthly or 50 mg per os daily (n=58) with placebo (n=53) during 2 years. Results: The frequency of pathological fractures (PF) and hypercalcemia (HC) is strongly depending on the efficacy of antitumor treatment: in periods of progression PF were 42%, in periods without progression only 6,8%, p&lt;0.0001. Ibandronate decrease frequency of PF and HC, as acute bone pain and narcotics requirement in progression periods. Hypercalcemia was observed in progression periods only. Ibandronate effectively suppressed osteolysis in periods of disease progression: level of dPyr decreased by 3% and CTx by 60%, while in placebo group dPyr increased by 25% and CTx by 58%. Conclusions: Ibandronate is effective in periods of disease progression. Development of new clinical research methodology of bisphosphonate trials is thus actual. No significant financial relationships to disclose.
Azacitidine Administration Following Hematopoietic Stem Cell Transplantation Is Safe and Feasible in Children with Acute Leukemia
Authors: Justin T. Wahlstrom, Biljana N. Horn, Carol Fraser-Browne, Rebecca Hoeweler, Ying Lu, Alexis Melton, Jennifer Willert, Christopher C. Dvorak
Journal: Blood (2016)
Categorization of gene expression subtypes in clear cell renal cell carcinoma with sarcomatoid features.
Authors: Shreyas Joshi, Suraj Peri, Eric A. Ross, Robert G. Uzzo, Alexander Kutikov, Daniel M. Geynisman
Journal: Journal of Clinical Oncology (2017)

519 Background: Presence of sarcomatoid features in Renal Cell Carcinoma (sRCC) tumors signals aggressive clinical behavior and poor prognosis compared to Clear Cell Renal Cell Carcinoma (ccRCC). However, the underlying gene expression patterns of sRCC are poorly understood. We sought to categorize ccRCC and sRCC gene expression subtypes and compare survival outcomes, as well as evaluate whether sRCC gene expression patterns are similar to non-renal sarcomas. Methods: We identified 511 ccRCC cases, of which 36 had a sarcomatoid component from The Cancer Genome Atlas. Enrichment analysis was used to measure associations between gene expression signatures for soft tissue sarcomas and expression profiles of sRCC and ccRCC cases measured by RNA-Seq. The resulting scores were used to identify distinct patient groups using K-means clustering. Overall survival (OS) was evaluated by Kaplan-Meier, log rank, and Cox regression methods. Results: Our analysis identified 4 distinct clusters that differ in enrichment for soft-tissue sarcoma gene expression profiles. The clusters showed significantly different OS distributions (p-value&lt;0.001 log rank). Most sRCC cases (69%) segregated into a single cluster with the worst prognosis. Among ccRCC cases, 57% of patients with higher levels of sarcoma signature enrichment were associated with a shorter OS, which is independent of tumor stage. 5-year/median OS survival estimates for ccRCC cases in the 4 clusters, by increasing levels of sarcoma profile enrichment, were 83%/NR, 75%/NR, 67%/90.9 mo, and 49%/56.7 mo. We also validated existence of these clusters in another sRCC cohort (Sircar 2015). Conclusions: We identified strong associations between sarcoma expression signatures and gene expression profiles of sRCC. We also found that 57% of morphologically non-sRCC cases demonstrate enrichment for sarcoma expression signatures, and these patients have worse OS than their non-sarcoma enriched ccRCC counterparts. The presence of sarcoma expression signatures has not been previously evaluated in RCC. These signatures portend poor survival and may be clinically actionable, as they describe unique subtypes of RCC that may not correspond to histologic characterization.
Hereditary diffuse gastric cancer (HDGC): Clinical characteristics of a prospective cohort of HDGC patients with and without <i>CDH1</i> mutation and patients with sporadic GC
Authors: M. A. Shah, Y. Pristyazhnyuk, M. Jhawer, S. Coombes, M. Harlan, J. Randazzo, R. J. Perera, K. M. Pascarelli, D. Coit, D. P. Kelsen
Journal: Journal of Clinical Oncology (2009)

4543 Background: HDGC is an autosomal dominant cancer syndrome associated with early onset diffuse GC. Germline mutations in E-cadherin(CDH1) cause the disease but are identified in only 20–30% of pts meeting clinical criteria. We began a prospective multicenter GC registry to capture epidemiologic and family history data matched with DNA and tissue to characterize phenotypic and risk factor profiles and their associations with HDGC and other non-HDGC hereditable GC. Herein, we report the clinical characteristics of HDGC, the subset of HDGC pts with CDH1 mutation, pts with sporadic GC, and non-cancer controls. Methods: All patients with GC are eligible for registry participation. HDGC criteria: diffuse GC(&lt; age 45), diffuse GC(&lt; age 50) with 1 relative with GC, diffuse GC(any age) with 2 or more relatives with GC, or a personal or family history of diffuse GC with lobular breast cancer or signet ring colon cancer. Non-HDGC high risk pts: diagnosed &lt; age 50 or with a family history of GC(at least one 1 st degree or two 2 nd degree relatives with GC), but do not meet HDGC criteria. Sporadic GC: diagnosed &gt; age 50, without family history. Participants complete a family history and epidemiology/ risk factor questionnaire, and provide blood and tissue for repository. Results: 465 participants have enrolled since Jan 2006. Questionnaires are available from 331 participants(69%), see table . CDH1 mutations have been identified in 10 families(16%) and prophylactic gastrectomies in CDH1 mutation carriers have been performed in 8 pts, each without major complications. Pt demographics and epidemiology were not notably different amongst all groups. Conclusions: Except for age and histology, the demographic breakdown and epidemiology of HDGC pts with and without CDH1 mutation is similar to other non HDGC high genetic risk pts and similar to pts with sporadic GC. The GC registry will expand to international sites. (Supported by the DeGregorio Family Foundation) [Table: see text] No significant financial relationships to disclose.
Pazopanib activity in pancreatic neuroendocrine tumors (pNETs).
Authors: Enrique Grande, Daniel E. Castellano, Rocio Garcia-Carbonero, Alex Teule, Ignacio Duran, Jose Fuster, Isabel Sevilla, Pilar Escudero, Javier Sastre, Jesús García-Donas, Teresa Alonso, Jaume Capdevila
Journal: Journal of Clinical Oncology (2014)

e15171 Background: The PAZONET trial analysed the efficacy and safety of the use of pazopanib (800 mg/qd) in patients (pts) with progressive metastatic NETs that had been previously treated with other novel targeted agents. Here we report the clinical outcome of those patients with pNETs treated with pazopanib. Methods: Fourty-four pts with locally-advanced or metastatic gastrointestinal or pancreatic NET with disease documented as progressive were treated at the PAZONET trial. Pazopanib 800 mg was given daily until disease progression (DP) or unacceptable toxicity. Within this substudy we have analysed the clinical outcome of those patients with pNETs compared with those without pancreatic primary origin. Results: 17 pts with pNETs were recruited. Median PFS in pNETs (12.8 [11.0-14.6]) was significantly longer than in gastrointestinal NETs (GINETs) (10.0 mo [4.9-15.1]) vs other primary tumors (Non-GEP-NETs) (3.4 mo [0.0-7.0]). Two pts had PR (11.8%), 10 SD (58.8%), and 5 DP (29.4%). Clinical benefit rate (CBR) at 6 months was 70.6%. By subgroups, CBR was 100% in pts with no previous targeted therapy (1 pts), 80% in pts with previous mTOR inhibitors (4 pts), 75.0% in pts with previous antiangiogenics (6 pts), and 33.3% in pts with previous antiangiogenics and mTOR inhibitors (1 pts). The sum of the longest diameter of target lesions had a decrease over 9.1% in 52.94% of pts (65.5% without previous biological treatment, 9.1% mTOR without prior multitarget, 15.4% prior multitarget without mTor, and -0.5% with previous multitarget and mTOR). Significant differences in mPFS were found in concomitant SSA treatment (12.4 mo [10.6-14.1]) vs. pazopanib alone (6.8 mo [2.5-11.1]) (p=0.245). No differences in mPFS were seen in functioning (12.4 mo) vs. non-functioning tumors (11.7 mo) and Ki67 status (< 2% NR, 3-10% 11.2 mo or >10% 24.7 mo: P=0.029). Most frequent toxicities at any grade in pNETs were: asthenia (82.4%), diarrhoea (76.5%), and nausea (47.1%). Conclusions: Pazopanib seems to display higher activity in pNETs rather than GINETs or non-GEP-NETs. Concomitant treatment of pazopanib plus somatostatin analogs result in synergistic activity. Clinical trial information: 2010-020749-28.
Combination of TLR9 agonist lefitolimod/MGN1703 with checkpoint inhibitors for cancer immunotherapy.
Authors: Manuel Schmidt, Kerstin Kapp, Barbara Volz, Detlef Oswald, Burghardt Wittig
Journal: Journal of Clinical Oncology (2017)

634 Background: TLR9 agonists are potent activators of the immune system via induction of cellular and humoral responses. Preclinical and ongoing clinical studies support the use of TLR9 agonists for immunotherapeutic approaches. Lefitolimod/MGN1703 is a covalently-closed dumbbell-like immune surveillance reactivator (ISR) with a broad immunomodulatory potential. After promising data from a phase II trial (IMPACT) as maintenance therapy after first-line induction chemotherapy in patients with metastatic colorectal cancer lefitolimod is recently evaluated in a phase III trial in mCRC patients (IMPALA). Methods: It was previously shown that lefitolimod can reduce tumor growth in several murine tumor models. Since the mode-of-action of lefitolimod starts upstream of the initiation points of checkpoint inhibitors aCTLA-4 or aPD-1/aPD-L1 a combinatory approach may result in an enhanced anti-tumor effect. Therefore, we employed two syngeneic murine tumor models: One with s.c. inoculation of CT26 cells and another with s.c. A20 cell challenge. Multiple doses of lefitolimod were injected s.c. or i.tu. Results: In the colon carcinoma CT26 model i.p. injection of aPD-L1 had no effect on the tumor growth, whereas peritumoral injection of lefitolimod led to a slowed tumor growth. The tumor growth was further inhibited by the combination (tumor growth inhibition, TGI - aPD-L1: no, lefitolimod: 28%, combination: 48%) resulting in prolonged survival of the mice. This combinatory effect was even more pronounced in the lymphoma A20 model: Injections of anti-PD-1 (i.p.) or lefitolimod (i.tu.) alone had a moderate anti-tumor effect which was vastly increased by the combination (TGI - aPD-1: 46%, lefitolimod: 50%, combination: 99%). Conclusions: In conclusion, we showed that lefitolimod, a member of dSLIM family of TLR9 agonists and an ISR, can enhance the limited anti-tumor effects of checkpoint inhibitors in pilot studies in murine colon carcinoma and lymphoma tumor models in vivo. These data show the promising potential for the combination with checkpoint inhibitors. In fact, a clinical trial in cooperation with MD Anderson evaluating the benefit of lefitolimod in combination with ipilimumab is currently ongoing.
Outcomes for men under 65 with high-risk prostate cancer with Medicaid versus private insurance.
Authors: Amandeep R. Mahal, Brandon Arvin Virgil Mahal, Paul L. Nguyen, James B. Yu
Journal: Journal of Clinical Oncology (2017)

198 Background: Increased Medicaid coverage, due to the Affordable Care Act, has been hypothesized to reduce racial disparities. We therefore examined the association between private insurance vs. Medicaid, race, and outcomes for the treatment of high-risk prostate cancer (CaP) among men &lt; 65 years old. Methods: The Surveillance, Epidemiology, and End Results Program identified 116,853 men &lt; 65 diagnosed with CaP from 2007-2011. Multivariable logistic regression modeled the association between insurance status (IS) and stage at presentation. Among men with high-risk CaP, the associations between IS and receipt of definitive therapy (DT) and prostate cancer-specific mortality (PCSM) were determined using multivariable logistic and Fine and Gray competing-risks regression models, respectively. Results: Compared to privately insured men, those with Medicaid were more likely to present with metastatic disease (Mets) (adjusted odds ratio (AOR) 5.79; 95% confidence interval (CI) 5.25-6.40; P &lt; 0.001). Among men with high-risk disease, men with Medicaid were less likely to receive DT (AOR 0.55; 95% CI 0.51-0.60; P &lt; 0.001) and had increased PCSM (adjusted hazard ratio (AHR) 1.8; 95% CI 1.27-2.54; P = 0.001). There were significant interactions (INT) between race and Medicaid for the outcomes of PCSM (P INT = 0.05) and Mets (P INT = 0.003). Specifically, gaps in PCSM and Mets were observed among privately insured men, with increased PCSM (AHR 1.51; 95% CI 1.18-1.94; P = 0.001) and Mets (AOR 1.33; 95% CI 1.20-1.48; P &lt; 0.001), while there were no observed disparities among men with Medicaid with regards to PCSM (AHR 0.72; 95% CI 0.34-1.52; P = 0.387) and Mets (AOR 1.03 95% CI 0.86-1.24; P = 0.730). Conclusions: Among men with CaP, African American men are more likely to present with Mets, less likely to receive DT, and have increased PCSM compared to non-black men. These disparities are observed in heterogeneous privately insured cohorts. However, among men with Medicaid, outcomes were equally worse. Furthermore, there was a significant INT between race and IS, indicating more-than-additive effects. Our study suggests that while increased access to Medicaid could act to reduce disparities seen in CaP, outcomes need to be improved overall.
Prediction of benefit from treatment beyond the first line in patients with metastatic breast cancer (MBC).
Authors: Marta Bonotto, Lorenzo Gerratana, Alessandro Minisini, Elena Poletto, Stefania Russo, Claudia Andreetta, Mauro Mansutti, Gianpiero Fasola, Fabio Puglisi
Journal: Journal of Clinical Oncology (2013)

e11565 Background: Despite the availability of several therapeutic options for MBC, palliative treatments beyond 1 st line lack of predictive factors that could help clinical decision making. We aimed to determine which is the impact of benefit at 1 st line into the benefit from subsequent therapeutic lines. Methods: We analyzed a consecutive series of 472 MBC patients treated with chemotherapy (CT) and/or endocrine therapy (ET) at the Department of Oncology of Udine, Italy, between 2004 and 2012. We evaluated Progression Free Survival at 1 st (PFS1), 2 nd (PFS2), 3 rd (PFS3) and 4 th (PFS4) line of treatment. Three distinct analyses were conducted: the first for the lines of CT, the second for the lines of ET and the third by considering both CT and ET as a line of treatment. A PFS longer than 6 months was defined as “6-month benefit". Results: Median Overall Survival was 34.5 mo (25 th – 75 th percentile: 14.5 – 58.8), median overall PFS1 and PFS2 was 8.9 mo and 4.3 mo respectively. Median PFS1 and PFS2 in CT lines only was 7 mo and 3.7 mo, respectively. Median PFS1 and PFS2 in ET lines only was 9.4 mo and 4.6 mo respectively. Overall, 289 patients (63.5%) presented 6-month benefit at 1 st line, 128 (40.5%) at 2 nd , 76 (33.8%) at 3 rd and 34 (23.3%) at 4 th . Not having a 6-month benefit in overall PFS1 was associated with a lack of benefit both at 2 nd line (OR=0.48; p=0.0026) and at any line beyond the 1 st (OR=0.39; p&lt; 0.0001). Taking into consideration CT lines only, not having a 6-month benefit in CT PFS1 was associated with a lack of benefit both at 2 nd line (OR=0.45; p=0.0072) and at any line beyond the 1 st (OR=0.43; p=0.0026). A lack of benefit at the 1 st ET line was not associated with further ET outcome neither in 2 nd line nor in any line beyond the 1 st . Stratification according to immunophenotype highlighted a statistical significance only among HER2 positive tumors (OR=0.2; p=0.0152 in 2 nd line and OR=0.14; p=0.0036 beyond 1 st line). Conclusions: Our results suggest that the absence of a “6-month benefit” in PFS1 predicts a lack of benefit in subsequent therapy lines, especially in HER2 positive disease. However, a lack of benefit at first line ET appears not to be detrimental to further anti-hormonal lines.