tbuckley/cabot-search huggingface dataset:
A National Cancer Data Base report on mesothelioma.
Authors: Lauren Brin, Mary Warlaumont, Timothy Fuller, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2013)

e18501 Background: This is the first report on mesothelioma using Commission on Cancer National Cancer Database information and this is the largest study on mesothelioma to date. Methods: Using the National Cancer Database (NCDB) 26,605 patients diagnosed with mesothelioma between 2000 and 2010 were identified and analyzed. The NCDB contains data from more than 70% of all new cancers diagnosed in the U.S. each year. Results: The majority of mesothelioma patients are Caucasian (89%), males (78%), over the age of 70 (60%), and are diagnosed with stage IV disease (41%). The majority of patients (41%) received no first course treatment. The patients that were most likely to have surgery include patients &lt;70 years old, at academic centers, with stage I-III disease, and of these only 37% received surgery and 15% received no first course treatment. The youngest patients &lt;50 years received the most surgical therapy (36%) and the oldest patients &gt;80 received the least (12%). Patients with private insurance received more surgical treatment (28%) than patients with Medicaid (22%), Medicare (18%), and VHA (12%)(p&lt;0.009). Private insurance holders also received no first course treatment less often (29.6%) than Medicaid (37%), Medicare (46%), VHA (52%), and uninsured patients (37%)(p&lt;0.002). Conclusions: The majority of patients with mesothelioma are elderly, Caucasian males and many of which do not receive treatment. The standard of care for resectable stage I-III mesothelioma includes surgery and chemotherapy. The results from this study indicate that 41% of all patients received no first course treatment and only 21% of patients received surgical treatment. Of patients most likely to receive surgery, only 37% of patients received surgical treatment and 15% of these patients did not receive any first course treatment. Age and insurance status also affect treatment as the youngest patients and private insurance holders received the most surgical treatment. [Table: see text]
Bioacoustic-enabled patterning of human iPSC-derived cardiomyocytes into 3D cardiac tissue
Authors: Vahid Serpooshan, Pu Chen, Haodi Wu, Soah Lee, Arun Sharma, Daniel A. Hu, Sneha Venkatraman, Adarsh Venkataraman Ganesan, Osman Berk Usta, Martin Yarmush, Fan Yang, Joseph C. Wu, Utkan Demirci, Sean M. Wu
Journal: Biomaterials (2017)
High-Exposure, Targeted Daily Busulfan and Fludarabine-Based Conditioning for Children Undergoing Hematopoietic Stem Cell Transplantation for Inherited Metabolic Disorders: Outcomes at a Single Center
Authors: Weston P Miller, Melisa Kay Stricherz, Cathryn Jennissen, Nicole Sando, Jennifer Danielson, Troy Lund, Paul J Orchard
Journal: Blood (2016)
Patient NCCN risk classification based on combined clinical cell cycle risk (CCR) score.
Authors: Steven Stone, Julia E. Reid, Michael K. Brawer
Journal: Journal of Clinical Oncology (2017)

249 Background: Improved prognostic tools for newly diagnosed prostate cancer are needed to more appropriately match treatment to a patient’s risk of progression. The cell cycle progression (CCP) score is a highly validated prognostic RNA expression signature which has been combined with CAPRA (CCR, combined clinical cell cycle risk score) to generate an estimate of prostate cancer mortality (PCM) within 10-years of diagnosis. Here, we evaluate how the prognostic information from CCR can reclassify patients compared to their initial assignment to an NCCN risk category based on clinicopathologic features alone. Methods: The CCR score was previously validated and is calculated as a linear combination of CAPRA and CCP score (0.39 x CAPRA + 0.57 x CCP). A risk reclassification scheme was applied to patients tested by the Myriad Genetics commercial laboratory (N = 16,442). First, PCM risk was assigned based on the patient’s CCR score. Next, patients whose PCM risks were outside the interquartile range (IQR) of their NCCN risk category were reclassified according to whether their PCM risks fell within the IQR of another NCCN risk category. Finally, patients whose PCM risks were below (or above) the IQR of the NCCN low (or high) category were reclassified as low (or high). Results: Based on clinicopathologic features alone the commercial cohort was classified according to NCCN Guidelines as low (N = 8,695), favorable intermediate (N = 3,347), intermediate (N = 3,086), or high risk (N = 1,224). After calculating patient risk of PCM based on CCR, 25% of the NCCN low risk men were reclassified to favorable intermediate or intermediate risk; 47% of the NCCN favorable intermediate risk men were reclassified (24% lower and 23% higher); 49% of the NCCN intermediate risk men were reclassified (24% lower and 25% higher); and 25% of the NCCN high risk were reclassified to favorable intermediate or intermediate risk. There is no outcome data associated with commercial samples. Conclusions: The prognostic information in the CCR score results in significant amounts of risk reclassification for all patients with localized disease when compared to stratification based only on NCCN risk categories.
Pazopanib prior to planned nephrectomy in metastatic clear cell renal cancer: A clinical and biomarker study.
Authors: Thomas Powles, Naveed Sarwar, Andrew Stockdale, Ekaterini Boleti, Robert J. Jones, Andrew Protheroe, Simon Chowdhury, John Peters, Grenville Oades, Tim S. O'Brien, Mark Sullivan, Grant Stewart, Michael Aitchison, Shah-Jalal Sarker, Dan Berney, Charlotte Rofe, Kevin Sharpe, Simon J. Crabb
Journal: Journal of Clinical Oncology (2013)

4508 Background: The safety and efficacy of upfront pazopanib, prior to nephrectomy in metastatic clear cell renal cancer (mRCC), has not been prospectively evaluated. The toxicity profile of pazopanib potentially makes it an attractive agent in this setting. Methods: A single arm phase II study (2009-016675-29) evaluated 12-14 weeks of pazopanib prior to planned nephrectomy in 102 untreated patients with mRCC. Patients had MSKCC intermediate (n=80) and poor risk disease (n=22). The Primary endpoint of the trial was to achieve at least a 75% clinical benefit rate (absence of disease progression) with pazopanib at the time of surgery. Sequential tissue was used for biomarker analysis (exploratory endpoint). Tissue from a previous sunitinib trials with a similar design was included for comparative purposes. Results: Overall 81% of patients obtained clinical benefit prior to surgery. The partial response rate of the primary tumor was 14% by RECIST v1.1. The median reduction in the size of the primary tumor was 14% (range 33% to - 41%). No patients became inoperable due to local progression of disease. A nephrectomy was performed in 66% of patients. The two commonest reasons for not having surgery were patient choice (9%) and progression of disease (16%). There were 2 (3%) post operative surgical death. Delayed wound healing occurred in 5%. Progression during the treatment free interval for surgery was 26%. Median PFS has not been reached. Results from biomarker analysis of sequential tissue revealed therapy resulted in a significant decrease in CD31 (-49%), PDL-1 (-31%) and pS6K (-26%), while FGF-2 (+147%), MET (+34%) and Ki-67 expression increased with therapy. Increased ki-67 and CD31 correlated with a poor outcome. Conclusions: Nephrectomy after upfront pazopanib can be performed safely in mRCC and obtains control of disease in the majority of patients. Biomarker analysis shows dynamic changes some of which are prognostically significant. Clinical trial information: NCT01512186.
Updated meta-analysis (MA) of salvage therapy for metastatic urothelial cancer (mUC): Comparing outcomes of immunotherapy (IT) versus single agent and doublet chemotherapy (CT).
Authors: Andrea Necchi, Daniele Raggi, Guru Sonpavde, Patrizia Giannatempo, Luigi Mariani, Matt D. Galsky, Joaquim Bellmunt, Rosalba Miceli
Journal: Journal of Clinical Oncology (2017)

341 Background: Doublet CT demonstrated improved overall response rate (ORR) and progression-free survival (PFS) compared to single agent CT in a MA of patients (pts) receiving II line CT in trials of mUC ( Raggi et al, Ann Oncol 2016). We aimed to update the analyses adding trials of salvage IT. Methods: We searched for arms of phase 2 or 3 studies of salvage single agent anti-programmed cell death-1/Ligand-1 (PD-1/PD-L1) agents pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, single agent CT and doublet CT. Random-effects models were used to pool trial level data according to treatment arm, including ORR, median PFS (mPFS), median overall survival (mOS). Univariable (UVA) and multivariable (MVA) analyses were performed, adjusting for ECOG-PS 2 and liver metastases. Results: 7 IT trials were analyzed (n=1,041), 22 arms received single agent CT (n=1,202), and 24 doublet CT (n=708). The pooled ORR was: 21.2% (95%CI: 14.9-29.2) with IT, 14.2% (95%CI: 11.1-17.9) with single agent CT and 31.9% (95%CI: 27.3-36.9) with doublet CT. Pooled mPFS was 1.8, 2.69 and 4.05 months, respectively. Pooled mOS was 8.27, 6.98 and 8.50 months. Pooled median ORR and mOS of IT for PD-L1+ pts were: 30.7% (95%CI: 23.2-39.2) and 11.60 months. Results of UVA and MVA are shown in the table. Only UVA was possible for PD-L1+ pts. Conclusions: Among trials of salvage therapy for mUC, IT was associated with significantly higher ORR and mOS in PD-L1+ pts compared with single agent or doublet CT, while significant differences were not seen in unselected pts. These results are hypothesis-generating and suggest the importance of developing companion predictive biomarkers. [Table: see text]
Postoperative mortality after esophageal and gastric cancer surgery: Does age still matter? Results from a nationwide study.
Authors: Christophe Mariette, Arnaud Pasquer, Florence Renaud, Flora Hec, Anne Gandon, Marguerite Vanderbeken, Sebastien Degisors, Gilbert Caranhac, Guillaume Piessen
Journal: Journal of Clinical Oncology (2017)

122 Background: More than age, patient comorbidity is increasingly considered as the prominent predictor of postoperative mortality (POM) in esophageal and gastric cancer surgery, leading a growing number of elderly to be operated on. However, the respective impact of age and comorbidity on POM remains to be elucidated. The study objective was to investigate the impact of age on POM according to patient comorbidity. Methods: All consecutive patients who underwent esophageal or gastric cancer surgery between 2010 and 2012 in France were included (n = 11,196). The 30-day POM was compared by age groups (20-39, 40-59, 60-79, ≥ 80) and stratified according to the Charlson score (0, 1-2, ≥ 3). The consistency across esophageal (n = 3286) and gastric (n = 7910) subgroups and variations between 30-day and 90-day POM were analyzed. Results: Patients ≥ 60 years represented 73.8% of cases. A linear increase in 30-day and 90-day POM was observed with increasing age, with rates of 0.9% and 2.1%, 2.4% and 5.4%, 4.8% and 8.8%, and 9.3% and 15.9% in 20-39, 40-59, 60-79, ≥ 80 years age groups, respectively ( P&lt; 0.001). Comparing 20-39 and ≥ 80 years age groups, 30-day POM was 1.0% vs. 7.0% for Charlson 0 ( P&lt; 0.001), 3.1% vs. 11.1% for Charlson1-2 ( P&lt; 0.001) and 0% vs. 19.5% for Charlson ≥ 3 ( P= 0.020) patients. A similar linear increase of POM by growing age groups was observed for 90-day POM and in esophagus and stomach subgroups. By multivariable analysis age groups (OR 1.03 95%CI 1.02-1.04, p &lt; 0.001) and Charlson score (OR 1.56 95%CI 1.43-1.70, p &lt; 0.001) were independent predictors of POM. Conclusions: Age and patient comorbidity have a similar and cumulative impact on POM after esophageal and gastric cancer surgery.
Strategies to Improve Cancer Photothermal Therapy Mediated by Nanomaterials
Authors: Duarte de Melo‐Diogo, Cleide Pais‐Silva, Diana R. Dias, André F. Moreira, Ilídio J. Correia
Journal: Advanced Healthcare Materials (2017)

The deployment of hyperthermia-based treatments for cancer therapy has captured the attention of different researchers worldwide. In particular, the application of light-responsive nanomaterials to mediate hyperthermia has revealed promising results in several pre-clinical assays. Unlike conventional therapies, these nanostructures can display a preferential tumor accumulation and thus mediate, upon irradiation with near-infrared light, a selective hyperthermic effect with temporal resolution. Different types of nanomaterials such as those based on gold, carbon, copper, molybdenum, tungsten, iron, palladium and conjugated polymers have been used for this photothermal modality. This progress report summarizes the different strategies that have been applied so far for increasing the efficacy of the photothermal therapeutic effect mediated by nanomaterials, namely those that improve the accumulation of nanomaterials in tumors (e.g. by changing the corona composition or through the functionalization with targeting ligands), increase nanomaterials' intrinsic capacity to generate photoinduced heat (e.g. by synthesizing new nanomaterials or assembling nanostructures) or by optimizing the parameters related to the laser light used in the irradiation process (e.g. by modulating the radiation wavelength). Overall, the development of new strategies or the optimization and combination of the existing ones will surely give a major contribution for the application of nanomaterials in cancer PTT.
Detection of prognostically distinct subpopulations in non-small cell lung cancer patients treated with epidermal growth factor receptor (EGFR) inhibitors
Authors: D. J. Stewart
Journal: Journal of Clinical Oncology (2007)

18178 Hypothesis: In patient survival curves that follow 1 st order kinetics, prognostically distinct subpopulations will be identified by inflection points in plots of log % survival vs time. Prognostically important dichotomous variables (present vs absent, or above vs below a threshold) will give inflection points while important continuous variables will shift curve slope without giving inflection points. Methods: For overall and progression-free survival curves from 35 published clinical trials of EGFR inhibitors, curve height at different times was measured manually and converted to % of height at time 0. Curve nonlinear regression analyses were performed using the Pharsight WinNonlin 5.0.1 program. Results: In assessments done to date, the most common survival curve pattern was conformity to a 2-compartment model, indicating a single inflection point and ≥ 2 prognostically distinct subpopulations. The second most common pattern was conformity to a 1-compartment model, suggesting that some populations are relatively homogenous. Only a minority of curves could be fit to 3-compartment models that would have indicated ≥ 3 distinct subpopulations. In different studies, EGFR inhibitors shifted some patients from poorer to better prognosis compartments compared to placebo, and/or decreased the slope (ie, increased the t1/2) of one or both individual compartments. Similarly, factors that have been found to be associated with prognosis in these studies were associated with formation of prognostically homogeneous groups or with alterations of relative compartment sizes or slopes. Conclusions: It is feasible to perform nonlinear regression analysis of log-linear survival plots to define prognostically distinct subpopulations. Preliminary assessments suggest that EGFR inhibitors and factors known to be important prognostically are associated with alteration of size and survival t1/2 of these subpopulations. Helpful data that could potentially be obtained from such analyses include minimum number, size and t1/2 of prognostically distinct subpopulations, and impact of a therapeutic modality or potential prognostic factor on each subpopulation. No significant financial relationships to disclose.
Survivorship care plan utilization and challenges.
Authors: Patti Migliore Santiago, Rose Guerrero, Chinmaya Rajderkar, Carol Vanevenhoven
Journal: Journal of Clinical Oncology (2017)

68 Background: Based on June and Dec. 2015 Survivorship Retreats hosted by WA Alliance for Cancer Survivorship (WACS), it was clear that staffing models, use of EMRs, cancer registry software programs or commercial products were program dependent with limited flexibility for facilities to adopt a single, state-wide, Survivorship Care Plan (SCP) model. Attendees at the retreats were concerned with financial sustainability of SCPs as the Commission on Cancer (CoC) requirement increased from 10-25-75% of all eligible patients by Dec. 31, 2018. The largest concern was the time spent on the preparation of the SCP. WACS wanted to validate resource needs across settings to identify needs/gaps being experienced. We asked the American Cancer Society (ACS) to conduct a survey of CoC accredited hospitals. Results would be limited to aggregate data and individual confidentiality would be maintained. Methods: ACS field staff made in-person appeals to each accredited program leveraging their existing relationship with CoC Liaisons. A 60% survey completion goal was set. A secure electronic survey was deployed in February. ACS staff promoted the project, followed up on non-responders, aggregated the data and prepared the results report. Results: We achieved a 70% participation rate for accredited programs. 75% of rural facilities, 71% urban but only 50% suburban facilities participated. Results showed they were spending 45 minutes to 2 hours to gather data to prepare the SCP and an equal amount of time being devoted to the patient SCP visit. There is a clear need and desire to have an efficient data gathering process for surveillance recommendations, latent side effect management and ready access for cancer site specific supportive care resources to reduce the time spent in preparation/delivery of the SCP and create a sustainable financial model. Conclusions: The transition from active treatment to survivorship care is a complex process, complicated by residual symptoms, educational needs and health risks. Our baseline information will inform our efforts to streamline the development of SCP as programs work to meet CoC goals. We plan to develop a survey to examine survivors recall and adoption of SCP recommendations to measure how SCPs are improving patient and facility outcomes.
Comprehensive genomic profiling of anal squamous cell carcinoma to reveal frequency of clinically relevant genomic alterations in the PI3K/mTOR pathway.
Authors: Eric M. Sanford, Siraj Mahamed Ali, Julia Andrea Elvin, Garrett Michael Frampton, James Sun, Norma Alonzo Palma, Juliann Chmielecki, Roman Yelensky, Doron Lipson, Vincent A. Miller, Philip J. Stephens, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2015)

3522 Background: Anal squamous cell carcinoma (ASCC) is an HPV-associated rare tumor that has nearly doubled in incidence since 1973, with cisplatin-based chemotherapy as the only treatment shown to be effective for patients with metastatic disease. We performed comprehensive genomic profiling (CGP) on 70 patients with ASCC to identify the spectrum of clinically relevant genomic alterations (CRGA). Methods: DNA was extracted from 40 microns of FFPE sections. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 692X for the entire coding regions of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. CRGA were defined as GA linked to FDA-approved agents or investigational agents in clinical trials. Results: There were 48 female and 22 male patients with a median age of 59.5 years (range 31-88). Three tumors (4%) were grade 1, 33 (47%) were grade 2, and 34 (49%) were grade 3. At the time of sequencing, 5 (7%) cases were stage II, 13 (19%) were stage III, and 47 (67%) were stage IV, with staging information unavailable for 5 (7%) patients. HPV-16 or HPV-18 was detected in 61 (87%) tumors: 59 were positive for HPV-16 and 2 were positive for HPV-18. CGP revealed 238 GA (3.4 per tumor), 111 of which were CRGA (1.6 per tumor). At least one CRGA was detected in 53 (76%) cases. The most common CRGA were in PIK3CA (27 cases; 39%), PTEN (10 cases; 14%), and FBXW7 (8 cases; 11%). For the 9 (13%) tumors where HPV DNA was not detected, a significant enrichment of LOF mutations was observed in TP53 (6 of 8 altered cases; p < 0.0001) and CDKN2A(5 of 5 altered cases; p < 0.0001). Clinical outcomes for PI3K/mTOR pathway-altered patients are being investigated. Conclusions: ASCC features a high rate of potentially targetable PI3K/mTOR pathway alterations, with 37 (53%) tumors harboring alterations in PIK3CA, PTEN, or FBXW7—a mutational profile similar to HPV positive head and neck and cervical SCC. The enrichment of TP53 and CDKN2A alterations in tumors where HPV DNA was not detected was similarly found in HPV negative head and neck squamous cell carcinoma, suggesting a distinct route to carcinogenesis for HPV negative ASCC.
NESC multicenter phase II trial in the preoperative treatment of gastric adenocarcinoma with chemotherapy (docetaxel-cisplatin-5FU + lenograstim) followed by chemoradiation (RTCT) based 5FU and oxaliplatin and surgery.
Authors: Laurent Mineur, Gael Deplanque, Francoise Desseigne, Laurence Moureau-Zabotto, Olivier Boulat, Khadifa Jalali, Denis Michel Smith, Stephane Obled, Mohamed Belkacemi
Journal: Journal of Clinical Oncology (2017)

95 Background: Perioperative chemotherapy is a standard treatment. The combination of Docetaxel- cddp-5FU(DCF) is a treatment in metastatic gastric cancer with high response rate. Preoperative RTCT is expected to increase the rate of curative resections and complete histological response. We investigate the efficacy of an optimal chemotherapy with DCF + lenograstim then preoperative RTCT with oxaliplatin - 5FU in gastric adk. Methods: Between 2009 and 2014, 33 patients with gastric adenocarcinoma(adk) were included. Inclusion criteria adk of stomach, cardia, Siewert II, III, according to staging classification T2bT3T4anyNM0 optional laparoscopy. Treatment consisted of 2 cycles docetaxel 75 mg/m2 I.V. day 1, cddp 75 mg/ m2 I.V. day 1, 5-FU 750 mg/m2 continuous infusion for 120 h, every 3 weeks and lenograstim followed by RTCT delivered in 25 daily fractions of 1.8 Gy in 5 weeks with 5Fu 250mg/m2 continuous infusion per day on days 1 to 35 and oxaliplatin 85mg/m2 day 1-14-28. Surgery was performed 4-6 weeks after RTCT. The primary endpoints were pathological response rate and secondary PFS, overall survival, morbidity and post operative mortality, toxicity. Results: 33 patients were included, 1patient progressive disease(PD) after 2 cycles of DCF, 32 patients received RTCT and 2 patients PD after RTCT, 1 patient refused surgery. 29 patients were operated and 3 non resected (peritoneal metastasis). 26 patients underwent surgery after RTCT (total gastrectomy n = 12, total gastrectomy and diaphragm surgery n = 1 lewis santy n = 11, subtotal gastrectomy n = 1, Enlarged gastrectomy transverse colectomy and partial pancreatic n = 1 D1 (n = 5) and D2 (n = 21) R0 resection rate was n = 26/26. Postoperative morbidity (n = 12) and mortality (n = 2), histology mean nods examined and involved respectively 16 and 2,5. pT0pN0 23% pT1pN0 19% pTpN2N3 20% others 38%. &lt; 10% residual tumor 27% histologic complete response 23%. Conclusions: Promising results from trials involving preoperative chemoradiation followed by surgery in gastric cancer need to be further evaluated in a Phase III and compared with perioperative CT. Clinical trial information: NCT01565109.