tbuckley/cabot-search huggingface dataset:
Immunoscore based on PD-L1/PD-1 and CD8+ T cells as prognostic marker for stage II/III gastric cancer.
Authors: Ti Wen, Xiujuan Qu, Yi Li, Zhi Li, Xiaofang Che, Yibo Fan, Shuo Wang, Ling Xu, Na Song, Yunpeng Liu
Journal: Journal of Clinical Oncology (2017)

69 Background: PD-L1/PD-1 pathway has become an important target in tumor immunotherapy. However, the prognostic value of PD-L1/PD-1 for gastric cancer (GC) remains controversial due to the complexity of immune response. Therefore, comprehensive evaluation of PD-L1/PD-1 expression and CD8 + T cells is necessary and superior to one factor in predicting survival. Methods: 166 patients with stage II-III GC were enrolled. Expression of PD-L1, PD-1, and CD8 protein in tumor tissues was examined by IHC staining, and their association with patient’s survival was analyzed by Kaplan-Meier method. Immunoscore classification was constructed using a scoring system, which was based on hazard ratios in a Cox proportional hazard analysis. Results: Expression of PD-L1 was found in 22.29% of immune cells (IC) and 38.55% of tumor cells (TC), while expression of PD-1 was found in 31.33% of IC. CD8 High was detected in 41.57% patients. PD-L1 + and PD-1 + IC were both correlated with worse overall survival (OS) ( P=0.0009 and P=0.0004, respectively). In contrast, TC PD-L1 + was associated with better clinical outcomes, including Borrmann classification 0-1, lower AJCC stage, CD8 High infiltration and better OS ( P&lt;0.05). Furthermore, IC PD-L1, IC PD-1, CD8, and TC PD-L1 had independent prognostic significance after TNM stage adjustment, and we built an immunoscore system based on these immune factors. Patients with same stage could be further categorized into low-/median-/high-risk subgroups according to their immunoscores. Conclusions: Immunoscore based on comprehensive evaluation of PD-L1/PD-1 and CD8 + T cells can separate GC patients with same stage into different risk subgroups, and might provide suggestion for immunotherapy options in GC.
Computer-aided bone scan lesion area quantitation: Inter-reader measurement variability.
Authors: Gregory H. Chu, Matthew S. Brown, Hyun J. Kim, Andrew Kaplan, Katherine Yang, Martin Allen-Auerbach, Cheryce Poon, Benjamin Levine, Christiaan Schiepers, Ramesh Verma, Juliette Bridges, Adria Vidovic, Bharath Ramakrishna, Judy Ho, Howard I. Scher, Jonathan Goldin
Journal: Journal of Clinical Oncology (2013)

e16019 Background: Bone scan is essential for response assessment in subjects with metastatic prostate cancer. However, visual assessment is subjective and prone to inter-reader variability. A commercial computer-aided (CAD) system for bone scan lesion area (BSLA) calculation has been developed (MedQIA, LLC). BSLA provides an objective and sensitive measure for response assessment. New VEGF treatments showing promising results in reducing lesion burden on bone scan present an urgent need for validated systems capable of accurately assessing treatment response. Measurement of inter reader variability is fundamental to such a validation. In this work we measure inter-reader variability in quantitation of BSLA change using the CAD system. Methods: In a multi-center clinical trial of cabozantinib (Exelixis, Inc), bone scans were acquired according to a standardized imaging protocol. Scans at baseline and Week 12 were available for 113 subjects for this analysis. Automated CAD lesion detection was performed following image intensity normalization to increase consistency between subject time points. Two nuclear medicine physicians independently edited and approved the CAD result as needed, primarily to remove false positives due to degenerative joint disease. The system then calculated the percent change in BSLA at Week 12 from baseline (BSLAPCT). The BLSAPCT values from the two readers were compared to assess inter-reader variability. Additional analytic validation of the BSLA measure was performed in which the readers provided a categorical assessment of responder vs non-responder, using the CAD-normalized images, and the classification performance of BSLAPCT was assessed using ROC analysis. Results: The median (IQR) difference in BSLAPCT between the two readers was -1.8 (20.0) percentage points. The absolute difference was 9.4 (23.9) percentage points. The BSLAPCT response classification had an ROC area under curve (AUC) of 0.96 for both readers. Conclusions: Computer-aided quantitative assessment of change using bone scan lesion area demonstrated low variability between two readers. This is an important step toward the validation of an objective, quantitative, and sensitive response assessment technique.
Government “must get tough” on food companies that miss sugar reduction targets
Authors: Anne Gulland
Journal: BMJ (2017)

Campaigners are urging the government to introduce legislation if the food industry does not cut back on sugar, as new guidelines from Public Health England (PHE) set out how the industry should meet targets aimed at reducing childhood obesity.1

The government’s childhood obesity strategy, published last year to charges that it was “weak” and “underwhelming,”2 set out voluntary targets for food manufacturers to reduce the sugar in their products by 5% by the end of this year and 20% by 2020.

The PHE guidelines, based on more than six months of meetings with the food industry and public health organisations, say that the industry could meet these targets by …
Routine molecular profiling of solid tumors in a community cancer center's genomic pathology laboratory.
Authors: Shelly Gunn, Xavier Reveles, Lon S. Smith, Gladys Isabel Rodriguez, Amita Patnaik, Muralidhar Beeram, Kyriakos P. Papadopoulos, Drew Warren Rasco, Anthony W. Tolcher
Journal: Journal of Clinical Oncology (2013)

e22088 Background: Selection of targeted therapeutics for solid tumors depends upon detection of actionable genomic alterations in archival tissue. High-throughput molecular profiling at the community level would allow local pathologists to participate with oncologists in the delivery of personalized cancer medicine. Methods: Between March and December 2012, molecular profiling was performed on FFPE tumor tissue sent to Oncopath (our in-house CAP/CLIA genomic pathology laboratory) from 330 patients with diverse types of metastatic and non-resectable solid tumors. Tumor-targeted DNA was analyzed for genome-wide copy number alterations by array-based comparative hybridization (CGH), and mutation analysis (MA) using multiplex PCR with mass spectrometric genotyping (mass spec), or single gene allele-specific PCR (PCR). Results for 96 actionable genes analyzed by CGH, and MA were correlated with clinically or pre-clinically available targeted therapeutics. Actionable biomarkers for FDA approved therapies (e.g. BRAF V600E/vemurafenib) and prospective biomarkers for Phase I/II trials (e.g. CCND1 gene amplifications and CDKN2A gene deletions/CDK inhibitors) were reported for each patient. Results: Of 330 cases, 216 had at least one and as high as seven actionable biomarkers. The remaining 114 cases had either no tumor specific changes (n=17) or non-actionable oncogenic changes (n=97). The most commonly analyzed tumors were breast, brain, lung, colorectal, pancreatic, head &amp; neck, and ovarian. Rare tumor types with positive biomarkers included an HRAS Q61R positive adenoid cystic carcinoma and a BRAF V600E positive pleomorphic xanthroastrocyoma. Tumor DNA was stored for 100% of patients and all cases were reported synoptically listing actionable biomarkers with therapeutic recommendations. Conclusions: Molecular profiling in a community cancer center facilitates biomarker detection for rational direction of patients to targeted therapeutics. New technologies for detection of actionable biomarkers will continue to be implemented in our center to improve the likelihood of effective treatment for each individual patient’s tumor.
Insulin and Glucagon-Like Peptide 1 Receptor Agonist Combination Therapy in Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Maria Ida Maiorino, Paolo Chiodini, Giuseppe Bellastella, Annalisa Capuano, Katherine Esposito, Dario Giugliano
Journal: Diabetes Care (2017)

OBJECTIVE The combination of basal insulin plus a glucagon-like peptide 1 receptor agonist (GLP-1RA) has been proposed as a treatment option to intensify insulin therapy in type 2 diabetes. We performed a meta-analysis of randomized controlled trials (RCTs) comparing this combination strategy to other injectable antidiabetes treatments on metabolic control in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted an electronic search until November 2016 on many electronic databases to identify RCTs assessing changes in HbA1c, proportion of patients at HbA1c target ≤7% (53 mmol/mol), hypoglycemia, and weight change. We used a random-effect model to calculate the weighted mean difference (WMD) or relative risk (RR) with the 95% CI. RESULTS We identified 26 RCTs, lasting 12–52 weeks, and involving 11,425 patients. When the combination strategy was compared with other injectable treatments (overall data), there were reductions in HbA1c (WMD = −0.47%, 95% CI −0.59 to −0.35), more patients at HbA1c target (RR = 1.65, 95% CI 1.44–1.88), similar hypoglycemic events (RR = 1.14, 95% CI 0.93–1.39) and a reduction in weight (WMD = −2.5 kg, 95% CI −3.3 to −1.7), with high heterogeneity (I2 &amp;gt; 89%, P &amp;lt; 0.001) and a significant publication bias for three outcomes. In preplanned subgroup analyses, the combination treatment was similar to basal-bolus insulin regimens for glycemic control, with less hypoglycemia (RR = 0.66, 95% CI 0.46–0.93) and reduced weight (WMD = −4.7 kg, 95% CI −6.9 to −2.4). Fixed-ratio combinations yielded results similar to the overall analysis (HbA1c WMD = −0.56%, 95% CI −0.72 to −0.40). CONCLUSIONS GLP-1RAs alone or as titratable fixed-ratio combinations with basal insulin may represent a promising option to advance basal insulin therapy or to initiate injectable therapy in patients with type 2 diabetes inadequately controlled on oral agents. Longer studies are needed to assess durability and tolerability.
Public health preparedness for two mass gathering events in the context of pandemic influenza (H1N1) 2009 - Serbia, July 2009
Authors: G Loncarevic, L Payne, P Kon, V Petrovic, D Dimitrijevic, T Knezevic, S Medić, N Milic, J Nedelijković, K Seke, D Coulombier
Journal: Eurosurveillance (2009)

Preparedness planning for two large mass gatherings events were considered in Serbia in the context of pandemic influenza (H1N1) 2009. Planning included approaches to prevention, detection and response in order to mitigate the situation at this early stage of the epidemic in Serbia. Cases of influenza A(H1N1)v were identified nationally immediately prior to the mass gatherings but also identified in association with both events, as expected in the context of the pandemic situation. This article describes the experiences of planning and the epidemiological situation during the period of the mass gathering events.
Laparoscopy compared to laparotomy in the management of granulosa cell tumors of the ovary.
Authors: John Nakayama, James Edwards, Jessica E. Stine, Elizabeth Pelkofski, Paola A. Gehrig, Angeles Alvarez Secord, Linda R. Duska
Journal: Journal of Clinical Oncology (2014)

e16510 Background: Minimally invasive surgery (MIS) has gained increasing acceptance as an alternative to standard laparotomy in gynecologic cancer, but surgical approach with respect to non-epithelial ovarian cancers has not been extensively studied. We compared perioperative and long-term outcomes of women with ovarian granulosa cell tumors (GCTs) who underwent laparoscopy versus laparotomy. Methods: Inclusion criteria were surgical treatment and stage I-IV GCTs. Abstracted data included: surgical modality (laparoscopic vs open), demographics, operative details, and disease course. Survival was analyzed using the Kaplan-Meier method and Cox model. The chi square test of association, Wilcoxon rank-sum test and t-test were used for the group comparisons. Results: 166 women with ovarian GCTs were identified of which 160 were evaluable; 32 and 128 underwent laparoscopy and laparotomy, respectively. The overall survival (OS) and disease-free survival (DFS) were not significantly different between those treated with laparoscopy and laparotomy (OS 92% vs 77%, p=.42; DFS 55 vs 47%, p=.79). Advanced age at diagnosis was associated with decreased OS (HR 1.04 95% CI [1.01-1.07], p=.013). MIS was associated with lower EBL (106 vs 430cc, p<.001), earlier discharge (1.5 vs 4.2 days, p<.001), smaller tumor size (7.9 vs 15.7cm, p<.001), and fewer complications (3.4 vs 19.2%, p=.039). There was no difference in age (p=.20), race (p=.37), BMI (p=.89), pre-operative Inhibin B (263 vs 786 pg/mL, p=.13), stage (p=.15), and intra-operative cyst rupture (p=.36). Conclusions: Our findings suggest that MIS is reasonable for women with GCT with similar survival outcomes compared to laparotomy. Laparoscopy was associated with lower EBL, earlier discharge, and fewer complications.
Infectious complications in AML patients treated with induction vs. hypomethylating therapy.
Authors: Marla M Jalbut, Andrew Mark Brunner, Philip C. Amrein, Eyal C. Attar, Karen K. Ballen, Gabriela Hobbs, Ashley M. Perry, Christelle P. Joseph, Donna S. Neuberg, Amir Tahmasb Fathi
Journal: Journal of Clinical Oncology (2015)

7065 Background: Infectious complications are common during AML treatment, partly related to cytopenias during standard induction. It is less clear whether the same degree of infectious complications occur with hypomethylating agents (HMAs), especially early in therapy. We compared incident infectious events, as well as death due to infection, among AML patients treated with HMAs vs. induction chemotherapy. Methods: We evaluated consecutive cases of newly diagnosed AML at Massachusetts General Hospital from 2010-2014, and identified 47 patients given upfront therapy with HMAs, and 126 given induction, typically “7+3.” The cumulative incidence of infectious events, including related death, was calculated by the method of Fine and Gray, with death/non-infectious death as a competing risk, as appropriate. Incidence rate ratios were calculated between groups. Survival was compared by the method of Kaplan and Meier and log-rank test. Results: Median follow-up was 596 days. Induction patients were younger (62 vs 76 y.o., p < 0.0001), and fewer had secondary AML (33% vs. 62%, p = 0.001). Patients given induction had improved CR/CRi rates (83% vs. 38%) and 1-year OS (64.2% vs. 35.3%) compared to HMAs. The 30-day cumulative incidence of febrile neutropenia (82.5% vs. 34.4%, p < 0.0001), bacteremia (23% vs. 8.6%, p = 0.0021), and colitis (18.3% vs. 4.4%, p = 0.0028) was higher with induction vs. HMA therapy, while incident cellulitis was lower (4.8% vs. 17.2%, p = 0.028). Induction patients also had an increased incidence rate of febrile neutropenia (IRR 7.07, p < 0.0001), and lower rate of cellulitis and UTI (IRR 0.26, p = 0.0006, and IRR 0.30, p = 0.0020, respectively). There was no significant difference in fungemia, pneumonia, non-invasive candida infection, nor the cumulative incidence of death due to infection at 120 days (4.0% induction vs. 4.3% HMA, p = 0.57). Conclusions: AML patients treated with induction had greater rates of febrile neutropenia, bacteremia, and colitis compared to those treated with HMA therapy, but lower rates of cellulitis and UTI. In spite of the marked increase in early infectious events during induction vs. HMA therapy, there was no significant difference in the cumulative incidence of death due to infection.
Early intervention of skin toxicities by panitumumab and clinical outcomes in the clinical setting.
Authors: Hagit Bergman, Tara Walton, Ryan Del Bel, Jack Toshimine Seki, Wei Xu, Gideon Koren, Neil Shear, Monika K Krzyzanowska, Doris Howell, Geoffrey Liu
Journal: Journal of Clinical Oncology (2014)

e20673 Background: Dermatologic toxicities from panitumumab can interfere with consistent cancer treatment. While treatment algorithms have been proposed for managing dermatologic toxicities, they are only stringently followed within a clinical trial setting. We assessed the impact of early versus late intervention of rash by initial grade in a cohort of patients treated outside of a clinical trial setting. Methods: We evaluated retrospectively the assessment and management of skin toxicities related to panitumumab in a consecutive cohort of patients receiving panitumumab for the treatment of metastatic colorectal cancer outside of a clinical trial from April 2009-August 2012. Results: Of 34 patients, 32 (94%) had a reported panitumumab-related skin toxicity (papulopustular rash). 85% developed the rash by the end of the second infusion cycle. A severity grading system was reported for 65% of patients: 31% used the CTCAE grading system, while 34% used mild/moderate/severe terminology; the remaining 34%, grading was performed by rash description in medical records. Rash was not related to clinicodemographic data. Among patients who initially presented with a mild rash (41%), the majority progressed when just observed without intervention, but all who received at least topical ointment (steroids or antimicrobial) remained stable or improved. The majority of patients presenting with a moderate rash (38%) were likely to get worse if they did not receive oral antimicrobials. Alternatively, among those presenting with a severe rash (21%), all improved to moderate rash after receiving oral antimicrobials (+/- topicals) but dose reductions and delays were also required. Conclusions: Dermatologic toxicities related to panitumumab are common. Early intervention, even with mild rash, reduces the risk of progression to more severe grades of skin toxicities.
Role of breast surgery in T1-T3 breast cancer patients with synchronous bone metastases.
Authors: Edoardo Botteri, Elisabetta Munzone, Vincenzo Bagnardi, Mattia Intra, Nicole Rotmensz, Barbara Bazolli, Bruno Montanari, Gaetano Aurilio, Angela Sciandivasci, Angela Esposito, Gianmatteo Pagani, Laura Adamoli, Franco Nole, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2012)

1115 Background: The role of breast surgery in advanced breast cancer (ABC) is controversial. The main potential advantage of removing the primary tumor is to eliminate the source of further metastatic spread. While previous studies addressed the question in very heterogeneous populations (e.g. patients with any local and distant extension), we have focused on a homogeneous series of ABC patients. Methods: From our institutional Tumor Registry we selected 191 consecutive women diagnosed between 2000 and 2008 with locally operable (T1-T3) ABC, synchronous bone metastases and no other distant sites involved. The progression free survival (PFS) was calculated from diagnosis to the date of progression, defined as either a new site of metastatic disease or clinical/radiographic evidence of increasing tumor burden at a previously known bone metastatic site. Results: Median age was 51 years and 92% of the women had an endocrine-responsive tumor. One-hundred and thirty patients out of 191 (68%) underwent surgery at the time of diagnosis, while 61 (32%) did not. Twenty-six of the operated patients (20%) had previously undergone neoadjuvant chemotherapy; 15 (12%) had positive or undetermined surgical margins. Operated and non-operated patients were similar with respect to age, tumor size, nodal involvement, estrogen and progesterone receptor status, HER2 overexpression and Ki-67, but differed in terms of number of bone metastatic sites: a single metastasis was detected in 34 (26%) operated and 7 (11%) non-operated cases (P=0.02). First-line treatment strategies with endocrine therapy, chemotherapy and Trastuzumab were similarly distributed between the two groups. The 5-year PFS was 22.0% and 10.4% in operated and non-operated patients, respectively. The multi-adjusted hazard ratio was 0.62 (95% confidence interval 0.39-0.98) in favor of surgery. The exclusion of the patients who had received neoadjuvant chemotherapy and patients with positive or undetermined surgical margins did not alter the results. Conclusions: In this large and homogeneous series of ABC patients with synchronous bone metastases, the role of breast surgery had a favorable impact on the progression of the disease, indicating a potential survival benefit.
Exposure–efficacy relationship of trastuzumab emtansine (T-DM1) in EMILIA, a phase III study of T-DM1 versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC).
Authors: Bei Wang, Jin Jin, Russell Wada, Liang Fang, Dan Lu, Ellie Guardino, Sandra M. Swain, Michael Untch, Sandhya Girish
Journal: Journal of Clinical Oncology (2013)

644 Background: T-DM1 is an antibody–drug conjugate composed of trastuzumab (T), a stable thioether linker, and the potent cytotoxic agent DM1. In the phase III study EMILIA, median PFS and OS were significantly prolonged with T-DM1 vs XL in patients (pts) with HER2-positive locally advanced or MBC previously treated with T and a taxane; (PFS hazard ratio [HR]=0.65, p&lt;0.001; OS HR=0.68, p&lt;0.001). We report the effects of T-DM1 exposure on efficacy outcomes in EMILIA. Methods: In EMILIA, pts were randomized 1:1 to receive T-DM1 3.6 mg/kg q3w (n=495) or XL (n=496) in 21-day cycles. Pharmacokinetic (PK) samples were from cycle 1 (n=350, T-DM1 arm only). Exposure variables were T-DM1 AUC, T-DM1 C min , total T AUC, and DM1 C max calculated by noncompartmental analysis. A logistic regression model was used to evaluate the relationship between T-DM1 exposure and objective response rates (ORR) in the T-DM1 arm. Multivariate Cox proportional hazards models were used to calculate HRs of OS and PFS for each T-DM1 exposure quartile vs all randomized pts in the XL arm, adjusting for baseline covariates. Results: For ORR, mean T-DM1 AUC was 536 day*ug/mL for responders and 502 day*ug/mL for non-responders (P=0.09); mean DM1 C max was 4.55 ng/mL and 4.64 ng/mL, respectively (P=0.64). OS and PFS HRs (and 95% CIs) of T-DM1 vs XL stratified by T-DM1 exposure quartiles are shown (Table). Conclusions: In EMILIA, no clear trends were observed between T-DM1 exposure and PFS, OS, or ORR, following administration of T-DM1 3.6 mg/kg q3w. However, there was a suggestion of improved OS HR by stratified T-DM1 C min quartiles, albeit with mostly overlapping 95% CIs. Ongoing T-DM1 clinical trials will further evaluate this potential relationship. [Table: see text]