tbuckley/cabot-search huggingface dataset:
Adherence to Children’s Oncology Group (COG) long-term follow-up guidelines for echocardiogram screening in young adult survivors of childhood cancer.
Authors: Nicholas Andrew Madden, Claudia Deng, Taylor Fitch, Karen Elizabeth Effinger, Chao Zhang, Subir Goyal, Sibo Tian, Mary M Batcha, Susmita Parashar, Bree Ruppert Eaton, Natia Esiashvili
Journal: Journal of Clinical Oncology (2018)

e22513 Background: Late morbidity is of increasing importance with improved survival from childhood cancer. The COG Long-term Follow-up Guidelines recommend echocardiogram screening in patients who received cardiotoxic treatments, with high risk patients receiving more frequent echos. We assessed adherence to screening guidelines and cardiotoxicity rates in a young adult (YA) survivor cohort. Methods: We reviewed survivors of childhood cancer seen in our YA clinic from 2005-14 who received cardiotoxic treatment. Ever smokers were those who currently or previously smoked. COG high-risk patients were those with recommended annual screening. Cardiomyopathy was defined as an EF < 50%, symptomatic heart failure, or requiring medications. Echo screening adherence was defined as the COG recommended interval +/- 6 months. One-way ANOVA test and Kruskal-Wallis test were performed for numerical covariates. χ2was used for categorial covariates. A multivariable logistic regression was fit by a backward variable selection method with an a = 0.2 removal criteria. Results: 94 consecutive survivors (median age 28, range 24-51, time off therapy 13.1 years, time in YA survivor clinic 4.3 years) were identified. Patients were mostly white (77%); employed (70%); and insured at last follow up (87%). 9 had a lapse in insurance. 87 received anthracyclines (median dose 210 mg/m2); 46 received radiation involving the heart. 69.6% of patients were adherent to echo screening guidelines. Insured patients were more likely to adhere to screening (OR 5.67 (1.15-28.02)), while longer follow up in survivorship clinic was associated with non-adherence (OR 0.77 (0.63-0.94)). Cardiomyopathy was found in 17 patients (18.1%). Ever smokers (p = 0.012, OR 5.56 (1.46-21.13)) and COG high risk patients (p = 0.016, OR 4.28 (1.31-13.99)) were at higher risk for cardiomyopathy. Conclusions: Participants in our program had high adherence to COG guidelines. Insurance lapses and longer follow up were associated with not receiving recommended screening. Ever smokers and COG high risk patients were at highest risk of cardiomyopathy and should be targeted for adherence initiatives.
Hypogonadism and effects on quality of life in previously treated germ cell tumor survivors: A single-centre, non-randomized, prospective observational study.
Authors: Nabin Khanal, Maitri Kalra, Shahid Sattar Ahmed, Trent James Miller, Nasser H. Hanna, Patrick O. Monahan, Timothy E. Stump, Victoria Champion, Mary J. Brames, Somer Case-Eads, Kayla Marie Lazzara, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2018)

10079 Background: Prior studies have shown that around 12% to 16% Germ Cell Tumour (GCT) survivors can have subnormal serum testosterone level as well as up to 15% reported decreased health related Quality of life (QOL). It is important to identify the correlation of hypogonadism with QOL scores in survivors of GCT. Methods: This is a single-centre, non-randomized, prospective observational study in GCT survivors 18-50 yrs of age previously treated with Surgery and Chemotherapy or Surgery alone. Total testosterone was measured at baseline, 3, and 6 months. Patients completed a validated QOL questionnaire at baseline, 3, and 6 months. Patients could get supplemental testosterone as standard of care. Mean QOL scores were compared between two treatment groups and within each group between survivors with hypogonadism (serum testosterone level < 300 ng/dL) versus without ( > 300 ng/dL). A two-sided independent-groups t test was used to compare means. Results: We evaluated 199 GCT survivors. At baseline, the prevalence of hypogonadism was 48.2% overall, 51.45% in Chemo + Surgery group (C) and 44.7 % in surgery alone (CN) (p = 0.39). Overall, there was no statistically significant difference in QOL scores between two groups, except the C group exhibited greater Aging Male Symptoms (AMS) on the AMS scale score than the CN group, at baseline and 6 months. However, compared to patients with testosterone ≥ 300, patients with hypogonadism reported more fatigue (p = .04), poor sleep quality (p = .02) and worse general health (p = .006) at baseline. There was no statistically significant difference in depression (p = .33), or sexual functioning (satisfaction, p = .44; interest, p = .56; ability to have an erection, p = .23). There were no statistical differences in QOL between testosterone groups at 3 months or 6 months; however, sample sizes were small for participants who were measured on the testosterone at 3 months and 6 months. Conclusions: GCT survivors treated with chemo exhibited greater Aging Male Symptoms compared to chemo naive group. Hypogonadism was associated with sleep disturbance, worse energy and lower general health QOL scores at baseline.
Relationship between level of PD-L1 expression and outcomes in the KEYNOTE-010 study of pembrolizumab vs docetaxel for previously treated, PD-L1–Positive NSCLC.
Authors: Paul Baas, Edward B. Garon, Roy S. Herbst, Enriqueta Felip, Jose Luis Perez-Gracia, Ji-Youn Han, Julian R. Molina, Joo-Hang Kim, Catherine Dubos Arvis, Myung-Ju Ahn, Margarita Majem, Mary J. Fidler, Fabrice Barlesi, Gilberto Castro, Marcelo Garrido, Yue Shentu, Gregory M. Lubiniecki, Ellie Im, Dong-Wan Kim
Journal: Journal of Clinical Oncology (2016)

9015 Background: In the phase III KEYNOTE-010 study (NCT01905657), pembrolizumab (pembro; MK-3475) provided superior OS over docetaxel (doce) in patients (pts) with previously treated, PD-L1–positive advanced NSCLC (P = 0.0008 for 2 mg/kg and P < 0.0001 for 10 mg/kg in the total [tumor proportion score (TPS) ≥ 1%] population). We assessed outcomes in KEYNOTE-010 when PD-L1 was further categorized as a TPS of 1%-24%, 25%-49%, 50%-74%, and ≥ 75%. Methods: Pts with progression after ≥ 2 cycles of platinum-doublet chemotherapy and PD-L1 TPS ≥ 1% assessed by IHC (22C3 antibody) were randomized to pembro 2 or 10 mg/kg Q3W or doce 75 mg/m2 Q3W for 24 mo or until progression, intolerable toxicity, or other reason. PD-L1 TPS 1%-49% vs ≥ 50% was a randomization stratification factor. Response was assessed centrally per RECIST v1.1 every 9 wk. Survival was assessed every 2 mo. Primary end points were OS and PFS; ORR was secondary. Pembro doses were pooled for this analysis. Results: Of the 2222 pts screened for PD-L1, 33.6% had TPS < 1% and were ineligible. Of the 1034 pts who met all eligibility criteria and enrolled, PD-L1 TPS was 1%-24% in 45.6% of pts, 25%-49% in 11.6%, 50%-74% in 15.3%, and ≥ 75% in 27.5%. Doce outcomes were similar regardless of TPS (Table). For pembro, OS, PFS, and ORR generally increased along with TPS, with the longest OS and PFS and highest ORR in pts with TPS ≥ 75% (Table). Pembro provided longer OS than doce in all 4 TPS categories evaluated. Conclusions: Increasing PD-L1 expression was associated with more favorable outcomes with pembro, but not with doce, verifying PD-L1 as a predictive biomarker for pembro in NSCLC. Pembro improved OS over doce even at the lowest TPS category assessed. Clinical trial information: NCT01905657.Pembro/Doce TPS 1%-24% n = 324/147 TPS 25%-49% n = 76/44 TPS 50%-74% n = 106/52 TPS ≥ 75% n = 184/100 OS Median, mo 9.7/8.5 9.8/9.9 15.8/8.2 16.6/8.2 HR (95% CI) 0.74 (0.56-0.96) 0.86 (0.51-1.45) 0.58 (0.36-0.95) 0.51 (0.36-0.73) P* .01 .29 .01 < .0001 PFS Median, mo 2.6/4.0 2.9/3.8 4.3/4.3 6.2/4.0 HR (95% CI) 1.08 (0.86-1.36) 0.95 (0.60-1.50) 0.78 (0.52-1.17) 0.52 (0.38-0.69) P* .74 .42 .12 < .0001 ORR, % 8.6/10.9 15.8/9.1 22.6/9.6 33.7/7.0 P* .76 .14 .01 < .0001 *P values are nominal.
Impact of intensity of post-treatment surveillance on survival in colorectal cancer.
Authors: Rebecca A Snyder, Chung-Yuan Hu, Amanda Cuddy, Amanda B. Francescatti, Jessica R. Schumacher, Y. Nancy You, Deborah Schrag, Daniel McKellar, David P Winchester, Benjamin D. Kozower, Caprice Christian Greenberg, George J. Chang
Journal: Journal of Clinical Oncology (2017)

10016 Background: The optimal strategy for CRC post-treatment surveillance is unknown. The frequency and type of testing remains controversial, and it is unclear whether surveillance impacts rates of detection or survival. The purpose of this study was to determine if the intensity of post-treatment surveillance is associated with time to recurrence detection, treatment, or overall survival (OS). Methods: Primary records of a random sample of 10,636 Stage I-III CRC patients from Commission on Cancer accredited hospitals (2006-2007) were abstracted, and detailed results of surveillance testing were reviewed. Data was merged with records in the National Cancer Database (NCDB). A predicted and observed number of imaging and CEA tests per patient were determined and clustered by hospital to categorize patients into high (HI, O/E ≥ 1) or low intensity (LI, O/E &lt; 1) categories. Results: 6,279 patients underwent imaging or CEA surveillance in the 3 years after CRC treatment. Patients with HI imaging (50.6%) or CEA (51.2%) had a mean of 2.9 imaging studies and 4.7 CEA tests. Patients with LI imaging underwent a mean of 1.4 imaging studies and 1.6 CEA tests. 5-year recurrence rates did not differ based on intensity of surveillance. Stage II and III patients who underwent HI imaging and CEA testing had a slightly higher resection rate, but this did not translate into an improvement in 5-year OS. Conclusions: High vs. low intensity surveillance was not associated with earlier detection of recurrent disease or improved OS. HI surveillance was associated with a slightly higher resection rate, but this did not result in a survival benefit. Our findings within a national hospital registry cohort failed to demonstrate a survival benefit of HI surveillance and suggest that an effective surveillance strategy may involve less frequent testing. [Table: see text]
P04.75 Tibolone, an estrogenic progestin of hormone replacement therapy reduces colony formation and 3-dimensional spheroid S-phase in C6 rat glioma in vitro
Authors: M A Altinoz, A Bilir, A Ozpinar, O Baskan, I Elmaci
Journal: Neuro-Oncology (2018)

Risk of high-grade gliomas is lower in young females and its incidence enhances after menopause suggesting a likely protective role of female hormones. Hormone replacement therapy (HRT) is being employed to treat osteoporosis and some epidemiological studies showed that HRT containing progesterone analogs decrease the risk of glial tumors. Tibolone is a unique progesterone analog used in HRT with tissue-specific estrogenic effects. According to some studies, tibolone may enhance the risk of mammary and female reproductive cancers; but peculiarly, there exist several basic scientific data that it acts antitumoral at higher concentrations than which can be achieved in HRT. This feature resembles to another progesterone analog, medroxyprogesterone acetate (MPA). MPA enhances risk of breast cancer in HRT protocols; nonetheless, at high dosages, it can cause regression of far advanced breast, endometrium and renal cancers. Moreover, molecular studies have shown that MPA and tibolone induce very similar gene expression patterns. Since tibolone’s pro-estrogenic effects occur particularly in bone and brain, we have hypothesized that high dose tibolone with both progestagenic and estrogenic actions may block glioma growth alone and/or in synergy with MPA or temozolomide. Soft agar colony assay, 3H-thymidine test to determine the S-phase (DNA synthesis phase) and transmission electron microscopy were performed to determine the effects of tibolone on C6 rat glioma. Tibolone dose-dependently blocked soft agar colony growth of C6 glioma. Tibolone potentiated MPA-induced growth inhibition in soft agar colonies. Tibolone potentiated temozolomide’s effect in reducing colony growth. Tibolone inhibited DNA synthesis in C6 rat glioma spheroids (as assessed by BrdU-labeling index) to similar levels which can be achieved with temozolomide. Transmission electron microscopical analyses revealed that mutual interactions between tibolone, MPA and temozolomide involve mitochondrial condensation, mitophagy and autophagy. Tibolone merits to be studied in further models of glioblastoma in vitro and in vivo.
P01.091 A robust method for rapidly simulating TTFields distributions within patient-specific computational head models
Authors: N Urman, S Levi, A Frenkel, A Naveh, D Manzur, H S Hershkovich, C Wenger, E Kirson, Z Bomzon
Journal: Neuro-Oncology (2018)

Tumor Treating Fields (TTFields) are delivered to the brain through two pairs of transducer arrays placed on the patient’s scalp. TTFields distribution in the brain depends on the array’s position, patient anatomy and the electric properties of the tissues and tumor. We aim to create realistic computational patient models in order to understand how field distribution influences disease progression. However, preparation of such models is a highly time consuming task. In addition, in clinical scenarios, MRI acquisition time is often reduced by increased slice spacing, limited field of view, or increased scan speed, leading to difficulties in creating automated models. Our method is designed to enable model creation under those restrictions. It does so by using a realistic head model of a healthy individual used as a deformable template with which the patient model is derived. A highly detailed healthy head model serves as a deformable template from which patient models are created. The first step is pre-processing, involving denoising and background noise reduction, as well as super-resolution algorithms when needed. To create the patient model, the tumor is first segmented manually and masked, leaving only healthy tissues in the MRI, which is then registered to the template space to yield the transformation from patient space to template space. The template is then deformed into the patient space using the inverse transformation, and the tumor is placed back creating a full patient model. Next, automatic identification of landmarks on the patient’s head is used to position the transducer arrays on the head, which are then introduced into the model. Finally, boundary conditions are set, and field distribution is simulated using Finite Differences Time Domain (FDTD) method (Sim4Life V3.0, ZMT-Zurich). We have simulated TTFields distribution of 317 patients treated with TTFields as part of the EF-14 trial. Our method is optimized for accurate contouring of tissues highly influencing the distribution of electric field (Scalp, skull, CSF, ventricles), and it is robust, having the ability to give sufficient results even when MRI data quality is low. Thus enabling a study correlating the spatial distribution of TTFields and patient outcome. Our process for rapidly creating patient models presents a breakthrough that enables the first study in which the spatial distribution of therapeutic electric fields correlates with patient outcome. In the future this method can be used for clinical studies investigating other clinical indications of large datasets.
Effect of Spag5 on proliferation and sensitivity to DNA-damaging chemotherapy.
Authors: Wangjun Liao, Lezhong Yuan, Yuhao Luo, Huanrong Ma
Journal: Journal of Clinical Oncology (2017)

e15556 Background: Chemotherapy based on DNA-damaging anti-cancer drugs remains the most predominant treatment for advanced gastric cancer. The predictors for their sensitivity are under development. Our data showed that sperm-associated antigen 5 (Spag5) contributed to cancer cell proliferation and decreased DNA-damaging drug sensitivity in vivo and vitro. Methods: Spag5 mRNA expression were compared in The Cancer Genome Atlas (TCGA) and GEO datasets (GSE56807, GSE63089, GSE65801), while protein level were detected in 52 patients diagnosed with gastric cancer in Nanfang Hospital by immunohistochemistry. BGC-823 and MGC-803 were transfected with spag5 and control siRNA and then subjected to MTT and EDU assay to verify proliferation rate. Cell viability and apoptosis were tested in spag5-silenced BGC-823 and MGC-803 treated with oxaliplatin, epirubicin and 5-fluorouracil independently. DNA-damaged were detected by comet assay and yH2ax level with western blot. Treatment of oxaliplatin was given intraperitoneally to nude mice carrying xerographs of Shspag5 or control BGC-823 cells every three days. Results: Spag5 mRNA level was significantly upregulated in cancer tissues compared with paired normal tissues in all of the datasets. Immunohistochemistry shows higher protein level of spag5 in paired cancer tissue. Knockdown of Spag5 BGC-823 and MGC-803 showed a significantly decreased proliferation in both MTT and EDU assay. Spag5 silencing led to increase vulnerability to oxaliplatin, epirubicin and 5-fluorouracil, thus less cell viability and more apoptosis. Spag5 knockdown BGC-823 and MGC-803 subjected to DNA-damaging drugs showed upregulated yH2ax level and increased DNA damage in comet assay. Tumor growth rate were significantly reduced in shspag5 group and treatment of oxaliplatin led to relatively higher inhibition of tumor growth. Conclusions: Spag5 serves as a candidate to predict proliferation and chemosensitivity to DNA-damaging chemotherapy.
Survival outcomes in extensive stage small cell lung cancer patients treated with thoracic radiation.
Authors: Kristin Ann Higgins, Xinyan Zhang, Renjian Jiang, Rathi Narayana Pillai, Taofeek Kunle Owonikoko, Conor Ernst Steuer, Nabil F. Saba, Suchita Pakkala, Pretesh R Patel, Chandra Prakash Belani, Fadlo Raja Khuri, Walter John Curran, Suresh S. Ramalingam, Madhusmita Behera
Journal: Journal of Clinical Oncology (2017)

8565 Background: The benefit of consolidation thoracic radiation in extensive stage small cell lung cancer (E-SCLC) remains unclear. This study utilized the National Cancer Database (NCDB) to evaluate overall survival outcome (OS) for patients receiving chemotherapy (CT) alone for E-SCLC versus CT + thoracic radiation (TRT). Methods: The NCDB was queried to capture patients (pts) with stage E-SCLC from 2010-2013. Patients with brain metastases at diagnosis were excluded, as were patients receiving radiation prior to initiation of chemotherapy. Univariate association of OS was assessed using Cox proportional hazards models and log-rank tests. A multivariable Cox proportional hazard model and Kaplan-Meier analyses were performed to compare treatment with CT only to CT + TRT. Propensity score matching method was also implemented to reduce treatment selection bias. All analyses were performed using SAS Version 9.4. Results: A total of 14,367 (12,019 received CT, 2,348 received CT + TRT) pts were included in the analysis. Patient characteristics included a median age of 66 years; 66 years for pts receiving CT, and 63 for pts receiving CT + TRT (p &lt; 0.001). Male gender comprised 51% of pts; 52% in CT group versus 49% in CT + TRT (p &lt; 0.001). Charlson-Deyo comorbidity score was zero in 53% of all patients; 52% in the CT group versus 57% of CT + TRT group (p &lt; 0.001). In the CT + TRT group, the median total thoracic radiation dose was 45 Gy. On multivariate analysis, CT only was associated with an increased risk of death relative to CT+ TRT (HR 1.74 [1.65 – 1.84], p &lt; 0.001). 5 year OS was 7% vs. 2% for CT + TRT versus CT alone (p &lt; 0.001). On propensity matched analysis, CT + TRT was associated with better 5-year OS compared to CT alone (8% vs. 2%; p &lt; 0.001). On multivariate analysis of propensity matched samples, chemotherapy alone continued to be associated with worse survival (HR 1.76 [1.62 – 1.91], p &lt; 0.001). Conclusions: For E-SCLC, CT alone as standard of care is associated with worse survival relative to CT + TRT.
Clinical significance of the tumor expression of PD-L1 in lung cancer.
Authors: Luigi De Petris, Cristian Ortiz-Villalon, Lorand Kis, Salomon Tendler, Signe Friesland, Rolf Lewensohn
Journal: Journal of Clinical Oncology (2016)

e20031 Background: PD-L1 status in lung cancer may be a predictive biomarker for the use of PD1/PD-L1 inhibitors. Nonetheless, it is still a matter of debate which immunohistochemistry (IHC) platform for PD-L1 assessment should be implemented in order to obtain optimal prognostic and predictive information. We investigated whether the PD-L1 expression in early-stage lung cancer is associated with specific clinical features or survival Methods: PD-L1 status was assessed with IHC (AB clone SP124 Ventana) on archival FFPE surgical tumor specimens, arrayed on tissue microarrays (TMAs) with duplicate 1 mm cores. All patients (n = 532) had early stage T1/T2-N0 lung cancer and underwent curative surgery between 1987 and 2002. The following cases were excluded from survival analysis (n = 23): R1 resection, early post-operative mortality, adjuvant chemo- or radiotherapy. PD-L1 staining was scored as positive if present in > 5% of tumor cells, independently of staining intensity Results: Patient and tumor characteristics were: median age (IQR) 67 years (59-73), gender male/female 53%/47%, smoking status never/former/current/missing 8%/28%/55%/12%, histology squamous-cell carcinoma (SCC)/Non-squamous (N-Sq)-NSCLC/carcinoid 36%/56%/8%, p-stage IA/IB 52%/48%. Median overall survival was 79 months. PD-L1 was positive in 8% of cases, corresponding to 13% of SCC and 5% of N-Sq cases (Pearson Chi-square p = 0.001). All carcinoids were negative for PD-L1, except for one. In PD-L1 positive cases, the staining intensity and distribution had a homogenous pattern between the 2 TMA cores. In NSCLC, PD-L1 status was associated with tumor size (5% vs 11% in T1 and T2 cases, respectively; p = 0.01) and grade of differentiation (1% vs 6% vs 14% in G1, G2 and G3 tumors, respectively; p = 0.0002). No statistically significant association between PD-L1 expression and OS was observed in NSCLC, neither in the entire patient cohort nor in histological subgroups Conclusions: In this surgical series, PD-L1 was expressed in a minority of cases and provided poor prognostic information. Validation with other antibodies as well as additional evaluation on PD-L1 status in bystander inflammatory cells in relation to PD1 expression is ongoing