tbuckley/cabot-search huggingface dataset:
Follow-up of early breast cancer (BC) patients by telephone or mobile software.
Authors: Johanna Mattson, Maria Peltola, Paula Poikonen-Saksela, Jenny Their, Terhi Hermanson, Niilo Färkkilä, Risto Roine, Carl Blomqvist
Journal: Journal of Clinical Oncology (2018)

e18883 Background: After primary treatment patients with local BC are followed-up for 5(-10) years. In 20% of the patients BC recurrence will be diagnosed later. All BC treatment modalities may cause long time morbidity. In 2000 at HUH CCC regular appointments during five year follow-up were reduced to three and a phone service operated by an experienced nurse was set up for patients who wanted counselling about symptoms related to side-effects or potential recurrence. In 2015 HUH CCC launched a mobile software for cancer patients. The primary end point was to find out patient preference for the modality of follow-up. Secondary endpoints were patient satisfaction, symptoms and quality of life during follow-up modalities. Methods: 765 patients with early breast cancer were randomized at the final visit of adjuvant radiotherapy to follow-up by phone calls or by mobile Noona software. Twenty-three patients discontinued the study, 7 due to disease recurrence (0.9%) and 16 for other reasons (2%). After six months the groups were crossed over to the other arm. At 12 months the patients were asked their preference. At baseline, 6 months and 12 months the patients answered the other questionnaires. Results: The median age was 61 years (range 28-83). 293 patients (39 %) did not contact the BC nurse during the first year. Preference was analyzed among the 143 patients who contacted the BC nurse at least once with both modalities. 40% of the patients preferred phone and 30% Noona while 30% considered both modalities equally good. The difference was not statistically significant. Most patients who preferred phone valued personal contact and the ones choosing Noona easiness to contact. In the whole patient population there was no difference in quality of life, symptoms or patient satisfaction between the modalities. Compliance was 98%. The cost of both follow-up modalities will be presented at the meeting. Conclusions: 30% of the patients prefer to contact BC nurse by mobile software rather than by phone. Compliance with both follow-up methods was excellent.
Hypoxia induced HIF1a-mediated O-GalNAc glycosylation of cytosolic O-GlcNAcylated proteins to regulate signaling pathways in pancreatic cancer.
Authors: Gerrit Wolters-Eisfeld, Baris Mercanoglu, Alina Strohmaier, Cenap Guengoer, Jakob R. Izbicki, Maximilian Bockhorn
Journal: Journal of Clinical Oncology (2017)

e15739 Background: Hypoxia induced reprogramming of cell energy metabolism and changes in glycosylation are hallmarks of cancer promoting the induction of an invasive and treatment-resistant phenotype, triggering metastases at an early stage of tumor development. We examined the impact of hypoxia on O-GalNAc glycosylation in human HEK293, PDAC cell lines and clinical specimens. Methods: We profiled the expression of 88 glycosylation related genes by qPCR in HEK293 cells subjected to hypoxia either induced by 1% O 2 or 200 mm CoCl 2 identifying key O-GalNAc glycosyltransferases downregulated. Functional assays and glycoprotein analysis displayed a pronounced rate of O-GalNAc modified cytosolic proteins derived from hypoxia treated cells and PDAC specimens. Glycosidase assays could validate specificity of detection method used. Aberrant glycotype could be induced by HIF pathway activator ML 228 and inhibited using Echinomycin. PTK and STK analysis of cell lysates displayed correlation between phosphorylation and O-glycosylation in hypoxic samples. Results: Mechanistically we could show, that hypoxia induced decreased levels of C1GALT1C1 results in reduced T-Synthase activity with subsequent expression of truncated O-glycans (Tn antigen). Differential O-GalNAc glycosylation is inducible using HIF pathway activator ML228 under normoxia and the effect is reversed using 5 µM Echinomycin under hypoxia underscoring the role of HIF1a regulated transcription. Interestingly, the pattern of Tn antigen modified proteins derived from hypoxic samples differs significantly from engineered COSMC deficient cells, displaying O-GalNAc moieties in addition to O-GlcNAc in cytosolic protein fractions. Conclusions: Our findings point to a novel crosstalk of O-GalNAc and O-GlcNAcylation under hypoxia extending the knowledge base of differential O-GalNAc glycosylation in pancreatic cancer.
EGFR to regulate angiogenesis in intact and tumor skin tissues in В16/F10 melanoma with chronic pain.
Authors: I. M. Kotieva, Oleg I. Kit, Elena M. Frantsiyants, Irina V. Kaplieva, Lidia K. Trepitaki, Valeria A. Bandovkina, Ludmila Ya. Rozenko, Natalia D. Cheryarina, Yulia A. Pogorelova
Journal: Journal of Clinical Oncology (2018)

e21632 Background: The tumor growth, invasion and metastasis require a pro-angiogenic trigger. The purpose of the study was to analyze the mechanisms of angiogenesis activation in tissues of tumor (T) and intact skin (IS) of female mice with chronic neurogenic pain in the dynamics of the В16/F10 melanoma development. Methods: The study included 64 female C57BL/6 mice weighing 21-22 g. B16/F10 melanoma cell suspension was injected to animals of the main group 2 weeks after the sciatic nerve ligation on both sides; the controls underwent the same procedure without the ligation. Levels of VEGF-A, VEGF-С, EGF, EGFR, IGF1 and IGF2 were determined by ELISA (CUSABIO BIOTECH Co., Ltd., China). The results were compared to the values in the skin of intact animals. Results: Levels of VEGF-A and VEGF-C in the skin of intact females with chronic pain demonstrated strong positive correlations with IGF1 (r1 = 81, r2 = 89; p1,2 < 0.01), IGF2 (r1 = 92, r2 = 79; p1,2 < 0.01) and EGF (r1 = 84; r2 = 92; p1,2 < 0.01). In IS of females of the main group, strong positive correlations were observed between VEGF-A and EGFR (r = 84; p < 0.01) and between VEGF-C and IGF1 (r = 81; p < 0.01). In IS of controls, VEGF-A and VEGF-C correlated with IGF2 until week 2 (r1 = 71, r2 = 69; p1,2 < 0.05), and then with IGF1 (r1 = 61, r2 = 59; p1,2 < 0.05). A moderate positive correlation of VEGF-A and EGFR (r2 = 67; p < 0.01) was found in tumor tissues in the main group; VEGF-А correlated with IGF1 and IGF2 (r1 = 73, r2 = 81; p1,2 < 0.05) in tumor tissues of controls. No correlations were found between VEGF-C and other growth factors in tumor tissues of all animals. Conclusions: Chronic pain was one of the factors modifying the course of the malignant process, in particular during neoangiogenesis and neo-lymphangiogenesis, and EGFR was one of the most important factors.
A population registry trend analysis of neoadjuvant chemotherapy and incidence of ovarian, peritoneal and fallopian tube carcinomas in England 2004-2015.
Authors: Rebecca Elleray, Cong Chen, Sean Kehoe
Journal: Journal of Clinical Oncology (2017)

e17037 Background: Two important developments in ovarian cancer have occurred over the last decade: i) EORTC 55971 and CHORUS trials reporting neoadjuvant chemotherapy as a management strategy in advanced disease and ii) recognition of fallopian tubes as the origin of many ovarian cancers. This study examines how these have impacted on care and registry data. Methods: The National Cancer Registry and Analysis Service (NCRAS) database identified women registered with ovarian, peritoneal and fallopian tube carcinomas during 2004-15. Treatment was defined as surgical intervention or chemotherapy starting within 6 months of diagnosis. Women were grouped into: Neoadjuvant chemotherapy, Primary surgery, Chemotherapy only, Surgery only or No record of therapy. Groups were analysed by year, FIGO stage and age. Results: 66,768 women were registered with an invasive carcinoma. Disease stage was not recorded in 44%. Of the remaining (n = 36,779) 32.1% stage I/II and 67.9% had stage III/IV disease. Of the 66,768 cases, 12.5 % had Neoadjuvant chemotherapy, 28.7% Primary surgery, 15.2% Surgery only, 19.7% Chemotherapy only and 23.2% No recorded therapy. Chemotherapy only was commonest at 36% in Stage IV, whereas primary surgery was in Stage III disease at 38%. No therapy was recorded in 11% and 25% of stage III and IV disease respectively. Neoadjuvant chemotherapy use trebled with time: comparing the rate in 2004-6 to 2013-15, there was an increase from7.7% to 21.7% ( p&lt; 0.001). Those diagnosed with primary peritoneal cancer were significantly more likely ( p&lt; 0.001) to have neoadjuvant chemotherapy compared to other groups. Cancers of the primary peritoneal and fallopian tube make up an increasing proportion of cases from 6% in 2004 to 13% in 2015. Conclusions: This is the largest reported study assessing trends in primary therapy and cases of ovarian, peritoneal and fallopian tube cancers during a time of novel developments. Neoadjuvant chemotherapy is becoming embedded in clinical practice. The reporting and analysis of ovarian cancer should include peritoneal and fallopian tube for consistent categorisation.
Improving lung cancer diagnosis at a large urban minority-based medical center: Where can we do better?
Authors: Christopher Su, Vincent Chau, Amit Bhargava, Chirag D Shah, Nitin Ohri, Rasim A. Gucalp, Stuart H. Packer, Roman Perez-Soler, Balazs Halmos, Haiying Cheng
Journal: Journal of Clinical Oncology (2017)

e18017 Background: Lung cancer diagnosis is a complex process with barriers to care which are more apparent in underserved communities. We examined factors affecting lung cancer diagnosis in an underserved urban community, including demographics, lung cancer screening, and survival outcomes. Methods: All new lung cancer diagnoses with confirmed pathology at an urban academic medical center in 2015 were identified. Retrospective chart review was conducted and time from initial abnormal imaging to tissue sampling was calculated. Analyses were performed with χ 2 , ANOVA, linear regression, and log-rank tests. Results: In 2015, 229 patients were diagnosed with lung cancer. 36 patients (16%) expired or were referred to hospice due to clinical deterioration without treatment. 162 patients (71%) were ultimately started on therapy. Patients were predominantly Black (38%), Hispanic (30%), underserved (mean per capita income $21729), and enrolled in Medicare or Medicaid (83%). Only 62% of the patients had a PCP at time of diagnosis. Most presented at an advanced stage (63% III or IV) and 88% were former/current smokers. 78 patients (48%) were eligible for low-dose CT screening but only 9 (12%) completed screening. Screening completion was correlated with established PCP (p = 0.012). Time from abnormal imaging to biopsy was 31±40 days without significant difference across age, gender, race, ethnicity, income, insurance, and primary language. Cancers diagnosed in the inpatient vs. outpatient setting were found at a more advanced stage (p = 0.002) and had lower survival (p &lt; 0.001). Hispanics had better survival (p = 0.008) despite lower per capita income and higher incidence of smoking. Conclusions: There was no significant difference in imaging to biopsy time across major demographic factors and they are unlikely to be a source of poor outcomes. However, the advanced stage and poor prognosis of cancers detected in the inpatient setting, proportion of patients who expired or were referred to hospice immediately after presentation, and disparity between screening eligible and completed patients underscores the critical importance of increasing lung cancer screening and establishment of primary care.
BCR-ABL mutation testing in patients with CML occurrence prior to a 10X rise in BCR-ABL test results.
Authors: Carol Smyth, Jason M. Bhan, Tatiana Sorokina, Ajitpal Singh Dhaliwal, Niyati Parikh
Journal: Journal of Clinical Oncology (2016)

e18546 Background: The NCCN guidelines recommend BCR-ABL kinase domain mutation testing when CML patients show a loss of response to treatment. About 20% of patients with CML started on a first-line TKI will develop treatment resistance due to mutation in the BCR-ABL kinase domain. A “rule of thumb” is to conduct mutation testing when BCR-ABL results rise 10X or higher. We studied a group of CML patients who had mutation testing after treatment started to determine if the 10X rule of thumb is being followed. Methods: We studied data from 183 CML patients in the nationwide Medivo lab test database who were tested for BCR-ABL between 2011 - 2014. This group of patients had at least 1 mutation test after a positive slope in their previous BCR-ABL tests. We performed a simple descriptive analysis to identify the proportion of these patients who were tested for mutation when previous BCR-ABL test results had risen < 10X. Results: We found 33 instances (18%) where patients were tested for BCR-ABL mutation soon after a 10X or higher rise in BCR-ABL results, and 150 instances (82%) where patients were tested for BCR-ABL mutation when previous BCR-ABL results had risen < 10X. We are 95% confident that the true proportion of patients tested for the BCR-ABL mutation when previous BCR-ABL results had risen < 10X is between 76% and 88%. The median value for the ratio of current BCR-ABL/previous BCR-ABL for all 183 patients before mutation testing is 2.4 [IQR: 1.4 - 6.2]. Conclusions: Current NCCN guidelines recommend mutation testing in patients with CML showing lack of response, loss of response or disease progression. Our results show that mutation testing is occurring more often prior to a 10X rise in BCR-ABL test results than after a 10X rise, indicating that the “rule of thumb” is not being followed in most cases. Further study is needed to determine the underlying reasons for the differences between the groups of patients tested prior to a 10X rise and the group tested after a 10X rise in BCR-ABL test results.
Longitudinal trajectory of frailty and related factors in 376 breast cancer patients aged 50+ compared to controls.
Authors: Allison Magnuson, Supriya Gupta Mohile, Lianlian Lei, Nikesha Gilmore, Benjamin Esparaz, Jeffrey K. Giguere, Jamal Ghazi Misleh, Michelle Christine Janelsins
Journal: Journal of Clinical Oncology (2017)

e21532 Background: Frailty, a clinical syndrome of vulnerability, is associated with adverse outcomes; however, the trajectory of frailty in cancer patients is not well understood. This longitudinal analysis evaluates frailty, and related factors, over the course of chemotherapy in breast cancer patients (BCa pts) aged 50+. Methods: BCa pts aged 50+ scheduled to receive adjuvant/neoadjuvant chemotherapy (n = 376) and age matched controls without cancer (n = 234) were recruited from the University of Rochester NCI Community Oncology Research Program as part of an observational study. Frailty was assessed by a modified Fried frailty score (range 0-4) using self-reported weakness, exhaustion, physical activity, and walk speed. Cognition was assessed objectively (Controlled Oral Word Association [COWA]) and subjectively (FACT-Cog). Frailty and cognition were measured pre- and post-chemotherapy (similar time lapse for controls). Linear regression models evaluated associations between cognition and frailty, controlling for age, race, marital status, education, performance status and baseline frailty score. Results: Average age was 59 (50-64: 77%; 65-79: 23%). At baseline, the cancer group had more people aged 65+ (24% vs 20%, p = 0.002), a higher mean frailty score (1.2 vs 0.73, p &lt; 0.001), and lower mean FACT-Cog score (158.5 vs 167.4, p &lt; 0.001) compared to controls. In unadjusted analysis, BCa pts had greater increase in frailty and cognitive problems than controls over time (mean change frailty score: cancer 0.87 vs control 0.05; mean change FACT-Cog: cancer 12.78 vs control 1.58; mean change COWA: cancer -0.41 vs control 0.43; p &lt; 0.001 for all). In adjusted analysis, cancer (p &lt; 0.001) and lower baseline FACT-Cog score (p = 0.01) were associated with an increase in frailty score over time. In a separate model, a decline in subjective and objective cognition was associated with increased frailty score (COWA p = 0.03, FACT-Cog p = 0.07). Conclusions: Frailty is prevalent in BCa pts prior to chemotherapy and increases during treatment. Lower baseline cognition and decline in cognition were associated with increased frailty. Frailty and cognition are important survivorship factors for BCa pts aged 50+.
P01.115 TERT as a biomarker in gliomas
Authors: A Vernadou, G Nasioulas, G Rigakos, Z Tsourti, E Papadopoulou, O Dafni, P Nomikos, S Lampropoulos, E Razis
Journal: Neuro-Oncology (2018)

Telomerase Reverse Transcriptase (TERT) is increasingly important in the molecular characterization of malignant gliomas. Its role differs between low and high grade gliomas and its association with other biomarkers and treatment outcome is still under investigation. In the present study, 115 patients at a median age of 46 years diagnosed from 2004 to 2017 with malignant glioma were studied. For all patients, we had information on their clinical and pathological characteristics, on their therapy and on: IDH1 expression (IHC or PCR), MGMT methylation (PCR), BRAF expression (IHC or PCR), expression of EGFRvIII (IHC or real time PCR), expression of ATRX (IHC), co-deletion of 1p/19q (MLPA), p53 expression (IHC). For TERT, DNA was isolated from formalin fixed paraffin embedded tissue and mutation analysis was performed using Nested PCR. Finally, sequence analysis was performed by Sanger sequencing. Of the 115 patients 77 were diagnosed with GBM, 11 with an astrocytoma grade III and 9 with an astrocytoma grade II, while 9 had grade III oligodendroglioma and 3 grade II oligodendroglioma. Median overall survival was 33,5 months for all patients, while glioblastoma patients had the worst survival (20,9 months). Patients with a mutation in IDH1 had a median overall survival of 78,8 months, much longer than the 42 months of IDH wild-type patients. Glioma patients with an MGMT methylation had also a longer median overall survival (42,7 months) than those with unmethylated MGMT (20,3 months). TERT promoter mutations were observed in 75 out of 115 patients. Of these, C228T mutation was detected in 59 patients, C250T mutation in 15 and C127 mutation in only 1 patient. Patients with a TERT mutation were older, they were diagnosed with glioblastoma or oligodendroglioma rather than astrocytoma and they were usually found to be IDH wild-type, the latter being the parameter most significantly associated with survival. TERT promoter mutation was a negative prognostic factor for the entire population, as well as for the high grade gliomas while we were not able to take any safe conclusion regarding low grade gliomas. The prognostic role of TERT concerning both the histological subtype of glioma and the other molecular markers has been demonstrated in this rather representative study. The potential therapeutic targeting of TERT and the study of its predictive role in both chemotherapy and radiotherapy will be the main axes of further research.
Expansion cohort of partially irradiated tumors on a phase 1 trial of pembrolizumab and ablative radiotherapy.
Authors: Sandeep Ramesh BHave, Jason J. Luke, Jeffrey M. Lemons, Linda A. Janisch, Robyn D. Hseu, Steven J. Chmura
Journal: Journal of Clinical Oncology (2018)

TPS3122 Background: Preclinical studies suggest multi-organ site ablative radiation therapy (MOSART) may enhance systemic anti-tumor response through altering the balance of innate and adaptive immunity within the tumor microenvironment and through direct tumor debulking. Previously, we opened a phase I study to evaluate the safety and efficacy of the combination of pembrolizumab with MOSART for patients with metastatic solid tumors. In the first cohort of 73 patients analyzed, the combined therapies were safe in all organ systems studied with no radiation dose reductions (Luke & Lemons et al. J Clin Oncol 2018, in press). Interestingly, large partially irradiated tumors exhibited control similar to smaller completely irradiated tumors (93% vs. 96% at 6 months, p = 0.32). In December 2017, we opened an expansion cohort to formally test the secondary hypothesis that partially irradiated tumors exhibit local control similar to completely irradiated tumors when combined with immunotherapy. Methods: We are accruing patients with metastatic disease progressing on standard of care treatment, two or more lesions amenable to MOSART, and have at least one lesion greater than 65cc. Enrollment is currently at six of forty planned subjects, and is actively accruing patients. MOSART dosing is based on NRG BR-001 (30 Gy in 3 fractions for osseous and spinal lesions; 45 Gy in 3 fractions for peripheral lung, liver, and abdominal-pelvic lesions; 50 Gy in 5 fractions for central lung, mediastinal, and cervical lesions). At least two lesions are targeted for each patient and not all sites of disease are treated. The maximum gross tumor volume (GTV) that is completely irradiated is 65cc. Partial tumor irradiation is administered to lesions > 65cc where the target volume is created by performing volume contraction down to 65 cc within the initial radiographically defined GTV. Pembrolizumab 200mg IV Q3W is to be initiated within seven days after final MOSART treatment. RECIST 1.1 will be used used to assess radiated tumor progression. Control (defined as CR, PR, or SD) will be calculated by the Kaplan Meier method and compared between partially irradiated tumors and completely irradiated tumors with the log-rank test. Clinical trial information: NCT02608385.