tbuckley/cabot-search huggingface dataset:
Gender differences in plasminogen activators and PAI-1 in tissues of esophageal squamous cell carcinoma.
Authors: Evgeniy N. Kolesnikov, Oleg Ivanovich Kit, Elena Mikhaylovna Frantsiyants, Larisa Kozlova, Yulia A. Pogorelova, Natalia D. Cheryarina, Vladimir Trifanov, Michail Averkin, Adlan Lechaevich Bazaev
Journal: Journal of Clinical Oncology (2016)

e15509 Background: Men (M) developesophageal squamous cell carcinoma (SCC) more frequently than women (W). The roles of urokinase (uPA), thromboplastin (tPA) and their inhibitor PAI-1 in SCC development in m and W has not been revealed. The purpose of the study was to determine uPA-Ag, uPA-act, tPA-Ag, tPA-act, PAI-1-Ag and PAI-1-act in tissues of SCC in m and W. Methods: Tumor tissue (T) and perifocal zone (PZ) of SCC was studied by ELISA (19 men, 8 women, G2, T2-3 N0-1 M0-1 ). All components were determined in 10% homogenates. Results: Significant gender differences were found in all studied indices. Both forms of uPA and PAI-1 increased compared to resection line (RL) in all patients in T and PZ (p < 0.01). Content and activity of tPA increased in m PZ only (p < 0.01), in m T and W PZ tPA-Ag it did not differ from RL and in W T it decreased by 30.1%; tPA-act did not differ from RL in m SCC and decreased in T of m and W (p < 0.01). uPA-Ag/uPA-act balance coefficient increased by 80-117%% in 97.2% of the cases only in W T, while in all m it decreased in T and PZ by 1.7 and 1.6 times. tPA-Ag/tPA-act balance was similar in RL in m and W, but it increased significantly in T of m and W (p < 0.01) and in PZ of m and W did not differ from RL. PAI-1 effectiveness concerning uPA increased in PZ by 1.5 times (W) and 2.4 times (M), but decreased in T by 1.4 times (W) and 3.6 times (M). PAI-1 effectiveness concerning tPA increased in m PZ by 2.7 times and did not differ in W RL, while in T it increased in both m and W by 12 and 2.4 times, respectively. However, PAI-1-Ag/PAI-1-act balance was 2.5 times decreased in m PZ and 2.6 times increased in W. PAI-1-Ag/PAI-1-act in T of both m and W was increased by 2.8 and 5.4 times in comparison with RL. Conclusions: The results demonstrated higher uPA aggressiveness in PZ and T of M, and in T of W uPA-act formation was less intensive. tPA role is still not clear; however, tPA-Ag/tPA-act increase in T of all patients, with its 3 times higher increase in m than in W, and absence of such an increase in PZ of all patients, taking into account morbidity statistics, allows supposing tumor-associated tPA presence in T of M. PZ of m has the lowest coefficient of PAI-1-Ag/PAI-1-act balance that escalates sequentially in increasing order in W PZ, m T and W T.
Clinical and molecular determinants of extrahepatic disease progression (ePD) in initially unresectable, liver limited metastatic colorectal cancer (mCRC).
Authors: Elena Ongaro, Daniele Rossini, Filippo Pietrantonio, Federica Morano, Filippo G. De Braud, Vincenzo Mazzaferro, Francesca Corti, Giovanni Randon, Alessandra Raimondi, Luigi Battaglia, Luca Morelli, Lucio Urbani, Gianluca Masi, Roberto Moretto, Carlotta Antoniotti, Federica Marmorino, Beatrice Borelli, Gemma Zucchelli, Chiara Cremolini, Alfredo Falcone
Journal: Journal of Clinical Oncology (2018)

e15511 Background: In the last years, availability of active upfront systemic regimens, development of surgical techniques and diffusion of locoregional treatments (LrTx) increased the therapeutic options for mCRC patients (pts) with liver limited disease (LLD). Estimating the likelihood to develop extrahepatic metastases (mts) may affect clinicians’ attitude towards LrTx. No tools to predict the probability of ePD of initially LLD are currently available. Methods: We analysed a cohort of 225 pts with initially unresectable LLD treated with 1st line doublet or triplet plus a biologic agent at two Italian Institutions. Information about clinical, pathological and molecular features, Tx received and mts sites from diagnosis of mCRC to death or last follow up were collected. The impact of baseline characteristics and Tx received on extrahepatic progression free survival (ePFS) was assessed in uni- and multivariable models. Results: Overall, 52 (23%) and 173 (77%) pts were ePD free or experienced ePD, respectively. 20%, 63%, and 86% of ePDs occurred within 1, 2 or 3 years (yrs) from diagnosis of mCRC, respectively. Globally, 164 (73%) pts underwent a secondary liver resection, and 66 (40%) of them underwent a subsequent LrTx. 118 (72%) out of 164 resected pts, experienced ePD, occurring within 1, 2 or 3 yrs from resection in the 43%, 71%, and 91% of cases, respectively. Age < 70 years, ECOG performance status (PS) 0, < 4 liver mts, longest diameter of liver mts < 30 mm, involvement of < 6 liver segments and secondary resection were significantly associated with prolonged ePFS. In the multivariable model, ECOG PS (p = 0.022), number (p = 0.011) and diameter (p 0.005) of liver mts and secondary liver resection (p = 0.006) were still associated with ePFS. In the subgroup of analysed pts (N = 35), microsatellite instability was associated with shorter ePFS (p = 0.029). Conclusions: Most ePDs occur between 1 and 2 yrs from the diagnosis of mCRC, and within 1 yr following secondary resection. ECOG PS, number and diameter of liver mts independently predict ePFS. These factors could help physicians in personalizing the intensity of liver directed Tx in mCRC pts with initially unresectable LLD.
State breast density inform mandate laws and utilization of adjunctive screening tests and cancer detection following screening mammography.
Authors: Cary Philip Gross, Jessica R Hoag, Xiao Xu, Ilana Richman, Jenerius Aminawung, Pamela R. Soulos, Susan Busch
Journal: Journal of Clinical Oncology (2018)

6579 Background: In response to concerns about the limited sensitivity of mammography among women with dense breasts, 32 states have enacted laws to inform patients about these limitations and recommend adjunctive screening tests such as breast ultrasound. Inform mandate laws represent a novel approach to ensure awareness of technologies that have not yet been proven to affect health outcomes. We evaluated the effect of inform mandate laws on utilization of adjunctive screening, biopsy and diagnosis of incident breast cancer. Methods: Using blinded administrative claims data from anonymous insurers conducting business in the United States, we included women age 40-59 who underwent screening mammography in 2015. We classified beneficiaries according to receipt of screening mammography in a state with an inform mandate law. Receipt of screening or diagnostic ultrasound, breast biopsy, and incident breast cancer within nine months of screening mammogram was identified from claims. Logistic regression was used to evaluate the association between inform mandate laws and receipt of screening ultrasound, diagnostic ultrasound, biopsy, and cancer detection, while adjusting for age and type of health plan. Robust variance estimates accounted for clustering by state. Results: Our sample included 1,595,864 women who received a screening mammogram in 2015. Of these women, 58.2% were living in a state with an inform mandate law in place at the time of index mammogram. The adjunctive screening ultrasound rate was 3.1% among women in inform mandate states vs 1.4% in non-mandate states. After adjustment, residence in an inform mandate state was associated with significantly higher odds of adjunctive screening ultrasound (OR 2.22, 95% CI 1.14-4.34). In contrast, inform mandate status was not associated with receipt of diagnostic ultrasound, breast biopsy, or cancer detection. Conclusions: Women residing in states with breast density inform mandate laws are more likely to receive screening breast ultrasound. However, there was no significant relationship between inform mandate laws and utilization of other adjunctive tests or the likelihood of cancer detection.
Psychological stress in long-term survivors of testicular cancer: A Danish nationwide cohort study.
Authors: Michael Kreiberg, Mikkel Bandak, Jakob Lauritsen, Klaus Kaae Andersen, Julie Wang Skøtt, Christoffer Johansen, Gedske Daugaard
Journal: Journal of Clinical Oncology (2018)

4554 Background: Survival in cancer is generally increasing and in case of testicular cancer (TC) the majority of patients become long-term survivors (TCS). The aim of the present study was to investigate if long-term TCS experience a higher level of psychological stress than the Danish male general population (GP) and whether psychological stress is influenced by treatment modality. Methods: In 2014-2016, 2409 TCS with a mean time since diagnosis of 18 years (range 7-33 years) answered a questionnaire covering psychological stress (Perceived Stress Scale (PSS)), sociodemographic factors and physical health variables. In PSS, scores are summed up with 0 representing the least stressed and 40 the most stressed. PSS scores were compared with the GP (n = 67151) from The Danish National Health Survey 2013. Age adjusted linear regression with TCS who had been treated with orchiectomy alone serving as reference explored the effect of treatment modality on PSS score. Results: In TCS < 65 years of age we found a higher mean PSS score than in the GP (p < 0.01) (table 1), while TCS > 65 years of age had a lower PSS score than the GP (p = 0.043) There was no association between treatment modality and PSS score. Conclusions: Long-term TCS < 65 years of age were more stressed than the general population, while treatment modality did not influence the levels of psychological stress. Research is needed to clarify if screening and treatment programs for psychological stress should be part of the follow-up for TCS. Perceived stress scale (PSS) scores in long-term testicular cancer survivors (TCS) and a male danish general population (GP). GP (N = 67151) TCS (N = 2409) p-value Age group mean PSS scores, (No.) < 45 11.02 (21680) 12.94 (508) < 0.001 45-54 10.87 (12668) 11.53 (803) 0.008 55-64 10.28 (13584) 11.81 (690) < 0.001 > 65 10.36 (19218) 9.68 (408) 0.043 Treatment mean PSS scores, (No.) Surveillance 11.35 (1138) 3-4 courses of BEP 11.95 (876) Abdominal RT 11.37 (312) More than one line of treatment 12.07 (83) Age group mean PSS Scores were analysed with independent t-test between GP and TCS. Abbreviations: BEP, bleomycin, etoposide, cisplatin; RT, radiotherapy.
Identification of somatic mutations to predict development of autoimmune adverse events to immune therapy in melanoma.
Authors: Keith Ryan Wells, Carol M Amato, Jennifer Hintzsche, William Robinson
Journal: Journal of Clinical Oncology (2016)

3041 Background: Immunotherapy has quickly altered the treatment paradigm for advanced melanoma. Prior studies in melanoma using whole exome sequencing (WES) in patient tumor samples who have received immunotherapy have focused on neoantigen formation in correlation with clinical response to immunotherapy, but no studies to identify genes have been done. Understanding mechanisms of immune-related adverse events (irAE) at a genomic level may lead to improved rational treatment design and better patient selection. Methods: DNA was extracted from 87 tumor samples from 49 patients with metastatic melanoma treated with ipilimumab (anti-CTLA-4) or with nivolumab or pembrolizumab (anti-PD-1) immunotherapy. WES was performed with exome capture on an Illumina HiSeq sequencer. Statistical analysis was performed with Chi-squared testing. Results: 27 patients with advanced or metastatic melanoma were treated with only ipilimumab, 11 with only anti-PD1, and 11 patients were treated with both anti-CLTA-4 and anti-PD1 either sequentially or in combination. irAE evaluated included rash, colitis, endocrinopathies, hepatitis, and pneumonitis. In 10 patients who developed colitis, 14 mutated genes were enriched in their tumor samples (P = 0.01-0.046) compared with patients without colitis. Analyzing all patients with any irAE versus no irAE treated with anti-CTLA-4, anti-PD1, or both (either sequential or combination) revealed 7 mutated genes enriched in patient samples who developed irAE (P = 0.02-0.04). Overall mutational burden of the tumor samples did not correlate with development of irAE. Conclusions: Autoimmune side effects are frequent and often serious side effects of immunotherapy for melanoma. Genetic analysis may provide insight in prediction of these side effects, understanding of tumor-immune response, and help direct therapeutic decisions.
Immuno-oncology and the elderly: A comparative analysis of participation and toxicities of senior adults aged 65 years and above vs mid age and adolescent/young adult patients on immunotherapy-based phase I clinical trials.
Authors: Ishwaria Mohan Subbiah, Kenneth R. Hess, Takeo Fujii, Anas Alshawa, Anna Lui, Sarath Roy, Rahil Khanji, Vivek Subbiah, Aung Naing, David S. Hong
Journal: Journal of Clinical Oncology (2017)

10034 Background: Senior adults ≥ 65 yrs remain underrepresented in early phase clinical trials in particular trials with novel immunotherapies. One general limitation to enrollment is the concern for immune-related toxicities in the context of older age and comorbidities. We analyzed the enrollment and incidence of toxicities of seniors in comparison to mid age and adolescent/young adult (AYA) pts enrolled in phase 1 immunotherapy trials. Methods: We identified 422 consecutive pts w advanced cancer treated on immunotherapy-based phase I trials bw 04/2009-09/2015. We divided pts into 3 cohorts based on age at start of trial (AYA 15-39y, mid age 40-64y, seniors 65y+) and collected pt/disease characteristics and immune-related adverse events (irAE) including endocrinopathies, diarrhea/colitis, pneumonitis, constitutional (eg fatigue, fever, anorexia), myalgia, and dermatitis. Results: Of 422 patients treated, 116 were seniors (27%, median 70y), 50 AYA (12%, median 30y), 256 mid age (61%, median 56y). Most common cancers were GI (n = 108, 26%), thoracic/head/neck (n = 84, 20%), GU (n = 54, 13%), and GYN (n = 47, 11%). Median PFS was comparable in all 3 cohorts (2.4m seniors, 2.1m AYA, 2.1m mid age). The incidence of irAE was higher in elderly than mid age or AYA (low grade [G1/2] 49% vs 34% vs 34%, p 0.02; high grade [G3/4] 19% vs 11% vs 12%. p 0.14). When comparing irAE rates of seniors to AYA and mid age pts, the odds ratio of high grade events was 1.81 (95% CI 1.01, 3.24; p 0.05) and low grade events was 1.85 (95% CI 1.20, 2.85; p 0.0055). Most common G1/2 irAE among all cohorts was fatigue (n = 76, 18%), dermatitis (n = 59, 14%), fever (n = 29, 7%) and anorexia (n = 28, 7%) with seniors having a greater incidence of low grade fatigue (25% vs 15%, OR 1.84, 95% CI 1.09, 3.10, p 0.025). Conclusions: Senior adults accounted for &lt; 1/3 of pts on immunotherapy-based phase I trials. When compared to mid age and AYA pts, seniors had a higher likelihood of experiencing a toxicity. Early phase immunotherapy trials may be an option for older adults but with a particular vigilance for adverse events in this population.
Accuracy of clinico-radiological methods in diagnosing axillary lymph node metastasis in carcinoma breast.
Authors: Amit Choraria, Sanjit Agrawal, Aditi Chandra, Saugata Sen, Sanjoy Chatterjee, Rosina Ahmed
Journal: Journal of Clinical Oncology (2016)

e18147 Background: Axillary lymphnode dissection was traditionally both staging method and also contributed to improved patient survival. However morbidity is significant, with lymphoedema in 5 to 39% of patients. Cytology or core biopsy of suspicious nodes, elastography and sentinel lymphnode biopsy can improve preoperative diagnosis. Our aim is to correlate clinical and radiological axillary nodal assessment with pathological findings in women with carcinoma breast. Methods: Prospective data for a consecutive series of breast carcinoma patients having upfront surgery was analyzed. Routine mammography with ultrasonography was performed as part of triple assessment, to evaluate both breast lesions and axilla. Ultrasonographic characteristics of metastatic nodes were increased size, rounded shape, cortical thickening and loss of hilar character. Clinical and radiological evaluation before surgery was correlated with pathological evaluation of nodal status after surgery. Results: In the study period 94 (52%) of 179 patients who had upfront surgery had pathologically positive lymph nodes. Clinically, 44 (24.5%) patients were correctly diagnosed with positive and 62 (34.6%) with negative axillary lymph nodes. There were 50 (27.9%) false negative and 23 (12.8%) false positive clinical evaluations. Sensitivity and specificity of clinical evaluation was 46% and 73% respectively. By ultrasonography, 56 (31.28%) patients were correctly diagnosed as positive and 70 (39.1%) as negative axillary lymph nodes. There were 38 (21.22%) false negative and 15 (8.37%) false positive results. Sensitivity and specificity of ultrasonography were 60% and 82% respectively. Combined clinical and radiological evaluation, with both modalities suggesting metastases, had a Positive Predictive Value of 84%. However the Negative Predictive Value was much lower at 57%, giving an Accuracy of 64% only. Conclusions: Even taken together, clinical and radiological assessment of axillary lymph nodes remains inaccurate, resulting in many patients having unnecessary axillary lymph node dissection. Wider application of Sentinel Node techniques in resource-poor countries is required to avoid the burden of complications.
Plasma levels of soluble programmed death ligand 1 (sPD-L1) and its clincial value in patients with nasopharyngeal carcinoma (NPC): A preliminary study.
Authors: Man Hu, Jia Yang, Li Xie, Xingchen Ding, Xinbin Bai, Bingjie Fan, Ji Ma, Jinming Yu
Journal: Journal of Clinical Oncology (2018)

e18048 Background: Programmed cell death-ligand 1 (PD-L1) expressed in tumor tissues is a key molecule for immune suppression for patients with nasopharyngeal carcinoma (NPC) . The significance and implication of soluble PD-L1 (sPD-L1) in the blood of NPC patients remain unknown. The aim is to evaluate the sPD-L1 in patients with NPC, and its correlation with clinico-pathological characteristic and laboratory data. Methods: Thirty-six patients with stage I-IV NPC were included at Shandong Cancer Hospital and institute. Plasma samples (7.5 ml) were obtained pretreatment, early-phase of treatment (in 2 weeks after starting treatment), and late-phase of treatment (6 weeks after RT). The plasma sPD-L1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Complete blood count and Epstein-Barr virus (EBV) were measured . The correlations of sPD-L1 levels with clinico-pathological characteristic and laboratory data of the patients were analyzed, the concentration changes of sPD-L1 before and after CRT were compared for patients. Results: Thirty-six patients (pts) with 61 blood samples were analyzed. Two pts received definitively RT alone for stage I disease and 34 pts received CRT for stage II-IV disease. Eleven pts had only one blood sample at pre-treatment, 25 pts had two blood samples including pre-treatment or early-phase and late-phase of treatment. The mean plasma sPD-L1 concentration of all the patients was 49.59 ± 27.61 pg/ml (range 6.44-114.97 pg/ml).The levels of sPD-L1 positively correlated with the clinical stage (r = 0.432, P = 0.042), however, no correlation of sPD-L1 with sex, age, histological subtypes were found (all P values > 0.05). There was also no correlation between sPD-L1 and complete blood count or Epstein-Barr virus (EBV) (all P value > 0.05). For 25 pts with two blood samples, sPD-L1 of late-phase of treatment was significant higher than that of pre- or early-phase of treatment (t = 2.764 , P = 0.011). Conclusions: sPD-L1 are quantifiable and trackable in patients with NPC. sPD-L1 may be induced by RT and/or chemotherapy. Sequentially assessing sPD-L1 in blood during therapy would benefit to immunotherapy for patients with NPC.
Symptom assessment of oldest old cancer patients.
Authors: Linda Pang, Maxine Grace De la Cruz, Jimin Wu, Diane D. Liu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2018)

e22035 Background: The older population is a growing segment of the United States. The oldest old, described as those aged 85 and older, experienced the fastest growth. Although this population is also undergoing active cancer treatment, there are limited studies evaluating the symptoms of the oldest old cancer patient population. Our study aimed to evaluate symptom severity as assessed by the Edmonton Symptom Assessment Scale (ESAS) of the oldest old (OO), older adult (OA) and general adult (OA) outpatient cancer patients on initial consult and followup visit. Methods: Retrospective review of 441 patients composed of 200 patients in the 18-64 age group (GA), 200 in the 65-84 age group (OA) and 41 in those over 85 years old (OO). Demographic and clinical characteristics were collected and the differences between the groups at initial consult and first follow-up using Chi-Squared, Kruskal-Wallis and Wilcoxon signed-rank tests. Results: The OO reported mild to moderate symptom severities on initial consult in all categories except nausea and spiritual pain, where median score was zero. Symptom severity of the OO was better than the younger population in pain and nausea, and similar in fatigue, depression, anxiety, and sleep. The OO reported highest severities in drowsiness and feeling of wellbeing. The OA reported highest severities in appetite loss and dyspnea. Dyspnea (p = 0.0225), financial distress (p = < 0.0001), and spiritual pain (p = 0.0026) were significantly associated with age on initial consult. For the OO, symptoms mostly improved on followup except for fatigue and spiritual pain. Anxiety (p = 0.0284) and sleep (p = 0.0486) significantly improved on follow-up visit. Conclusions: Our study shows that the oldest old cancer patients had significant symptoms on initial consult, with several physical symptoms such as fatigue, appetite, drowsiness, and feeling of wellbeing in the range of moderate severity. In the first palliative care followup visit, many symptoms decreased in intensity. With continued palliative care support, these changes may result in clinically important symptom improvements. More research is needed to address the needs of this growing cancer population and focus on symptoms that can improve with palliative care intervention.