tbuckley/cabot-search huggingface dataset:
After cancer, what’s more important? The survivorship care plan or the survivorship care visit?
Authors: Harish Saiganesh, Christine M. Duffy, Camille Higel-Mcgovern, Mary Lorraine Lopresti, Mary Anne Fenton, Rochelle Strenger, Susan F. Korber, Tara Szymanski, Don S. Dizon
Journal: Journal of Clinical Oncology (2019)

11618 Background: The Commission on Cancer has made the provision of survivorship care plans (SCPs) a prerequisite for accreditation of cancer programs. However, whether all patients desire or derive benefits from an SCP is not established. This study sought to characterize the provision of survivorship care at the Lifespan Cancer Institute (LCI) to (1) determine clinical and distress characteristics at first visit to the LCI among patients treated with curative intent for a solid tumor diagnosis; (2) characterize which factors are associated with receipt of an SCP with or without a survivorship care visit (SCV); and (3) determine referral patterns and outcomes among patients with an SCP with or without an SCV. Methods: We have retrospectively reviewed 650 patients at Lifespan Cancer Institute so far, all of whom were initially seen between the years 2014-2017. As part of routine practice, all new patients are screened with the NCCN Distress Thermometer (DT). Data related to demographics, treatment variables, and presenting distress score were gathered using our electronic medical records. Categorical data were analyzed using Fisher’s Exact Test or Chi-Square. Multinomial logistic regression was performed for multivariate analysis. All analyses were performed in STATA 15.0. Results: The median age was 63 (range 29 to 90), 74.8% were female, and 39.5% were married or partnered. The major cancers represented included breast (52.2%), lung (16.6%), and prostate (6%) cancers. Severe distress (DT≥4) was reported in 49.5% of patients at their first visit with top concerns being worry (54.3%), nervousness (46.6%) and fatigue (37.3%). An SCP was documented in 461 patients (71.1%) and of these, 267 (57.9%) were seen in an SCV as well. On multivariate analysis, gender, marital status, and stage were significantly associated with the receipt of an SCP. However, only disease site was significantly associated with being seen in an SCV. Compared to those with an SCP but not seen in an SCV, those who attended an SCV were significantly more likely (p &lt; 0.005) to be referred for post-treatment evaluation, including psychological counseling (15.7 vs 6.7%), physical therapy (56.9 vs 22.7%), and nutrition (26.6 vs 8.2%). The majority of patients followed up with referrals, though it was significantly higher among those with an SCV (95.4 vs 87%, p = 0.015). Conclusions: Survivorship care varies by cancer type, with highest rates of visits for patients with gynecologic and GI cancers. Referral to other resources is significantly higher among those seen in visits, and those who are referred will follow up.
Role of the oncological-multidimensional prognostic index in older patients with metastatic colorectal cancer treated in a real-world setting.
Authors: Letizia Procaccio, Antonella Brunello, Pasquale Fiduccia, Annunziata Lettiero, Giuseppina Tierno, Grazia Pusole, Francesca Bergamo, Marta Schirripa, Chiara Manai, Vittorina Zagonel, Sara Lonardi
Journal: Journal of Clinical Oncology (2019)

11552 Background: About 50% of diagnoses of colorectal cancer (CRC) occur in patients (pts) older than 70 years. Though a comprehensive geriatric assessment (CGA) is recommended for proper management of older cancer pts, there is still no consensus on the best form of geriatric assessment. We investigated possible prognostic factors in elderly metastatic (m)CRC pts in a real-world setting, focusing on the role of the oncological-multidimensional prognostic index (onco-MPI). Methods: Pts aged ≥ 70 years with mCRC referred to the Medical Oncology 1 Unit from May 2010 to May 2017 were assessed by a multidisciplinary team and received a basal CGA. Onco-MPI was calculated by a validated algorithm as a weighted linear combination of the CGA domains, as previously described. The following 3 different prognostic groups were identified: low (scores 0.0-0.46), medium (scores 0.47-0.63) and high risk (scores 0.64-1.0). Results: A total of 206 mCRC pts were included, 123 males. Mean age was 76.1 years (69.2-90.8). ECOG PS was &lt; 2 in 90% and mini-mental state examination was ≥ 24 in 85% of pts. Primary tumor was located in rectum, left and right side in 18%, 42% and 40% of pts, respectively. RAS and BRAF mutations were detected in 44% and 9% of pts, respectively. According to onco-MPI score, 32%, 39% and 28% of cases were low, medium and high risk, respectively. According to CGA as per Balducci’s criteria, 56% of pts were classified as fit, 31% vulnerable and 13% frail. Median overall survival (OS) was 26 months (95% CI 19.7-32.4). The following factors were significantly associated with OS: ECOG PS (0-1 vs &gt; 1, 31% vs 15%, p = 0.004); onco-MPI score (low vs medium vs high risk, 29% vs 38% vs 19%, p = 0.005), treatment (monotherapy vs doublet vs triplet, 20% vs 31% vs 30%, p = 0.01). No significant difference in OS was observed in CGA-based groups (p = 0.15). In high onco-MPI score, doublet-regimen correlated with higher OS compared to monotherapy (79% vs 51%, p = 0,03). Conclusions: Onco-MPI emerged as a significant prognosticator in mCRC elderly pts. It may be useful in daily clinical practice for driving decision-making in this age group. Thanks to its marked standardization it may be also applied in clinical trials.
Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity
Authors: Yu Fu, Qing Lin, Zhirong Zhang, Ling Zhang
Journal: Acta Pharmaceutica Sinica B (2019)

The T cell co-stimulatory molecule OX40 and its cognate ligand OX40L have attracted broad research interest as a therapeutic target in T cell-mediated diseases. Accumulating preclinical evidence highlights the therapeutic efficacy of both agonist and blockade of the OX40-OX40L interaction. Despite this progress, many questions about the immuno-modulator roles of OX40 on T cell function remain unanswered. In this review we summarize the impact of the OX40-OX40L interaction on T cell subsets, including Th1, Th2, Th9, Th17, Th22, Treg, Tfh, and CD8+ T cells, to gain a comprehensive understanding of anti-OX40 mAb-based therapies. The potential therapeutic application of the OX40-OX40L interaction in autoimmunity diseases and cancer immunotherapy are further discussed; OX40-OX40L blockade may ameliorate autoantigen-specific T cell responses and reduce immune activity in autoimmunity diseases. We also explore the rationale of targeting OX40-OX40L interactions in cancer immunotherapy. Ligation of OX40 with targeted agonist anti-OX40 mAbs conveys activating signals to T cells. When combined with other therapeutic treatments, such as anti-PD-1 or anti-CTLA-4 blockade, cytokines, chemotherapy, or radiotherapy, the anti-tumor activity of agonist anti-OX40 treatment will be further enhanced. These data collectively suggest great potential for OX40-mediated therapies.
P12.05 Evaluating the compatibility of tumor treating electric fields with key antitumoral immune functions
Authors: G Diamant, H Simchony, T Shiloach, A Globerson-Levin, L Gasri Plotnitsky, Z Eshhar, N Pencovich, R Grossman, Z Ram, I Volovitz
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND TTFields has the ability to induce immunogenic cell death (ICD). As immunotherapy and TTFields have different mechanisms of action (MOA), combining these therapies is a rational approach. Contrarily, TTFields may interfere with immune functions critical for effective T cell function. MATERIAL AND METHODS We cultured T cells from healthy donors’ peripheral blood or from viably dissociated glioblastoma samples under normal or TTFields conditions, with or without superantigen-stimulation. In order to assess T cell responses we used eight-color flow cytometry by monitoring select pivotal antitumoral functions: proliferation (CFSE), IFNγ secretion, cytotoxic degranulation (CD107a), activation/exhaustion (PD1) and viability. Evaluation of direct cytotoxicity was done by using chimeric antigen receptor (CAR) T cells. RESULTS TTFields did not change T cell activation rates for all evaluated functions with the exception of reduced proliferation - in line with TTFields’ MOA. TTFields substantially reduced the viability of activated proliferating T cells, moderately affected activated nonproliferating T cells and had almost no effect on the viability of non-activated cells. Polyfunctionality analysis of T-cells, associated with effective antitumoral responses, demonstrated that under TTFields, the activated non-proliferating T cells retained polyfunctional capabilities. PD1-expressing TILs, a subset containing most of the tumor antigen-specific TILs, exhibited unaltered viability and functionality under TTFields. CAR T-cells, which utilize the same killing machinery as unmodified T cells, exhibited unaltered cytotoxic capability under TTFields. Immunohistochemical evaluation of GBM samples before TTFields treatment and after recurrence showed that some patients had accommodated large increases in their CD8 and CD4 counts. RNA-Seq performed on GBM samples from 6 standardly-treated and 6 TTFields-treated patients before treatment and after recurrence. The data shows differential increases in TTFields-treated patients to controls, in the expression of immune genes associated with favorable prognosis (e.g. t-bet, NKG2D, ICOS-L, CD70) and concurrent decreases in genes associated with poor prognosis (e.g. IL4, TSLP, various complement genes). CONCLUSION The preclinical data showed that all antitumoral T cell functions examined, but proliferation, were unhindered by TTFields. The clinical data showed that TTFields may shift treated tumors to a state more conducive of antitumoral immune responses. Our findings support the further preclinical and clinical investigation into combining TTFields with immunotherapy.
Tumour serine proteases C1r and C1s as novel biomarkers and therapeutic targets in invasive sporadic and recessive dystrophic epidermolysis bullosa‐associated cutaneous squamous cell carcinoma
Authors: Z. Kopecki
Journal: British Journal of Dermatology (2019)

Linked Article: Riihilä et al. Br J Dermatol 2020;182:658–670.
P13.01 TERTpromoter methylation is significantly associated withTERTupregulation and tumor progression in pituitary adenomas
Authors: J Adachi, Y Miyake, T Suzuki, K Mishima, R Araki, R Nishikawa
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Activation of telomerase plays a critical role in tumor development. Somatic alterations in the promoter of the telomerase reverse transcriptase (TERT) gene are a major mechanism of upregulating telomerase. Several mechanisms have been associated with TERT abnormalities, including TERT promoter mutations or methylation. Mutations in the TERT promoter have been observed in a subset of brain tumors, especially in adult gliomas. In pituitary adenomas (PAs), however, TERT abnormalities are not fully understood. The present study aimed to investigate not only mutational but also methylation status changes in the TERT promoter in PAs and to analyze their correlations with clinical variables. MATERIAL AND METHODS We retrospectively studied 70 PAs consisting of 53 primary and 17 recurrent samples. Clinical data, including age at surgery, sex, tumor size, tumor subtype, resection rate, presence or absence of postoperative irradiation, and progression-free survival (PFS), were obtained from medical records. First, we investigated TERT promoter hotspot mutations via Sanger sequencing. Next, we quantified the methylation status of the TERT promoter using methylation-sensitive high-resolution melting analysis (MS-HRM). Finally, we investigated TERT mRNA expression levels using real-time quantitative PCR. Fisher’s exact test was applied to evaluate the statistical significance between TERT promoter methylation status and tumor recurrence. PFS was calculated using Kaplan-Meier estimates and compared between methylated with ummethylated PAs with the log-rank test. The correlation between TERT promoter methylation status and mRNA levels was analyzed with the Mann-Whitney U-test. PFS was analyzed using multivariate analysis with the Cox proportional hazards model and included the following variables: age, sex, tumor size, tumor subtype, resection rate, radiation therapy, and methylation status. RESULTS TERT promoter hotspot mutations were not observed in any PA sample. Nineteen percent of PAs exhibitedTERT promoter methylation, which was significantly predominant in recurrent PA samples. PFS was significantly shorter in the methylated cases than in the unmethylated cases. Higher TERT expression levels were correlated with methylation status. CONCLUSION We found that TERT promoter methylation upregulated TERT expression and was associated with shorter PFS in PAs. Our results suggest thatTERT promoter methylation may be a potential biomarker for predicting tumor recurrence in PAs.
Positive Childhood Experiences and Adult Mental and Relational Health in a Statewide Sample
Authors: Christina Bethell, Jennifer Jones, Narangerel Gombojav, Jeff Linkenbach, Robert Sege
Journal: JAMA Pediatrics (2019)

Associations between adverse childhood experiences (ACEs) and risks for adult depression, poor mental health, and insufficient social and emotional support have been documented. Less is known about how positive childhood experiences (PCEs) co-occur with and may modulate the effect of ACEs on adult mental and relational health.To evaluate associations between adult-reported PCEs and (1) adult depression and/or poor mental health (D/PMH) and (2) adult-reported social and emotional support (ARSES) across ACEs exposure levels.Data were from the cross-sectional 2015 Wisconsin Behavioral Risk Factor Survey, a random digit-dial telephone survey of noninstitutionalized Wisconsin adults 18 years and older (n = 6188). Data were weighted to be representative of the entire population of Wisconsin adults in 2015. Data were analyzed between September 2016 and January 2019.The definition of D/PMH includes adults with a depression diagnosis (ever) and/or 14 or more poor mental health days in the past month. The definition of PCEs includes 7 positive interpersonal experiences with family, friends, and in school/the community. Standard Behavioral Risk Factor Survey ACEs and ARSES variables were used.In the 2015 Wisconsin Behavioral Risk Factor Survey sample of adults (50.7% women; 84.9% white), the adjusted odds of D/PMH were 72% lower (OR, 0.28; 95% CI, 0.21-0.39) for adults reporting 6 to 7 vs 0 to 2 PCEs (12.6% vs 48.2%). Odds were 50% lower (OR, 0.50; 95% CI, 0.36-0.69) for those reporting 3 to 5 vs 0 to 2 PCEs (25.1% vs 48.2%). Associations were similar in magnitude for adults reporting 1, 2 to 3, or 4 to 8 ACEs. The adjusted odds that adults reported "always" on the ARSES variable were 3.53 times (95% CI, 2.60-4.80) greater for adults with 6 to 7 vs 0 to 2 PCEs. Associations for 3 to 5 PCEs were not significant. The PCE associations with D/PMH remained stable across each ACEs exposure level when controlling for ARSES.Positive childhood experiences show dose-response associations with D/PMH and ARSES after accounting for exposure to ACEs. The proactive promotion of PCEs for children may reduce risk for adult D/PMH and promote adult relational health. Joint assessment of PCEs and ACEs may better target needs and interventions and enable a focus on building strengths to promote well-being. Findings support prioritizing possibilities to foster safe, stable nurturing relationships for children that consider the health outcomes of positive experiences.
Perioperative management of patients with distal esophagus and gastroesophageal junction tumors: Three years of results.
Authors: Milada Zemanova, Zdenka Pechacova, Tomas Harustiak, Pavel Fencl, Pavel Vitek, Lubos B. Petruzelka
Journal: Journal of Clinical Oncology (2012)

e14631 Background: In patients with operable gastroesophageal adenocarcinoma, a perioperative regimen ECF significantly improved survival (MAGIC trial - Cunnigham 2006) and has been accepted as standard treatment option. In our study we present experience with modified MAGIC protocol in patients with lower esophagus or GE junction tumors. Methods: 67 patients (pts) (60 men, 7 women), median age 59 years (37-74), with resectable adenocarcinoma in lower esophagus or gastroesophageal junction were included in period 01 Mar 2008 – 15 Jun 2010. Fifty one (76%) pts had clinical stage nodal positive. Chemotherapy (CT) consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg/m 2 ) and cisplatin (60 mg/m 2 ) on day 1, and a continuous infusion of fluorouracil (200 mg/m 2 per day) for 21 days or oral capecitabine 1000 mg/m 2 for 14 days. Postoperative radiochemotherapy (CRT) with fluorouracil or capecitabine after the end of CT was indicated in pts with two and more positive lymphnodes in surgical specimen if feasible. Results: Preoperative CT completed 64 (94%) pts, 52 (78%) had surgery, 46 (69%) had radical resection with 3 cases of complete pathological response, 22 pts had pN0 and 21 pts pN plus finding. Postoperative CT was started in 39 (58%) pts and was completed in 32 (48%) pts. 10 (22%) pts had postoperative CRT. Adverse events grade 3-4 were: neutropenia 10%, vomiting 8%, fatigue 5%, diarrhea 3%. Reasons for omitting surgery in 15 (22%) pts were: progression in 7 pts, medically unfit in 4 pts, other in 4 pts. With a median follow-up of 31 months (17-47) there were recurrences in 35 (52%) of all pts, in 5 (7%) pts locoregional only, in 7 (11%) distal plus locoregional and in 23 (34%) pts distal metastases. Recurrence rate in radically resected pts was 39%, in patients with pN0 28% and in pN1 86%, despite adding CRT. Thirty one patients are alive with 3-year survival 46%. Conclusions: Perioperative chemotherapy ECF/ECCap in our set was feasible and well tolerated. Patients with node positive postoperative stage had poor prognosis, despite completing adjuvant treatment including postoperative CRT. This work was supported by grant NO: IGA MZ(CR) NT/12331-5/2011.
Associations of uncertainty with psychological status and quality of life (QoL) among 527 older patients with advanced cancer.
Authors: Dilip Sankar Babu, Kah Poh Loh, Javier Bautista, Huiwen Xu, Eva Culakova, Beverly E. Canin, Alison Katherine Conlin, James Bearden, Jeffrey L. Berenberg, Yingzi Zhang, Megan Wells, Ronald M. Epstein, William Dale, Paul Duberstein, Supriya Gupta Mohile, Mohamedtaki Abdulaziz Tejani
Journal: Journal of Clinical Oncology (2019)

11544 Background: Older patients with advanced cancer face considerable uncertainty related to their disease and treatment. The aim of our study was to evaluate the associations of uncertainty with psychological status and QoL. Methods: This is a secondary analysis of baseline data from a national geriatric assessment (GA) cluster randomized trial (URCC 13070; PI: Mohile). Patients aged ≥70 years with ≥1 GA domain impairment (e.g., function, cognition) and advanced cancer who were considering or receiving any line of cancer treatment were enrolled (n=541). Uncertainty was measured using the modified 9-item Mishel Uncertainty in Illness (MUIS), where respondents with higher scores perceive more uncertainty (range 9-45). QoL and psychological measures consisted of Functional Assessment of Cancer Therapy-General (FACT-G), emotional wellbeing (EWB; FACT-G subscale), distress (distress thermometer), anxiety (Generalized Anxiety Disorder-7), and depression (Geriatric Depression Scale-15). Multiple linear regressions were used to evaluate the associations of MUIS scores with each measure, adjusted for demographics, cancer type, and number of impaired GA domains. Results: Mean age was 77 years (SD 5, range 70-96); 26% had gastrointestinal cancer and 26% had lung cancer. Mean number of GA domain impairments was 4 (SD 1, range 1-7). Mean MUIS score was 20 (SD 5, range 9-37). On multivariate analyses, higher MUIS score was associated with lower QoL (β=-1.08, SE=0.11) and EWB (β=-0.29, SE=0.03), as well as higher distress (β=0.12, SE=0.02), anxiety (β=0.11, SE=0.04), and depression (β=0.09, SE=0.03; all P&lt;0.01). Conclusions: Distress associated with uncertainty was common in a vulnerable population of frail older patients with advanced cancer and ≥1 GA domain impairment. A higher degree of uncertainty was associated with poorer psychological health and QoL. Our results underscore the important role that uncertainty plays in older patients' psychological status. Previous tested uncertainty management interventions (mainly including information and coping strategies) could be revised, tailored and tested to meet the unique needs of older patients with cancer. Clinical trial information: NCT02107443.
Integrated Pan-Cancer Map of EBV-Associated Neoplasms Reveals Functional Host–Virus Interactions
Authors: Srishti Chakravorty, Bingyu Yan, Chong Wang, Luopin Wang, Joseph Taylor Quaid, Chin Fang Lin, Scott D. Briggs, Joydeb Majumder, D. Alejandro Canaria, Daniel Chauss, Gaurav Chopra, Matthew R. Olson, Bo Zhao, Behdad Afzali, Majid Kazemian
Journal: Cancer Research (2019)

Epstein-Barr virus (EBV) is a complex oncogenic symbiont. The molecular mechanisms governing EBV carcinogenesis remain elusive and the functional interactions between virus and host cells are incompletely defined. Here we present a comprehensive map of the host cell-pathogen interactome in EBV-associated cancers. We systematically analyzed RNA sequencing from >1,000 patients with 15 different cancer types, comparing virus and host factors of EBV+ to EBV- tissues. EBV preferentially integrated at highly accessible regions of the cancer genome, with significant enrichment in super-enhancer architecture. Twelve EBV transcripts, including LMP1 and LMP2, correlated inversely with EBV reactivation signature. Overexpression of these genes significantly suppressed viral reactivation, consistent with a "virostatic" function. In cancer samples, hundreds of novel frequent missense and nonsense variations in virostatic genes were identified, and variant genes failed to regulate their viral and cellular targets in cancer. For example, one-third of patients with EBV+ NK/T-cell lymphoma carried two novel nonsense variants (Q322X, G342X) of LMP1 and both variant proteins failed to restrict viral reactivation, confirming loss of virostatic function. Host cell transcriptional changes in response to EBV infection classified tumors into two molecular subtypes based on patterns of IFN signature genes and immune checkpoint markers, such as PD-L1 and IDO1. Overall, these findings uncover novel points of interaction between a common oncovirus and the human genome and identify novel regulatory nodes and druggable targets for individualized EBV and cancer-specific therapies. SIGNIFICANCE: This study provides a comprehensive map of the host cell-pathogen interactome in EBV+ malignancies.See related commentary by Mbulaiteye and Prokunina-Olsson, p. 5917.