tbuckley/cabot-search huggingface dataset:
Epigenetic regulation of cancer self-renewal differs between endocrine tumors.
Authors: Ines Faleiro, Ramon Andrade De Mello, Joana Dias Apolonio, Vania Palma Roberto, Uri Tabori, Pedro Castelo-Branco
Journal: Journal of Clinical Oncology (2017)

e15717 Background: Cancer cells achieve limitless self-renewal capacity mainly through telomerase reactivation. Methylation of a specific region in the h TERT promoter, termed TERT Hypermethylated Oncologic Region (THOR), has been associated with telomerase reactivation, increased telomerase activity and patient outcome in several cancers. Methods: In this study, we assessed the methylation status of THOR using The Cancer Genome Atlas (TCGA) data on cohorts of two endocrine cancers with distinct cell proliferation rates: the highly proliferative pancreatic adenocarcinoma (n = 194 patients) and the more indolent thyroid carcinoma (n = 571 patients). Results: THOR was significantly hypermethylated in malignant cancer when compared to benign adjacent tissue in pancreatic cancer (p &lt; 0.0001), but not in thyroid cancer. In pancreatic cancer, THOR hypermethylation could also distinguish normal tissue from early stage I disease and it associated with worst patient prognosis. Conclusions: These preliminary findings indicate that THOR can discriminate aggressive tumors from non-aggressive ones, and evidenced the diagnostic and prognostic value of THOR in pancreatic cancer.
Evaluating the utility of pretreatment C-reactive protein (CRP) in survival stratification of advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint blockade (ICB): A prospective cohort study.
Authors: Abdul Rafeh Naqash, Chipman Robert Geoffrey Stroud, Cynthia R. Cherry, Nitika Sharma, Mohammed Umer Butt, Mahvish Muzaffar, Li V. Yang, Paul R. Walker
Journal: Journal of Clinical Oncology (2018)

e15122 Background: Quantification of baseline systemic inflammation using readily available peripheral blood-derived inflammatory biomarkers such as CRP has demonstrated prognostic and predictive utility in various tumor types. However, the nature of the association of CRP with survival in NSCLC patients treated with ICB has not been investigated. Methods: We conducted a prospective observational study to analyze correlation between baseline CRP and ICB. We recruited 133 patients with advanced NSCLC initiated on ICB between April 2015 to November 2017. We measured CRP prior to initiating ICB. Data analysis after follow-up was done in February 2018. The primary outcome was overall survival after immunotherapy (OSI). Results: The median age was 64 years with male predominance (60.4 %). Predominant histology was adenocarcinoma (53.0 %) followed by squamous cell carcinoma (39.6 %). Stage IV disease was present in 69.9 %, with skeletal involvement (49.5 %) and brain (32.3%) being the most common metastatic sites. 49.1% patients were noted to have at least 1 index immune-related adverse event (irAEs) during or after ICB completion. Median pretreatment CRP was 23.9 mg/l. No correlation was observed between baseline CRP and future probability of an irAE. After a median follow up of 7.6 months, 50% patients were alive. Using multivariate Cox regression and adjusting for confounders, patients with baseline CRP > 50 mg/l were noted to have significantly inferior OSI [3.3 vs. 9.3 months, p < 0.01; HR 2.83, CI (1.71-4.65)]. Conclusions: Our analysis demonstrates the correlation of high baseline CRP ( > 50 mg/l) with inferior OSI in advanced NSCLC. This suggests that despite ICB, high baseline inflammation fosters an oncogenic microenvironment and acts as an independent driver for tumor growth and propagation. To better understand the role of baseline inflammation in influencing the efficacy of ICB within the tumor microenvironment, we are currently also investigating the relationship of high baseline CRP with inflammatory cytokines and other molecular signatures that may contribute to an immune resistant milieu.
Conversion therapy using S1/paclitaxel chemotherapy plus apatinib in unresectable gastric cancer: Updated data from a phase II trial.
Authors: Xiangdong Cheng, Zhiyuan Xu, Yian Du, Ping Hu, Guofa Yu, Conggang Hu
Journal: Journal of Clinical Oncology (2018)

e16010 Background: Ahead-G325 trial (ClinicalTrials.gov: NCT02529878) is a multicentre, single-arm phase II clinical trial to investigate application of S1/paclitaxel chemotherapy plus apatinib, an anti-angiogenesis inhibitor targeting VEGFR-2, in conversion therapy for unresectable gastric cancer (GC). The preliminary results have been reported in 2017 Gastrointestinal Cancers Symposium (abstract 53). We further released the updated data mainly focusing on long-term efficacy and safety. Methods: Patients (pts) with histologically proved unresectable, HER-2 negative, advanced GC were recruited to receive 2 cycles of S1/paclitaxel chemotherapy (S1: 60 mg, oral, bid for 2 weeks followed by a drug-free interval of 1 week; paclitaxel: 150 mg/m2, iv, 3 h, on day 1) plus apatinib (500 mg, oral, qd) and 1 cycle of S1/paclitaxel prior to radical surgery. Three cycles of adjuvant chemotherapy (S-1 and apatinib) were given 4-6 weeks after surgery. Primary endpoint was R0 resection rate. Results: A total of 31 eligible pts were enrolled. Thirty pts were available for preoperative efficacy evaluation. The overall response rate was 73.3% (22 partial response [PR]), and a disease control rate was 93.3% (22 PR and 6 stable disease). Of the 22 pts with PR, 18 received predesigned gastrectomy. Four, 5, 6 and 3 achieved grade Ia, Ib, II and III pathological response, respectively. The R0 resection was up to 94.4% (17/18). The 12-month overall survival of the all participants was 83.4%, while that was 100.0% in the pts with successful conversion therapy and scheduled surgery and 58.6% for the others. The incidence of adverse events (AEs) was 93.6%, whereas 58.1% pts experienced AEs of Grade 3 or 4. The common hematologic AEs were neutropenia (45.2%), leukopenia (45.2%) and anemia (42.0%), and nonhematologic AEs included hyperbilirubinemia (38.7%), oral mucositis (38.7%), fatigue (29.0%), hand-foot syndrome (19.4%), hypertension (19.4%) and proteinuria (16.1%). There was no severe surgery-related complication. Conclusions: Combination of apatinib with S1/paclitaxel chemotherapy shows clinical benefits in unresectable GC, with acceptable safety profile and long survival. Clinical trial information: NCT02529878.
Performance of a 31-gene expression profile melanoma test in clinically relevant clinicopathologic subgroups.
Authors: Brian Gastman, Sarah Kurley, Kyle R. Covington, Robert W. Cook
Journal: Journal of Clinical Oncology (2018)

9583 Background: Accurate assessment of risk for recurrence and metastasis and early identification of low-burden metastatic disease is of utmost importance for cutaneous melanoma (CM) patient care. Although CM staging has improved with the development of new inflection points to define risk, additional information for risk assessment is critical, particularly considering advances in effective adjuvant therapy. A 31-gene expression profile (GEP) test accurately predicts risk of recurrence and metastasis, classifying CM as Class 1 (1A lowest risk) or Class 2 (2B highest risk). Herein, we analyze its utility for risk stratification beyond traditional staging factors in clinically-relevant subgroups of CM patients. Methods: Using an IRB-approved protocol, CM specimens and clinical data were collected from 16 centers. 690 samples met the inclusion criteria of stage I-III disease with at least 5 years follow up or an event. Low-risk patients (stage I-IIA) by national guidelines and the subpopulation of patients with microscopic nodal disease (stage IIIA), were selected to test the association of clinical factors and GEP with patient outcomes. Results: GEP Class was a significant predictor of recurrence, distant metastasis, and melanoma-specific survival independent of thickness, ulceration, node-status, and mitotic rate using multivariate Cox regression (p < 0.05 all endpoints), and the only significant factor for stage I-IIA cases. Stage I-IIA patients with a GEP Class 2B test result had 5-year recurrence free survival (RFS), distant metastasis free survival (DMFS), and melanoma-specific survival (MSS) rates of 61, 76, and 86% compared with 96, 97, and 100% for Class 1A patients (n = 393 p < 0.0001). Stage IIIA patients also exhibit statistically significant RFS, DMFS, and MSS when comparing GEP-test class results (n = 75 p < 0.05 all endpoints). Conclusions: GEP class is a robust and independent predictor of metastasis risk that adds prognostic information to clinically-relevant subpopulations. Accordingly, GEP results add benefit to traditional staging factors and thus can be incorporated in clinical decision-making regarding follow-up, surveillance, and may inform adjuvant therapy decisions.
Patient-reported psychosocial needs and psychological distress: the influence on survival in geriatric oncology patients.
Authors: Bonnie Leung, Aria Shokoohi, Alan Bates, Cheryl Ho
Journal: Journal of Clinical Oncology (2018)

10033 Background: Little is known about how psychosocial factors and distress affect geriatric oncology patients and their survival. The study goals were: review patient-reported needs from all cancer types; identify factors associated with increased risk for psychological distress, defined as moderate to severe anxiety (ANX) and depression (DEP); and determine whether ANX and DEP are independent prognostic variables for patients ≥65 years. Methods: All patients ≥65 years, referred to BC Cancer from 2011 – 2016 who completed the Psychosocial Screen for Cancer (PSSCAN-R) and the Canadian Problem Checklist (CPC) within 6 m of cancer diagnosis were included in the study. Baseline demographics and disease characteristics were collected retrospectively. Univariate analysis using the X2 test were used to compare patient groups. OS was calculated using the Kaplan Meier method and compared using the log rank test. MVA conducted using Cox-regression analysis. Results: 26, 323 patients were included in the analysis. Baseline characteristics: female 50%; age 65-69 29%, 70-79 46%, ≥80 27%; GI 20%, Breast 18%, GU 16%, Lung 16%, Other 29%; M0 66%, M1 19%, MX 15%. Patients presenting with ANX and DEP were more likely to be female, be aged 65 to 69, have lung cancer and metastatic disease (p-values < 0.001). Patients reporting emotional, informational, physical, and social/family problems or needs were more likely to present with ANX and DEP (p < 0.001). Median OS ANX 34 m vs no symptoms 43 m (p < 0.001) and DEP 31m vs no symptoms 43m (p < 0.001). MVA including age, sex, M status, ANX, DEP showed all variables were statistically significant; increasing age HR 1.05, male vs female HR 1.11, M1 vs M0 HR 3.62, ANX vs no symptoms HR 1.30, DEP vs no symptoms HR 1.50. Conclusions: Geriatric oncology patients who are female, are aged 65-69, have metastatic disease or lung cancer are at risk for distress. ANX and DEP are independent prognostic variables, negatively impacting survival. This vulnerable cohort of geriatric oncology patients should receive psychological support and follow up to better improve survival.
Global epidemiology and clinical spectrum of rosacea, highlighting skin of color: Review and clinical practice experience
Authors: Andrew F. Alexis, Valerie D. Callender, Hilary E. Baldwin, Seemal R. Desai, Marta I. Rendon, Susan C. Taylor
Journal: Journal of the American Academy of Dermatology (2018)

Rosacea has been reported less frequently among individuals with skin of color than in those with white skin, but rosacea is not a rare disease in this population. In fact, rosacea might be underreported and underdiagnosed in populations with skin of color because of the difficulty of discerning erythema and telangiectasia in dark skin. The susceptibility of persons with highly pigmented skin to dermatologic conditions like rosacea, whose triggers include sun exposure, is probably underestimated. Many people with skin of color who have rosacea might experience delayed diagnosis, leading to inappropriate or inadequate treatment; greater morbidity; and uncontrolled, progressive disease with disfiguring manifestations, including phymatous rosacea. In this article, we review the epidemiology of rosacea in skin of color and highlight variations in the clinical presentation of rosacea across the diverse spectrum of patient populations affected. We present strategies to aid in the timely diagnosis and effective treatment of rosacea in patients with skin of color, with an aim of promoting increased awareness of rosacea in these patients and reducing disparities in the management of their disease.
NORA trial (GECP 15/02): First efficacy results of the Spanish Lung Cancer Group (SLCG) phase II trial of concurrent chemo-radiotherapy (CT-RT) with cisplatin (P) plus metronomic oral vinorelbine (mOV) for unresectable locally advanced non-small cell lung cancer (LA-NSCLC).
Authors: Dolores Isla, Margarita Majem, Maria Guirado, Bartomeu Massuti, Ramon De Las Penas, Ana Laura Ortega Granados, Manuel Domine, Raquel Marse Fabregat, Maria Angeles Sala Gonzalez, Alfredo Paredes, Teresa Moran, Sergio Vazquez Estévez, Juan Coves, Jose Luis Gonzalez Larriba, Miguel Sánchez, David Vicente, Nuria Farre, Luis Fernandez Fornos, Francisco Valcarcel, Mariano Provencio-Pulla
Journal: Journal of Clinical Oncology (2018)

8537 Background: CT-RT is the standard treatment for unresectable LA-NSCLC. P plus vinorelbine is widely used. Metronomic CT is a frequent administration of low doses of CT. mOV has shown good efficacy and improved safety, and could improve the RT effect. Our goal is to evaluate the efficacy and safety of P-mOV with radical RT in patients (pts) with LA-NSCLC. Methods: Pts aged 18-75 years with histologically proven untreated and unresectable LA-NSCLC, adequate bone marrow, hepatic & renal function, ECOG PS0-1, received P 80mg/m2 D1 every 3 weeks combined with mOV 50mg/day on days D1, 3 & 5/weekly, 2 cycles (cy) as induction; patients without progression received 2 more cy of P at the same dose with mOV 30mg/day on D1, 3 & 5/weekly, concurrently with RT (66Gy in 6.5weeks). Primary endpoint was progression-free survival (PFS) by RECIST v1.1; secondary endpoints were: overall response rate (ORR), disease control rate (DCR), overall survival and safety profile. To guarantee an overall type-1 α error no greater than 0.05 and a type II (β) error 0.1 for PFS, a sample size of 67 pts was planned. Results: Sixty-seven pts were recruited in 17 Spanish sites from 04/2016 to 06/2017. One of them didn’t meet all the inclusion criteria. We analyzed the first 57 pts included. Pt characteristics: Male 77.3%; median age 62 (range 33-75); PS 0/1 50/50%; smokers 45.5%; adenocarcinoma/squamous 34.8/43.9%; stage IIIA/B 43.9/56.1%. Only 29.8% of pts presented any grade 3-4 adverse event, including: neutropenia 22.8%; anemia 3.5%; febrile neutropenia 7%; esophagitis 1.8%; pneumonitis 1.8%. There were two deaths non-related to the treatment, during this period. Forty-four pts have completed the treatment. ORR: 66.7%. DCR: 79%. With a median follow-up of 11.2 months (range 1.1-21.7), the median PFS is 11.9 months (CI95%; 10.1-NR). Conclusions: mOV-P with RT is as effective as the standard administration of vinorelbine, improving its safety profile. EudraCT 2015-003312-21. Clinical trial information: EudraCT 2015-003312-21.
<i>Regional socio-demographic determinants of melanoma incidence in the United States.</i>
Authors: Hermann T Simo, Zaid A Ammari, Abhinav Tiwari, Mohammad S Khan, Andrew J Wodarcyk, Chinonso B Agubosim, Aubin Sandio, Reham Bakhsh, William Barnett
Journal: Journal of Clinical Oncology (2018)

e13560 Background: According to the American Cancer Society, the incidence of melanoma has been rising for the last 30 years. The incidence is mainly related to sunlight and ultraviolet exposure. We wanted to investigate the correlation between the following socio-demographic factors (Body Mass Index, smoking rate, median income, insurance coverage rate) and melanoma incidence at the population level. We plan to use regional variations in these socio-demographic factors to examine correlation patterns with U.S melanoma incidence geographical variations between 1999-2012. Methods: From 1999 to 2012, data for median income and insurance coverage rate per state were obtained from the United States census bureau, data for BMI per state were obtained from the Robert Wood Johnson Foundation, data for smoking rate per state were obtained from the Institute for Health Metrics and Evaluation, data for melanoma incidence were obtained from the Centers for Disease Control and Prevention to construct the dataset. All 50 states were grouped into 7 regional subdivisions (West, Southern Rockies, Northern Rockies, South Central, North Central, Southeast and Northeast). A multiple regression analysis was performed using R 3.4 for data analysis. Results: Our study revealed that the incidence of melanoma is rising in most regions with the exception of the West. The incidence increases with increase in BMI in the West, but the opposite is occurring in the other regions. In the Southeast region, the incidence increased as the smoking rate increases, which is unique only to that region. Only in the West region did melanoma incidence decrease as income increased. The incidence increased with an increase in insurance coverage with the exception of the Northern, Southern Rockies and the Southwestern US. Conclusions: We found regional differences in our analysis between melanoma incidence and these socio-demographic factors. Excluding the influence of exposure to sunlight and Ultraviolet light on the incidence, our results suggest that these socio-demographic factors do not have a great impact on melanoma incidence. Addressing these socio-demographic factors may not help decrease melanoma incidence in the entire country but may have an impact regionally.
Clinicopathologic features and survival outcomes of sarcomatoid carcinoma presenting as cancer of unknown primary.
Authors: Ryan Huey, Shalini Makawita, Michael J. Overman, Linus Ho, Kanwal Pratap Singh Raghav, Gauri R. Varadhachary
Journal: Journal of Clinical Oncology (2018)

e23565 Background: Sarcomatoid carcinoma is a rare histologic subtype of cancer of unknown primary (SCUP) characterized by poorly differentiated carcinoma with a component of sarcoma-like differentiation or a true mixed lineage neoplasm. There is limited data regarding the presentation, diagnostic algorithm and natural history of patients (pts) with SCUP. Methods: We retrospectively reviewed the MD Anderson CUP database and tumor registry from 2012-2015 and identified 26 pts with SCUP. Data regarding pathologic nomenclature, immunohistochemistry (IHC), molecular diagnostics, treatments, and outcomes were obtained. Kaplan Meier method was used for survival analyses (OS). Results: The most common nomenclature was sarcomatoid carcinoma, followed by sarcomatoid malignant neoplasm, and carcinoma with sarcomatoid features. Median age at diagnosis was 61 years (range 33-77). 54% of pts were female. Majority of pts presented with more than 3 metastatic sites, commonly lung, liver, and bone. 22 pts (85%) received chemotherapy, most commonly gemcitabine + docetaxel (10 [38%]) and carboplatin + paclitaxel (4 [15%]). Epithelial IHC markers included Pankeratin (AE1/AE3), CK7, BerEp4, Low Molecular Weight keratin and mesenchymal IHC markers included Calretinin, SMA, Vimentin, Mesothelin. Median OS for entire cohort was 7 months (m) (95% CI: 2.1-11.9). Pts who underwent definitive multimodality management did significantly better compared to pts with palliative therapy alone (median OS 26 vs 7 m: HR 0.25; 95% CI: 0.11-0.58, P = 0.003). Poor PS (HR 3.49; 95% CI 1.28-9.53, P = 0.0005), elevated LDH (HR 2.81; 95% CI 0.68-11.63; P = 0.03), and elevated neutrophil-to-lymphocyte ratio (NLR) (HR 3.18; 95% CI: 1.07-9.48, P = 0.002) were associated with poor OS. 5 pts underwent NGS which demonstrated p53 (3), BRAF V600E (2) and EGFR amplification (1). Conclusions: SCUP is a rare presentation with an aggressive course and limited survival. The diagnosis is difficult to make and requires a careful review and synthesis of histology, IHC, and molecular diagnostics. Further research is needed to better understand the optimal use of molecular diagnostics in order to more optimally diagnose and treat this disease.
A Single Institution of Review of Patients Complaints and Compliments.
Authors: Danny Landau, Annette Sturtz
Journal: Journal of Clinical Oncology (2016)

e18205 Background: Recent projected shifts in payment models for healthcare have emphasized the importance of ensuring patient satisfaction. Concerns about this system have been expressed as patients are not restricted in the sorts of issues that can be mentioned in reports. This could lead to inappropriate damaging of a physician’s reputation and financial penalty. Numerous systems exist for the documentation of these scores. Within the UF Health Cancer Center at Orlando Health, patients are able to voice their satisfaction levels via the Press Gainey Survey and leave comments on areas in which they have been satisfied and on areas in which improvement is needed. We opted to look back at these comments for trends on where improvement can be made. Methods: Patient comments from August 2015 to November 2015 were included. The comments were broken into categories to help us understand where deficiencies exist and where we have strength. The results are reported below. The results are reported for the hematology and medical oncology section where we have 14 providers. Results: Negative comments were broken into categories including: - Time issues (time it took for labs to be drawn, time in waiting room, time for physician to come in): 10/25 - Customer service (staff being available, friendliness of staff): 4/25 - Issues with physicians directly: 3/25 - Other (bathrooms not cleaned properly, slow working elevators): 8/25 Positive comments were broken into categories including: - Satisfaction with physicians and staff 38/46 - Timeliness (for appointments and visits) 4/46 - Other (use of cold caps to prevent hair loss, cleanliness of facility) 4/46 Conclusions: Negative comments were mostly directed toward time based issues, particularly when there were long waits to have labs drawn or excessive waits in the waiting. Only rarely were direct issues with a provider noted. Patients were also far less likely to voice complaints than they were satisfaction. Patient who left positive comments mostly did so to express their satisfaction with providers or staff. Concerns about complaints being potentially damaging to a providers reputation were not founded based on this sampling of comments.