tbuckley/cabot-search huggingface dataset:
The association of marital status, socioeconomic status, and race on the survival of ovarian cancer patients.
Authors: Austin Blake Gardner, Brooke Sanders, Amandeep Kaur Mann, Cheng-I Liao, Daniel Stuart Kapp, John K. Chan
Journal: Journal of Clinical Oncology (2019)

e17056 Background: To evaluate the influence of marital status, socioeconomic status, and race on the survival of ovarian cancer patients. Methods: Data were obtained from the SEER database from 2010 to 2015. Analyses were performed with Kaplan–Meier and multivariate Cox proportional hazard models. Results: Of 19,772 patients with ovarian cancer (median age: 60), 82.8%, 7.1%, 9.4%, and 0.7% were White, Black, Asian, and Native American, respectively. 54.5%, 21.7%, 11.5%, and 12.3% were married, single, divorced, and widowed. Married patients were older than single patients but younger than divorced and widowed patients (59 vs. 54 vs. 61 vs. 75 years; p &lt; 0.001). 55.5%, 30.7%, 64.1%, and 38.8% of White, Black, Asian, and Native American patients were married (p &lt; 0.001). 90.6% of married patients were insured compared to 71.8% single, 78% divorced, and 86.1% widowed (p &lt; 0.001). Patients who were married presented at earlier clinical stages (I-II) and lower tumor grades (I-II) compared to widowed and divorced patients (p &lt; 0.001). Married patients were more likely to receive chemotherapy compared to single, divorced, and widowed patients (79.1% vs. 71.3% vs. 76.7% vs. 67.6%; p &lt; 0.001). The 5-year disease-specific survival (DSS) of the overall group was 60.1%. Married patients had similar DSS compared to single patients at 62.3% vs. 65.0%, but improved survival vs 53.7% divorced and 46.6% widowed (p &lt; 0.001). In multivariate analysis, patients with stage II-IV or grade III-IV disease, older age (HR: 1.002, 95% CI: 1.001 to 1.003, p &lt; 0.01), Medicaid (HR:1.16, 95% CI: 1.11-1.22 p &lt; 0.0001) or no insurance (HR:1.20, 95% CI: 1.11-1.30, p &lt; 0.0001) had worse prognosis. Married patients had improved survival relative to widowed patients (widowed HR = 1.08; 95% CI: 1.03-1.14; p &lt; 0.01). Race did not influence DSS when controlling for surgery, chemotherapy, and radiation. Conclusions: Married patients were younger, had less advanced diseases relative to divorced and widowed patients, and were more likely to receive adjuvant chemotherapy compared to unmarried patients. Marital status is an independent predictor for survival relative to widowed status. DSS among races was not significant.
Improvement of lung cancer risk prediction adding SNPs to the HUNT Lung Cancer Model: A HUNT Study.
Authors: Oluf D. Røe, Olav Toai Duc Nguyen, Klio Lakiotaki, Ioannis Tsamardinos, Vincenzo Lagani, Maria Markaki
Journal: Journal of Clinical Oncology (2019)

e20696 Background: A novel validated model for risk prediction of lung cancer, the HUNT Lung Cancer Model predicts 6- and 16-year risk of lung cancer with a C-index = 0.879 and 6-year AUC = 0.87. The model is valid for smokers and ex-smokers of any intensity and quit time and includes seven variables; age, BMI, pack-years, smoking intensity (cigarettes per day), quit time, daily cough in periods of the year and hours of daily indoors smoke exposure. Genome-wide association studies (GWAS) have consistently identified specific lung cancer susceptibility regions. We aimed to improve performance of the HUNT model by integrating the most significant Single Nucleotide Polymorphisms (SNPs). Methods: Lung cancer cases (n = 484) and controls without other cancer (n = 50337) were genotyped for 22 SNPs located in GWAS-identified lung cancer susceptibility regions. Variable selection and model development used backwards feature selection with Akaike Information Criterion in multivariable Cox regression models. Internal validation used bootstrap to assess the change in area under the receiver operator characteristic curve (AUC) in order to compare nested models with and without genetic variables in the ever-smokers´ population (n = 456 cases, n = 28633 controls). We also used likelihood based methods for significance testing. Results: Variable selection and model development in the general population yielded six SNPs, rs1051730, rs11571833, rs13314271, rs2131877, rs2736100 and rs4488809. The added genetic information from these SNPs to the HUNT model, resulted in an improvement according to F test of the nested models (ANOVA p-value 0.000002425). The AUC of the augmented model was 0.881 (95% CI [0.869 0.892]) vs 0.869 without SNPs. Conclusions: In a highly predictive clinical risk prediction model, the integration of SNPs could further improve model performance according to likelihood based methods. Further refinement and validation of this integrated model is needed for clinical use.
Analysis of patient diaries in the NETTER-1 Study of 177Lu-DOTATATE versus high-dose octreotide in progressive midgut neuroendocrine tumors.
Authors: Jonathan R. Strosberg, Edward M. Wolin, Beth A. Chasen, Matthew H. Kulke, David L Bushnell, Martyn Caplin, Richard P. Baum, Timothy J. Hobday, Andrew Eugene Hendifar, Paola Santoro, Per Broberg, Arnaud Demange, Kjell E. Oberg, Philippe B. Ruszniewski, Laura Ravasi, Eric Krenning
Journal: Journal of Clinical Oncology (2019)

4111 Background: The primary statistical analysis for the NETTER-1 trial showed a clinically and statistically significant PFS benefit with 177 Lu-DOTATATE vs. high-dose octreotide. 177 Lu-DOTATATE treatment was also correlated with a significant delay in time to deterioration in HRQoL. In addition to HRQoL questionnaires, patients were asked to record presence or absence of a range of symptoms in a daily diary. Methods: A Mixed Model Repeated Measures (MMRM) was used to analyze the change, compared to baseline, of the occurrence of abdominal Pain, diarrhea and cutaneous flushing as these symptoms were regarded as the most relevant to judge the overall disease status. For each visit (week = 0, 4, 8, etc.) the number of days with symptoms during the previous period was calculated. At baseline, the number of days with symptoms was counted over the previous 6 weeks, whereas the time frame between visits lasted 4 weeks. Results: The estimated number of days with symptoms declined significantly more in the 177 Lu-dotatate arm compared to the octreotide arm. The difference in change and the confidence intervals for the symptoms abdominal pain, diarrhea and flushing of skin are, respectively: -3.11 [-4.88; -1.34], -3.11 [-5.04; -1.18] and -1.98 [-3.88; -0.08]. Conclusions: Analysis of symptom diaries confirms that 177 Lu-Dotatate can palliate clinically relevant symptoms when compared to high-dose octreotide.
ONC201 in previously-irradiated pediatric H3 K27M-mutant glioma.
Authors: Sharon L. Gardner, Jeffrey C. Allen, Wafik Tharwat Zaky, Yazmin Odia, Doured Daghistani, Ziad Khatib, Carl Johannes Koschmann, Dolly Aguilera, Tobey J. MacDonald, Andrew S. Chi, Rohinton Tarapore, Krystal Merdinger, Wolfgang Oster, Joshua E. Allen, Soumen Khatua
Journal: Journal of Clinical Oncology (2019)

10046 Background: ONC201 is the first DRD2 antagonist for clinical oncology. The recommended phase 2 dose (RP2D) of 625mg ONC201 orally once a week has been established in adult patients. ONC201 efficacy has been shown in high-grade glioma preclinical models and radiographic regressions with single agent ONC201 have been reported in adult recurrent H3 K27M-mutant glioma patients. We report results from the first Phase I pediatric clinical trial of ONC201. Methods: This multicenter, open-label, dose-escalation and dose-expansion clinical trial (NCT03416530) determined the RP2D of ONC201 in pediatric H3 K27M-mutant glioma patients as a single agent. ONC201 was orally administered once a week and scaled by body weight. Dose escalation was performed by a 3 + 3 design beginning with one 125mg capsule less than the adult RP2D equivalent. Three patients were treated at the starting dose and 19 were treated at the adult RP2D equivalent. Results: The primary endpoint was achieved by establishing the safety of the adult RP2D scaled by body weight to pediatric patients. Twenty-two patients with a median age of 9 (range 3-18) years old who received at least prior radiation have been treated with ONC201: 15 with diffuse intrinsic pontine glioma (DIPG) (4 recurrent; 11 not recurrent) and 7 with non-DIPG H3 K27M-mutant glioma (all not recurrent). As of February 5, 2019, patients have received a median of 18 ONC201 doses (range 3-41) without instance of dose-limiting toxicity. Pharmacokinetic profiles were comparable to those observed in adults (Cmax ~2.1ug/mL; AUC ~2.3hr*ug/mL) and exposure was similar across body weights. Nine of 22 patients remain on therapy, 13 have discontinued due to progression, and 4 off-study patients are alive with a median follow up of 5.8 months. Five of the 11 (45%) DIPG patients who initiated ONC201 following radiation, but prior to recurrence, remain on therapy (median 7.4 months; range 4.4-9.6): median PFS is 4.4 months from initiation of ONC201 and 9.7 months from diagnosis; 7 of 11 (64%) patients are alive with median follow up of 11.8 months from diagnosis. Conclusions: ONC201 was well tolerated and achieved therapeutic exposure in pediatric H3 K27M-mutant glioma patients at the adult RP2D scaled by body weight. Further investigation of first-line ONC201 to treat H3 K27M-mutant glioma and/or DIPG is ongoing. Clinical trial information: NCT03416530.
Value of adjuvant chemotherapy using paclitaxel plus carboplatin after radical surgery with or without radiotherapy in stage IB-iia cervical adenocarcinoma with risk factors.
Authors: You Wu, Li Nan, Jusheng An, Manni Huang, Shaokang Ma, Lingying Wu
Journal: Journal of Clinical Oncology (2019)

e17016 Background: The aim of this study was to evaluate the efficacy and safety of paclitaxel/carboplatin as an adjuvant systemic chemotherapy for stage IB-IIA cervical adenocarcinoma patients after radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy(RT). Methods: The cases of all patients (n = 152) with FIGO IB-IIA cervical adenocarcinoma who were treated by radical hysterectomy and pelvic lymphadenectomy with or without RT at Chinese academy of medical sciences cancer institute and hospital between January 2008 and January 2017 were reviewed. Of these, 35 patients displayed high-risk prognostic factors (high-risk group), 65 displayed intermediate-risk prognostic factors meeting sedlis criteria(intermediate-risk group),and 54 cases presented poorly differentiated status or LVSI, without other risk factors. In the high-risk group,18 patients received adjuvant radiotherapy and concurrent cisplatin chemoradiotherapy(RT-CCRT ) and 17 received adjuvant radiotherapy plus systemic chemotherapy using Paclitaxel Plus Carboplatin (RT-CT ). In the intermediate-risk group, 47 patients were treated with RT-CCRT and 16 were treated with RT-CT ,among the patients with poorly differentiated status or LVSI ,20 were treated with adjuvant chemotherapy using Paclitaxel Plus Carboplatin (CT ) and 34 received no further treatment (NFT). Results: In the high-risk group, adjuvant RT-CT was significantly superior to RT-CCRT with regard to median PFS and 2-year PFS rate(93.07months vs 52,44months, 94.1% vs 72.2%), but the recurrence rate and survival rate showed no significantly difference(11.8% vs 33.3%,100% vs 83.3%) . In the intermediate-risk group, Patients receiving RT-CT showed a better 2-year PFS rate and recurrence rate compared to those with RT-CCRT (100% vs 90.7%, 6.3% vs 12.6%), but the differences were not statistically significant. Among the patients with poorly differentiated status or LVSI, addition of adjuvant systemic chemotherapy resulted in significantly improved 2-year PFS rate compared with the NFT group (95% vs. 75.2%,p = 0.032). Conclusions: Adjuvant systemic chemotherapy using Paclitaxel Plus Carboplatin improved the prognosis of FIGO stage IB-IIA cervical adenocarcinoma patients in the high-risk group and patients who presented 2 or more intermediate-risk factors. Early cervical adenocarcinoma patients with low differentiation or LVSI can also benefit from postoperative adjuvant TC chemotherapy.
Opportunistic off-target cancer screening in organized programs: The EDIFICE 6 survey.
Authors: Jean F. Morere, Sebastien Couraud, Morgan Roupret, Chantal Touboul, Christine Lhomel, Francois Eisinger, Jerome Viguier, Laurent Greillier, Thibault De La Motte Rouge
Journal: Journal of Clinical Oncology (2019)

1535 Background: The efficacy and benefit/risk ratio of organized nationwide cancer screening programs rely on the age range of eligible average-risk populations. We studied the characteristics of off-target populations who underwent opportunistic screening for colorectal (CRC), breast (BC) or cervical (CC) cancer, ≤5y prior to the recommended age. Methods: The French nationwide observational survey, EDIFICE 6, was conducted online (June 26-July 28, 2017) on a core sample of 12 046 individuals (18-69y). Representativeness was ensured by quota sampling on age, sex, profession, and stratification by geographical area/type of urban district. Opportunistic screening for BC (in 533 women, age 45-49y), CRC (in 1331 individuals, age 45-49y) or CC (in 633 women, age 20-24y) was assessed in terms of smoking status (current, former/never smoker), marital status (single, living with a partner), type of residential area (urban, rural), having a close relative with cancer, social vulnerability (EPICES score), and self-reporting own cancer risk (higher, identical/lower than average). Results: In the off-target populations, screening rates were 78% for BC (N = 418, mammogram), 13% for CRC (N = 172, fecal test or colonoscopy) and 42% for CC (N = 264, cervical Pap smear test). Premature BC screening rates were significantly higher (P &lt; 0.05) in non-vulnerable than in vulnerable individuals (84% vs 69%), and among those self-reporting their own BC risk as higher than average (84% vs 76% reporting own BC risk as identical/lower than average). Premature CC screening rates were correlated with: smoking status (66% in current smokers vs 35% in former/never smokers), and marital status (63% in those living with a partner vs 34% single). Lastly, factors correlated with premature CRC screening were: type of residential area (urban, 15% vs rural, 8%), and believing own risk of CRC to be higher than average (27% vs 8% of those who self-reported their own CRC risk as identical/lower than average). Conclusions: This analysis reveals several factors related to premature screening for BC, CRC and CC, provides clear insight into off-target cancer screening uptake profiles, and hints at new strategies to ensure the optimal risk/benefit ratio of screening practices.
Human genes influence the interaction between Streptococcus mutans and host caries susceptibility: a genome-wide association study in children with primary dentition
Authors: Ying Meng, Tongtong Wu, Ronald Billings, Dorota T. Kopycka-Kedzierawski, Jin Xiao
Journal: International Journal of Oral Science (2019)

Streptococcus mutans is a well-known cause of dental caries, due to its acidogenicity, aciduricity, and ability to synthesize exopolysaccharides in dental plaques. Intriguingly, not all children who carry S. mutans manifest caries, even with similar characteristics in oral hygiene, diet, and other environmental factors. This phenomenon suggests that host susceptibility potentially plays a role in the development of dental caries; however, the association between host genetics, S. mutans, and dental caries remains unclear. Therefore, this study examined the influence of host gene-by-S. mutans interaction on dental caries. Genome-wide association analyses were conducted in 709 US children (<13 years old), using the dbGap database acquired from the center for oral health research in appalachia (COHRA) and the Iowa Head Start programmes (GEIRS). A generalized estimating equation was used to examine the gene-by-S. mutans interaction effects on the outcomes (decayed and missing/filled primary teeth due to caries). Sequentially, the COHRA and GEIRS data were used to identify potential interactions and replicate the findings. Three loci at the genes interleukin 32 (IL32), galactokinase 2 (GALK2), and CUGBP, Elav-like family member 4 (CELF4) were linked to S. mutans carriage, and there was a severity of caries at a suggestive significance level among COHRA children (P < 9 × 10−5), and at a nominal significance level among GEIRS children (P = 0.047–0.001). The genetic risk score that combined the three loci also significantly interacted with S. mutans (P < 0.000 1). Functional analyses indicated that the identified genes are involved in the host immune response, galactose carbohydrate metabolism, and food-rewarding system, which could potentially be used to identify children at high risk for caries and to develop personalized caries prevention strategies.
Real-world evidence evaluating the use of single versus combination chemotherapy in salvage therapy for metastatic breast cancer.
Authors: Bruce A. Feinberg, Kevin Lord, Jonathan Kish, Jalyna R. Laney, Dhruv Chopra, Djibril Liassou
Journal: Journal of Clinical Oncology (2019)

e12600 Background: Metastatic breast cancer (mBC) patients often receive multiple lines of systemic chemotherapy (Chemo) to extend life, manage disease symptoms and improve quality of life. Combination chemotherapy (cChemo) provides no survival advantage over single agent sequential chemotherapy (sasChemo) in mBC, but it may increase the risk of toxicity and adverse events while decreasing quality of life. The National Comprehensive Cancer Network guideline states that sasChemo is preferred for recurrent or stage IV mBC. This study aimed to explore adherence to this recommendation by evaluating contemporary real-world treatment patterns in mBC. Methods: Patients were identified from a third-party, administrative claims database. Using medical and pharmacy claims, any female with mBC (both BC and metastatic ICD9/10 codes) diagnosed between 01-Jan-2013 and 31-Dec-2017, followed for at least 6 months, and who had initiated systemic therapy was selected. Patients who received any HER2 targeted therapy, any oral or infused hormonal therapy, and/or had other malignant diagnoses were excluded. The proportion of patients receiving each line of chemotherapy was calculated in addition to the proportion of sasChemo and cChemo. Results: 10,342 patients met the selection criteria. Mean age at initiation of treatment was 61.7 years (SD = 12.12), 35.7% of patients had Medicare/Medicare advantage insurance coverage. All patients received first line (1L) systemic chemotherapy, 59% received 2L, 39% 3L, 25% 4L, 16% 5L, and 12% 6L respectively. 4 patients received ≥ 7L. The distribution between sasChemo vs cChemo was 50%/50% in 1L, 42%/58% 2L, 43%/57% in 3L, 44%/56% in 4L, 45%/55% in 5L and 46%/57% in 6L. Conclusions: Despite medical evidence which resulted in clinical guideline preference for sasChemo, cChemo use continues to have significant use in the salvage treatment of mBC. Research is warranted to understand and lessen this low value practice.
Association of polybromo-associated BAF (PBAF) complex mutations with overall survival (OS) in cancer patients (pts) treated with checkpoint inhibitors (ICIs).
Authors: Sarah Abou Alaiwi, Amin Nassar, Ziad El Bakouny, Jacob E Berchuck, Pier Nuzzo, Ronan Flippot, Abdallah Flaifel, John A. Steinharter, Sylvan Baca, Claire Margolis, Natalie Vokes, Heng Du, Sachet A Shukla, David A. Braun, Sabina Signoretti, Guru Sonpavde, David J. Kwiatkowski, Eliezer Mendel Van Allen, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2019)

103 Background: ICIs have shown benefit across several metastatic carcinomas, yet predictive biomarkers are still lacking. 20% of malignancies harbor alterations in ≥1gene that is part of PBAF complex. With recent data suggesting an association between PBRM1 mutations (mts) and outcomes in renal cell carcinoma (RCC) pts treated with ICIs (Miao, Science, 2018), we examined the association between PBAF mts and OS in ICI-treated patients across several solid cancer (ca) types. Methods: Of 6007 pts with different ca histologies and targeted exome sequencing (Oncopanel) at Dana Farber Cancer institute (DFCI), 138 pts had truncating mts in any PBAF gene (SMARCA4, PBRM1, and ARID2) or oncogenic missense mts in SMARCA4 and were treated with ICIs. 138 histology-matched DFCI pts had none. A publicly-available cohort (2:1 histology matched) from Memorial Sloan Kettering (MSKCC) (Samstein et al., Nature Genetics, 2019) of 621 ca pts (PBAF mutant [MT] = 207, PBAF wild type [WT] = 414) treated with ICIs was analyzed for association between PBAF mts and OS. OS was defined from time from ICI initiation. OS was compared by Cox regression between PBAF MT and PBAF WT. Hazard ratio (HR) was derived using univariable and multivariable analysis (MVA) adjusted for ICI regimen (single vs combination) and age. Results: Median (Md) follow-up for the combined cohort (n = 897) was 27 months (m). Major histologies were non-small cell lung ca (268; 29.9%), melanoma (220; 24.5%), RCC (181; 20.2%), and bladder ca (65; 7.2%). Results on univariable and MVA analyses from individual and combined cohorts are presented below. Conclusions: PBAF mts are associated with survival in ICI-treated ca pts. Work in progress with non-ICI treated pts will determine if this is prognostic or predictive of response. [Table: see text]
The effects of immunotherapy and novel therapies on medical oncology work load in a Canadian province.
Authors: Ravi Ramjeesingh, Bruce Colwell, Daniel Rayson
Journal: Journal of Clinical Oncology (2019)

6532 Background: Both novel targeted therapies and immunotherapies have dramatically changed the landscape in a number of disease sites with previously limited treatment options. This has resulted in an impact on clinical workload for oncologists with subspecialty practices in the areas of non-small cell lung, (NSCLC), melanoma (M), and genitourinary (GU) cancer. Our aim was to investigate the shift in workload amongst these practices as compared to other disease sites within a single academic cancer center in Nova Scotia (NS), Canada. Methods: The NS Cancer Center is the academic cancer center for the province of NS providing consultative and ongoing care for approximately 72% of provincial patients. We manually quantified appointment visits (new consultation, treatment and follow up visits) as well as telephone toxicity and chart checks booked from February 1 to April 30 across a 3-year interval (2016, 2017, and 2018) and then extrapolated this data to derive full year estimates. Disease sites most impacted by therapies that have changed treatment landscape (NSCLC, M and GU) were compared with the Breast and Gastrointestinal disease sites. Results: Clinical workload increased across all domains over the 3 year period but the majority of the increase is attributed to the 3 disease sites (Table). Conclusions: Medical oncology workloads are increasing over time and novel treatments (including immunotherapy) in disease sites with previously limited options likely account for a significant portion of that increase. New patient consultation metrics, taken in isolation, do not reflect current trends in medical oncology workload. Hiring practices, space allocation and use of physician extenders must take into account these shifting workload dynamics to mitigate physician burnout and potential impacts on quality and timeliness of care. [Table: see text]
Vocal Cord Dysfunction in Patients Hospitalized with Symptoms of Acute Asthma Exacerbation
Authors: Christopher P. Daley, Laurence E. Ruane, Paul Leong, Kenneth K. Lau, Kathy Low, Kais Hamza, Paul Finlay, Martin MacDonald, Malcolm Baxter, Philip G. Bardin
Journal: American Journal of Respiratory and Critical Care Medicine (2019)