tbuckley/cabot-search huggingface dataset:
The clinical utility of neuron-specific enolase serum levels as a biomarker for Merkel cell carcinoma.
Authors: Linde M. van Veenendaal, Eduardo Bertolli, Catharina M. Korse, W. Martin. C. Klop, Margot Et Tesselaar, Alexander Christopher Jonathan Van Akkooi
Journal: Journal of Clinical Oncology (2019)

9570 Background: To date no adequate biomarker for Merkel Cell carcinoma (MCC) has been identified. The introduction of immunotherapy (IT) for metastatic MCC increases the need for a biomarker. Serum Neuron-specific enolase (NSE) has already been tested and is commonly used as a biomarker for several small cell malignancies. However, the role of NSE in MCC is still unclear. Aim: To investigate the role of NSE as a biomarker in MCC. Methods: A prospective cohort of MCC patients treated from 2016 to July 2018 was analyzed. Kaplan Meier curves with log rank test, Cox regression and mixed models were used to analyze NSE. A separate evaluation was performed for patients treated with IT. Results: A total of 78 patients (42 males, median age 71 years, stage I&amp;II, III and IV MCC in 37(47%), 39(50%) and 2(3%) patients at time of diagnosis with 474 NSE levels (median 15 ; IQR 12,6-22 ng/ml were included. Baseline NSE (n=36) had no influence on survival or progression. During follow-up (FU) NSE levels correlated with tumorload (p=0,01) with increase of 15 ng/ml per class (no tumorload, localized MCC, nodal and distant metastases, respectively). NSE level during FU was able to detect progression (AUC 0,89). Several cut off values were evaluated. A NSE of 18,2 ng/ml was considered the most optimal level for clinical use (sensitivity 91%, specificity 78%, PPV 48%, NPV 98% to detect progression). During IT (n=16; 195 NSE values) all complete responders (n=7) had a normalized NSE (&lt;18,2 ng/ml), all partial responders (n=3) had a decreasing NSE. In non-responders (n=6) all NSE levels remained elevated, one patient responded after switching to different IT with normalizing NSE values. Conclusions: NSE seems to be a valuable biomarker in MCC. NSE correlates with tumorload; is able to rule out progression and distinguishes responders from non-responders during IT.
A phase I/II first-in-human trial of oral SRA737 (a Chk1 inhibitor) given in combination with low-dose gemcitabine in subjects with advanced cancer.
Authors: Udai Banerji, Elizabeth Ruth Plummer, Victor Moreno, Joo Ern Ang, Amy Quinton, Yvette Drew, Tatiana Hernández, Desamparados Roda, Louise Carter, Alejandro Navarro, Rebecca Sophie Kristeleit, Hendrik-Tobias Arkenau, Debashis Sarker, Daniel E. Castellano, Harriet Walter, Patricia Roxburgh, Sarah Patricia Blagden, Alan Anthoney, Ines Verdon, Robert Hugh Jones
Journal: Journal of Clinical Oncology (2019)

3095 Background: SRA737 is a potent, highly selective and orally-bioavailable inhibitor of checkpoint kinase 1 (Chk1). SRA737-02 was designed to investigate the safety, tolerability and preliminary activity of SRA737 in a novel combination with sub-therapeutic doses of gemcitabine (low dose gemcitabine; LDG) utilized to potentiate SRA737’s activity by induction of replication stress in subjects with advanced solid tumors. Methods: Phase 1 dose escalation investigated cohorts of 3 to 6 subjects receiving escalating doses of SRA737 for 2 days after LDG administration on days 1, 8, 15 of 28-day cycles. Phase 2 expansion cohorts explored the hypothesis that LDG strongly synergizes with SRA737 in subjects with genetically-defined tumors hypothesized to be sensitive to Chk1 inhibition: urothelial, high grade serous ovarian, small cell lung, soft tissue sarcoma, and cervical or anogenital cancers. Results: A total of 55 subjects received SRA737 in 13 dose escalation cohorts at doses of 40 to 600 mg SRA737 combined with LDG doses of 50 to 300 mg/m 2 . No protocol-defined dose limiting toxicities (DLTs) have been observed. The pharmacokinetic profile of SRA737 revealed an AUC 0-24 and C max of 3550 ng∙h/mL and 548 ng/mL at 150 mg SRA737. At this dose, the C min (52 ng/mL) exceeded that determined in preclinical models to be effective. Enrollment into expansion cohorts was initiated at 500 mg SRA737 plus 100 mg/m 2 LDG with intra-patient dose escalation permitted to 250 mg/m 2 LDG. Approximately 80 subjects were planned and 82 have been treated. Median treatment duration was 51 days (range 1 to 358). The most common treatment-emergent adverse events were nausea (53%), vomiting (45%), fatigue (40%), diarrhea (38%), and anemia (28%); the majority were of mild to moderate severity. Proof-of-concept clinical activity has been seen in tumor types such as anal, cervical, and rectal. Conclusions: The combination of LDG and SRA737 has been well tolerated. This first-in-human clinical study provides proof-of-concept that sub-therapeutic LDG effectively potentiates SRA737. This novel replication stress-targeted therapy warrants further evaluation in genetically pre-defined solid tumors. Clinical trial information: NCT02797977.
The impact of ACA on medical financial hardship among cancer survivors.
Authors: Aaron N Winn, Parker Knueppel, Joan Marie Neuner
Journal: Journal of Clinical Oncology (2019)

e18160 Background: Prior research has documented that privately insured cancer patients are exposed to significant financial burdens which can result in bankruptcy. A key provision of the Affordable Care Act (ACA) was to set limits on patients out-of-pocket (OOP) spending, which was implemented in 2014. This study aims to assess if OOP limits reduces financial hardship. Methods: Using the 2000-2017 National Health Interview Survey we identified cancer survivors under age 65. We performed a difference in difference analysis which compared financial hardship for low- or moderate-income individuals (LMII), family income under $50,000, to those with higher incomes before and after OOP limits were implemented for privately insured patients. Financial hardship was measured in the following ways: delayed medical care due to cost and the number of family members delayed medical care due to costs, could not afford a prescription, medical care or seeing a specialist, and problems paying medical bills. We used multivariate regression models adjusting for age, race, marital status, gender and size of family. All analyses accounted for the complex survey design and weights. Results: We identified 20,879 privately insured, cancer survivors age 65 or younger. The impact of the ACA resulted in lower financial hardships for LMII compared to higher income persons for most outcomes. The impact of the OOP limits on financial hardship for LMII was seen in any family member delaying care due to costs (difference-in-difference (DiD) = -3.6%; 95% CI = -5.9%, -1.5%; p-value = 0.002), number of family members delaying care due to costs (DiD = -0.048; 95% CI = -0.082, -0.135; p-value = 0.002), had problems paying medical bills (DiD = -3.3%; 95% CI = -6.3%, -0.4%; p-value = 0.028), could not afford prescription medication (DiD = -2.3%; 95% CI = -4.2%, -0.3%; p-value = 0.023), could not afford medical care (DiD = -1.9%; 95% CI = -3.5%, -0.3%; p-value = 0.021), but there was no statistically significant difference in the ability to afford seeing a specialist (DiD = -1.1%; 95% CI = -2.6%, -0.5%; p-value = 0.002). Conclusions: Little research has examined the impact of the ACA’s OOP spending limits. In this study we find that after the introduction of OOP spending limits, financial hardship measured in a variety of ways significantly decreased for LMII.
A new method towards calculating the cancer cell fraction in cell-free DNA.
Authors: Tiancheng Han, Jianing Yu, Xiaojing Lin, Hongyu Xie, Xue Song, Ji He, Weizhi Chen
Journal: Journal of Clinical Oncology (2019)

e13053 Background: Circulating tumor DNA (ctDNA) has been applied and showed potential in cancer early/late-stage detection, tumor genotyping and post-operation recurrence monitoring. The fraction of ctDNA in cell-free DNA (noted as ccf hereby), in addition to standard SNV/INDEL/CNV analysis, has also been showed to associate with the tumor progression and prognosis. In theory, accurate ccf can further be useful in correcting and improving given SNV/INDEL/CNV results. Existing tools capable for calculating ccf (PureCN, FACETS, Sequenza, etc.) use coverage data in targeted regions and SNP allele frequency to calculate the tumor fraction, which fail to give accurate estimation at relatively low ctDNA concentrations. Methods: A Maximum Likelihood model was built to estimate ccf. We first select informative SNPs with significantly different VAF in the case and paired-control samples. The mutation type of an informative SNP is determined by the variant allele frequency (VAF) in the paired samples and the copy number of the case sample. Likelihood of each SNP given a specific ccf was then calculated. After clustering SNPs into clones, the ccf of each clone was estimated using a global likelihood. Results: Performance of the method was validated by ctDNA dilution series analysis. 6 cfDNA from cancer patient was diluted (concentrations: 1/3 - 1/81). Detection limit of the method is ~2%, and correlation between estimated and expected ccf ranged from 0.93 to 0.98. Conclusions: We have developed a novel method to better estimate cancer cell fractions in cell-free DNA. Results showed our method is able to calculate ccf at lower ctDNA concentrations with higher accuracy and stability than benchmarked tools. We describe here a method for target-sequencing data that is more sensible, accurate and stable than currently available tools.
Treatment and outcomes for patients (pts) with selected advanced/metastatic cancers by place of care.
Authors: Yihua Xu, Lisa M. Hess, Cliff Molife, Gebra Cuyun Carter, Yajun Emily Zhu, Suvapun Bunniran, Bryan A. Loy, Collin Churchill, Radhika Nair
Journal: Journal of Clinical Oncology (2019)

e20717 Background: Place of care may be an important factor affecting treatment &amp; economic outcomes for pts in advanced stages of cancer. This retrospective observational study compared treatment patterns, healthcare resource use &amp; costs, and overall survival (OS) for pts treated for selected cancers in the hospital outpatient department (HO) vs community oncology practices (CP) including physician offices &amp; freestanding ambulatory centers. Methods: Claims data from a large national health plan were used to identify adult pts with newly diagnosed advanced/metastatic non small cell lung cancer (aNSCLC), metastatic breast (mBC) or metastatic colorectal cancer (mCRC) between 07/2012 &amp; 12/2016, who initiated anticancer therapy in HO or CP settings. Pts enrolled in Medicare Advantage Prescription Drug (MAPD) or commercial plans for ≥ 6 months prior &amp; ≥ 30 days after start of first line (1L) (index date) were included. OS was evaluated among pts enrolled in MAPD and costs were evaluated among pts enrolled ≥ 6 months pre- &amp; post-index, by cancer type &amp; by place of care. Outcome analyses were adjusted using multivariable models. Results: Among 8,333 eligible pts, there were 4,618, 2,304 &amp; 1,411 pts with aNSCLC, mCRC &amp; mBC, respectively and each cohort was evenly split by place of care. No notable differences in baseline characteristics or the most commonly used 1L, 2L or 3L regimens were observed by place of care for the 3 cancers. For aNSCLC pts, mean 1L treatment duration was shorter (96 v 102 days, P = 0.02) and time between 1L &amp; 2L was longer (125 v 106 days, P = 0.04) in the HO than the CP setting, respectively. For mBC, mean 1L treatment duration was longer in the HO setting (156 v 190 days, P &lt; 0.01). Adjusted total all cause healthcare costs were higher in HO than CP for mBC ( P &lt; 0.01) &amp; mCRC ( P &lt; 0.01), but no significant difference in median OS was observed between HO &amp; CP settings for the 3 cancer types. Conclusions: This study showed no major differences between HO &amp; CP settings in baseline characteristics, the first 3 lines of therapy, or adjusted median OS for aNSCLC, mCRC, or mBC cohorts. However, total costs were higher in the HO setting for mCRC &amp; mBC pts. These findings may be useful for healthcare decision &amp; policy makers but warrant further evaluation.
Germline variants in urothelial carcinoma: Analysis of pathogenic and likely pathogenic variants in 645 subjects.
Authors: Sarah Abou Alaiwi, Amin Nassar, Kent William Mouw, David J. Kwiatkowski, Toni K. Choueiri, Catherine Curran, Eliezer Mendel Van Allen, Edward D. Esplin, Shan Yang, Judy Ellen Garber, Huma Q. Rana, Guru Sonpavde
Journal: Journal of Clinical Oncology (2019)

1528 Background: While small studies have supported a genetic cancer predisposition among subjects with urothelial carcinoma (UC), systematic germline evaluation of this population is lacking. Here, we report the prevalence of germline variants among subjects with UC from multiple centers completing panel-based testing at a large, commercial laboratory. Methods: 1149 UC subjects underwent germline testing of 1 to 126 genes using massively parallel sequencing with customized capture bait-sets to analyze exonic regions, flanking intronic sequences, and copy number alterations. Pathogenic (P) and likely pathogenic (LP) were confirmed using orthogonal technology in accordance with Invitae standard operating practices. Analysis was limited to 645 subjects who completed testing of a shared set of 42 genes. P/LP variants including single nucleotide variants/indels/ copy number variants are reported. De-identified personal and family cancer histories were evaluated. Fisher’s Exact test and the Mann-Whitney test were used to analyze categorical and continuous variables respectively. Results: Among the 645 UC subjects with 42-gene testing for any indication, median age at testing was 60 years (6-88) and 326 (51%) were female. P/LP variants were identified in 21 (50%) of the 42 genes in 98 (15%) of subjects, including Lynch syndrome genes (n = 26 [4%]), BRCA1/2 (n = 16 [2.5%]), CHEK2 (n = 15 [2.3%]), and heterozygous MUTYH (n = 12 [1.9%]). Among 18 DNA damage repair (DDR) genes assessed, 90 P/LP variants were detected in 88 subjects (12.2%). There was no significant association between presence of a DDR gene variant and age at diagnosis, gender or reported family history of UC in a first degree relative (n = 48). Among subjects with documented history of UC only without other cancers (n = 195), 24 (12.3%) had P/ LP variants, of which 23 (11.8%) were in a DDR gene. Conclusions: Germline P/LP variants were identified in 15% of UC subjects most of which (92%) were in DDR genes, including 27% in Lynch syndrome genes. PARP and T-cell checkpoint inhibitors may warrant evaluation in subjects with germline DDR mutations. Further validation in unselected UC pts is warranted to propose examining germline P/LP variants in all UC patients.
Contraception and fertility counseling in patients receiving chemotherapy.
Authors: Alexa Calfee, Taylor Hasley, Laura Becca Daily, Todd D. Tillmanns, Adam ElNaggar
Journal: Journal of Clinical Oncology (2019)

e23055 Background: Cancer care advances allow more patients to pursue fertility. Unfortunately, treatments may have detrimental effects both on fertility and risks to fetus should pregnancy occur. This study examines patient perceptions of fertility and contraception counseling, as well as physician documentation thereof. Methods: After IRB approval, a cross-sectional study was performed identifying men and women, ages 18-50, seen between May 2017 and 2018 with newly diagnosed malignancy. Patients with previous sterilization procedures, a secondary or synchronous cancer, or prior lines of chemotherapy, were excluded. Consented patients received a survey regarding their perception receipt and quality of counseling. Demographic data, including contraception use, reproductive history, and physician documentation were obtained. Differences in receipt of counseling and perception of received counseling were evaluated using chi-square tests. Results: Of 179 patients identified, 53 ultimately participated. Majority were women (75 v 25%). Counseling documentation for contraception and fertility occurred in 5% and 32% of charts, respectively. Though 42% and 49% perceived receipt, respectively. Of those receiving counseling, it was perceived as sufficient by 64% regarding contraception and 72% regarding fertility. Race, gender, and reproductive history were not found to be associated to whether patients perceived counseling on contraception (p &gt; 0.1). Men were more likely than women to be perceive counseling regarding fertility (85 v 43%, p = 0.010). However, both felt fertility counseling to be sufficient with similar rates of documentation. Caucasians were more likely to perceive receipt of fertility counseling and to perceive it to be sufficient, then African Americans (68 v 29% and 70 v 40%, respectively) at same rate of documentation (35%). Conclusions: Significant discrepancies in perception of contraception and fertility counseling were seen, though documentation rates were similar across all groups examined. Despite equal rates of physician documentation, gender and race were important factors for the perception of fertility counseling, while race was a factor to quality of perceived counseling.
Patterns of local failure after definitive radiotherapy in patients with esophageal squamous cell carcinoma: Implications for the longitudinal clinical target volume design.
Authors: Bo Cheng, Xue Meng
Journal: Journal of Clinical Oncology (2019)

e15504 Background: The correlation between the clinical target volume (CTV) margin and esophageal squamous cell carcinoma (ESCC) recurrence pattern is not completely clear. Our aim was to retrospectively evaluate the recurrence patterns in ESCC patients who received definitive radiotherapy (RT) with different CTVs, and determine the optimum longitudinalmargin. Methods: Patients with histologically proven ESCC (N = 134) were classified into the following three groups according to the initial expanding margin of CTV at the recurrence side: CTV1 with longitudinal margin ≥ 3cm (N = 73), CTV2 with 2-3cm (N = 37), and CTV3 with &lt; 2cm (N = 24). The recurrence patterns were analyzed relative to the CTV margins, as well as the radiation dose, tumor stage, comorbidities etc. Results: The recurrence sites were significantly different between the CTV1 and CTV3 (p &lt; 0.001), but not between the CTV1 and CTV2 groups (p = 0.052). In addition, 42 (91.3%) of the 46 patients that received low-dose (55-60Gy) RT showed recurrence at the site of the primary tumor, an obviously greater proportion compared to those who underwent a high-dose ( &gt; 60Gy) treatment (77.3%, p = 0.018). Drinking was also a clear contributing factor (p = 0.025). Age, smoking, comorbidities,tumor location, stage and treatment mode were not significant prognostic factors for ESCC recurrence. Conclusions: CTV with a 2-3cm longitudinal expansion to the gross tumor volume (GTV) is acceptable for radical RT for ESCC, and recurrence at the primary tumor site is associated with low radiation dose ( &lt; 60Gy).
Implementation of malignant bowel obstruction multidisciplinary case conferences (MCCs) to improve clinical decision making in malignant bowel obstruction (MBO) in gynecologic oncology.
Authors: Gita Bhat, Ainhoa Madariaga, Luisa Bonilla, Yeh Chen Lee, Neesha C. Dhani, Nazlin Jivraj, Tanya Chawla, Sarah Buchanan, Sarah Ferguson, Catherine O'Brien, Preeti Dhar, Eran Shlomovitz, Jenny Lau, Susan Mulumba, Katherine Karakasis, Muralidharan Chllamma, Amit M. Oza, Stephanie Lheureux
Journal: Journal of Clinical Oncology (2019)

e18322 Background: Though patients (pts) with gynecological cancer are at higher risk of MBO, clinical management is not well defined. We implemented a coordinated team approach to evaluate MBO at Princess Margaret Cancer Centre. The Princess Margaret Cancer Centre inter-professional MBO management program includes nurse led ambulatory symptom management, inpatient treatment algorithm, patient directed bowel management education &amp; MCCs. This study evaluates the utility of MBO MCC on clinical decision making in gynecologic oncology. Methods: Monthly MBO MCCs are conducted to discuss complex clinical management issues. A clinical summary is presented prior to the discussion with each case incorporating radiology review followed by interdisciplinary discussion. In this study, the initial management plan was compared to post-MCC consensus. A change in plan was defined as a consensus plan different from the pre-MCC plan or no definite plan prior to MCC. Barriers to implementation of the consensus were analyzed. Results: From December 2016 to November 2018, 90 pts were discussed in 22 MCCs. Of these, 60 had high grade serous ovarian carcinoma (67%) &amp; 64 had small bowel obstruction (71%). Discussion in MCCs lead to a change in management plan in 49 cases(54%). These changes included recommendations for palliative surgery (25%) or radiation (10%), interventional radiology (23%), pharmacologic management alone (14%), imaging studies (4%) &amp; total parenteral nutrition (TPN) (4%). Chemotherapy continuation, break or regimen changes were recommended in 20%. MCC consensus plan could not be implemented in 11 cases (23%). The barriers were refusal of surgery (8%), interventional radiology procedures (2%), TPN (4%) by patients, functional decline (6%) &amp; inability to create a colostomy due to dense adhesions (2%). During MCC referrals to the dietitian &amp; palliative care team were planned for 16 (18%) &amp; 22 (24%) pts respectively. Conclusions: Interdisciplinary MBO MCCs have a significant impact on decision making in complex MBO cases. Radiology review &amp; group discussion facilitates greater clarity in formulation of a management plan.
Implementing physician education to increase lung cancer screening compliance.
Authors: Coral Olazagasti, Devi Sampat, Adam Rothman, Nagashree Seetharamu, David Steiger
Journal: Journal of Clinical Oncology (2019)

e18282 Background: Lung cancer is the leading cause of cancer-related deaths worldwide. The USPSTF recommends annual low-dose CT chest (LDCT) for lung cancer screening in adults who meet the appropriate criteria: age 55-80, current smokers or former smokers who quit within 15years, with a 30 pack-year smoking history. Even with these recommendations, screening rates in these patients remain low. We created a study to assess compliance in an outpatient Internal Medicine clinic to assess the barriers for obtaining LDCT. We hypothesized that by providing an educational program, overall compliance would increase. Methods: The study was divided in two arms: a pre-intervention arm and a post-intervention assessment. Initially, 35 physicians completed a questionnaire on their attitudes to LDCT screening and their reasons for not screening high risk patients. We created a lung cancer screening education program, which consisted of lectures provided to physicians. Following the lectures, consecutive patient visits were reviewed to assess compliance with screening. Results: In the first arm, 678 visits were reviewed. 115 patients met USPSTF criteria of whom only 26% underwent screening with LDCT. The most common reasons for not ordering LDCT scans in patients meeting criteria included: poor knowledge of criteria (22%), failure to determine if patients qualified (13%), patient refusal (8%). Following the education, 208 patients out of the 955 visits reviewed met USPSTF criteria, of which 78% underwent LDCT. Our study showed how after education, physicians were ten times more likely to screen patients for lung cancer (Odds ratio 9.98, 95% CI 5.87-16.94, p &lt; 0.0001). Conclusions: We confirmed there was suboptimal adherence to established LDCT lung cancer screening guidelines, mainly due to unfamiliarity with the screening criteria. By providing educational lectures, compliance improved significantly. We concluded that educating physicians about lung cancer screening guidelines increased LDCT screening tenfold, and therefore benefit patients that are at high risk for developing lung cancer.