tbuckley/cabot-search huggingface dataset:
KEYNOTE-052: Phase 2 study evaluating first-line pembrolizumab (pembro) in cisplatin-ineligible advanced urothelial cancer (UC)— Updated response and survival results.
Authors: Peter H. O'Donnell, Arjun Vasant Balar, Jacqueline Vuky, Daniel E. Castellano, Joaquim Bellmunt, Thomas Powles, Dean F. Bajorin, Petros Grivas, Noah M. Hahn, Elizabeth R. Plimack, Mary J. Savage, Xiao Fang, James Luke Godwin, Tara L. Frenkl, Ronald De Wit
Journal: Journal of Clinical Oncology (2019)

4546 Background: Initial results of the phase 2 KEYNOTE-052 (NCT02335424) study led to approval of pembro for cisplatin-ineligible patients (pts) with advanced UC. Updated results representing follow-up of over 2 y since last pt enrolled are presented. Methods: Pts had confirmed advanced UC, were cisplatin-ineligible (ECOG PS 2, CrCl ≥30 to ˂60 mL/min, grade ≥2 neuropathy/hearing loss, NYHA Class III heart failure), and received no prior chemotherapy for metastatic disease. Pts received pembro 200 mg IV Q3W until progression, unacceptable toxicity, withdrawal, or 24 mo of therapy, whichever occurred first. Primary end point was confirmed ORR (RECIST v1.1, independent central review). Key secondary end points: duration of response (DOR), overall survival (OS), and safety. Data cutoff was September 26, 2018. Results: Among pts assessed (N = 370), median age was 74 y, 85% had visceral disease, and 30% were PD-L1 positive (combined positive score [CPS] ≥10). Median follow-up was 11.4 mo (range, 0.1-41.2) for all pts and 29.3 mo (range 7-41.2) for responders. Confirmed ORR was 29% (95% CI, 24-34): complete response, 9% (n = 33); partial response, 20% (n = 73). Median DOR was 30.1 mo (95% CI, 18.1-not reached [NR]); 67% and 52% of pts had DOR ≥12 and ≥24 mo, respectively. Median OS was 11.3 mo (range 9.7-13.1); 12- and 24-mo OS rates were 47% and 31%, respectively. In pts with CPS ˂10 (n = 251) and ≥10 (n = 110), respectively, confirmed ORR was 20% (95%CI, 16-26) and 47% (95% CI, 38-57). Median DOR for pts with CPS &lt; 10 and ≥10 was 18.2 mo (95% CI, 9.7-NR) and NR (95% CI, 18.1-NR); DOR ≥24 mo was 45% and 57%, respectively. Median OS for pts with CPS &lt; 10 and ≥10 was 9.7 mo (95% CI, 7.6-11.5) and 18.5 mo (95% CI, 12.2-28.5); 24-mo OS rates were 24% and 47% respectively. Treatment-related adverse events (AEs) occurred in 67% of pts. Most common were fatigue and pruritus (18% each); 21% were grade ≥3, including 1 death (myositis). Conclusions: With extended follow-up, pembro continued to elicit clinically meaningful, durable antitumor activity in cisplatin-ineligible pts with advanced UC and was more pronounced in those with PD-L1 expression CPS ≥10. Pembro safety profile was as expected. Clinical trial information: NCT02335424.
Scientists Restore Some Functions in Slaughtered Pig Brains
Authors: Rita Rubin
Journal: JAMA (2019)

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Pilot study investigating an oncofertility program in adults with breast or sarcoma cancers.
Authors: Manali A. Bhave, Fang Fang, Kelley M. Kidwell, Gloria Lola Smith, Rashmi Chugh, Monika Leigh Burness
Journal: Journal of Clinical Oncology (2019)

e23096 Background: Cancer survival is at an all-time high; however, patients often face long-term consequences including infertility. Loss of fertility can be devastating and lead to long-lasting emotional distress. Despite consensus guidelines encouraging providers to discuss infertility risk and refer for fertility preservation (FP) consultations, fertility counseling and FP occur in only 10-29% of patients of childbearing age. A few identified barriers include lack of provider knowledge on FP, constraints on time and lack of available resources. Methods: This is a prospective pilot study evaluating the efficacy of an oncofertility program in increasing discussions on infertility risk and FP between providers and patients. The oncofertility program includes medical provider education, an electronic medical record (EMR)-based best practice alert with smart order set, patient education pamphlets and a patient navigator through Reproductive Endocrinology and Infertility (REI). Our primary objective was to increase documentation on fertility in the EMR, while our secondary objective was to increase referrals to REI for females and orders for semen cryopreservation for males. Provider and patient-reported outcomes were also obtained. Results: 19 patients with a new diagnosis of breast or sarcoma (7 pre-intervention and 12 post-intervention) were enrolled and 17 providers participated in the study at the University of Michigan. There was no change in documentation on fertility in the EMR and no increase in fertility referrals placed. However, patients reported a statistically significant change in amount of information provided on infertility risk and FP from "too little" to "the right amount." Providers also reported increased confidence in initiating a conversation about FP and a trend towards increased comfort documenting their conversations on FP in the EMR. Conclusions: With an increase in cancers diagnosed in young adults, there is a need to improve counseling on the risk of infertility with cancer treatment and FP options. Through an easily implemented oncofertility program, we were able to improve medical provider confidence in initiating this important conversation, provide patients with education on infertility risk and FP and streamline the process for FP referrals utilizing the EMR.
TransLiG: a de novo transcriptome assembler that uses line graph iteration
Authors: Juntao Liu, Ting Yu, Zengchao Mu, Guojun Li
Journal: Genome biology (2019)

We present TransLiG, a new de novo transcriptome assembler, which is able to integrate the sequence depth and pair-end information into the assembling procedure by phasing paths and iteratively constructing line graphs starting from splicing graphs. TransLiG is shown to be significantly superior to all the salient de novo assemblers in both accuracy and computing resources when tested on artificial and real RNA-seq data. TransLiG is freely available at https://sourceforge.net/projects/transcriptomeassembly/files/ .
A retrospective review on extended carboplatin infusion and incidence of hypersensitivity reaction in gynecologic malignancies in a single institution.
Authors: Jennifer Park, Matthew C. Lee, Erik Kockenmeister, Veena S. John
Journal: Journal of Clinical Oncology (2019)

e17102 Background: Carboplatin has been the standard treatment for advanced gynecologic malignancies in the first line setting as well as treatment of relapsed disease. Carboplatin induced hypersensitivity reaction (HSR) is observed more frequently in a second line setting and symptoms can range from rash to life threatening symptoms such as anaphylaxis, which could preclude further treatment. A retrospective study by O’Cearbhaill showed HSR rate with extended infusion protocol to be 3.4%. However, two subsequent prospective studies by Lax and O’Cearbhaill did not find that extended infusion reduced the risk or severity of HSR. We reviewed the incidence of HSR with three hour extended-infusion carboplatin at our institution. Methods: Our practice at the Monter Cancer Center changed from standard 1 hour carboplatin retreatment infusion to extended-infusion in 2011. We reviewed charts of 162 patients from 2011 to present who received a three hour extended infusion of carboplatin. All patients received prophylactic H1 and H2 blockers along with steroids. HSR was determined in two ways: 1) Identifying patients who reported clinical symptoms of HSR. 2) Identifying which patients had received diphenhydramine, hydrocortisone and/or epinephrine as indicated for an infusion reaction. Results: 162 patients were identified: 83 with ovarian cancer, 44 with uterine cancer, and 16 with fallopian tube cancer, 10 with primary peritoneal cancer, and 9 with cervical/vulvar cancer. Most had relapsed disease and were previously treated for stage IV (35%), or stage III (47%) with platinum doublet chemotherapy at least six months prior. Only 1 out of 162 (0.6%) had a grade 1 reaction with hives and was treated with dexamethasone and diphenhydramine. She was previously treated with carboplatin 17 months prior. Her current HSR occurred during her fifth cycle of retreatment. She was not re challenged with the drug and elected not to undergo desensitization. Conclusions: Hypersensitivity reactions develop in about 12-33% of women retreated with carboplatin peaking at eight cycles (Lax et al.). The mechanism behind HSR is unclear but considered to be from repeated exposure to free platinum metal concentration. Incidence of HSR at our institution was lowest ever-reported at 0.6%, suggesting that our extended infusion protocol with the appropriate premedication is appropriate for carboplatin-retreat patients. Further prospective studies to evaluate this regimen is warranted.
Feasibility of text-based symptom monitoring of ovarian and endometrial patients during treatment.
Authors: Michelle Joy Naughton, Ritu Salani, Juan Peng, Floor Backes, David M. O'Malley, David E. Cohn, Kristin Leigh Bixel, Cecilia DeGraffinreid, Jennifer Moon, Hibaq Loyan, Electra D. Paskett
Journal: Journal of Clinical Oncology (2019)

e18299 Background: Unreported symptoms during cancer treatment can lead to poorer patient care and quality of life. Newer technology enables effective means to track patients’ health in real time. We evaluated the feasibility of implementing systematic patient symptom monitoring during the first 12 months after diagnosis. Methods: Newly diagnosed endometrial and ovarian cancer patients were enrolled post-surgically to respond to monthly text message symptom surveys. Patients’ fatigue, sleep quality, pain, and quality of life during the past 7 days were rated on a 0 (worst) -10 (best) scale, and depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9). Patients’ responses were captured in REDCap and monitored by program staff, with patients’ oncologists receiving monthly feedback. Patient navigators were also engaged for patients needing assistance during treatment. We provide the results of the first 6 months of this program. Results: 134 patients were approached, and 120 patients (ovarian [n = 70] and endometrial [n = 50]) were enrolled among 5 physicians. The mean participant age was 63 (range: 35-87), 85% were non-Hispanic White, and 66% had education beyond high school. The most commonly reported monthly symptoms for both cancer types were moderate levels (scores of ≥ 4-7) of fatigue and sleep disturbance. 35 patients with PHQ-9 scores ≥ 10 and/or with suicidal ideation were reported to their oncologists for appropriate follow-up. At the 6 month survey, patients were asked to evaluate the text messaging program: 97% found the symptom surveys easy to complete on their smart phone or computer; 77% believed reporting their symptoms monthly was useful all or most of the time; 78% liked being monitored for symptoms all or most of the time; and 89% liked being asked if they needed any assistance prior to their next clinic visit. Patient navigators were used by 13 patients, and 17 patients dropped from the program over the 6 months due to death (n = 9) or lack of need/interest (n = 8). Average monthly compliance was 81%. Conclusions: We established the feasibility of enrolling patients in a monthly text-based monitoring program to facilitate symptom management during treatment. Patient follow-up is continuing.
Clinical and genomic hallmarks of low PSA secretors in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Gustavo Rubio Romero, Alana Weinstein, Verena Friedl, Adam Foye, Denise Playdle, Alexis Sabol, Patricia Li, Jiaoti Huang, Felix Y Feng, Joshua M. Stuart, Eric Jay Small, Rahul Raj Aggarwal
Journal: Journal of Clinical Oncology (2019)

5051 Background: Metastatic disease burden out of proportion to low serum PSA level is frequently used as a clinical surrogate for the diagnosis of treatment-emergent small cell neuroendocrine prostate cancer (t-SCNC), although many t-SCNC patients (pts) have normal or elevated PSA levels. The clinical and genomic characteristics of mCRPC pts who are Low PSA Secretors have not been previously described. Methods: Eligible mCRPC patients (pts) underwent image-guided needle biopsy. Formalin-fixed paraffin embedded tissue was evaluated with targeted next-generation DNA sequencing. Fresh frozen tissue from the same metastatic tumor underwent RNA-seq. A validated AR transcriptional signature was applied. Low PSA Secretors were defined as pts with PSA &lt; 5 ng/mL plus ≥ 6 metastases on conventional imaging at the time of tumor biopsy. Clinical and genomic characteristics were compared between low PSA Secretors and all other pts. Results: Of 89 evaluable pts, 9 (10%) were identified as Low PSA Secretors. There was no difference between Low PSA Secretors and all other pts in: serum PSA at diagnosis, frequency of Gleason ≥ 8 adenocarcinoma at diagnosis, and serum level of LDH, alkaline phosphatase, or hemoglobin at the time of biopsy. Lung and/or liver metastases were more common in low PSA secretors (67% vs. 33%, p = 0.04). There was no difference in serum level of LDH, alkaline phosphatase, or hemoglobin. Tumor biopsies from Low PSA Secretors were more likely to fall within a previously defined t-SCNC transcriptional cluster (80% vs. 6%, p &lt; 0.001). RB1 loss or inactivating mutations appeared to be enriched in Low PSA Secretors (40% vs. 12%, p = 0.09); there was no difference in frequency of TP53 alterations between subgroups. AR transcriptional signature scores were lower in the Low PSA Secretor group (median score -3.63 vs. 0.66, p &lt; 0.001). Conclusions: Low serum PSA levels in relation to metastatic tumor burden may be a reliable surrogate for the detection of mCRPC that harbors the transcriptional and genomic hallmarks of t-SCNC. Validation studies are warranted.
Trial in progress: Phase II study of stereotactic body radiation therapy and atezolizumab in the management of recurrent, persistent, or metastatic cervical cancer.
Authors: Kamran A. Ahmed, Youngchul Kim, Sachin M. Apte, Hye Sook Chon, Jing-Yi Chern, Jose Conejo-Garcia, Daniel Celestino Fernandez, Mitchel Hoffman, Sungjune Kim, Cesar Lam, Michael E. Montejo, Mian M. Shahzad, Robert Michael Wenham
Journal: Journal of Clinical Oncology (2019)

TPS5596 Background: There is no consistent recommendation for management of metastatic cervical cancer beyond first line therapy with chemotherapy and bevacizumab. Pembrolizumab is now approved for PD-L1 positive or MSI-H/dMMR metastatic or recurrent cervical cancer. Numerous pre-clinical studies have provided evidence to combine radiation therapy with immune checkpoint inhibition to improve response rates. The evidence is strongest for short course, hypofractionated radiation regimens. We hypothesize treatment with atezolizumab with hypofractionated radiation therapy will improve objective response rate (ORR) compared with atezolizumab alone in patients with recurrent, persistent, or metastatic cervical cancer. Methods: The study is designed as a prospective, single arm, nonrandomized, open-label, phase II trial of stereotactic body radiation therapy (SBRT) with 24 Gy in 3 fractions to patients with ≥ 2 metastatic sites followed 1 week later by atezolizumab (1200 mg IV every 3 weeks) for patients with recurrent, persistent, or metastatic cervical cancer. Dose reductions will not be allowed. The primary objective of the study is to evaluate the ORR by Immune-Modified Response Evaluation Criteria in Solid Tumors (irRECIST) criteria following SBRT and atezolizumab. Secondary endpoints include progression free survival, overall survival, local control, and adverse events. Correlative aims include assessing blood and tissue biomarkers (i.e. PD-L1, mutation burden, TCR repertoire etc.) for association with clinical benefit. A total of 26 patients will be enrolled. An interim analysis will be performed to assess efficacy after 13 patients become evaluable.This study is open with 2 patients enrolled at the time of submission. Clinical trial information: NCT03614949.
Disparities in HER2 testing in breast cancer.
Authors: Vijay Paryani, Mary Chen Schroeder, Heidi D. Klepin, Susan Anitra Melin, Greg B. Russell, Karen Marie Winkfield, Alexandra Thomas
Journal: Journal of Clinical Oncology (2019)

e13084 Background: Although targeted therapies directed at human epidermal growth factor-2 (HER2) impact breast cancer outcomes, studies have found geographic variation in testing rates. We report population-based patterns of HER2 testing by patient, tumor and geographic characteristics. Methods: Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER) data included women diagnosed 2010-2015 with de novo breast cancer. Women were categorized by age, race, stage, year of diagnosis, and receipt of estrogen receptor (ER), progesterone receptor (PR), and HER2 testing. SEER classified lack of testing with “test ordered, results not in chart” and “test not done.” We report on cases with HER2 “test not done”. Records missing any variables were excluded. County-level measures of socioeconomic status were included for each woman. Univariate and multivariate logistic regressions identified factors associated with testing. Results: Of 281,214 new breast cancer diagnoses, 1.75% had HER2 “test not done”. ER and PR testing were “not done” in 0.57% and 0.74% of cases, respectively. HER2-testing rates improved over time: 2.54% not tested in 2010 and 1.30% in 2015 (p &lt; 0.01). The following characteristics were associated with higher rates of “test not done”: age &gt;70 vs &lt; 50 (OR = 1.33, p &lt; 0.01), blacks vs whites (OR = 1.23, p &lt; 0.01), Stage IV vs I (OR = 2.27, p &lt; 0.01). Regional variation was also seen, with registries reporting HER2 “test not done” ranging from 0.18%-2.89%. On multivariate analysis (Table), HER2 testing was less likely for women age ≥ 70, blacks, Stage IV disease, and those living in counties with high rates of less than high school education. Conclusions: Rates of HER2 testing have increased. However, disparities exist and are associated with age, race, stage, geography, and education. Understanding the cause of these disparities could ultimately enhance access to appropriate therapy and improve disease outcomes. Odds of not having HER2 testing (select results from multivariate analysis). [Table: see text]
Comparison of diagnostic methodologies to detect chromosomal abnormalities.
Authors: Cynthie Wong, Maya Thangavelu, Michele Hibbard, Forrest Blocker, Lawrence M. Weiss, Vincent Anthony Funari
Journal: Journal of Clinical Oncology (2019)

e14617 Background: Traditional technologies such as cytogenetics, FISH, and microarray (CGH) are utilized in most clinical laboratories. Next-Generation Sequencing (NGS) is a relatively new tool to evaluate the cancer genome. Applications of this method include assessing single nucleotide variants (SNVs), indel mutations, and copy number variations (CNVs), including some large chromosomal deletions or gains. Methods: We used a custom Discovery+LOH NGS panel (Agilent, Santa Clara) to determine the utility of NGS in detecting CNV and loss of heterozygosity (LOH) events. Thirty six patients with known DNA structural abnormalities and hematologic disease were tested using cytogenetics, the NGS panel, and CytoScan HD microarray. Results: As shown in the table, NGS detected all abnormalities reported by CGH. NGS failed to detect 14 abnormalities reported by cytogenetics, but detected additional gains and losses from small chromosomal regions as well as LOH events. Notably, NGS found a 16p loss, but cytogenetics detected a full chr16 loss and a 7q loss. NGS detected an 11p loss which was missed by cytogenetics. Table: Comparison of Detection by Methodologies. Conclusions: This study highlights the benefits and limitations of each method using clinical samples with hematologic disease. Cytogenetics provided a gross view of a karyotype, but lacked resolution to detect small aberrations and LOH events. NGS provided high resolution of numerical aberrations and detected LOH events, but was unable to detect some gain and loss events. In examining those missed events, &lt; 30% abnormal cells were found in those specimens, possibly explaining the reduced sensitivity. Importantly, we found two significant discrepant chromosomal aberrations between cytogenetics and NGS. This may result from cytogenetic culture where preferential growth of cells influence the detection of a chromosome gain or loss. These findings suggest advantages in assessing chromosomal abnormalities using NGS in coordination with more traditional methods to improve diagnostic and prognostic determination to assist in treatment selection.[Table: see text]