tbuckley/cabot-search huggingface dataset:
A case-study using big data to increase scientific productivity in cancer research.
Authors: Hannah Beird, Jennifer Brooke Goldstein, Jianjun Zhang, Shivaprasad Narayanan, Chris Belmont, Bryan Lari, Robert Fassett, Dhiraj Pathak, Praveen Akella, Jeff Jin, Gregory Barbosa, Trey Kell, Vamshi Punugoti, Edward Suh, Brett Smith, Andrew Futreal
Journal: Journal of Clinical Oncology (2016)

e23202 Background: One of the greatest challenges to cancer research is compiling millions of patient records to investigate complex hypotheses. The Translational Research Accelerator (TRA) is a large scale technological effort at MD Anderson Cancer Center (MDACC) to revolutionize this process. Our group presented an abstract, “A Rare Look at a Deadly Disease: A Retrospective Single Institution Review of 90 Pancreatic Adenosquamous Cancer Patients,” at the American Society of Clinical Oncology 2015 annual meeting. This retrospective review assessed pancreatic adenosquamous carcinoma patients seen at MDACC from 1990 to 2014. We use natural language processing (NLP) and TRA to extract data and assess the accuracy of information retrieval from the electronic medical record (EMR) against this “golden” set presented as a poster. Methods: Structured clinical and NLP data was compiled from the MDACC EMR into TRA. The dataset was matched against the records described above to calculate percent agreement. Results: We investigated all 90 patient records. Seventy-seven records were excluded due to data acquisition initiation in 2012. We identified 13 patients. Six attributes sourced from structured data sources (Gender, Race, Medical Record Number (MRN), birthdate, death date, admission date) and 3 attributes from NLP sources (diagnosis date, diagnosis and grade) were compared. Gender, birth date, race and MRN showed 100% concordance. Death date and admission date showed 8% match. NLP attributes - diagnosis, grade and diagnosis date matched 23%, 92% and 77% respectively. Conclusions: TRA is a powerful way to mine clinico-pathologic patient variables via NLP and EMR structured research data. Grade and diagnosis date were more accurate than researcher curated list. Death date inaccuracy was reflective of the source. Alternative databases have been identified to capture this attribute accurately. Admission date did not match due to alternative user definition of dates and other characteristics emphasizing need for common definitions. Diagnosis attribute indicated correct diagnosis, but lacked specificity. NLP programs are being enhanced to improve precision. Using TRA we can acquire data under an hour as compared to 10-15 hours manually.
Clinical Impact of extensive molecular profiling (EMP) in advanced cancer patients (pts) referred to early phase trial unit: The BIP (Bergonie Institute Profiling) Program.
Authors: Sophie Cousin, Maud Toulmonde, Thomas Grellety, Celine Auzanneau, Emmanuel Khalifa, Yec'han Laizet, Kevin Tran, Anne Floquet, Delphine Garbay, Jacques Robert, Isabelle Hostein, Isabelle Soubeyran, Antoine Italiano
Journal: Journal of Clinical Oncology (2016)

11593 Background: BIP is an institution-wide permanent screening program (NCT02534649) started in 2014 to identify pts referred to Institut Bergonié (Bordeaux, France) with somatic alterations that can be matched to targeted therapies in early phase clinical trials (EPCT). Methods: Pts with advanced solid tumors and ECOG performance status ≤ 2 were eligible. Tumor DNA was isolated from a FFPE archived sample when available or from a fresh tumor biopsy. DNA analysis was performed by next generation sequencing using a panel of 287 genes and by comparative genomic hybridization. Results for each pts were discussed during a weekly multidisciplinary molecular tumor board (MTB). Results: From January 2014 to June 2015, 568 pts were enrolled. Median number of prior lines was 2 (range 0-9). Most common primaries were: lung (16.9%), colorectal (14.4%), breast (10.6%), ovarian (10.2%), and sarcomas (10.2%). Median age was 63 years (range 19-88). In 28 cases (5%) molecular analysis failed because of insufficient tissue. Median time from first referral to reporting was 9 weeks (range 1-36). The 20 genes most frequently altered were TP53, CDKN2A, KRAS, PTEN, PI3KCA, RB1, APC, ERBB2, MYC, EGFR, CDKN2B, ARID1A, SMAD4, FGFR1, MDM2, BRAF, ATM, CCNE1, FGFR3, FRS2. 292 pts (51.4%) had at least one actionable genetic alteration. 159 pts (28%) were included in a clinical trial (CT). The treatment was matched with the tumor profile in 86 cases (15%). Main reasons for non-inclusion in a CT for pts with actionable mutation were: non progressive disease (31.5%), general status deterioration (25%), death (16.5%), CT not available (10.5%), screening failure (6.5%), lost of follow-up (7%), and patient refusal (3%). 135 pts were evaluable for response according to RECIST 1.1. The disease control rate (objective response + stable disease) was 47.7% for pts included in “matched” CT versus 47.7% (p = 0.4) for pts included in other CT. Median progression-free survival was 3 months (95 CI 1.7-4.3) versus 3.4 months (95 CI 1.7-5) (p = 0.4). Conclusions: EMP is feasible in routine practice, allows identification of actionable mutations in most of cases and can be used to enroll pts in matched EPCT. Clinical trial information: NCT02534649.
Response and survival rates with frontline hypomethylating agent (HMAs) in favorable risk AML.
Authors: Michael Richard Grunwald, Daniel T. Peters, Myra M. Robinson, Michael Keith Allister Zimmerman, Jing Ai, Thomas Gregory Knight, Peter N. Lalli, Jared G. Block, Elton Travis Smith, Edward H. Lipford, Edward Alan Copelan, James Thomas Symanowski, Jonathan Michael Gerber
Journal: Journal of Clinical Oncology (2017)

7039 Background: HMAs are an accepted frontline therapy for AML patients (pts) who are unfit for intensive induction therapy (IIT), particularly pts with unfavorable cytogenetics and/or p53 mutations. However, little is known about the response of favorable risk AML to HMAs. We previously reported that NPM1 mutated and/or CD34- AML status were predictors of response to HMAs. Here, we evaluated responses to frontline HMAs in AML. Methods: A total of 117 patients with de novo AML diagnosed between 7/2013 and 9/2016 were evaluated based on pt and disease related variables, overall response rate (ORR = CR + CR with incomplete count recovery + hematologic remission (ANC &gt; 1000/µL, Hgb &gt; 10g/dL, Plts &gt; 100,000/µL, &amp; no circulating blasts)), and overall survival (OS). Categorical variables were compared using Fisher’s exact test. Kaplan Meier methods estimated survival outcomes, and log rank tests compared survival between groups. Multivariable analyses were performed using Cox proportional hazards models. Results: 51 pts, considered unfit for IIT, received frontline HMAs. ORR and OS were highest in the ELN favorable risk AML pts (n = 13; ORR = 92%, p = .009; median OS = 17.5 months, p = .022). Among 41 NPM1 mutated pts, 15 received HMAs; and 26 received intensive induction. ORRs were 73% and 84%, respectively (p = .434). No difference was found in OS distributions between the HMA and IIT groups in univariate and multivariate (adjusted for age and FLT3 status) models (p = .329 and .241, respectively). Interestingly, ORR was 100% among 9 HMA-treated pts with NPM1 mutated, CD34-, FLT3/ITD-, cytogenetically normal AML. Conclusions: HMA therapy is highly effective frontline treatment in favorable risk AML pts considered unfit for IIT. Survival results with HMAs in NPM1 mutated AML are comparable to those of fitter pts treated with IIT. In selected favorable risk pts considered unfit for standard induction, HMAs can be a successful bridge to potentially curative therapy, including more intensive therapy or transplant. Cytogenetically normal AML with an isolated NPM1 mutation and CD34- status appears to be exceptionally responsive to frontline treatment with HMAs. Prospective validation of these findings is necessary.
Safety and effectiveness of transoral surgery for superficial head and neck cancer: The National Registration Survey of superficial head and neck cancer in Japan.
Authors: Chikatoshi Katada, Satoshi Fujii, Tetsuji Yokoyama, Yasutoshi Sakamoto, Masaaki Ichinoe, Tabito Okamoto, Akihito Watanabe, Daisuke Kikuchi, Shigetaka Yoshinaga, Tomohiro Tsuchida, Yuichi Shimizu, Tsuneo Oyama, Tomoyuki Kamijo, Noboru Hanaoka, Yoshiro Kawahara, Akihiro Shiotani, Atsushi Ochiai, Takakuni Kato, Manabu Muto, Ryuichi Hayashi
Journal: Journal of Clinical Oncology (2018)

6066 Background: The national registration survey of transoral surgery (TOS) for superficial head and neck cancer (SHNC) was performed to retrospectively examine safety and effectiveness. Methods: From April 2001 through July 2012, a total of 599 patients with SHNC (954 lesions) who underwent TOS as initial treatment were enrolled in 27 hospitals in Japan. Of these patients, we studied 899 lesions (665 initially treated lesions and 234 metachronous multiple cancers) in 568 patients who were given a central pathological diagnosis of initially treated squamous-cell carcinoma. The study variables were clinicopathological findings, the incidences of adverse events, and treatment outcomes. Results: The median age was 66 years, and 534 (94%) of the patients were men. A total of 202 lesions (22.4%) were located in the oropharynx, 660 (73.3%) in the hypopharynx, 23 (2.6%) in the larynx, 12 (1.3%) in the oral cavity, 2 (0.2%) in other sites. The surgical procedures were endoscopic mucosal resection in 374 lesions (41.6%), endoscopic submucosal dissection in 359 (39.9%), endoscopic laryngopharyngeal surgery in 48 (5.3%), transoral videolaryngoscopic surgery in 40 (4.4%), direct mucosectomy in 28 (3.1%), laser microlaryngeal surgery in 20 (2.2%), and others in 28 (3.1%). The median clinical tumor diameter was 12 mm. The histopathological findings of the 869 lesions treated by TOS were carcinoma in situ in 536 lesions (61.7%) and subepithelial invasive cancer in 333 lesions (38.3%). The median treatment time of 777 sessions of TOS was 49 minutes. Adverse events occurred in 89 patients (11.5%). Life-threatening complications occurred in 10 patients (1.3%), but there was no treatment-related death. Tracheotomy was performed in 72 patients (9.3%). Local recurrence was found in 53 lesions (5.9%), nodal recurrence in 26 patients (4.6%), and distant recurrence in 3 patients (0.5%). The median follow-up period was 46.1 months. At 3 years, the overall survival rate, the relapse-free survival rate and the cause-specific survival rate were 88.1%, 84.4% and 99.6%, respectively. Conclusions: TOS for SHNC is a safe and effective, minimally invasive treatment option. Clinical trial information: UMIN000008276.
Novel phase 1a/1b dose-finding study design of CWP232291 (CWP291) in relapsed or refractory myeloma (MM).
Authors: Sung-Soo Yoon, Elisabet Esteve Manasanch, Chang Ki Min, Jin Seok Kim, Robert S Hauptschein, Jeongeun Choi, Jae Kwang Chun
Journal: Journal of Clinical Oncology (2017)

TPS8058 Background: CWP291, a novel peptidomimetic small molecule, has potent, selective inhibitory activity on a Wnt gene reporter, decreasing expression of β-catenin target genes, cyclin D1 and survivin. With broad anti-cancer efficacy in vitro, it significantly outperforms lenalidomide as a single agent combination in MM bone marrow engraftment models. Methods: This Phase 1a/1b study (NCT #02426723) was designed to define a well-tolerated dose of CWP291 as a single agent in subjects with R/R MM. CWP291 was administered IV over ≥30 minutes 2x weekly for 3 weeks out of a 4-week cycle, with standard 3+3 dose escalation design. But an important objective in terms of patient benefit and further clinical development was to explore activity of a combination regimen with lenalidomide. Thus, a novel study design allowed initiation of the Phase 1b as soon as CWP291 achieved a well-tolerated dose as a single agent. Combination therapy would start at one dose level lower. Enrollment of patients onto each arm was guided by Safety Review Committee assessments, including baseline laboratory values, performance status, extent of prior therapy, or prior adverse events related to lenalidomide. Results: Initiated September 2015, the starting dose was based on a prior Phase 1 study in AML, 198 mg/m 2 . There were 4 sites involved, and 11 patients enrolled over 12 months. Approval of the new design by regulatory authorities and IRBs was completed by November 2016. A well-tolerated single agent dose (297 mg/m 2 ) was identified, allowing initiation of the Phase 1b at a dose of 198 mg/m 2 (one dose level lower) combined with lenalidomide. Four subjects were enrolled in ~2 months to the Phase 1b. Enrollment to both arms is continuing and the status of this study will be updated at presentation. Conclusions: The ability to consider combination therapy with a novel drug is clearly a motivation for patient participation in clinical trials; especially true in MM, as multiple new therapies are available. This trial design was approved and allowed based on assessment of individual patient safety and potential benefit. Rapid enrollment in the combination therapy arm may significantly foster development of novel agents with this study design. Clinical trial information: NCT #02426723.
Title: A real-world study of chemotherapy treatment and costs in metastatic urothelial cancer (mUC) patients in the United States.
Authors: Elisabetta Malangone-Monaco, Kathleen Wilson, Helen Varker, Diana Stetsovsky, Lin Shih-Wen, Darren Tayama, Sarika Ogale
Journal: Journal of Clinical Oncology (2017)

e16009 Background: Cisplatin (CIS)-based regimens are recommended for first-line (1L) treatment of mUC. Carboplatin (CAR) serves as an alternative for patients unfit to receive CIS. This study examined treatment patterns and costs for patients treated with CIS, CAR, and other treatment (OT). Methods: This was a retrospective cohort study of 9,436 patients from a U.S. insurance claims database between 1/1/2005-6/30/2015. Adult patients with ≥ 2 diagnosis codes for UC, ≥ 2 diagnosis codes for metastasis (first metastasis = index date), ≥ 6 months of continuous enrollment pre-index and no evidence of cystectomy were included. Results: The population was majority male (74%); with a mean age of 70. Sixty percent of the mUC patients did not receive 1L chemotherapy during the study period. Among the 3,750 who received treatment, 935 (25%) received 1L CIS, 1,505 (40%) received 1L CAR, and the remaining patients received OT. Patients treated with CIS were younger (62 vs. 69 and 68) and healthier (NCI comorbidity score 0.7 vs. 1.1, and 1.0) vs. patients treated with CAR and OT, respectively. Among CAR patients, 87% received it as combination therapy (CT), with GEM being the most common agent used with CAR. Only 16% of OT patients received CT. Per-patient-per-month (PPPM) 1L all-cause healthcare costs were similar across 1L regimens ($16,540 CIS, $15,739 CAR, and $16,443 OT) and 1L mUC-related healthcare costs were $9,043, $6,975 and $6,191 for CIS, CAR, and OT, respectively. Conclusions: In this real-world study, the majority of mUC patients did not receive 1L chemotherapy, and only a small fraction of those treated received CIS. The remaining patients were treated with CAR or OT, often as monotherapy, which tend to have poorer outcomes compared with CIS. Despite CAR and OT treated patients being younger and healthier, their total health care costs were similar to CIS patients. Newer therapies may provide safer and more efficacious treatment alternatives for patients who are not considered a good fit for CIS therapy.
Measuring serum neurofilament light (sNfL) levels to determine correlation with activity of brain metastases (BM) and gliomas (G).
Authors: Jason Porter, Madison Boles, Manjari Pandey, Philippe Prouet, Felicia Hare, Syed Sameer Nasir, Henrik Zetterberg, Michael Gary Martin
Journal: Journal of Clinical Oncology (2018)

e24028 Background: Currently there are no serum biomarkers associated with activity of cancer in the brain. We hypothesized that sNfL would correlate with the activity of either BM or G. Methods: sNfL (pg/mL) was measured prospectively using an ultrasensitive single molecule array (Simoa) instrument (Quanterix, Lexington, MA) (Rohrer Neurology. 2016 Sep 27;87(13):1329-36.) and correlated with status of BM and G. Statistical analysis was performed using GraphPad Prism7 and all p-values were 2-tailed. Results: 36 patients (pts) were enrolled across disease states. sNfL levels varied with disease status (ANOVA p =0.0037). Conclusions: sNfL may correlate with activity of BM and G. Further studies are needed to validate our encouraging early results. Control BM (remote) Cancer without BM BM (active) G controlled G uncontrolled Pts 4 1 9 7 7 8 Age (Range) 49 (36-62) 61 62 (30-78) 57 (43-75) 57 (40-81) 49 (42-60) Ethnicity (%W) 50 100 89 43 57 88 sNFL (Range) 7.3 (3.2-14.8) 13.9 11.8 (4.7-51.4) 142.3 (67.8-284.9) 23.0 (12.6-135.3) 239.5 (96.7-1101.4) t-test p-value 0.0004 0.0307
A retrospective analysis of lymph node status in advanced ovarian, fallopian, and peritoneal cancer.
Authors: Yoshio Itani, Sayuri Morita, Hitomi Sugimoto, Yoshiki Takeda, Yoshikazu Sasaki, Satoko Ishibashi, Atsushi Shugiura, Hitoshi Hirano, Shinji Toyoda, Tsunekazu Kita
Journal: Journal of Clinical Oncology (2017)

e17074 Background: The purpose of this study was to assess lymph node (LN) status; greatest dimension (D), D of metastatic LN (LN (+)) foci (MF), number of LN (+) of each patient, and MF area aggregated in each patient affected by LN metastasis in FIGO stage III and IV ovarian, fallopian, and peritoneal cancer. Methods: We researched the consecutive 25 patients who underwent primary debulking surgery or neoadjuvant chemotherapy (NAC) followed by interval debulking surgery including systemic lymphadenectomy from 2004 to 2015. Non-serous histology was 20 % (5/25). LN (+) were detected in 12.6% (169/1344) of lymph node preparations. Results: The patients’ median age was 53 years. Median number of LN (+) and sum of MF area in each patient were 2 (range 0-37) and 2 mm 2 (range 0- 498). Mean D of the entire LN and of the MF were 4.7mm (95%Confidence Interval (CI); 4.5,4.9) and 6.1mm(95% CI; 5.2, 7.0). The LN (+) displayed a significantly larger mean D value (7.9 mm, 95% CI: 7.4, 8.5) than the non-metastatic lymph nodes (LN (-)) (4.2 mm, 95% CI: 4.0, 4.4) (p&lt;0.05; student t test). D of MF (mm) was approximated by LN (+) area (mm 2 ) as follows; (D of MF) = 2.58+ 0.094*(LN (+) area)+ 0.062* ( ( LN (+) area)-43.2) 2 ; R 2 =0.75; p&lt;0.0001. The D of MF with NAC, 5.0 mm (95%CI: 3.6, 6.4) demonstrated smaller than that without NAC, 7.0 mm (95%CI: 5.8, 8.1) (p&lt;0.05; student t test). The proportion of LN (-) patients was significantly higher in the NAC group (44%, 4/9) than in the non-NAC group (6%, 1/16) (p=0.022). D of LN (+), D of MF ≥10 mm, sum of MF area, and number of LN (+) ≥ 2 did not achieve statistical significance in analysis with the relative risk (RR) of death. Conclusions: LN (+) exhibits larger D than LN (-) and D of MF could be estimated by LN (+) area. Some MFs shrink after NAC, and hence, become difficult to detect pathologically. In advanced ovarian, fallopian, and peritoneal cancer LN size and sum of MF area could not show an impact on prognosis.
A confirmatory survey regarding public misconception about cardiopulmonary resuscitation (CPR) in advanced cancer patients.
Authors: Santhanam Sundar, Theresa Teoh Chiu Hoong, Anmar Alharganee
Journal: Journal of Clinical Oncology (2016)

e21507 Background: CPR can be a highly successful, lifesaving, medical intervention following an acute or reversible cardiorespiratory/metabolic dysfunction. However, CPR is futile in patients with disseminated treatment-refractory cancer. The positive portrayal of CPR in television and films leads to patients and families significantly overestimate the likelihood of a successful CPR in terminally ill cancer patients. This repeat survey was done to confirm the results of our previous survey conducted in 2014 (Sundar S Resuscitation 2015 Jan 86 e3). Methods: Subjects perception of successful CPR in three different clinical scenarios was assessed by a questionnaire survey. Subjects were randomly approached in different public places like town centers, shops, car parks and schools by a medical student. No identifiable information was collected to protect anonymity. Results: 74 subjects completed the survey. 57% were male; Mean age: 29yrs (range 16 to 76yrs), 65% were 21 to 60 years old. 94.6% of subjects rightly reckoned that CPR has at least 30% chance of resuscitating a healthy young tennis/football player. But worryingly, 50% of subjects believed that CPR has at least 30% chance of saving 60-yr-old woman in a hospice with disseminated cancer (Table). Conclusions: This repeat survey worryingly confirms that general public significantly overestimate the probability of successful CPR in a terminally ill cancer patient. This misconception can cause distress during 'do-not-resuscitate (DNR)' discussions. There is an urgent need to educate public about the futility of CPR in terminal cancer patients. Three hypothetical scenarios where subject has collapsed suddenly and become unconscious A 25-yr-old tennis/ football player, who has been previously fit and healthy A 60-yr-old woman, with widespread cancer, currently in a hospice and has exhausted all che motherapy & other treatment options. An 80-yr-old man, who lives in a nurs ing home, has re cently developed severe pneumonia. Perceived CPR success % (Median) 70% 25% 20% (Range) Subcategory 10 to 100% 5 to 70% 0 to 70% 0 to 10% success 3% 23% 27% 11 to 29% success 3% 27% 28% 30 to 59% success 22% 46% 37% 60 to 100% success 73% 4% 8% Repeated measures ANOVA P < 0.005.