tbuckley/cabot-search huggingface dataset:
Automated concordance estimation between radiology and pathology reports.
Authors: Vadiraj Hombal, Rebecca Mieloszyk, Prescott Klassen, Sandeep Dalal, Sooah Kim
Journal: Journal of Clinical Oncology (2018)

e18862 Background: We present a system for automated estimation of diagnostic concordance between radiology and pathology reports, with a focus on prostate. Such a system can play a critical monitoring and signaling role in the diagnosis of prostate cancer. Methods: The proposed NLP-based system correlates lesions mentioned in radiology reports with biopsy samples mentioned in pathology reports. Both lesions and samples are localized using textual anatomy descriptions in the reports. For lesions, diagnoses are extracted from PIRADS v2 scores. For samples, diagnoses are extracted from both diagnosis phrases and Gleason scores. We determine concordance both at the lesion level and at the aggregated report level, by comparing the diagnoses of location-matched lesions and samples, and by comparing the highest PIRADS in the radiology report and the dominant diagnosis of samples in the pathology report, respectively. Results: We present concordance analysis of 119 patients’ prostate radiology-pathology report pairs. A total of 169 lesions and 770 samples were extracted. The pathology samples were classified as grid or targeted based on their location descriptors. Table 1 shows the concordance between radiology and pathology outcomes aggregated at a report level across all samples. The value missing represents cases where the diagnosis was not explicitly mentioned in the context of the corresponding lesion or sample in the reports. In 7 of the 27 PIRADS-5 cases, the pathology outcome was benign. 26% of PIRADS 4/5 yielded a benign outcome. We demonstrate that 41% of grid samples, and 32% of targeted samples corresponding to PIRADS 4/5 lesions are benign. Conclusions: Actionable insight is gained by determining the diagnostic concordance in radiology and pathology using a system for automated extraction. Radiology (gross) and Pathology (in-situ) represent different views of the disease, our analysis shows that grid samples, although non-targeted, play a critical role in establishing the extent of disease. PATH BENIGN 3+0 = 3 4+0 = 4 3+3 = 6 3+4 = 7 4+3 = 7 3+5 = 8 4+4 = 8 4+3+5 = 9 4+5 = 9 MISSING INVASION ALL RAD 1 2 2 1 5 2 4 1 1 6 3 10 9 5 1 1 26 4 12 2 1 9 9 2 1 5 41 5 7 1 6 7 2 1 1 1 1 27 MISSING 6 4 1 2 1 14 ALL 41 2 2 30 24 7 1 1 1 1 8 1 119
Circulating free DNA and circulating tumor cells as new serum biomarkers in advanced ovarian cancer.
Authors: Jeronimo Martinez Garcia, Asuncion Soto, Pilar Sanchez-Henarejos, Ana Puertes Boix, Edith Rodriguez, Marta Guirao Maran, MDolores Jimenez-Lucas, Miler Cuellar, Alicia Cano, Jose Luis Alonso Romero, Guadalupe Ruiz Merino, David Collados, Miguel Marin, Silver Ros, Maria Del Rosario Garcia Hernandez, Rosario Salgado
Journal: Journal of Clinical Oncology (2017)

5566 Background: Circulating free DNA (cfDNA) and circulating tumor cells (CTC) are new biomarkers for malignant tumors. Its role on ovarian epithelial cancer (OEC) is not yet well stablished. We analyze its role on advanced OEC compared with CA125 and HE4. Methods: Multicentric prospective observational study from November 2013 until February 2017, with OEC patients group (OECG), benign ovarian tumors group (BENIGNG) and health subjects control group (HEALTHG). CTCs were analysed by the CellSearch method and cfDNA by ALU-sequences-based quantitative PCR using two primers (115 and 247 bp); cfDNA integrity was calculated by ALU247/ALU115 ratio. Samples were obtained before treatment (M0), after primary peritoneal surgery (M1), after one cycle of chemotherapy (M2), before (M3) and after interval surgery (M4). This study was approved on May 2013 by the corresponding Central Research Independent Ethics Committee. Results: We analyized 102 subjects from all 3 groups (81 OECG, 14 BENIGNG y 7 HEALTHG); 68% were high grade serous subtype; most frequent staging was IIIC (58%). Within the follow-up (FU) period (average 14 months: min 0, max. 35) 36% relapses and 23% deaths were reported. CTCs were positive on 23% of OECG. In HEALTHG no positive were seen and only 1/14 in the BENIGNG group. Monitoring of cfDNA at the treatment points shows significant differences between M0 and M4 (p = 0.02). No differences were seen in the other determinations. cfDNA-ALU115 was 1.40178 ng / mcL (95% CI 1.18066-1.62290) in the OECG, 0.66383 (95% CI 0.44832-0.87935) in BENIGNG and 0.59923 in HEALTHG ( 95% CI, 0.14449-1.05397). The difference was significant between OECG and BENIGNG (P = 0.017) and near the significance between OECG and HEALTHG (p = 0.69). cfDNA integrity in OECG and HEALTHG was significantly different (P = .012). The area under the curve of Ca125, HE4, CTC, cfDNA and CFDNA integrity was 0.490, 0.526, 0.621, 0.587 and 0.450 respectively. New generation sequencing of circulating TP53 is ongoing. Conclusions: CTC and cfDNA are new biomarkers that might have an important role in the diagnosis and monitoring of OEC.
Association of PSA and number of cores positive with likelihood of adverse pathology at radical prostatectomy based on a 17-gene expression assay.
Authors: Michael Bonham, Brooke Nightingale, Anson Tharayanil, Bela Stephen Denes, Megan Rothney, Debbie McCullough, John Bennett, Phillip G. Febbo, Athanasios C. Tsiatis
Journal: Journal of Clinical Oncology (2016)

e16570 Background: The overtreatment of prostate cancer and underutilization of active surveillance in men with Gleason 6 (GS6) cancer stems from uncertainty with current risk instruments such as volume of GS6 tumor and PSA > 10 ng/ml. The 17-gene biopsy-based RT-PCR assay has been analytically and clinically validated as an independent predictor of adverse pathology at prostatectomy. We report on the impact of volume of GS6 disease and PSA at biopsy on the biologic aggressiveness of the disease as measured by the assay (GPS). Methods: 1,055 pathology reports received at Genomic Health, Inc. were reviewed to record GS, number of cores positive, and PSA. GPS was calculated from a single block for each case with an associated path report using the validated algorithm of 12 cancer and 5 reference genes; median GPS was calculated for each sub-group ( ≤ 2 cores positive, > 4 cores positive, PSA < 4 ng/ml, PSA 4-10 ng/ml, PSA > 10 ng/ml). Results: 803 cases (76%) were submitted as GS6. 66% of cases contained 12 cores, 4% of cases had < 12 cores and 30% of cases had > 12 cores. The median GPS for GS6 cases with ≤ 2 cores positive was 24 (IQR 16.5 to 30.5) compared to a median GPS of 26 (IQR 20 to 34) for 4 or more cores positive. After incorporating the GPS, risk refinement, a change in categorical risk assessment was seen in 24% of cases with ≤ 2 cores positive and 26% of cases with > 4 cores positive. 294 of cases with GS6 also reported a PSA value. 25% of GS6 cases had a PSA < 4, 67% were 4-10, and 8% were > 10 ng/ml. No significant correlation was seen between PSA and GPS. The median GPS values for cases with a PSA < 4, 4-10, and > 10 were 25(IQR 16-31), 24(IQR 17-32), and 25(IQR 17-39), respectively. Risk refinement following GPS occurred in 48% of cases with a PSA < 10 and 23% with a PSA > 10. Conclusions: The GPS results highlight the broad spectrum of tumor aggressiveness in a series of 803 biopsies containing GS6 independent of % cores positive and PSA. The degree of risk refinement among all GS6 cases independent of tumor volume or PSA highlight the utility of the GPS to provide predictive information beyond traditional clinical variables used for risk stratification in the management of men with GS 6 disease at the time of diagnosis.
Kidney cancer: The next decade
Authors: Samra Turajlic, Charles Swanton, Chris Boshoff
Journal: The Journal of Experimental Medicine (2018)

Chris Boshoff, Senior Vice President of Immuno-Oncology, Translational and Early Development at Pfizer, and colleagues Samra Turajlic and Charles Swanton from the Francis Crick Institute and University College London give us their personal point of view on new insights and future therapeutic approaches for renal cancer.
Racial disparities in non-small cell lung cancer, analysis of the Indiana University Cancer Center registry database 2000-2015.
Authors: Ahmad Abdelfattah Al-Hader, Weili Wang, Olumide B. Gbolahan, Feng-Ming Spring Kong
Journal: Journal of Clinical Oncology (2018)

e18622 Background: Racial disparities have been documented for many malignancies including lung cancer. The purpose of this study is to investigate whether there are racial differences in our non-small cell lung cancer (NSCLC) patient outcomes at Indiana University. Methods: A retrospective analysis was performed on patients with NSCLC diagnosed between 2000 and 2015 in the Indiana University Cancer Center registry. Demographic data, clinical stage at diagnosis, histology and survival were analyzed. Results: A total of 2728 patients with NSCLC were evaluated. Clinical stage was documented in 2013 patients of all races as following: (Stage I: 29.9%, Stage II: 9.1%, Stage III: 24.9%, Stage IV: 36.1%). The vast majority of patient were Caucasian or African American, the clinical stages on presentation among 1686 Caucasian patients and the 275 African American patients with documented clinical stage in the registry were: Stage I (32.7% vs 14.2%), Stage II (9.3% vs 7.3%), Stage III: (23.5% vs 34.2%) and stage IV (34.5% vs 44.4%) respectively. Median overall survival (OS) for patients of all races was 18.7 months, it was 19.6 months in Caucasians and 12.2 months in African Americans (P value < 0.001). Refer to the table below for stage-specific OS. Conclusions: There were significant racial disparities among the NSCLC patients studied. There were significantly less stage I, more stage III and IV African American patients leading to decreased overall survival. More studies should be performed to evaluate the causes and potential solutions overall and specifically in the state of Indiana. More patients diagnosed in advanced stage suggest that a more aggressive screening effort may increase early disease detection and potentially improve survival in African American NSCLC patients. Stage Race Median OS (months) I Caucasian 55.4 African American 29.5 Overall 55.4 II Caucasian 39.0 African American 40.4 Overall 39.0 III Caucasian 16.5 African American 17.5 Overall 16.7 IV Caucasian 7.2 African American 5.6 Overall 7.1 All stages Caucasian 19.6 African American 12.2 Overall 18.7
A multistate model for follicular lymphoma (FL) patients (pts) who experience early progression.
Authors: Hiromi Terawaki, Caglar Caglayan, Qiushi Chen, Ashish Rai, Turgay Ayer, Christopher Flowers
Journal: Journal of Clinical Oncology (2017)

e18164 Background: FL is the second most frequent lymphoma subtype. Approximately 20% of FL pts experience disease progression within two years of initial chemo-immunotherapy. Currently, there is no standard of care approach for treatment of these pts. Methods: Using Surveillance, Epidemiology, and End Results (SEER) registry data from 2000 through 2009 linked to Medicare claims data through 2011, we identified pts who received second line therapy within 2 years of their initial therapy and incorporated their clinical, demographic, treatment, and outcomes data into a multi-state Markov model to study the impact of first, second and third line therapies. Treatments were categorized as rituximab (R), R-cyclophosphamide and vincristine (RCVP), R- cyclophosphamide, hydroxydaunorubicin, and vincristine (RCHOP), and other R-containing regimens. The Aalen-Johansen estimator was used to estimate the likelihood of being in 1 of 4 health states: dead or alive following treatment (TX) 1, 2 or 3. A Cox proportional hazards regression model was fitted for each possible transition between the model states to identify significant factors affecting time of progression to the next line treatment or death. Results: Data for 5234 pts were incorporated into the model. The median observation time before TX1 was 1.4 months (range 0-125 months). Overall, the median time from TX1 to TX2 was 3.1 (95% CI 2.9-3.2) months and median survival was 33.3 (32.2-34.3) months. For pts who received R, RCVP, and RCHOP as TX1, the median time to TX2 (range) was 5.4 (4.9-5.8), 4.2 (3.6-4.7), and 3.3 (2.9-3.5) months, respectively. These treatments were associated with a median survival of 33 (31-35), 31 (28-32), and 36 (34-39) months, respectively. For pts who received R, RCVP, and RCHOP as TX2 the median time to TX3 was 5.0 (4.3- 5.3), 3.2 (2.7-3.9), and 2.7 (2.3-3.1) months, respectively. Conclusions: This multi-state Markov model using SEER-Medicare data, provides means to examine sequential treatment strategies that influence outcomes for pts with poor-risk FL and factors that influence transition points within each strategy. This modeling approach can help identify where interventions can have the greatest impact for these pts with unmet clinical needs.
Expression of PTEN, Akt, MAPK, p53, p95 for predicting trastuzumab resistance in breast cancer.
Authors: Berna Bozkurt Duman, Berksoy Sahin, Melek Ergin, Suzan Zorludemir, Arbil Acikalin
Journal: Journal of Clinical Oncology (2012)

e11088 Background: The activation of the oncogene PIK3CA and the loss of the tumor suppressor gene PTEN are mutations commonly found in breast tumors. AKT is a key activator of cell survival mechanisms. Mutant p53 proteins can actively contribute to tumorigenesis. Trastuzumab in particular are the primary treatment in the adjuvant and recurrent settings for breast cancer. Many studies reported that selected patients may present with resistance to trastuzumab due to the presence of p95 HER2 fragments. To address this challenge,we analyzied PTEN, Akt, MAPK, p53, p95expressions in breast cancer treated with trastuzumab therapy. . Methods: Ninety patients were assessed for this study and in the guidance of inclusion and exclusion criteria 25 patients were enrolled to the study. HER2 positivite, metastatic or locally advanced patients were enrolled to the study.. All of the patients that included to the study were treated with trastuzumab. Trastusumab resistance was assessed. Antracylin and taxane containing regimens were given to all patients. Gemcitabine, cisplatine capectabine, navelbine containing regimens were given on second and third line treatment choices. Tissue samples were obtained from parafine blocks and evaluated for PTEN, Akt, mapk, p53, p95 expression with immunohistochemical method. Results: The median age was 54±12. PTEN, Akt, MAPK, p53, p95 expressions were found in different levels on tumor tissue samples. Trastuzumab resistance were detected in 5 (20%) patients. Akt expression was positive in 2(8%) patients, MAPK expression was positive in 1 (4%) patient, p95 expression was positive in 1 (4%) patient, p53 expression was positive in 1 (4%) patient, PTEN expression was negative 3 (12%). Statistically significant difference was not found between trastuzumab resistance and PTEN, Akt, MAPK, p53, p95 expressions (respectively p:0,11, 0,79, 0,95, 0,88, 0,74). Conclusions: PTEN, Akt, MAPK, p53, p95expressions were assessed on HER2 positive breast cancers for predicting trastuzumab resistance. There was no statistically significant correlations between trastuzumab resistance and the expressions of these biomarkers. This study is ongoing, this is the preliminary results of this study.
Phase II trial of valproic acid combined with cisplatin-based chemoradiation in locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) patients (pts).
Authors: Milena Perez Mak, Fatima Solange Pasini, Lixia Diao, Fabyane Oliveira Teixeira Garcia, Tiago Kenji Takahashi, Alex Vitorio Amadio, Sheila Aparecida Coelho Siqueira, Laura Sichero, Igor M. L. Snitcovsky, Marco Aurelio Vamondes Kulcsar, Jing Wang, Gilberto Castro
Journal: Journal of Clinical Oncology (2017)

e17546 Background: Cisplatin-based chemoradiation (CRT) offers LA HNSCC pts a high local control rate, however, relapses are frequent. Here we evaluated if epigenetic regulation by VA, a histone deacetylase inhibitor (HDACi), combined with CRT in LA HNSCC improves response rate (RR). Methods: Patients with unresectable oropharynx (OP) and oral cavity LA HNSCC were included in this Simon two-stage phase II trial. After two weeks of VA (P1), CRT was initiated. Primary goal was RR at 8 weeks after CRT+VA (P2) by RECIST v 1.1. 8/20 and 25/32 responses were needed in the first and second stages for the trial to be considered positive (α = 0.05, β = 0.2). MicroRNA (miR) PCR-array profiling in plasma samples at baseline, P1 and P2, was compared to healthy controls by two sample t-test for each miR. Distribution of p-values was analyzed by beta-uniform mixture. HDAC2 and HR23B tumor immunohistochemistry were also evaluated. Results: Ten LA p16 negative OP pts were included. High-risk HPV was detected in 3 pts samples. Median age was 55 years (41-65). All pts were male, smokers or ex-smokers and with previous moderate/high alcohol intake. Due to significant toxicities seen in an interim safety analysis, accrual was terminated. A RR of 88% was achieved in 9 evaluable pts. A total of 169 miRs were differently expressed among pts and controls (FDR 0.05), including lower expression of known tumor suppressors (TS) such as miR-31, -222, -let-7b and -145. There were no significant differences in the pattern of miR expression at P1 vs. baseline. P2 vs. baseline had lower levels of miR-31, particularly in responders (p 0.007). TCGA HNSCC pts with low levels of miR-31 had a trend towards higher relapse free survival (HR 1.11, 95% CI 0.99-1.25; p = 0.073). Non-responders had no difference in miR expression between baseline and P2. HDAC2 H-score above 170 was 90% accurate in predicting 6-month disease free survival. Conclusions: Although improved RR was seen with VA+CRT, prohibitive toxicities prevented the trial from continuing. Cancer pts and controls had distinct pattern of miR expression, mainly with low levels of TS targeting TP53. miR-31 deregulation in HNSCC needs to be further elucidated. Clinical trial information: NCT01695122.
JCOG0504: A phase III randomized trial of surgery with whole brain radiation therapy versus surgery with salvage stereotactic radiosurgery in patients with 1 to 4 brain metastases.
Authors: Takamasa Kayama, Shinya Sato, Kaori Sakurada, Junki Mizusawa, Ryo Nishikawa, Yoshitaka Narita, Toshihiro Kumabe, Yoshiki Arakawa, Takaaki Beppu, Kazuhiko Sugiyama, Hirohiko Nakamura, Motoo Nagane, Yoko Nakasu, Naoya Hashimoto, Minako Sumi, Motohiro Hayashi, Hidefumi Jokura, Takashi Mizowaki, Haruhiko Fukuda, Soichiro Shibui
Journal: Journal of Clinical Oncology (2016)

2003 Background: Whether salvage stereotactic radiosurgery (SRS) alone is effective for patients with brain metastases (BM) is not yet clarified, although clinical benefits such as better preservation of cognitive function and a shorter treatment period are reported with SRS compared to whole-brain radiation therapy (WBRT). We conducted a non-inferiority, randomized study of the effectiveness of salvage SRS for residual and recurrent tumors after surgical resection in comparison to tumor resection plus WBRT. Methods: Patients between 20-79 years with ECOG performance status (PS) 0-3 and ≤4 BM with only one lesion ≥3 cm in diameter having been surgically resected were eligible. Within 21 days after surgery, patients were randomized to WBRT or salvage SRS for residual and recurrent tumors. The primary end point was overall survival (OS) and the secondary end points were intracranial progression-free survival (IC-PFS), adverse events, and proportion of non-worsening in PS and Mini Mental Status Examination (MMSE) scores. The planned sample size was 270 patients with a power of 80%, a one-sided alpha of 5%, and the non-inferiority margin of the hazard ratio (HR) as 1.385. Results: Of 271 patients with BM, 137 were randomized to WBRT (median age, 61 years) and 134 to salvage SRS (median age, 63 years). The primary cancers included lung (47.6%), breast (19.6%), and colon (13.7%) cancers. The median OS was 15.6 months in both arms and the hazard ratio was 1.05 (90.0% confidence interval [0.83–1.33], one-sided p = 0.027). The IC-PFS of the WBRT group (10.4 months) was significantly longer than that of the salvage SRS group (4.0 months; p <0.0001). The proportion of non-worsening in the MMSE scores and PS of both groups at 12 months after enrollment was similar but that of grade 2-4 cognitive dysfunction at more than 90 days after enrollment in WBRT was significantly higher than in SRS arm (16.4% vs. 7.7%). The WBRT arm had 1 treatment-related death. Conclusions: Non-inferiority of salvage SRS to WBRT was confirmed by OS. Salvage SRS is considered as a new standard strategy for patients with ≤4 BM based on pre-specified decision criteria. Clinical trial information: C000000307.
Cell-free tumor DNA in peri-operative blood samples from advanced high-grade serous ovarian cancer patients with and without complete resection.
Authors: Florian Heitz, Sotirios Lakis, Philipp Harter, Jalid Sehouli, Jatin Talwar, Mareike Sprokmann, Miriam Bertrand, Beyhan Ataseven, Erika Mariotti, Stephanie Schneider, Judith N Müller, Roopika Menon, Sonia Prader, Frauke Leenders, Alexandra Hengsbach, Christian Gloeckner, Elena Ioana Braicu, Lukas C. Heukamp, Johannes Heuckmann, Andreas Du Bois
Journal: Journal of Clinical Oncology (2017)

5555 Background: Surgical outcome is an important prognostic factor in advanced high-grade serous ovarian cancer (HGOC). Intra-operative determination of residual disease may be prone to subjective bias. Methods: We prospectively collected and analyzed tumor tissue and plasma from 21 pts with FIGO IIIC-IV HGOC. All tumor specimen showed loss of TP53 in immunohistochemistry. Tumor DNA from tissue and peri-operative cell-free DNA at baseline (BL) and at d(ays) 1, d4 and d10 were subjected to comprehensive hybrid-capture based next-generation sequencing (NEO New Oncology GmbH, Cologne, Germany). Results: The initial cohort comprised 10 pts without (TR&gt;0) and 11 pts with complete resection TR0, with a total of 43 somatic genomic alterations. TP53 was mutated in 20/21 (95.2%) of tissue samples and in 15/21 (71.4%) corresponding plasma samples at BL. Therefore, TP53 mutations were used as a molecular marker of circulating tumor DNA levels post-surgery. In the remaining 5 BL cases the TP53 mutations were either not present in plasma (N= 3) or rested below the detection limit (N= 2). In d1, d4 and d10 post-surgical samples, the sample specific TP53 mutations were detected in 12 out of 15, 10 out of 14 and in 7 out of 13 cases, respectively. TP53variant allele frequency (VAF) did not differ among TR0 and TR&gt;0 at BL (mean= 1.91 versus 1.73, Mann-Whitney test p = 0.86) whereas it was significantly lower for TR0 at d1 (mean= 0.06 versus 2,06; p value= 0.002), d4 (mean= 0.07 versus 1.8; p= 0.04) and d10 (mean VAF= 0 versus 1.04; p= 0.008). Five out of 9 TR&gt;0 cases showed at least one increase in VAF between d0 and any additional time-point. In 8 out of 9 mutations remained detectable at d10 (VAF: 0.076 – 3.26). By contrast, TR0 cases showed consistent reduction in VAF throughout the follow-up period which maximized at d10. Conclusions: Liquid biopsycan efficiently detect somatic mutations in the cfDNA of pts with HGOC following debulking surgery. Variation of the TP53 VAF in sequential post-surgical samples appears to be restricted to TR&gt;0 cases, whereas in TR0 pts VAF progressively decreases. Liquid biopsy may hold promise as a tool for the objective determination of residual disease after debulking surgery.