tbuckley/cabot-search huggingface dataset:
The role of digital clinical measures in improving cancer care and research.
Authors: Jennifer Goldsack, Ariel Aguilo, Andrea Coravos, Chris Economos, Kate Lyden
Journal: Journal of Clinical Oncology (2021)

e13584 Background: From objectively assessing performance status to recording simple vital signs, the adoption of high quality digital clinical measures offers enormous possibilities for transforming cancer care &amp; research. However, the development &amp; deployment of high quality digital measures in oncology lags behind adoption in other therapeutic areas. At the time of submission, the DiMe library of digital endpoints reports 166 unique digital endpoints being used in industry sponsored trials of new medical products, but none are being used in an oncology trial. There are seven digital clinical measures working their way through the FDA qualification program, but none in oncology. During the pandemic, care for patients with cardiac and other chronic conditions transitioned out of the clinic &amp; into the home powered not only by virtual visits, but high quality information from remote monitoring. A study of oncology care facilities worldwide reported 89% finding difficulty in delivering usual care due to the challenges of safely bringing patients into the clinic during COVID. Methods: From March to Sep 2020, cross-industry stakeholders at the Digital Medicine Society (DiMe), Elektra Labs, Genentech, Koneksa, Myokardia, Sage Bionetworks, Scripps Research, and the US Food &amp; Drug Administration came together to synthesize best practices from the digital health field, breaking down silos to create ‘ The Playbook’, the comprehensive and accessible “how-to” guide to support all stakeholders working to advance the safe, effective, ethical, and equitable use of digital clinical measures to improve lives. In October 2020, DiMe -- a 501c3 non-profit dedicated to advancing digital medicine to improve lives -- convenened a pre-competitive collaboration of 44 participants from 29 organizations to drive the adoption of the best practices articulated in The Playbook. Results: The Playbook describes trans-industry consensus for best practices for developing and deploying digital clinical measures across patient care, clinical research, and public health, including for oncology. Conclusions: The clinical, technical, and operational best practices necessary to develop and deploy high quality digital clinical measures into cancer care &amp; research have been established. There is no reason for their successful adoption in oncology to lag behind other therapeutic areas. The Playbook and additional resources to support implementation due for launch on April 30 are critical tools for the field of oncology.
Clinical treatment pathways utilization in an outpatient academic cancer center.
Authors: Anna Chen, Seojin Park, Valerie Pracilio Csik, Vittorio Maio, Karen Walsh, Adam F Binder
Journal: Journal of Clinical Oncology (2021)

e18673 Background: Clinical treatment pathway (CTP) tools have been incorporated into oncology practices to help standardize treatment, reduce care variation in cancer patients, and move towards value-based care. CTP tools incorporate the latest guidelines and are developed through multidisciplinary committees. Treatment decisions are prioritized by efficacy, toxicity, and cost to improve quality and value. This is especially important in cancer care which is associated with high drug costs. However, use and implementation of CTP tools has been met with mixed reviews and published data from academic medical centers are limited. Methods: Outpatient treatment decisions for patients across different cancer types, including colorectal, gastroesophageal, and breast cancers from July 2018 to March 2020 at an urban NCI-designated cancer center were evaluated. Every treatment decision was evaluated in relation to physician utilization of CTP tools. Treatment decisions were categorized as choosing a CTP recommended option ( pathways dependent), not choosing a CTP recommended option ( pathways independent), or not using the CTP tool at all ( non-pathways). Descriptive statistics and significance testing were used to explore CTP utilization over time, physician years in practice, cancer type, and cancer stage. Multinomial and binary logistic regression models were used to evaluate associated factors with CTP utilization. Results: During the study period, 1,007 treatment decisions were identified. Of these, 76% were pathways dependent, 13% were pathways independent, and 11% were non-pathways. CTP utilization was statistically significant in association with cancer type, cancer stage, physician years in practice, and year of encounter. In multinomial logistic regression models, physicians with more years in practice were more likely to be pathways independent and non-pathways than pathways dependent. Physicians treating colorectal or gastroesophageal cancer were more likely to be pathways independent [OR 3.27; 95% CI: 1.98-5.42 and OR 2.25; 95% CI: 1.12-4.49, respectively] or non-pathways [OR 2.98; 95% CI: 1.65-5.37 and OR 3.21; 95% CI: 1.58-6.54, respectively] than pathways dependent compared to physicians treating breast cancer. Treatment decisions for patients with either stage 2 and stage 4 cancers were more likely to be pathways independent than stage 1 cancers [OR 4.13; 95% CI: 1.44-11.84 and OR 4.37; 95% CI: 1.27-15.04, respectively]. Conclusions: This study found that a large proportion of treatment decisions for patients across different cancer types were made utilizing CTP tools, but utilization varies according to cancer type, stage, and physician years in practice. Further research is needed to better understand the physician decision making process and implementation of CTP tools to drive improvement in design, education, and training.
Underutilization of germline BRCA testing in commercially-insured women diagnosed with ovarian cancer.
Authors: Stephanie Cham, Alexi A. Wright
Journal: Journal of Clinical Oncology (2021)

5539 Background: Germline BRCA (gBRCA) testing has prognostic, therapeutic, and familial implications for patients with ovarian cancer. Since 2010, national guidelines have recommended universal genetic testing, but few data are available about rates and timeliness of testing or factors associated with testing. Methods: We examined rates of gBRCA testing and the time from index procedure to testing among commercially-insured women aged 18 to 64 with claims for ovarian, fallopian tube, or primary peritoneal cancers cancer who received cytoreductive surgery and chemotherapy between 2008-2018. We used logistic regression to assess patient-, clinician-, and practice-level characteristics associated with testing. Results: Overall, the rate of g BRCA testing was 33.9%, increasing from 14.7% in 2008 to 46.4% in 2018; the median time to testing decreased from 280.0 to 72.5 days. Patients who were tested were younger than those who were not (mean [SD] 54.7 [9.9] years vs. 58.1 [11.8] years, P&lt;.001) and had fewer comorbidities (Charlson score ≥2: 3.7% vs. 9.5%, P=0.01). There were no differences in testing rates by US region, rurality of practice location, or medical vs. gynecologic oncology providers. However, testing rates were higher in academic and NCI-designated cancer centers (36.2% and 32.5%, respectively), compared with community practices (25.5%; P&lt;0.001) (Table). In adjusted analyses, lower test rates were associated with older age (aOR=0.97, 95%CI=0.96-0.98), more medical comorbidities (Charlson score ≥2: aOR=0.77, 95%CI=0.61-0.97), and community practices vs. NCI cancer centers (aOR=0.64, 95%CI=0.46-0.88). Conclusions: While the rates and time to testing for gBRCA in patients with new diagnoses of ovarian cancer have improved over time, testing remains underutilized, even among well-insured populations. Future studies should examine barriers to timely genetic testing and identify scalable strategies for increasing testing in women with ovarian cancer, particularly for women treated in community practices.[Table: see text]
FDG-PET/CT response and outcome of neoadjuvant immunotherapy for clinical stage III melanoma.
Authors: Milton Jose De Barros E. Silva, Caio Dabbous Liz, Marcos Rezende Teixeira, José Augusto Rinck, Monique Celeste Tavares, Daniel Garcia, Joao Paulo S. N. Lima, Matheus Lobo, Clovis Pinto, Marcelo Cavicchioli, Eduardo Lima, Eduardo Bertolli, Andre Molina, Kenneth Gollob, Amanda Figueiredo, Joao Duprat
Journal: Journal of Clinical Oncology (2021)

e21569 Background: Neoadjuvant immunotherapy with nivolumab 3mg/kg and ipilimumab 1mg/kg for two cycles(N3+I1) or anti-PD1 for 3-8 weeks for clinical stage III melanoma have shown rates of pCR/near-pCR about 60% or 30%, respectively. The prognosis of this group seems to be excellent so far. On the other hand, patients classified as pathological non-response have a worse outcome and early identification of this group may allow us to tailor treatment before surgery. Methods: We conducted a retrospective analysis of patients with clinical stage III melanoma treated with neoadjuvant immune checkpoint blockade who did baseline and pre-operative FDG-PET/CT. The total number of FGD avid lesions and the percentual difference between the maximum SUV per lesion was calculated. The pathological results were correlated to FGD-PET/CT findings. Results: Between January 2019 and January 2021, nine patients with clinical stage III melanoma were identified. Six patients received Nivolumab 3m/kg and Ipilimumab 1mg/kg for two cycles and 3 received anti-PD1 for 60 days. Baseline FDG-PET/CT showed just one avid lesion in 7 patients, 2 avid lesions in one patient and 3 avid lesions in one patient. All known lesions identified by CT scan were also captured by FGD-PET/CT. After the neoadjuvant treatment, 4 patients achieved pCR/near-pCR. All of them were treated with N3+I1. Two of them had metabolic complete response (including the one with 3 PET- avid lesions) and 2 had reduction on FDG concentration (-31% and – 76%). Three patients had absence of response: 100% of viable tumor cells (VTC), all of them with increase in FDG concentration (+12% to + 307%) and appearance of a new lesion in one case. Two out of them were treated with anti-PD1. One patient had partial response (40% of VTC). Interestingly, this patient developed sarcoidosis-like reaction with increase of SUV in the index lesion (+68%) and appearance of mediastinal lymph-nodes. One patient, who had two lesions, presented a mixed response: complete response in one and 90% of VTC in the other. FDG-PET/CT was able to detect both responses (metabolic complete response and increase of FGD concentration of 17%, respectively). Conclusions: Reduction in FGD-PET/CT concentration with no appearance of new lesion(s) is associated with significant pathological response. An increase of SUV or appearance of new lesion(s) should be carefully interpreted.
Invasive Paget’s disease of the breast versus genitalia versus skin: What are the demographic and prognostic differences?
Authors: Ashley S. Moon, Cheng-I Liao, Hsiu-Min Chen, Danny Lee, John Chan
Journal: Journal of Clinical Oncology (2021)

e17577 Background: Invasive extramammary Paget’s disease is most commonly in the vulva but can also occur in other genitalia as well as primary skin locations (face, scalp, neck, trunk, extremities). We aim to determine the clinicopathologic and prognostic factors of invasive Paget’s disease of the breast, genitalia and skin. Methods: Data on patients with invasive Paget’s disease of the breast, genitalia and skin were collected between 2001 and 2015 from the National Cancer Data Base Participant Use File 2016. Univariate, multivariate analyses, and Kaplan-Meier survival analysis were performed by SAS. Results: 10, 122 female patients were eligible, of which 7, 051 had invasive disease (breast n = 5, 105, genitalia n = 1, 717, skin n = 229) and the remainder had in situ disease. Median age for invasive disease was 63 years for breast, 73 years for genitalia and 75 years for skin. Among Whites, the proportion of invasive Paget’s of breast, genitalia, and skin was 70.8%, 25.8%, 3.4%; Blacks 93.8% breast, 5.3% genitalia and 0.9% skin; Asian/Pacific Islanders 65.0% breast, 31.8% genitalia and 3.2% skin. Among treatment institutions, academic centers treated 30.2% of invasive breast, 48.9% genitalia and 51.5% skin. Surgery was performed in 89.4% of invasive breast compared to 21.1% genitalia and 46.7% skin. Radiotherapy was administered to 25.3% of invasive breast, 3.0% genitalia and 15.3% skin. Chemotherapy was given to 28.0% of breast, 1.9% genitalia and 5.7% skin. Early stage (I or II) disease was diagnosed in 70.8% of invasive breast, 63% genitalia and 30.6% skin. Five-year OS from any cause for patients with invasive Paget’s disease of breast, genitalia and skin was 81.9%, 83.8%, and 69.9%, respectively. In univariate analysis, older age (HR 3.75, 95% CI 3.27-4.31, p &lt; 0.001), Black race (HR 1.21, 95% CI 1.00-1.46, p = 0.046), history of other cancer (HR 1.53, 95%CI 1.36-1.71, p &lt; 0.001), higher comorbidity score (HR 2.12, 95%CI 1.88-2.39, p &lt; 0.001), higher stage (HR 4.25, 95%CI 3.73-4.85, p &lt; 0.001), and no surgical treatment (HR 3.47, 95% CI 2.87-4.19, p &lt; 0.001) were associated with worse survival. In multivariate analysis, invasive Paget’s of the skin was associated with the worst survival (HR 1.56, 95% CI 1.19-2.05, p = 0.001). For all three types of invasive Paget’s disease, better prognosis was associated with Asian/Pacific Islander race (HR 0.49, 95% CI 0.31-0.80, p = 0.004), income ≥ $63, 000 (HR 0.83, 0.70-0.98, p = 0.028) and treatment at an academic/research center (HR 0.78, 0.62-0.99, p = 0.037). Conclusions: Invasive Paget’s disease of the breast is 3-fold more common than genitalia with younger age at diagnosis. Most are diagnosed at early stages with good prognosis. Blacks have a higher proportion of invasive Paget’s disease of the breast than other races. Invasive Paget’s disease of primary skin had the poorest prognosis.
Improved risk stratification via integration of radiomics and dosiomics features in patients with recurrent high-grade glioma undergoing carbon ion radiotherapy (CIRT).
Authors: Patrick Salome, Francesco Sforazzini, Andreas Kudak, Laila König, Philipp Kickingereder, Nina Bougatf, Wolfgang Wick, Oliver Jäkel, Juergen Debus, Maximilian Knoll, Amir Abdollahi
Journal: Journal of Clinical Oncology (2021)

2043 Background: Unique radiobiological and physical properties of carbon ion radiotherapy (CIRT) may be favorably utilized to improve outcome in recurrent High-Grade Glioma (rHGG). There are currently no standardized criteria for stratification of rHGG patients for re-irradiation (re-RT). This study evaluated the impact of morphological data (radiomics) and physical information (dosiomics) in stratifying rHGG patients for CIRT. Methods: Quantitative radiomics and dosiomics features were extracted from CIRT planning CTs with dose distribution (DD) and multiparametric MRIs (mpMRI, pre re-RT) of 141 patients (recurrent grade III: n=56 40%, grade IV: n=85 60%) treated with a median dose of 42 Gy (RBE) and a median fraction of 13. The MR sequences considered are T1 weighted pre-and post-contrast agent, fluid-attenuated inversion recovery (FLAIR) and apparent diffusion coefficient (ADC). Benefit of a re-RT risk score (RRRS), comprising the initial tumour grade, age and the Karnofsky Performance Score was shown to correlate with superior outcome in CIRT and conventional re-RT and was also studied here in parallel. Feature sets - a) RRRS, b) radiomics, c) dosiomics features - were evaluated both separately and combined. Multiple feature selection methods were used independently on the CT, DD and the MR sequences, followed by a stepwise Cox's Proportional Hazard model selection per modality or combination thereof. Multivariable models were ranked by 10-fold cross-validated concordance index (C-I). Results: Compared to the RRRS model (OS/PFS, C-I: 0.68/0.61), the multimodality model considering radiomics and dosiomics features (RD) allowed improved prognostic separation (OS/PFS, C-I: 0.77/0.70). The RD signature consisted of 12 and 10 textural features for the OS and PFS models. Combining the RD model with RRRS yielded the best performance (OS/PFS, C-I: 0.78/0.73). No significant correlation between the textural features and the prescribed dose, tumor grade and volume was found, with the Spearman's correlation coefficient ranging between -0.06 to 0.17. Conclusions: Integrating multimodal information outperforms unimodal prognostic separation of rHGG following CIRT, highlighting the importance to consider biological, physical and morphological data for patient stratification. Prospective validation studies of this multimodal stratifier is warranted.[Table: see text]
Abstract DP-006: THE EFFECT OF AGE AND OCP USE ON THE INCIDENCE OF PRE-CANCEROUS P53 LESIONS AND THE DEVELOPMENT OF HIGH GRADE SEROUS OVARIAN CARCINOMA
Authors: Kendall Greening, Anthony Karnezis, Dawn Cochrane, Gillian Hanley, David Huntsman
Journal: Clinical Cancer Research (2019)

Abstract BACKGROUND: High grade serous ovarian cancer (HGSOC) accounts for &amp;gt;70% of ovarian cancer related deaths and is the most common ovarian cancer histotype, most originating from pre-cancerous p53 lesions in the fallopian tube (FT) fimbria. Use of oral contraceptive pills (OCPs) for 5 years or more is associated with &amp;gt;40% reduction in risk of HGSOC, but the mechanism is unknown. We hypothesize that OCP use reduces the incidence of p53 lesions. Our preliminary data show higher incidence of p53 lesions in post- compared to pre-menopausal women, therefore we aim quantify p53 lesions in post-menopausal women who previously did or did not use OCPs. This will provide insight into the protective effects of OCPs against HGSOC. PRELIMINARY RESULTS: We determined the presence of p53 lesions by immunohistochemistry (IHC) in FT of women up to 40 years old (n=27) and &amp;gt;60 years old (n=24) who underwent salpingectomies for non-cancer reasons. p53 lesions were identified in 3/27 cases of the younger cohort (11%) and in 10/24 of the older cohort (42%). Thus, we conclude an increased incidence of p53 lesions in older compared to younger women. PROPOSED DESIGN: IHC for p53 will be performed on FT fimbria of women &amp;gt;55 years old who received salpingectomy/hysterectomy for non-cancer reasons. Based on an assumed reduction in p53 lesions of 35% in women who used OCPs for 5 years or more compared to non-users (25 vs. 42%), analysis of 190 cases from each group will provide &amp;gt;80% power (p&amp;lt;0.05). Cases will be identified through Population Data BC and blind analysis by tp53 IHC will be performed at the Vancouver General Hospital. Post-menopausal status will be confirmed by endometrium histology and data flowed back to Pop Data BC to compare to OCP data. CONCLUSION: Our preliminary study found that 42% of post menopausal women had p53 lesions, informing this study design. The study registered through this abstract will be the first to examine the impact of OCPs on the earliest known precursors of HGSOC. Citation Format: Kendall Greening, Anthony Karnezis, Dawn Cochrane, Gillian Hanley, David Huntsman. THE EFFECT OF AGE AND OCP USE ON THE INCIDENCE OF PRE-CANCEROUS P53 LESIONS AND THE DEVELOPMENT OF HIGH GRADE SEROUS OVARIAN CARCINOMA [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-006.
ctDNA analysis in patients with cancer of unknown primary and its value in guiding targeted treatment when combined with predicted cancer types by 90-gene reverse-transcription polymerase chain reaction assay.
Authors: Xin Liu, Shiyu Jiang, Xiaowei Zhang, Xiaoyan Zhou, Zhiguo Luo, Xichun Hu
Journal: Journal of Clinical Oncology (2021)

e18730 Background: No targeted agents except for drugs against NTRK fusion, dMMR/MSI-H or TMB-H are recommended for the treatment of cancer of unknown primary (CUP), despite of the occurrence of multiple actionable mutations identified by NGS. We aimed to explore the characteristics of circulating tumor DNA (ctDNA) and its value in guiding targeted treatment in combination with predicted cancer types by 90-gene reverse-transcription polymerase chain reaction assay for tissue origin. Methods: 172 treatment-naïve CUP patients with ctDNA testing were retrospectively included between April 2017 and Oct 2020. Of them, 98 patients had primary site predicted. Genetic alterations were reclassified based on their predicted primary site and the oncoKB scale. 153 patients treated with the first-line therapy and available survival data were used to explore prognostic value of detected genetic alterations in ctDNA. Results: We identified 82.6% (142/172) of patients had alterations detected, with the most commonly seen mutations of TP53 (51%), ARID1A (11%), KRAS (10%), RB1 (9%), APC (8%), PI3KCA (8%) and NFE2L2 (7%). The most commonly observed actionable mutations were PIK3CA (n=14, 9.8%), ERBB2 (n=7, 4.9%), BRAF (n=6, 4.2%), MET (n=6, 4.2%) and EGFR (n=5, 3.5%). After introducing predicted primary site in the 98 patients, 6.1% (n=6) of patients upgraded to a Level 1 alteration, 1.0% (n=1) to a Level 2 alteration (Table). In these 7 patients, only one patient with predicted lung cancer and EGFR 19 del received gefitinib with partial response for 5+ months. In multivariate analysis, NFE2L2 (hazard ratio [HR] = 2.96, 95%CI=1.32-6.61, P = .008) and CDKN2A mutation (HR = 2.50, 95%CI=1.26-4.96, P = .009) were independently associated with shorter PFS. Furthermore, NFE2L2 (HR = 4.96, 95%CI=1.98-12.43, P ＜ .001) and CDKN2A mutation (HR = 4.84, 95%CI=1.63-14.40, P = .005) were correlated with worse OS. Conclusions: This is the first attempt to integrate ctDNA sequencing and gene expression profiling for tissue of origin in OncoKB classification schema, resulting in 7.1% (7/98) of the genetic alterations reclassified to level 1 or 2, which might identify patients benefiting from corresponding targeted treatment. NFE2L2 and CDKN2A mutations in ctDNA were associated poor prognosis.[Table: see text]