tbuckley/cabot-search huggingface dataset:
An ethnographic study illuminating the effect of endogenous and exogenous uncertainty on tumor board decision making.
Authors: Barbara Oureilidis-DeVivo
Journal: Journal of Clinical Oncology (2020)

e19156 Background: Hospital tumor boards (TBs) exist to help multidisciplinary specialists determine the best treatment plan for patients through multidisciplinary input and evidence-based treatment recommendations. However, decision-making processes and outcomes vary and may not consistently follow a linear, rational decision-making process or represent evidenced-based clinical guidelines. The ad hoc nature of multidisciplinary cancer teams can create limitations in interoperable functioning, especially in ambiguous environments. Methods: This qualitative ethnographic study explores levels of patient situational complexity under TB review within different structural dynamics in a group and describes how TBs cope with uncertainty when making treatment decisions. The study reports on original research and used ethnographic methods in 44 tumor boards at seven research hospitals in the United States and United Kingdom. Results: Results show TB decision-making process and outcomes are obstructed by the level of situational complexity in each patient’s case depending on the social dynamics of the group. Conclusions: Although multidisciplinary teams provide the benefit of variety in backgrounds and expertise, this structural diversity can also lead to limitations in the actual functioning of a group. By exploring the variations in this decision-making process, a deeper understanding can be reached of how oncology physicians make decisions about the clinical pathway for cancer patients and how this affects TB functionality.
Prognostic and predictive value of neutrophil/lymphocyte ratio in patients with triple-negative and HER2-positive breast cancer undergoing neoadjuvant systemic therapy.
Authors: Agnieszka I. Jagiello-Gruszfeld, Magdalena Jodkiewicz, Maria Kowalska, Wojciech Michalski, Wojciech P Olszewski, Anna Niwinska, Anna Gorniak, Katarzyna Pogoda, Roman Dubianski, Katarzyna Gorska, Ewa Glinka, Tadeusz Pienkowski, Zbigniew Nowecki
Journal: Journal of Clinical Oncology (2020)

e12620 Background: Preoperative neutrophil-lymphocyte ratio (NLR) have been suggested to be correlated with the prognosis of patients with breast cancer (BC). However, the results still remain controversial. The goal of our study was to evaluate the predictive and prognostic value of NLR in early stage triple negative and HER2-pos breast cancer patients undergoing NAC. Methods: 96 female patients (pts) with histologically proven breast cancer (51 TNBC, and 45 HER2 pos) were analysed in this retrospective analysis. The NLR before the initiation of NAC was documented. Histopathological response in surgically removed specimens was evaluated using the Residual Cancer Burden (RCB) Calculator (by MD Anderson Cancer Center). The pCR was defined as no invasive tumor in primary tumor bed and lymph nodes. The NLR variable was analyzed as both continuous and categorical. The impact on pCR and RCB was tested using Mann-Whitney, Kruskal-Willis or the Chi-2 test, respectively. Results: Only 4 categories of NAC were used: in TNBC 4 x ACdd followed by 12 x PCL (38 pts) or 4 x ACdd followed by 12 x PCL+ carboplatin AUC 1.0-2 (13 pts), in HER2-pos 39 pts received 6 x TCH (docetaxel + tratuzumab + carboplatin AUC 6) and 6 pts 4 x ACdd followed by 12 x PCL iv + 4 x trastuzumab. In 27 pts (53%) with TNBC and 24 pts (53%) with HER2-pos breast cancer pCR was obtained after NAC. RCB distribution was: 0-53.1%, 1-22%, 2-17.6%, 3-7.3%. No association with NLR and pCR could be observed (p &gt; 0.26). No association with NLR and RCB could be observed (p &gt; 0.18). Conclusions: In our retrospective analysis we could not demonstrate predictive or prognostic value of NLR in the cohort of early stage triple negative and HER2-positive breast cancer patients treated with NAC. Further studies are planned in a group of patients with Luminal B, HER2 – negative breast cancer, who received NAC.
Racial disparities in patients with unresectable stage III/IV esophageal cancer at time of diagnosis: A National Cancer Database Analysis.
Authors: Meena Sadaps, Neal Mehta, Ran Zhao, Wei Wei, Amit Bhatt, Alok A. Khorana
Journal: Journal of Clinical Oncology (2020)

e16589 Background: Significant racial disparities exist in the patterns of care and clinical outcomes for patients with early stage, non-metastatic esophageal cancer but data in advanced esophageal cancer are lacking. In this study, we aim to evaluate racial disparities in patients with locally advanced/metastatic, unresectable esophageal cancers. Methods: We identified patients in the National Cancer Database with esophageal cancer, from 2004 to 2016, with unresectable stage III/IV disease at time of diagnosis. We compared overall survival (OS) between different racial groups as well as other demographic and socioeconomic factors that may have contributed to this disparity. Secondary factors that were studied included age, sex, education, histology, and location of tumor. Results: 49,139 patients were included in this analysis. Median age was 64.5 years and 39,314 (80.0%) were male. 16,723 (34.0%) patients had stage III disease and 32,416 (66.0%) patients had stage IV disease. 16,208 patients (33.0%) had squamous cell carcinoma and 32,931 (67.0%) had adenocarcinoma. Patients were stratified into one of the following six categories for race: Caucasian (40,139; 81.7%), African American (5,571; 11.3%), Asian (907; 1.8%), Hispanic/Latino (1,793; 3.6%), Native American (145; 0.3%), and other (167; 0.3%). African Americans had worse median OS (Table) than Asians (p = 0.000), Hispanic/Latinos (p = 0.000), and Caucasians (p = 0.001) when analyzed in a pairwise comparison using log-rank testing. Within the African American subset, older age ( &gt; 70 years) (p = 0.00), male gender (p = 0.00), and tumor location in the mid (p = 0.02) or upper third (p = 0.00) of the esophagus were associated with worse outcomes using Cox’s multivariate regression model. Conclusions: Racial disparities persist even in unresectable stage III/IV esophageal cancer patients with African Americans noted to have worse clinical outcomes as compared to most other races including Caucasian, Asian, and Hispanic/Latino patients. Further research is warranted to determine the cause for this disparity and to implement the necessary changes to improve outcomes for these patients. [Table: see text]
Rates of Symptomatic SARS-CoV-2 Infection in Patients With Autoimmune Liver Diseases in Northern Italy: A Telemedicine Study
Authors: Cristina Rigamonti, Micol Giulia Cittone, Carla De Benedittis, Eleonora Rizzi, Giuseppe Francesco Casciaro, Mattia Bellan, Pier Paolo Sainaghi, Mario Pirisi
Journal: Clinical Gastroenterology and Hepatology (2020)
Phase Ib study of a novel, small-molecule MDM2 inhibitor APG-115 combined with pembrolizumab in U.S. patients with metastatic solid tumors.
Authors: Anthony W. Tolcher, Raghad Karim, Yuefen Tang, Hengbang Wang, Jiao Ji, Jason Chen, Angela Kaiser, Piyush Sheladia, Mohammad Ahmad, ZHIYAN LIANG, Dajun Yang, Yifan Zhai
Journal: Journal of Clinical Oncology (2020)

3512 Background: APG-115 activates p53-mediated apoptosis in tumor cells retaining wild-type TP53. It also functions as a host immune modulator and enhances antitumor activities when combined with PD-1 blockade preclinically. MDM2 amplification is associated with hyperprogression in patients treated with checkpoint inhibitors. Methods: The Phase Ib / II study was designed to evaluate APG-115 combined with pembrolizumab in patients with metastatic solid tumors (NCT03611868). APG-115 was administered orally every other day for 2 weeks, at dose ranging from 50 mg – 200 mg, with pembrolizumab at 200 mg IV on Day 1 of a 21-day cycle. Study objectives were to assess safety including dose-limiting toxicity (DLT), serious adverse events (SAEs), treatment-related AEs (TRAEs), pharmacokinetics (PK), pharmacodynamics (PD), and efficacy (assessed by RECIST v1.1), to determine recommended phase 2 dose (RP2D). Results: As of December 25, 2019, the enrollment of phase 1b study was completed. Total 19 patients had been treated in four APG-115 cohorts: 50 mg (n = 3), 100 mg (n = 3), 150 mg (n = 6), and 200 mg (n = 7). No DLT was observed, The TRAEs (≥15%) were nausea (47.4%), fatigue (36.8%), decreased platelet count (26.3%), and decreased appetite (21.1%), as well as diarrhea, vomiting, decreased neutrophil or white blood cell count, and hypothyroidism in 15.8% each. Grade &gt; 3 TRAEs included decreased neutrophil and thrombocytopenia in 15.8% each. Two SAEs were treatment related: G3 febrile neutropenia and G3 adrenal insufficiency. No new safety finding from combination with Pembrolizumab. The RP2D of APG-115 was 150 mg. One patient with ovarian cancer has a CR lasting for 15 months, 2 patients had PR for 8-9 months: one NSCLC failed IO therapy, another with appendix cancer, and 7 had SD for 1.5-7 months. The objective response rate was 15.8%, and the disease control rate (DCR) was 52.6%. PK data indicated an approximately dose-proportional increase in APG-115 exposure over the range of 50-200 mg on Day 1. PD-PK analyses showed that serum macrophage inhibitory cytokine-1 (MIC-1) increase was time and dose dependent, the MIC-1 elevation correlated with APG-115 exposure, indicating p53 activation in these patients. Conclusions: APG-115 in combination with pembrolizumab is well tolerated. Encouraging antitumor effects were observed in several tumor types. The phase II study is ongoing in the cancer patients with specific bio-marker profiling. Clinical trial information: NCT03611868 .
Increased favorability of small breast cancers.
Authors: Shigeto Maeda, Kosho Yamanouchi, Takanori Hirayama, Shinichiro Kobayashi, Hiroyuki Tokunag, Hiroaki Takeshita, Shiro Miura, Masahiro Ito, Tamotsu Kuroki
Journal: Journal of Clinical Oncology (2020)

e12576 Background: Breast cancer is classified into three prognostic groups based on the following biologic factors: estrogen-receptor (ER) status, progesterone-receptor (PR) status, and nuclear grade (NG). According to this classification, we determined the biological behavior in order to understand if a small breast cancer is biologically more favorable than a large one (T1-2 breast cancers). Methods: The inclusion criteria for this study were (1) presence of T1-2 breast cancer measurable by magnetic resonance imaging (MRI) or ultrasound(US), and (2) availability for determination of ER, PR, and NG histological status. Inflammatory breast cancer, male breast cancer, tumors of unknown size on MRI or US, and complications due to other cancers were excluded from this study. From April 2007 to December 2019, 1173 patients with surgically proven breast cancer presented at National Hospital Organization Nagasaki Medical Center, and 1080 patients were retrospectively analyzed. The favorable (F), intermediate (I), and unfavorable (UF) groups were defined as follows. F: NG1 (ER+PR+, ER+PR-, ER-PR+), UF: NG2 (ER-PR-) or NG3 (ER-PR-, ER+PR-, ER-PR+). IF: all other types of F and UF. Overall survival (OS) was calculated using the Kaplan-Meier method. All statistical analyses were performed using JMP 9.0.2, and probability values of &lt;0.05 were considered statistically significant. Results: Number (%), age (year), size (cm), and 10-year OS (%) in the F, I, and UF groups are presented in the table. The tumor size in F group was significantly smaller than that in the other groups and had better prognoses. The F, I, and UF distribution of tumors less than 1 cm in size were 66%, 29%, and 5%, respectively. On the other hand, the F, I, and UF distribution of tumors 1-2 cm, 2-3 cm, 3-4 cm, 4-5 cm in sizes were (42%, 41%, 17%), (34%, 46%, 20%), (31%, 39%, 30%), and (27%, 45%, 28%), respectively. The 10-year OS of F group stage I, I group stage I, F group stage II, and UF group stage I were 99%, 94%, 93%, and 80%, respectively. Conclusions: Small breast cancers, especially those less than 1 cm in size, were shown to be significantly biologically favorable. Small breast cancers are candidates for de-escalation of treatment. [Table: see text]
<i>Notes from the Field:</i> Impact of a Mass Drug Administration Campaign Using a Novel Three-Drug Regimen on Lymphatic Filariasis Antigenemia — American Samoa, 2019
Authors: Marisa A. Hast, Aifili Tufa, Tara A. Brant, Lynette Suiaunoa-Scanlan, Janet Camacho, June Vaifanua-Leo, Keri Robinson, Emily Dodd, Ben Sili, Loretta S. Lees, Kimberly Y. Won, Fara Utu
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Progress has been made toward lymphatic filariasis elimination in American Samoa, but success will depend on continuing recommended control activities in the territory, including mass drug administration.
Weighing the role of concomitant medications during PD-1/PD-L1 checkpoint blockade: A preliminary analysis.
Authors: Alessio Cortellini, Domenico Mallardo, Maria Grazia Vitale, Sergio Bracarda, Serena Macrini, Pietro Di Marino, Michele De Tursi, Nicola Petragnani, Clara Natoli, Olga Nigro, Alessandro Tuzi, Leonardo Valerio Patruno, Giampiero Porzio, Katia Cannita, Maria Concetta Fargnoli, Corrado Ficorella, Paolo Antonio Ascierto
Journal: Journal of Clinical Oncology (2020)

e15132 Background: The role of concomitant medications, such as steroids, antibiotics and proton pump inhibitors, during immunotherapy has already been investigated, without conclusive results. Methods: This is a multicenter retrospective study, of advanced cancer patients (any histology) treated with anti-PD-1/PD-L1 immunotherapy. Baseline concomitant medications were collected. Results: From June 2014 to November 2019, 277 consecutive patients were evaluated. Median age was 69 years; male/female ratio was 190/87. Primary tumors were: NSCLC (41.9%), melanoma (40.1%), renal cell carcinoma (11.9%) and others (6.1%). 63 patients (22.7%) had ECOG-PS ≥ 2. 120 patients (43.3%) had ≥ 2 metastatic sites. Conclusions: Cancer-related steroids administration, systemic antibiotics, proton pump inhibitors, anticoagulants, opioids, oral anti-diabetics and insulin therapy seem to significantly affect survival in patients receiving PD-1/PD-L1 inhibitors. In interpreting such data, it is important to consider the prevalent role of poor clinical condition. Our preliminary results warrant further investigation in a larger cohort of patients and in a perspective way. [Table: see text]
Therapeutic effect and safety of individualized chemotherapy combined with sequential immunotherapy based on BRCA1 mRNA expression level in the treatment of unresectable pancreatic cancer.
Authors: Juan Du, Linxi Zhu, Huizi Sha, Zhengyun Zou, Lixia Yu, Jie Shen, Weiwei Kong, Lianjun Zhao, Yudong Qiu, Baorui Liu
Journal: Journal of Clinical Oncology (2020)

e16773 Background: Pancreatic cancer is a kind of digestive tumor with low incidence but high degree of malignancy. It is characterized by difficult in early detection and invasive metastasis. Together with high recurrence and metastasis rate after resection, the prognosis of pancreatic cancer is extremely poor. To explore the role of BRCA1 mRNA expression in the chemotherapy of unresectable pancreatic cancer and the synergistic effect of chemotherapy and immunotherapy, our center has carried out a clinical trial which focuses on individualized chemotherapy combined with sequential immunotherapy according to BRCA1 mRNA expression in the first-line treatment of unresectable pancreatic cancer. Methods: The expression of BRCA1 mRNA in tumor tissues of patients with pancreatic cancer was detected. According to the expression level, gemcitabine combined with nab-paclitaxel-based or gemcitabine combined with oxaliplatin-based biweekly chemotherapy combined with sequential GM-CSF and IL-2 immunotherapy was applied. Patients’ conditions and the efficacy and safety were assessed every 4 cycles. Results: A total of 25 patients were enrolled in the study. All of them were observed for toxic side effects and 24 of them were evaluated for efficacy. The median overall survival and median progression-free survival were 11.9 months and 6.3 months. The disease control rate was 91.7%, of which 37.5% (9/24) patients achieved partial remission (PR), 54.2% (13/24) patients achieved stable disease (SD) and 8.3% (2/24) patients were assessed as progressive disease(PD). Of the 15 patients with medium or high expression in BRCA1 mRNA, 7 achieved PR and 8 achieved SD. Of the 9 patients with low BRCA1 mRNA expression, 2 achieved PR, 5 achieved SD and 2 had PD. The proportion of eosinophils in the blood of some patients with good therapeutic effects was significantly higher than that before treatment. Hematological and non-hematological toxicity during the treatment were mostly grade 1~2. The two most common grade 3~4 adverse events were fever and thrombocytopenia. Conclusions: Our results suggest that individualized selection of chemotherapy combined with sequential immunotherapy according to BRCA1 mRNA expression level in the treatment of unresectable pancreatic cancer have curative effect and controllable adverse reactions. The improvement of treatment efficiency may be related to the activation of non-specific immune response.
The role of routine surveillance imaging in detecting oral cavity cancer recurrence in asymptomatic patients.
Authors: Jeffrey Chi, Su Yun Chung, Carlos Alberto Lopez, Douglas K. Frank, Lucio Pereira, Edward Z. Gabalski, Sewit Teckie, Maged Ghaly, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2020)

e18561 Background: The optimal surveillance approach for patients who were definitively treated for oral squamous cell carcinoma (OSCC) is unclear, but it includes physical exams (PE) and surveillance imaging (SI) studies at intervals that vary amongst institutions. At our institution, patients are seen in office and underwent PE monthly for the first 3-6 months then every 3 months thereafter. SI is performed every 3 months during the first 2 years, every 6 months till year 4, and yearly thereafter. Concerning symptoms or findings resulting from PE or SI may trigger further tests including biopsies as deemed necessary by treating team. In this study, we investigated value of SI in detecting recurrence of OSCC. Methods: Retrospective chart review was performed for the patients who were diagnosed with OSCC from 2014 to 2017 at our institution. Eligible patients included those who underwent definitive treatment (surgery, chemotherapy, radiation) of OSCC with curative intent. Patients without evidence of disease on post treatment imaging were included. Results: Two hundred OSCC patients were treated definitively. 138 (69%) patients had local disease and 62 (31%) patients had regional disease. 183 patients (%) had no clinical evidence of disease on post treatment baseline imaging. Patients who had residual disease on post-to scab were excluded from further analysis. The median follow-up was 29 months. 2-year overall survival was 87.4%. 82 patients underwent biopsy for suspicious findings and 44 patients had confirmed recurrence. 37 (84.1%) of the recurrences occurred in the first two years. 28 (63.6%) of recurrences were local, 13 (29.5%) were regional and 3 (6.8%) were metastases. 31 (70.6%) of patients with disease recurrence presented with clinical symptoms or had suspicious findings on PE. 13 (29.4%) of the recurrences were detected by SI alone (PPV=54.2 %) in asymptomatic patients most of which (92.3%) occurred within first 2 years. Conclusions: Majority of OSCC recurrence were detected due to clinical symptoms or positive findings on PE. However, 29.4% of recurrences were detected by SI alone in asymptomatic patients suggesting a role for SI for the first 2 years post-treatment of OSCC. Larger prospective studies are needed to determine the optimal frequency of SI.
Factors affecting recurrence rates in women with borderline ovarian tumors.
Authors: Lauren Scanlon, Gary L. Goldberg
Journal: Journal of Clinical Oncology (2020)

e18055 Background: Borderline or low malignant potential tumors of the ovary (BOTs) make up approximately 15-20% of all ovarian neoplasms. These tumors are considered indolent and usually confer an excellent overall survival in women who are treated utilizing a conservative surgical approach. However, recurrence rates can approach 30%. The aim of this study was to compare the type and mode of surgery and its impact on outcomes in patients with BOTs. Methods: An Institutional Review Board approved, retrospective cohort study identified all patients at Long Island Jewish Medical Center, North Shore University Hospital and USC Medical Center with BOTs who underwent surgery between January 2008 and May 2018. Demographics and outcome measures were obtained from the medical records. Prognostic factors for disease recurrence were studied including histological subtypes type of surgical procedure, including minimally invasive or open ovarian cystectomy and oophorectomy. Results: 260 patients were identified. 226 of these women (88%) had stage I disease at the time of diagnosis. There were 26 recurrences noted in the cohort, a recurrence rate of 10 percent. The median age was 50 years old (range 16-86). 145 patients (56%) underwent minimally invasive surgical procedures compared to 115 (44%) who had open laparotomy. 30 (12%) of the women underwent an ovarian cystectomy and 230 (88%) had an oophorectomy. The median time to disease recurrence was 25 months (range 4-94 months). There was significant difference in the recurrence free survival between the patients who had minimally invasive procedures and those who had open laparotomy (hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.11-6.52). There was also significant difference in Recurrence Free Survival (RFS) and in those who underwent ovarian cystectomy and oophorectomy (HR 7.32, 95%CI 3.34-16.06). No difference in recurrence rates were noted between those with serous and mucinous histology. Conclusions: In this cohort of women with BOTs, the risk of recurrence was associated with minimally invasive surgery versus open laparotomy as well as ovarian cystectomy compared with oophorectomy. Conservative surgery for BOTs in young patients plays an important role for fertility preservation in these young women and can be curative. This study allows us to present additional information to address surgical approach and risk for disease recurrence in young women having fertility sparing and conservative surgery for BOTs.