tbuckley/cabot-search huggingface dataset:
Overuse of organ biopsies in immunoglobulin light chain (AL) amyloidosis: The consequence of failure of early recognition.
Authors: Eli Muchtar, Angela Dispenzieri, Martha Lacy, Francis Buadi, Prashant Kapoor, Suzanne R. Hayman, Wilson I. Gonsalves, Taxiarchis Kourelis, Rajshekhar Chakraborty, Stephen J. Russell, John A. Lust, Yi Lin, Ronald S. Go, Steven R. Zeldenrust, S.Vincent Rajkumar, David Dingli, Nelson Leung, Robert A. Kyle, Shaji Kumar, Morie A. Gertz
Journal: Journal of Clinical Oncology (2017)

e19532 Background: The diagnosis of amyloidosis requires histological confirmation of Congo-red (CR) deposits. The tissue source is preferably fat and/or bone marrow biopsy, but at times organ biopsy is required. Methods: We studied 612 patients with systemic light chain amyloidosis to characterize the tissues used to establish the diagnosis Results: The median number of tissue samples biopsied for CR staining was 3. Ninety-five percent of bone marrow (BM) biopsies were stained for CR, while 79% of patients had fat aspiration performed for CR staining. Overall, 76% of patients underwent both procedures. CR stain sensitivity was 69% in BM samples, 75% in fat aspiration and in 89% for both sources combined. CR stain sensitivity was 97-100% for heart, renal and liver biopsies. 42% of patients with renal involvement, 21% of patients with liver involvement and 13% of patients with heart involvement underwent organ biopsy, when a less invasive safer biopsy would have established the diagnosis. Predictors of need for organ biopsy were male sex, limited organ involvement and lack of fat aspiration (Table). Conclusions: Fat aspiration is underutilized for histologic confirmation of amyloidosis. Organ biopsies (particularly renal biopsies) were performed at a high rate, which represents a failure to recognize the disease (i.e. failure to screen with a light chain assay etc.). Early awareness of amyloidosis in the differential diagnosis of patients with organ dysfunction may lead to fewer unnecessary organ biopsies [Table: see text]
Autoimmune hyperphosphatemic tumoral calcinosis in a patient with FGF23 autoantibodies
Authors: Mary Scott Roberts, Peter D. Burbelo, Daniela Egli-Spichtig, Farzana Perwad, Christopher J. Romero, Shoji Ichikawa, Emily Farrow, Michael J. Econs, Lori C. Guthrie, Michael T. Collins, Rachel I. Gafni
Journal: Journal of Clinical Investigation (2018)

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 (FGFR1) were identified. He subsequently developed type 1 diabetes mellitus, which raised the possibility of an autoimmune cause for hyperphosphatemic tumoral calcinosis. Luciferase immunoprecipitation systems revealed markedly elevated FGF23 autoantibodies without detectable FGFR1 or Klotho autoantibodies. Using an in vitro FGF23 functional assay, we found that the FGF23 autoantibodies in the patient's plasma blocked downstream signaling via the MAPK/ERK signaling pathway in a dose-dependent manner. Thus, this report describes the first case, to our knowledge, of autoimmune hyperphosphatemic tumoral calcinosis with pathogenic autoantibodies targeting FGF23. Identification of this pathophysiology extends the etiologic spectrum of hyperphosphatemic tumoral calcinosis and suggests that immunomodulatory therapy may be an effective treatment.
PET/CT and regional brain metabolic changes associated with depression in metastatic breast cancer.
Authors: Chandler H. Park, Mohammed Almubarak, Ketu Patel, James Flannery, Marc Haut, Gerry Hobbs, Gary Marano
Journal: Journal of Clinical Oncology (2016)

e21630 Background: Cancer patients with undiagnosed depression have poorer quality of life and can negatively impact overall survival. Studies have shown that non adherence was three times higher in depressed patients compared to non depressed patients. Early evaluation and treatment of depression leads to improved medical management for our cancer patients. Imaging studies using FDG-PET/CT measuring glucose uptake in the brain, have implicated certain regions of the brain with abnormal glucose metabolism in major depressive disorder in the absence of other medical illnesses. Our study is the first to explore the PET/CT and regional brain metabolic changes associated with depression in metastatic breast cancer patients Methods: We retrospectively analyzed the imaging and clinical data of patients with metastatic breast cancer patients who received systemic chemotherapy at our institution from 2009 to 2015. Results: 47 female patients with median age 60 had two brain scans done before chemotherapy and after chemotherapy to assess response to treatment. A matched pair t-test was used to see if activity changes in each of 70 locations within the brain. P-values were used to assess the changes in the z-scores. No correction (Bonferroni or otherwise) was used to adjust the p-values. In the 8 patients with depression, nine locations produced p-values that were either significant at the .05 level or were very close to it. Conclusions: Metastatic breast cancer patients on chemotherapy diagnosed with depression have comparable regional brain metabolic changes to that of published data of depression patients without cancer. However specific areas of the brain including the anterior cingulate gyrus, subcallosal area, and temporal lobe brain metabolic changes deserve further exploration. Our study is limited due to smaller sample size. Larger studies are required to assess the potential use of [F-18] FDG-PET/CT to aid the clinician in the evaluation of patients with depression. [F-18] FDG-PET/CT imaging is often a part of standard treatment protocol for metastatic breast cancer patients before start of systemic chemotherapy.
Prognosis and predictor role of PD-L1 expression in breast cancer patients between early recurrence and late recurrence.
Authors: Tao Qin, Xin-ke Zhang, Jiabin Lu, Cong Xue, Wen Xia, Xin An, Fei Xu, Roujun Peng, Yanxia Shi, Zhongyu Yuan, Shusen Wang
Journal: Journal of Clinical Oncology (2016)

e23241 Background: Recent clinical trials have shown that immune-checkpoint blockade yields remarkable response in different carcinomas. However, the role of PD-L1 expression in breast cancer patients between early recurrence and late recurrence have not been investigated. We compared PD-L1 expression impact on late versus early recurrence in breast cancer with long-term follow-up. Methods: A total of 345 patients with operable breast cancer with over 10 years followed-up were enrolled. All patients were divided into three groups including recurrence in 0~5 year (early recurrence), recurrence after 5-year (late recurrence) and no recurrence. The primary tumor samples were conducted via immunohistochemistry staining tissue microarray. The correlations between PD-L1 expression and clinical characteristics and ER/PR/HER2 status and survival parameters were analyzed. Results: A median follow-up duration was 129 months (17-265 months). Among 345 102 (29.6%) had early recurrence and 37 (10.7%) had late recurrence. The rate of PD-L1 expression in breast cancer was 23.8% (82/345). The primary analysis showed significant differences in risk of recurrence in PD-L1 expression group compared with PD-L1 negative. PD-L1 expression was significantly higher in patients with early recurrence than that of patients with late recurrence. PD-L1 expression was inversely associated with tumor size, tumor grade, lymph node positive number, lymph node ratio, ER and PR status. PD-L1 expression was an independent risk factor for DFS, DMFS and OS. Patients with PD-L1 positive had a relative risk of 1.97 (95%CI 1.17 to 3.318, P = 0.011) for DMFS, 2.187 (95%CI 1.323 to 3.615) for DFS, 2.76 (95%CI 1.659 to 4.591, P < 0.001) for OS and 1.902 (95%CI 1.138 to 3.179, P = 0.014) for tumor specific survival compared with PD-L1 negative breast cancer. Conclusions: PD-L1 expression should be considered as an important unfavorable indicator of late recurrence in breast cancer patients.
Disparities in health-related quality of life in women undergoing treatment for ovarian cancer: The role of individual-level and contextual social determinants.
Authors: Jennifer L Moss, Jeanne Murphy, Virginia L. Filiaci, Lari B. Wenzel, Lori M. Minasian, Sarah Madhu Temkin
Journal: Journal of Clinical Oncology (2018)

e18628 Background: Social determinants may influence health-related quality of life (HRQOL) among women with ovarian cancer, potentially creating disparities in clinical outcomes. We investigated the relationship between HRQOL and social determinants of health, including travel distance to access cancer care and health insurance type, among women participating in a randomized trial of primary adjuvant treatment for advanced ovarian cancer. Methods: The Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaire captured HRQOL (physical wellbeing, functional wellbeing, ovarian-specific, and trial outcome index [TOI]) prior to chemotherapy (baseline), during the trial, and 84 weeks after initiation of chemotherapy. We constructed bivariate and multivariable linear mixed effects models examining the associations of social determinants of health (individual-level and contextual factors) with HRQOL scores at 84 weeks, clustering participants (n= 993) within treatment centers and Census regions and controlling for baseline HRQOL. Results: Individual-level (race, age, cancer stage, adverse events) and contextual (travel distance to treatment center, community socioeconomic status) factors were not statistically-significantly associated with HRQOL. Compared to participants with private health insurance, other participants had lower mean HRQOL (physical wellbeing: public insurance: -1.00 (standard error[SE] = 0.49) points, uninsured: -1.93 (SE= 0.63) points; functional wellbeing: public: -1.29 (SE= 0.59), uninsured: -1.98 (SE= 0.76); ovarian cancer-specific: public: -1.60 (SE= 0.59), uninsured: -1.66 (SE= 0.75); TOI: public: -3.81 (SE= 1.46), uninsured: -5.51 (SE= 1.86); all p< .05). Conclusions: Private health insurance was associated with improved HRQOL at the completion of treatment for advanced stage ovarian cancer. Implications of health insurance on HRQOL should be further investigated.
Efficacy and safety of lurbinectedin (PM1183) in small cell lung cancer (SCLC): Results from a phase 2 study.
Authors: Jose Manuel Trigo Perez, Alexandra Leary, Benjamin Besse, Daniel E. Castellano, Santiago Ponce Aix, Jennifer ARRONDEAU, Victor Moreno, Bernard Doger, Rafael Lopez, Ahmad Awada, Christiane Jungels, Martin David Forster, Valentina Boni, Pilar Lardelli, Mariano Siguero, Carmen Maria Kahatt, Arturo Soto-Matos, Rebecca Sophie Kristeleit
Journal: Journal of Clinical Oncology (2018)

8570 Background: SCLC is a deadly cancer and despite initial 80% response, almost all patients (pts) will relapse and die of this disease. Limited options exist after failure of first line, with a median time to progression (TTP) of around 3.5 months. New therapeutic agents are needed. Lurbinectedin (L) is a new anticancer drug that blocks transcription and induces DNA double-strand breaks, leading to apoptosis. Methods: A multicenter phase 2 basket trial to assess the efficacy and safety of L in several types of advanced solid tumors, including SCLC, is ongoing. In the SCLC cohort, 15 adult patients without brain metastases, who had received one prior chemotherapy line, were recruited. If at least one confirmed response was observed, recruitment would be increased to 100 patients. The study intervention comprised L 3.2 mg/m2 in a 1-hour infusion every 3 weeks. Results: 50 pts were treated and evaluable for efficacy. Median age was 60 years (range, 40-83) and 29 (58%) were males. 45 (80%) had an ECOG of 0/1. 34 pts (68%) had metastatic disease at study entry. 25 (50%) pts had a chemotherapy free interval (CTFI) ≥ 90 days and 22 (44%) had a CTFI < 90 days (unknown in 3). Pts received a median of 5 cycles of therapy (range, 1-18) and a median total dose of 15.9 mg/m2 (range, 2.9-58.2). Nineteen pts (38%) had a partial response (PR); among pts with CTFI ≥ 90 days, 52% (13/25) had a PR. Twenty pts (40%) had disease stabilization, 6 of them for > 4 months. Median response duration was (K-M) 5.3 (CI 95% 2.8-8.8) and median progression free survival (PFS) was 4.2 months (CI 95% 2.8-6.3). Median PFS for pts with CTFI ≥ 90 days was 4.7 months 95% CI (3.1-7.4). Myelosuppression was the most common adverse event: 44% neutropenia grade (G) 3/4, 12% febrile neutropenia, and 8% thrombocytopenia G 3/4; 8 pts had dose delay due to neutropenia G2-4, and 10 pts had dose reduced because of neutropenia G4. G-CSF was given to 9 pts. There was one protocol-defined withdrawal due to neutropenia. Conclusions: Lurbinectedin as a single agent shows compelling activity as second line treatment in SCLC, with an acceptable tolerability and manageable safety profile. No unexpected or grade 5 toxicity occurred. Updated results will be presented. Clinical trial information: NCT02454972.
Comparative genomic profiling of distant metastatic and nondistant metastatic lung adenocarcinoma.
Authors: Henghui Zhang, Gang Chen, Beibei Mao, Wanning Yang, Jianing Yu, Hao Guo, Zhiming Chen
Journal: Journal of Clinical Oncology (2018)

e24182 Background: The majority of deaths from lung cancer are due to distant disseminated disease rather than the primary tumor. Understanding of the biology behind distant metastasis (DM) is helpful for the effective prediction of it and is crucial for reduction of the recurrence rate. Comprehensive genome analysis of the tumor provides a new strategy for uncovering the pathogenesis and molecular diagnosis of distant metastasis in lung adenocarcinoma. Methods: 22 eligible lung adenocarcinoma patients (pts) were enrolled in this study. DNA was extracted from FFPE samples of the primary tumors from 8 pts with distant metastasis (DM) and 14 pts without distant metastasis (non-DM). Comprehensive genomic profiling was performed using a 1.15M size panel covering exon regions of 1,086 genes based on next generation sequencing assay. Tumor gene alterations were analyzed to investigate the difference of molecular features between the lung adenocarcinoma with or without distant metastasis. Results: The most frequently mutated genes were TP53 (73%). Mutations of EGFR were more common in DM pts (7/8 in DM, 6/14 in non-DM). The most frequently amplified gene was RICTOR (55%). Amplification was also detected for other genes such as RAC1 (36%), EGFR (36%), FDPS (32%), CCND1 (18%), HRAS (14%), RNF43 (14%). Interestingly, the amplification of RNA43 and HRAS were only identified in DM pts rather than non-DM pts (p < 0.05). In addition, copy number variation of RICTOR, RAC1 and CDKN2B occurred more often in DM pts (p < 0.05). Conclusions: Comprehensive genomic profiling of lung adenocarcinoma reveals distinctive genomic alterations between DM pts and non-DM pts. Several possible candidate genes that may be helpful for distant metastasis of lung adenocarcinoma were identified in this small cohort. The molecular features of the primary tumor may be used as predictors of distant metastasis in lung adenocarcinoma. Expanded prospective cohorts are warranted to further elucidate these findings.
The density of cancer-associated fibroblasts as a prognostic indicator for hepatocellular carcinoma.
Authors: Tian Tian Wang, Chang-Chang Jia, Ying-Fen Hong, Dan-Yun Ruan, Dong-hao Wu, Xing Li, Xiang-yuan Wu
Journal: Journal of Clinical Oncology (2016)

e15606 Background: Cancer-associated fibroblasts (CAFs) reportedly regulate tumor progression by inducing tumor-stromal interaction; however, the roles of CAFs in hepatocellular carcinoma (HCC) development remain unclear. This study aims to evaluate the impact of the density of cancer-associated fibroblasts on progression free survival (PFS) and overall survival (OS) in patients of hepatocellular carcinoma (HCC). Methods: A total of 124 patients who undergoing radical hepatectomy were recruited for this study. CAFs density was divided into the low- density and high-density groups (CAFslow and CAFshigh) based on the IHC staining of α-SMA. Univariate and multivariate analyses were used to assess variables. Results: The overall 1-, 3- and 5-year cumulative survival rates were 87.1%, 66.9% and 57.0%, respectively. The 1-, 3- and 5-year PFS ratios were 62.9%, 44.4%, and 30.4%, respectively. CAFs were abundant in the tumor tissue samples of 72.6% (90/124) of HCC patients. Kaplan-Meier analysis demonstrated that the low density of CAFs predicted a better OS and PFS (OS, P = 0.001; PFS, P = 0.001). And the low density of CAFs was closely correlated with less rate of HBV infection (P = 0.025) and well histological grade (P = 0.011). Importantly, the multivariate analysis indicated that the CAFs’ density was an independent prognostic factor for PFS (hazard ratio = 2.235; 95% confidence interval, 1.188-4.203, P = 0.013) and OS (hazard ratio = 2.284; 95% confidence interval, 1.008-5.179, P = 0.048) in all enrolled patients. Conclusions: According to our study, the high density of CAFs predicts tumor recurrence and poor survival after radical liver resection in HCC patients. These findings may have implications of the CAFs may serve as a novel candidate prognostic indicator and a potential therapeutic target of HCC.
Distress screening completion experience: Can a robot get the job done?
Authors: Tomas Dvorak, Diane Robinson, Chelsea Wiener, Christopher Spencer, David Metcalf, Julio Hajdenberg
Journal: Journal of Clinical Oncology (2018)

e22153 Background: Distress screening is an important part of cancer patients’ care. Programs accredited by Commission on Cancer must implement distress screening programs, which can result in improved doctor-patient relationships and clinical outcomes. Previously, we have shown that a robot animation on an iPad increased patient engagement with the distress survey. We are now evaluating an anthropomorphic robot (“Betty”) to further improve the patient experience with the screening process. Methods: The same validated distress screening survey was scheduled for 50 patients in 2017 in a prospective IRB-exempt survey study. Patients were randomly assigned to fill out the survey on iPAD (N = 21), or using a 3D-printed robot “Betty” (N = 29). Patients were then asked to fill out a Technology Acceptance Model questionnaire (TAM) evaluating ease of use. The TAM uses a five-point Likert scale; higher scores indicate more usability. Patients were additionally asked: 1) “Were you more interested in filling out the distress screening survey because of the “Betty” robot?”, and 2) “Did the “Betty” robot make filling out the distress screening survey more enjoyable?” Results: Average TAM usability score was 4.4 in the iPAD group and 3.8 in the “Betty” group (p = < 0.01). The total usability score was normally distributed (p = 0.7). Of the patients randomized to the robot arm, the additional two questions evaluating “Betty” were answered by 79% and 69% patients, respectively. Of these, 43% were more interested in completing the distress screening because of “Betty,” and 60% reported the experience as more enjoyable with “Betty”. Patient comments included that “Betty” was “cute,” “more entertaining,” but also “annoying.” Patients also felt that “Betty” was not judgmental about the results their distress screening. Conclusions: The presence of the “Betty” robot as part of the survey made the distress screening process somewhat more complicated compared to an iPAD. However, almost half of the patients taking the distress survey with “Betty” felt they were more interested in filling out the survey and almost two thirds felt that the process was more enjoyable. Verbal feedback was directionally positive on the concept of using a robot to administer distress screening.
Targeting RET in patients with <i>RET</i>-rearranged lung cancers: Results from a global registry.
Authors: Oliver Gautschi, Juergen Wolf, Julie Milia, Thomas Filleron, David Paul Carbone, D. Ross Camidge, Jin-Yuan Shih, Mark M. Awad, Florian Cabillic, Nir Peled, Michel Van Den Heuvel, Dwight Hall Owen, Mark G. Kris, Pasi A. Janne, Benjamin Besse, Byoung Chul Cho, Daniel D. Karp, Rafael Rosell, Julien Mazieres, Alexander E. Drilon
Journal: Journal of Clinical Oncology (2016)

9014 Background: Alongside prospective clinical trials for patients (pts) with non-small cell lung cancers (NSCLC) driven by rare genomic alterations, registries can provide complementary information on response to targeted therapies. We present the results of a global registry of RET-rearranged NSCLC, providing the largest data set on outcomes with RET-directed therapy so far. Methods: Pts were identified by a global, multicenter network of thoracic oncologists. IRB approval was obtained according to local requirements. Eligibility included a diagnosis of NSCLC harboring a RET fusion by FISH, RT-PCR or NGS. Anonymized data (age, gender, smoking, histology, stage, systemic therapy, survival) were collected centrally and evaluated by an independent statistician. In an analysis of pts treated off-protocol with multikinase inhibitors known to target RET, the primary endpoint was best objective response (RECIST). Results: 132 pts with RET-rearranged NSCLC from the USA, Asia, and Europe were registered. Median age at diagnosis was 61 years (range: 28-89), 52% were female, 62% were never-smokers, 97% had adenocarcinoma, and 91% had stage III/IV disease. 41 pts (31%) received RET inhibitor therapy off-protocol: cabozantinib (14), vandetanib (11), sunitinib (10), sorafenib (2), alectinib (1), lenvatinib (1), nintedanib (1), and ponatinib (1). Most pts received a RET inhibitor in the third-line setting (range: 1st-8th line). Median PFS was 2.9 months (95%CI: 1.3-5.6), OS 6.8 months (95%CI: 3.9-14.3), median duration of therapy 2.2 months (range: 0.5-12.2). 8 pts remain on treatment. In 35 pts with serial imaging evaluated by RECIST, ORR was 23% (1 CR, 7 PR, 12 SD, 14 PD, 1 not measurable) and DCR 57%. Individual ORR (DCR) for cabozantinib and vandetanib was 31% (62%) and 18% (46%), respectively. No unexpected adverse effects were reported. Conclusions: RET inhibitors are active in a proportion of pts with RET-rearranged NSCLC. Consistent with results from an ongoing phase II trial of cabozantinib (Drilon, ASCO 2015), this proportion is lower than that observed with targeted therapy for EGFR-mutant and ALK-rearranged NSCLC. New therapeutic approaches and an improved understanding of tumor biology and response are needed.