tbuckley/cabot-search huggingface dataset:
Understanding quality of life in hepatocellular carcinoma patients.
Authors: Stacie Hudgens, Ronda Copher, Lysbeth Floden, Genevieve Meier
Journal: Journal of Clinical Oncology (2018)

4093 Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer causing morbidity and adversely affects quality of life (QoL) from serious symptom burden. Methods: HRQoL collected in a multicenter, randomized, open-label, Phase 3 study compared first-line systemic treatment lenvatinib (LEN) to sorafenib (SOR) in unresectable HCC, were evaluated descriptively. Key QoL outcomes for patients progressing ≤3 months v > 3 months were modeled longitudinally and summarized using area under (AUC) the time curve analyses. The difference in AUC was calculated with contrasting domain parameter estimates of a mixed model with time, group, time*group, and a random intercept at baseline and Day 1 each cycle through Cycle 18. Results: 954 patients were randomized to LEN (N = 478) or SOR (N = 476). Trial outcomes: median OS LEN (13.6 mos) v SOR (12.3 mos), HR 0.92; 95% CI, 0.79–1.06; median PFS 7.4 v 3.7 mos, respectively (HR 0.66; 95% CI, 0.57–0.77; P < 0.0001). Baseline HRQoL outcomes (e.g. EORTC QLQ-C30, HCC18, and EQ-5D) were markedly worse across most domains for patients who progressed earlier on treatment for both LEN and SOR arms (EQ-5D health utility index = 0.82 and 0.84 (respectively; ≤ 3 months) v 0.88 and 0.86 (respectively; > 3 months). The difference in AUC for EORTC QLQ-C30 role functional status was 0.1644 (95% CI = -0.2281, 0.5569; p-value = 0.4113) and for physical function was 0.0974 (95% CI = -0.3963,0.5911; p-value = 0.6989) favoring LEN. The difference HCC specific symptoms (HCC18) markedly favored LEN on sex life (dif = -0.4244), fatigue (dif = -0.1830), and nutrition (dif = -0.1522) and favored SOR on abdominal swelling (dif = 0.2021). Differences in symptoms related to jaundice, body image, and fever was minimal between treatment arms (dif ≤ 0.05). Conclusions: More patients experienced disease progression earlier on therapy with SOR compared to LEN. In our analysis baseline QoL was more severely impacted HCC patients who progress earlier while on therapy, suggesting that patients treated with LEN have an added benefit in terms of QoL as progression occurred later compared to SOR treated patients. Functional and symptom differences in QOL measures, while not statistically significant, also favored patients treated with LEN. Clinical trial information: NCT01761266.
Adherence to pomalidomide in patients with multiple myeloma: A US-based claims study.
Authors: Justin Gatwood, Ankur Dashputre, Katie S Gatwood
Journal: Journal of Clinical Oncology (2018)

e20008 Background: Pomalidomide is indicated for use in multiple myeloma (MM) for those who have received at least two prior therapies. Data on real world medication use and factors associated with pomalidomide adherence in MM patients are lacking. Methods: This was a retrospective cohort analysis of the MarketScan®Commercial Claims and Medicare Supplement Databases for years 2013-2015. Patients were included if they had ICD-9/10 diagnosis code for MM (203.xx/C90.XX) and ≥ 2 claims for pomalidomide, aged ≥ 18 years, continuous eligibility for 12 months pre-index (first fill) and 6-months post-index, and without evidence of HIV. Adherence was measured using the proportion of days covered (PDC) metric and was calculated for the 6-month post-index period. Multiple linear regression and logistic regression (PDC ≥ 80) were used to assess predictors. Results: A total of 357 patients with pomalidomide fills were identified. Mean age of the sample was 63.4 ± 10.9 years and 58% were males. Mean PDC was 85.4 (±13.9). Using a PDC ≥ 80 threshold for adherence, 74% of the sample was adherent. Receipt of previous cancer therapy was the only factor associated (p < 0.05) with increased adherence in the multiple regression model. Logistic regression indicated that those with > 2 existing comorbidities were less likely to be initially adherent (OR: 0.39; 95% CI: 0.19-0.81) to pomalidomide. Conclusions: A high percentage of MM patients were initially adherent to pomalidomide but further studies including additional covariates need to be conducted to assess predictors of adherence in this population.
P01.086 Health-Related Quality of Life in recurrent Glioblastoma treated with re-irradiation with active scanning Protontherapy
Authors: D Scartoni, D Amelio, I Giacomelli, M Amichetti
Journal: Neuro-Oncology (2018)

Protontherapy (PT) could minimize the risk of side effects compared to conventional photon therapy and therefore reduce the possible detrimental effect on QoL of re-irradiation. We report the effect of re-irradiation with active scanning PT of recurrence GBM in terms of quality of life scored by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)--C30 and EORTC Quality of Life Questionnaire Brain Cancer Module (QLQ-BN20) Between January 2015 and May 2018 twenty-eight patients with recurrence GBM were re-irradiated with active scanning PT. All patients had been previously treated with photon radiotherapy (60 Gy) with concomitant and adjuvant temozolomide (TMZ). Median age and Karnofsky performance status at re-irradiation were 53 years (range, 30–68 years) and 80%, (range, 60–100%), respectively. Target definition was based on CT, MR, and 18F-DOPA PET imaging. All patients received 36 GyRBE (RBE: relative biologic effectiveness) in 18 fractions, with concomitant TMZ in 7 patients (25%). Subscales within the EORTC QLQ-C30 include five functional scales (physical, role, emotional, cognitive, and social), three symptoms scales (nausea, vomiting, and fatigue), six single-item scales (insomnia, appetite loss, constipation, diarrhea, dyspnea, and financial effect of tumor/treatment) and global QoL. The BN20 is specifically developed for brain patients and assessed visual disorders, motor function, communication deficit, various disease symptoms, treatment, toxicity and future uncertainty. The patients completed the EORTC questionnaires before starting PT, the day of the end of PT and every follow-up consult (1-month, 3-months) until progression of disease. Twenty-six patients completed the questionnaires at baseline until progression of disease. The treatment was associated with improvement or stability in most of the preselected HRQOL domains. Global health improved over time with a maximum difference of 6 points between baseline and 3-months follow-up. Social functioning and motor dysfunction improved over time with a maximum difference of 8 and 2 points, respectively. We showed only a small not significance decrease in cognitive and emotional functioning. Interestingly, fatigue remained stable during the analysis such as the other preselected domains. Re-irradiation with PT is a safe treatment without a negative effect on HRQOL until the time of disease progression.
Treatment pattern and unmet need in adults with Philadelphia positive (Ph+) relapsed or refractory (R/R) B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) in EU-5 countries.
Authors: Xinke Zhang, Lirong Zhang, Merel Gijsen, Ze Cong
Journal: Journal of Clinical Oncology (2018)

e18869 Background: Ph+ R/R BCP ALL is a rare disease with poor prognosis. Tyrosine kinase inhibitors (TKIs) are usually recommended for these patients but it is unclear how they are treated. This study was aimed to understand the current treatment pattern and unmet need in adults with Ph+ R/R BCP ALL in EU-5 countries. Methods: A Delphi-based methodology was employed: a survey sent to clinicians and a country-specific panel were used to discuss the survey results to generate point estimates. Physicians must be board certified with at least 5 years’ experience in R/R ALL. The percentage of using each treatment was estimated for patients who were relapsed/refractory to at least one 2nd-generation TKI or were intolerant to 2nd-generation TKIs and intolerant/refractory to imatinib. Limitations of the current treatments for Ph+ R/R ALL were examined. Results: Four physicians from the UK, 4 from Germany, and 3 from each of the remaining 3 countries were enrolled with a median of 10 years’ experience in R/R ALL. Regimens are widely distributed in each country and across the countries (Table). TKI (mainly ponatinib) combined with chemotherapy is the most commonly used regimen. Most physicians agree or strongly agree with these limitations of the current treatments: The risk of developing resistance to TKIs is very high; Survival is short, particularly once the disease becomes resistant to TKIs; Chemotherapy alone does not significantly extend overall survival; Patients may experience different adverse events (AEs) with each TKI. Conclusions: TKI plus chemotherapy is the most commonly used regimen for adults with Ph+ R/R BCP ALL in the EU-5 countries. There remains significant unmet need due to limited survival, resistance to TKIs and AEs associated with the current treatments. Regimen Proportion of Patients (%) France Germany Italy Spain UK TKI only 15 86 17 10 TKI + Clofarabine based chemo 1 15 TKI + FLAG-IDA based chemo 2 10 50 TKI + Hyper-CVAD 20 7 10 TKI + Other chemo (e.g. vincristine + steroids) 67 35 17 25 TKI + Blinatumomab 7 7 Blinatumomab 29 22 Inotuzumab 6 14 5 Chemo only 5 Best supportive care only 18 TKI Ponatinib 60 71 100 90 100 Dasatinib 7 15 10 Nilotinib 33 14.5
Treatment outcomes of cutaneous adverse events to immune checkpoint inhibitors.
Authors: Jennifer Wu, Azael Freites-Martinez, Matthew David Hellmann, Jonathan E. Rosenberg, Robert J. Motzer, Paul B. Chapman, Naiyer A. Rizvi, Larisa J. Geskin, Vanessa A. Reed, Stephen W Dusza, Alina Markova, Margaret K. Callahan, Donald Chan, Adriana Lopez, Chih-Hsun Yang, Wen-Hung Chung, Mario E. Lacouture
Journal: Journal of Clinical Oncology (2018)

e22093 Background: Pruritus and rash are among the most early and frequent immune-related adverse events (irAEs) with immune checkpoint inhibitors (ICIs). Although several management guidelines have been published, the effect of these interventions has not been reported on dermatologic irAEs (dirAEs). Methods: Medical record analysis of patients treated with ICIs (ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab) from January 2014 to December 2017 was performed. Relevant data was abstracted including demographics, cancer diagnosis, grade and treatment modalities of dirAEs. Treatment outcomes were reported as changes in severity grades (CTCAE v4.03): complete response (grade 0), partial response (decrease ≥1 grade but not grade 0), stable disease (grade unchanged), and progression of disease (increase by ≥1 grade). Results: 292 patients (M:F = 123:169, median age 65 years [range 17-89]) with dirAEs attributed to ICIs were included. 433 dirAEs were recorded including 138 pruritus, 120 maculopapular rash (MPR), 21 psoriasiform rash (PsO), 21 bullous pemphigoid (BP), 20 lichenoid rash (LR), 22 eczematous dermatitis, 5 alopecia, 12 vitiligo, and 64 others. For the dirAEs of interest, mean CTCAE grade significantly decreased from pre-treatment to post treatment.(Table 1) Systemic steroids were used in 60% patients with BP, 33.3% LR, 27.7% MPR, 21.9% pruritus, and 15% PsO. Of treated patients, 66.7% of patients with PsO, 44% pruritus, 21.4% MPR, 16.7% BP, and 16.7% LR showed stable disease or progression of disease. Conclusions: Current algorithmic management reduces dirAE severity. However, 29.3% of dirAEs treated with systemic steroids were steroid-refractory. These findings highlight the importance of accurate diagnosis and proper management of dirAEs, and also demonstrate the need for investigating alternative, non-steroid treatment strategies of ICI-induced dirAEs. Table 1. MPR (n = 101) PsO (n = 20) LR (n = 18) Pruritus (n = 114) Eczematous dermatitis (n = 17) BP (n = 20) Grade (mean) Pre- treatment 1.92±0.73 1.65±0.67 1.78±0.73 1.65±0.55 1.59±0.62 1.75±0.79 Post treatment 0.51±0.73** 1.15±0.88* 1.00±0.84* 0.70±0.74** 0.41±0.62** 0.95±0.69* *P < 0.01; **P < 0.001
Accuracy of profiling of circulating tumor DNA for CRC MRD and monitoring using NGS technology equipped with concatemer-based error correction.
Authors: Grace Q. Zhao, Li Weng, Xin-Xing Li, Min Li, Paul Tang, Yontao Lu, Yingyu Wang, Yi Huang, Hongyan Wang, Lingchen Guo, Dana Yeo, Zhaohui Johnny Sun, WeiWei Xiao, Zhi-Qian Hu, Ming Li, Kang Ying, Malek Faham, Shengrong Lin
Journal: Journal of Clinical Oncology (2017)

e23067 Background: Circulating tumor DNA (ctDNA) is a promising biomarker for the detection of minimal residual disease and monitoring treatment in patients with CRC. The performance demands of any technology used for this purpose, however, are tremendous. Here we aim to develop a high-performance multiplex NGS platform suitable for cancer MRD using ctDNA. Methods: We have developed Firefly, a NGS method capable of detecting low-frequency variants with high precision in plasma cfDNA. In our protocol, denatured double-stranded cfDNA is circularized and converted into long tandem repeats using rolling-circle amplification enabling consensus-based concatemer error correction. We demonstrated Firefly’s performance sensitivity and specificity by testing our technology on cfDNA samples with known variant frequencies and cfDNA collected from healthy individuals (n = 82). Further analysis of Firefly as a tool for MRD and treatment monitoring was performed by tracking ctDNA mutation profile concordance between 81 CRC tumor samples and their corresponding plasma samples collected from patients before and after treatment. Results: Performance sensitivity of Firefly NGS was 0.1% with an error-rate was 1 in 1 Million for 20ng of input ctDNA. Concordance analysis was performed on CRC tumor/plasma pairings derived from patients with CRC using, Accu-Act, a 61-gene assay. The number of tumor-matching mutations detected in plasma varied greatly on a per-patient basis (range, 0-28). Pre and post-treatment ctDNA profiling was performed on all 81 patients included in our study (surgery, n = 56; chemotherapy/radiotherapy, n = 30). Among patients who underwent surgery, 46% had detectable tumor-matching mutations in their plasma. Among patients who received neoadjuvant therapy, 70% ctDNA fluctuations consistent with tumor reduction based on surgical tumor regression grades evaluation(TRG1-3). Conclusions: We report a novel ultra-accurate NGS-based ctDNA assay suitable for MRD and monitoring in CRC patients. Firefly should ultimately make a significant contribution in the development of personalized cancer treatment.
Impact and diagnostic gaps of multiplex genomic profiling (MGP) in an academic community-based cancer center.
Authors: Aditi Puri Singh, Elaine Shum, Haiying Cheng, Lakshmi Rajdev, Balazs Halmos
Journal: Journal of Clinical Oncology (2018)

e24154 Background: NGS-based MGP on tumor tissue and plasma is becoming common practice, identifying potentially clinically actionable genetic alterations. Its impact as part of routine management across all cancers in the community remains unknown. Methods: This is a retrospective study of all pts that underwent MGP (Foundation Medicine or Guardant Health) from January 2013 - June 2017 at an academic community-based NCI-designated cancer center with established first tier reflex molecular testing as per national guidelines. Results: 337 samples were sent from 321 pts; 79.2% (n = 267) were tissue and 20.8% (n = 70) plasma. Reported results - 20.8% (n = 70) of pts were listed with an FDA approved targeted therapy for their tumor, 60.2% (n = 203) had an off-label FDA approved targeted therapy available and 77.8% (n = 262) were potentially eligible for clinical trials. Real world impact - With a median follow-up of 1.3 yrs, management changed in 11% (n = 37/ 337) based on MGP and in 8 pts, it was planned but pt declined or died. Of these 45 pts, 28 had lung cancer, 3 had bladder cancer, 2 had colorectal cancer (CRC) and 12 had other cancers. Diagnostic gap - Of the 70 pts with FDA approved therapies identified by testing platforms, 44 did not result in change in management (12 with previously known mutations in NSCLC/CRC/gastric/breast cancer as part of first tier reflex testing, 26 where targeted therapy was not standard of care, 4 with early disease where targeted therapy was not indicated, 1 with therapy reserved for future disease progression and 1 pt who died). Although 51 pts (15.1%) participated in clinical trials, only 3 were placed on clinical trials based on MGP. Conclusions: Our study demonstrated that MGP resulted in change in management in 11% pts. Most pts who benefited had expanded molecular testing in lung cancer and such testing should become routine for this tumor type. MGP beyond guideline-recommended markers (e.g. extended KRAS in CRC, HER2 in breast and gastric cancer) in a community setting currently has a relatively low yield that is anticipated to increase with careful patient selection, more biomarker-driven targeted and immunotherapy options and early MGP perhaps eliminating the need for selective biomarker testing.
miR-125a and miR-34a expression predicts Richter syndrome in chronic lymphocytic leukemia patients
Authors: Veronica Balatti, Luisa Tomasello, Laura Z. Rassenti, Dario Veneziano, Giovanni Nigita, Huan-You Wang, John A. Thorson, Thomas J. Kipps, Yuri Pekarsky, Carlo M. Croce
Journal: Blood (2018)
The role of the induction chemotherapy followed by RCT in advanced rectal cancer assessed by MRI.
Authors: Andrea Craciunescu, Alina Muntean
Journal: Journal of Clinical Oncology (2016)

e15133 Background: Induction chemotherapy (IC) followed by concurrent radiochemotherapy (RCT) and total mesorectal excision (TME) is a treatment option for loco-regionally advanced rectal carcinomas (T3/T4 N0 and any T with positive adenopathies). Postoperatively, depending on the findings of the histopathological examination performed on the excision sample, patients shall undertake or not adjuvant CT. Induction chemotherapy (IC) has major benefits: rapid symptomatic response, early treatment of micrometastases, high compliance of patients with the treatment, decreased acute and chronic toxicity as compared to adjuvant CT. Concurrent RCT has shown a decrease in local recurrence rate, possibility of performing sphincter-preserving surgery or even full sterilization of surgical sample. Methods: The patients enrolled in the study have undertaken 4-6 cycles of induction CT with CapeOx and concurrent preoperative RCT. All patients have been preoperatively restaged based on MRI, for the purpose of assessing the efficacy of the induction treatment, translated through the decrease of the PT dimension, the numerical and size decrease of N and the decrease of the distance between the lower pole of the PT against the anus and the correlation of MRI response to neoadjuvant therapy with the histopathological examination of the resection sample. Results: During January-September 2015, 27 patients who had received clinical and imaging diagnosis of rectum adk, stage cTNM II and III, have been included in a prospective phase 2 trial. All patients have concluded the neoadjuvant therapy. This trial has shown the efficacy of induction CT based on an objective response rate of 72.84%. The MRI reassessment following RCT has shown an objective response rate of 90.91% and negative MRF in 61.81% of the patients. R0 resection margin has been 100% until now. Out of the 27 patients, TME has been performed up to present day in 13 of the patients, obtaining a pCR in 4 of them and a partial response in 5 of them. Conclusions: The efficacyof induction chemotherapy with CapeOx followed by concurrent RCT has been proved by the substantial reduction of the primary tumour size, the numerical and size decrease of adenopathies.
Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium
Authors: Haider H. Dar, Yulia Y. Tyurina, Karolina Mikulska-Ruminska, Indira Shrivastava, Hsiu-Chi Ting, Vladimir A. Tyurin, James Krieger, Claudette M. St. Croix, Simon Watkins, Erkan Bayir, Gaowei Mao, Catherine R. Armbruster, Alexandr Kapralov, Hong Wang, Matthew R. Parsek, Tamil S. Anthonymuthu, Abiola F. Ogunsola, Becca A. Flitter, Cody J. Freedman, Jordan R. Gaston, Theodore R. Holman, Joseph M. Pilewski, Joel S. Greenberger, Rama K. Mallampalli, Yohei Doi, Janet S. Lee, Ivet Bahar, Jennifer M. Bomberger, Hülya Bayır, Valerian E. Kagan
Journal: Journal of Clinical Investigation (2018)

Ferroptosis is a death program executed via selective oxidation of arachidonic acid–phosphatidylethanolamines (AA-PE) by 15-lipoxygenases. In mammalian cells and tissues, ferroptosis has been pathogenically associated with brain, kidney, and liver injury/diseases. We discovered that a prokaryotic bacterium, Pseudomonas aeruginosa, that does not contain AA-PE can express lipoxygenase (pLoxA), oxidize host AA-PE to 15-hydroperoxy-AA-PE (15-HOO-AA-PE), and trigger ferroptosis in human bronchial epithelial cells. Induction of ferroptosis by clinical P. aeruginosa isolates from patients with persistent lower respiratory tract infections was dependent on the level and enzymatic activity of pLoxA. Redox phospholipidomics revealed elevated levels of oxidized AA-PE in airway tissues from patients with cystic fibrosis (CF) but not with emphysema or CF without P. aeruginosa. We believe that the evolutionarily conserved mechanism of pLoxA-driven ferroptosis may represent a potential therapeutic target against P. aeruginosa–associated diseases such as CF and persistent lower respiratory tract infections.
Enumeration of circulating tumor cells using a non–EpCAM-dependent device.
Authors: Robert J. Amato, Reynolds Brobey, Yue Wang, Kent Murphy, Jeff Smith
Journal: Journal of Clinical Oncology (2017)

e23064 Background: One component of the metastatic process is the circulation of tumor cells. Identification of these circulating tumor cells (CTCs) provides important insights into cancer biology. There is enormous heterogeneity among CTCs, necessitating capture of both epithelial and non-epithelial subtypes. Detection and monitoring of CTCs will provide a non-invasive biomarker for the detection of early progression and assessing therapeutic response. Methods: The AxonDx nCyte™ System is designed to detect rare circulating cells from peripheral blood without enrichment or selection. An epi-fluorescence microscope scans pathology glass slides on which a sample has been applied, and high-resolution images of potential CTCs are captured at four emission wavelengths. The proprietary Cancer Cell Detection Cocktail is designed to detect CTCs from numerous solid tumors, including various stages (e.g., mesenchymal-epithelial transformation) and stem cells. The software distinguishes cancer-derived material (nucleus+/cytokeratin+/WBC marker-/ &gt; 4 µm); from leukocytes (nucleus+/cytokeratin-/WBC marker+). Vimentin is used to distinguish epithelial from mesenchymal CTCs. We obtained informed consent from 32 genitourinary cancer patients to participate in this IRB-approved study. Red blood cells from 6 mL of whole blood were lysed and removed from 32 patient samples. Nucleated cells from the blood sample were fixed, permeabilized, and stained with AxonDx’s Cancer Cell Detection Cocktail. The prepared cells were dispensed onto two microscope slides, cover-slipped, and analyzed. Results: We detected CTCs in 32 of 32 samples (100%), in a range of 0.6–64.3 CTCs/mL. Number of CTCs correlated with metastatic tumor burden. Conclusions: The AxonDx nCYTE™ system can reliably detect CTCs from genitourinary patient samples. The AxonDx nCyte™ System has also successfully detected CTCs in other tumor types, e.g., breast, lung, CRC, and HCC. Because the system is not EpCAM-dependent, it captures the heterogeneous population of CTCs. Prospective longitudinal studies are ongoing to determine trends in CTC counts.