tbuckley/cabot-search huggingface dataset:
Practice patterns in children, adolescents, and young adults with mycosis fungoides: Single institution study.
Authors: Madeline Hooper, Yumeng Zhang, Eric Taylor, Lucia Seminario-Vidal, Lubomir Sokol
Journal: Journal of Clinical Oncology (2021)

e19553 Background: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, but management remains heterogenous. MF management is based on disease stage, comorbidities, availability, and physician preference. Few studies have assessed treatment in children, adolescents, and young adults because prognosis in these groups is generally favorable; however, optimizing therapeutic protocols for these patients will improve clinical care and reduce adverse effect incidence. Here, we retrospectively describe the practice patterns and disease response for the child, adolescent, and young adult with MF. Methods: We retrospectively reviewed clinical data on 46 patients younger than 40 years with MF treated at Moffitt Cancer Center between 2009 and 2019. Mean time to next therapy (mTTNT) was used as a surrogate marker for the duration of clinical benefit. Group differences in mTTNT for patients with early-stage MF was assessed using Kaplan-Meier analysis. P-values were calculated using the log-rank test. Results: Overall, mean age was 29.2 years (range: 6.6-39.8). Topical steroids (47.8%) and narrowband-UVB (nbUVB) (19.6%) were the most utilized first line treatments regardless of disease stage. Forty patients had early-stage MF (stage IA-IIA). Among them, mean age was 27.8 years (6.6-36.6); 55% received topical steroids and 22.5% received nbUVB first line. These patients received a mean of three (1-7) unique therapies throughout their treatment course. Other reported topicals were retinoids, nitrogen mustard and pimecrolimus. Systemic retinoids were used in one early-stage case. Used first line in early-stage disease, topical therapy resulted in a mTTNT of 25 months ( p= 0.015); mTTNT after combination and systemic therapy was 12 and 5.5 months. As second line treatment, phototherapy resulted in a mTTNT of 58 months, but this finding was not statistically significant ( p= 0.11). Topical and systemic agents used second line resulted in mTTNT of 34 and 33 months. Six patients had advanced-stage MF (stage IIB-IVB) with a mean age of 27.6 years (19.9-35.8), two of which died from the disease. Each patient received a different first line therapy: topical nitrogen mustard, systemic steroids, systemic retinoids, radiation, psoralen and UVA light, or CHOP chemotherapy. Mean number of therapies administered to this cohort was five (2-9). Conclusions: In children, adolescents, and young adults with MF, topical and phototherapies were used more frequently than systemic therapies or radiation. In early-stage disease, the longest clinical response was achieved with topical treatments. Used second line, phototherapy demonstrated promising disease response trends compared to those of other modalities. Systemic therapy does not produce durable disease response in the first line setting; however, its utility in advanced-stage disease and as a second line agent requires further research.
Sixty seconds on . . . dengue
Authors: Jacqui Wise
Journal: BMJ (2021)

This is good news. A three year randomised controlled trial, published in the New England Journal of Medicine , showed that releasing mosquitoes infected with Wolbachia reduced the incidence of dengue fever by 77% and dengue hospital admissions by 86%.1

It’s a bacteria that occurs naturally in 60% of insect species but not in the Aedes aegypti mosquito, the main source of the spread of dengue. Researchers worked out how …
Ixazomib (IXA), carfilzomib (CAR), elotuzumab (ELO) or daratumumab (DAR) with lenalidomide and dexamethasone (LEN+DEX) versus LEN+DEX only in relapsed/refractory multiple myeloma (R/R MM): A comparative cost-effectiveness analysis.
Authors: Mavis Obeng-Kusi, Daniel Arku, Neda Alrawashdh, Briana Choi, Nimer S. Alkhatib, Ali McBride, Ivo Abraham
Journal: Journal of Clinical Oncology (2021)

8043 Background: IXA, CAR, ELO and DARin combination with LEN+DEXhave been found superior in efficacy compared to LEN+DEX in the management of R/R MM. Applying indirect treatment comparisons from a network meta-analysis (NMA), this economic evaluation aimed to estimate the comparative cost-effectiveness and cost-utility of these four triplet regimens in terms of progression-free survival (PFS). Methods: In the absence of direct treatment comparison from a single clinical trial, NMA was used to indirectly estimate the comparative PFS benefit of each regimen. A 2-state Markov model simulating the health outcomes and costs was used to evaluate PFS life years (LY) and quality-adjusted life years (QALY) with the triplet regimens over LEN+DEX and expressed as the incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR). Probability sensitivity analyses were conducted to assess the influence of parameter uncertainty on the model. Results: The NMA revealed that DAR+LEN+DEX was superior to the other triplet therapies, which did not differ statistically amongst them. As detailed in the Table, in our cost-effectiveness analysis, all 4 triplet regimens were associated with increased PFSLY and PFSQALY gained (g) over LEN+DEX at an additional cost. DAR+LEN+DEX emerged the most cost-effective with ICER and ICUR of $667,652/PFSLYg and $813,322/PFSQALYg, respectively. The highest probability of cost-effectiveness occurred at a willingness-to-pay threshold of $1,040,000/QALYg. Conclusions: Our economic analysis shows that all the triplet regimens were more expensive than LEN +DEX only but were also more effective with respect to PFSLY and PFSQALY gained. Relative to the other regimens, the daratumumab regimen was the most cost-effective.[Table: see text]
Algorithm to derive progression-based lines of therapy from a real-world non-small cell lung cancer (NSCLC) dataset.
Authors: Smita Agrawal, Vandana Priya, Rohini George, Sai Vinod Manirevu, Tapasya Bhardwaj, Rambaksh Prajapati, Sangavai Chakkrapani, Mark S. Walker, Vivek Prabhakar Vaidya, Babu Narayanan
Journal: Journal of Clinical Oncology (2021)

e21172 Background: Analysis of Real World Data (RWD) from Electronic Health Records (EHR) for applications such as Health Economics and Outcomes Research (HEOR) or regulatory submissions requires identification of the lines of therapy (LoT) patients have received. LoTs are typically not captured in EHR and must be manually abstracted. As the use of RWD increases, there is a growing need to create algorithms that can work on RWD to extract LoT information in an automated manner with high accuracy. We present here the results of such an algorithm created on NSCLC RWD. Methods: 10950 advanced NSCLC patients from the ConcertAI Oncology RWD database who had received anti-neoplastic treatment after advanced diagnosis were used to build and validate this algorithm. These data were further enriched by expert nurse curators to fill in missing oral drug information and identify progression events. We developed a progression-based LoT (pLoT) model that identified LoT changes in sync with tumor progressions. If patients received multiple regimens before progression they were captured as nested regimens within the LoT. The algorithm uses complex rules to define combination of drugs as regimens (combination rule), identify resumption of regimens (gap rule) or dropping of drugs from regimens as new lines and to handle noisiness in RWD etc. Results: The LoT model accurately captures line changes triggered by progression events as well as any nested regimen changes due to adverse events etc. Patient level validation of LoT was carried out by clinical experts using an in-house tool and found to be consistent with literature &amp; individual drug data. Cohort level analysis of top 3 combinations of therapies used in 1st &amp; 2nd line treatment between 2015-2020 (8200 patients) are shown in Table. Sensitivity analysis on the combination rule showed that this parameter can be changed between 28-33 days without significantly impacting the LoT output (&lt;1% impact). We use a 30 day combination rule as the default. Similarly, the gap rule parameter is quite robust and does not show significant variation between 45 – 90 days (&lt;2% impact). We use 63 days. Conclusions: We have developed a robust algorithm to derive pLoT on RWD at scale assuming availability of curated progression data which can be used to support use cases such as HEOR, clinical development and regulatory submissions. pLoT is better suited for outcomes analysis compared to regimen based LoT since it distinguishes changes in treatment due to progression events from changes due to toxicity, drug availability, etc., and allows analysis on a more homogeneous patient population relating to their past clinical experience. [Table: see text]
A phase 1/2 study with open-label, dose escalation phase followed by single-arm expansion at the maximum tolerated dose to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of NT219 injection alone and in combination with cetuximab in adults with advanced solid tumors and head and neck cancer.
Authors: Alberto Bessudo, Ezra E.W. Cohen, Rodolfo Gutierrez, Daniel H. Johnson, Ari Rosenberg, Ammar Sukari, Salomon M. Stemmer, Benjamin Adam Weinberg, Hadas Reuveni, Michael Schickler, Bertrand C. Liang
Journal: Journal of Clinical Oncology (2021)

TPS3156 Background: NT219 is a small molecule, dual inhibitor of insulin receptor substrates (IRS) 1/2 and signal transducer and activator of transcription 3 (STAT3), effecting IRS1/2 degradation and inhibiting STAT3 phosphorylation. IRS1/2 and STAT3 are major signaling junctions regulated by various oncogenes, altered during epithelial to mesenchymal transition (EMT) and drug resistance, and play an important role in the tumor and its microenvironment. Patient derived xenograft (PDX) models have shown that inhibition of both IRS and STAT3 is essential to overcome targeted epidermal growth factor receptor inhibitor (EGFRi) resistance, and NT219 has demonstrated efficacy as monotherapy and in combination with immune oncology therapies. Particularly, both pathways have been found to be relevant in resistance to cetuximab in head and neck squamous cell carcinoma (HNSCC) PDX models. Methods: This phase 1/2 study (Clinical trial: NCT04474470) began in September 2020. The phase 1 component has a dose escalation arm of NT219 as a single agent at doses ranging between 3mg/kg and 50mg/kg in adult subjects with recurrent and/or metastatic solid tumors enrolled in sequential dose cohorts of 3 to 6 subjects, in a conventional 3+3 design aiming to establish the safety of single agent NT219. Following the conclusion of follow up on the third dose cohort, an additional dose-escalation arm of NT219 in combination with standard dose cetuximab will be opened in patients with recurrent and/or metastatic HNSCC and colorectal cancer, aiming to establish the safety of NT219 when combined with cetuximab. In the expansion phase, 29 patients will be enrolled at the recommended phase 2 dose in combination with standard dose cetuximab in patients with recurrent/metastatic HNSCC. The primary objectives of the trial are safety, tolerability, MTD, and RP2D and preliminary efficacy of NT219 alone and in combination with cetuximab. Measurements of STAT3 and IRS1/2 phosphorylation in biopsy specimens and TILs will be evaluated as potential biomarkers. NT219 provides a first-in-class treatment for patients with resistant neoplastic disease. The current trial will provide important data in patients with recurrent/metastatic cancers, particularly, HNSCC on the effects of the inhibition of STAT3 and IRS1/2 pathways as a novel therapeutic approach. Clinical trial information: NCT04474470.
RAD52 polymorphisms contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population
Authors: Abdul Siraj, Maha Al-Rasheed, Muna Ibrahim, Fouad Al-Dayel, Shahab Uddin, Khawla Al-Kuraya
Journal: Cancer Research (2008)

544  Genetic polymorphisms of DNA repair genes seem to determine the DNA repair capacity, which in turn may affect the risk of thyroid cancer. We hypothesized that polymorphisms of genes responsible for DNA repair may be associated with risk of thyroid cancer. To evaluate the role of genetic polymorphisms of DNA repair genes in thyroid cancer, we conducted a hospital-based case-control study in Saudi population. 223 incident papillary thyroid cancer cases and 229 controls recruited from Saudi Arabian population were analyzed for 21 loci in eight selected DNA repair genes by PCR-RFLP including non-homologous end joining pathway genes LIGIV (LIGlV A62H, P231S, T46T), XRCC4 A298S and XRCC7 I3434T; homologous recombination pathway genes XRCC3 A94H and T241M, RAD51 UTR T15452658C, A15455419G, RAD52 2259 and G221G, conserved DNA damage response gene Tp53 P47S, P72A, Tp53 UTR A7178189C and base excision repair gene XRCC1 A194T, A280H, A399G, A559G. We found that the RAD52 221 genotypes GC and variants carrying C allele, showed statistical significance and very high risk of developing thyroid cancer compared to wild type (GC vs. GG; p
Using 3D perfusion bioreactor system to studying cell biology of ovarian cancer.
Authors: Alba Martínez, Molly Buckley, Joel Berry, Rebecca Christian Arend
Journal: Journal of Clinical Oncology (2021)

e17558 Background: Epithelial Ovarian Cancer (EOC) is the most common cause of death among gynecological malignancies. This is a result of the high rate of recurrence and chemo-resistance in EOC patients. Therefore, the development of new therapeutics is crucial. A major factor contributing to this is the lack of therapeutic candidates is lack of translational accuracy in preclinical models. Recently, 3-dimensional (3-D) models have aided in accurately recreating tumor biology. We have developed an EOC 3-D perfused bioreactor system that recapitulates EOC tumor biology and incorporates tumor biomechanical regulation. This model allows for us to more accurately predict the clinical response of new drug candidates, which aids in elimination of ineffective candidates prior to clinical trials. Methods: EOC cell lines (luciferase-taggedSKOV-3 and OVCAR-8) were embedded in a relevant extracellular matrix (ECM) and injected into a perfused, polydimethylsiloxane (PDMS) bioreactor. Microchannels were embedded in matrigel so that the cell culture media with or without chemotherapy could flow through the perfused PDMS to provide nutrient delivery and gas exchange enhancing viability and function of surrounding cells. The bioreactors were connected to a peristaltic pump that allowed for the cell culture media to perfuse over a 7-day period. We monitored cell viability using bioluminescence imaging (BLI), immunohistochemistry (IHC), and lactate dehydrogenase (LDH) release in media. Results: BLI showed a linear increase in SKOV-3 and OVCAR-8 cell growth over 7 days. These results were confirmed by IHC measuring the number of nucleated cells per micron 2 . Graphical representation of the region of interest (ROI) showed a high correlation between IHC staining of nucleated cells and BLI score. IHC analysis of PAX8 staining was positive and proved that the perfusion bioreactor system maintains EOC biology over time. In addition, our results suggest that the bioreactor is a suitable model for drug preclinical testing in both cell lines as well as in patients’ samples. Conclusions: Our preliminary results using the 3D EOC perfused, PDMS bioreactor model showed increased EOC cell growth overtime, while maintaining original EOC histology. Moreover, our results suggest that this model could provide a novel platform to study therapeutic interventions in EOC. Our ultimate goal is to implement ovarian cancer microenvironment components (e.g. immune cells) into bioreactor system to study different drug treatments to better determine drug candidate’s translational efficacy.
Adjuvant chemotherapy in nonmetastatic goblet cell carcinomas: A population-based analysis.
Authors: Valentina Tateo, Elisa Andrini, Davide Campana, Giuseppe Lamberti
Journal: Journal of Clinical Oncology (2021)

e16203 Background: Goblet cell carcinoma (GCC) is a rare mixed endocrine-neuroendocrine tumor arising almost exclusively in the appendix. The optimal management of these patients is still unclear, given GCC rarity and the difficulty in proper pathology diagnosis. We sought to explore the efficacy of adjuvant chemotherapy (ACT) in GCC extracted from the Surveillance, Epidemiology and End Result (SEER) US registry. Methods: Patients with pathology diagnosis of GCC were identified in the SEER registry by the 8243 ICD-09 code. Data about sex, age, tumor stage at diagnosis, number of analyzed and positive lymph-nodes, chemotherapy and survival were collected. Lymph node ratio (LNR) was calculated as the ratio between the number of metastatic lymph-nodes and removed lymph nodes. The best cutoff to predict survival state at 5-year from diagnosis was calculated. The primary endpoint was overall survival (OS). Results: Overall, 1055 GCC patients (51.7% male, median age 57 years) were identified. The median tumor diameter was 20 mm. According to the American Joint Committee on Cancer staging manual 7 th edition, 128 patients (12.1%) had nodal involvement (N+): 95 were N1 and 33 were N2, while 66 (6.3%) had distant metastasis (M+). Prognostic LNR cutoff was 0.16. Using this cutoff, LNR was ≤0.16 in 674 patients (63.9%), and &gt; 0.16 in 125 patients (11.8%). The median OS was 232 months (95% confidence interval [95%CI]: 153.4-310.5). Overall, 5-year survival rate (OS-5) was 73.4% (N = 453). At univariate analysis age, tumor diameter, M+, N+, number of lymph nodes removed, number of metastatic lymph nodes and LNR were significantly associated with the risk of death. At multivariate analysis, age, M+, N+, number of removed lymph nodes, and number of metastatic lymph nodes retained their association. After excluding M+ and N+ patients, 897 localized GCC patients (52.8% male) were analyzed. Fifty-five patients (6.1%) received ACT and OS-5 was 83.8% (N = 425). CT was administered more often in tumors with higher histological grade, higher T stage and greater tumor diameter. At the multivariate analysis, only age and number of removed lymph nodes were independently associated with the risk of death. Notably, ACT was not associated with increased survival. Ninety-two patients (57.6% male) had nodal involvement without distant metastases: 73 were N1 and 19 were N2. In 56 patients (60.9%) LNR was ≤0.16, while it was &gt; 0.16 in 35 (38.0%). Thirty-five patients (38%) received ACT, without significant imbalances. OS-5 was 45.2% (N = 28). At univariate analysis, age, N2, number of metastatic lymph nodes and LNR were significantly associated with the risk of death. At multivariate analysis, only the number of metastatic lymph nodes retained its association. Of note, ACT was not associated with increased survival. Conclusions: In GCC, ACT was not associated with increased survival in our population-based analysis, irrespective of nodal involvement.
Associations between diet and chronic disease burden in adult survivors of childhood cancer in the St. Jude Lifetime Cohort (SJLIFE) study.
Authors: Elizabeth M. Foley, Geehong Hyun, Fang Fang Zhang, Kevin R. Krull, Nickhill Bhakta, Matthew J. Ehrhardt, Tara M. Brinkman, Jennifer Q. Lanctot, Leslie L. Robison, Melissa M. Hudson, Kirsten K. Ness
Journal: Journal of Clinical Oncology (2021)

e22017 Background: Nutritional intake can impact health. Data describing associations between diet or specific dietary components and chronic health conditions in long-term survivors of childhood cancer are limited. This study evaluated the associations between specific components of diet and chronic disease burden in childhood cancer survivors. Methods: Adult survivors (≥5 years) of childhood cancer participating in SJLIFE (n = 2822), who completed a clinical evaluation and the Block Food Frequency Questionnaire were included. 168 chronic conditions were graded using a modified Common Terminology for Adverse Events. Conditions were summed within grade category, multiplied by weights (1, 2, 3, and 8 for grades 1-4, respectively) and standardized (z-scores) with higher scores indicating more disease burden. Adherence to the 2015 Dietary Guidelines for Americans was scored with the Healthy Eating Index-15 (HEI). Intake of key food groups and nutrients was estimated and divided into quartiles for analysis. Multivariable logistic regression, adjusted for sex, age, and race was used to compare dietary intake and higher disease burden (defined as a z-score &gt; 0). Results: Survivors (median [range] survival time 23 [10-49] years, diagnosis age 7 [0-24] years, 47.6% female, 16.9% non-white, 38.0% leukemia, 19.5% lymphoma, 10.3% CNS tumor, 32.2% other solid tumor) had an average of 10.0 (95% CI 9.7-10.3) conditions by 30 years of age and had a mean score on the HEI of 57.9±12.2 (out of 100 where the population average is 59). Scores on the HEI were not associated with disease burden z-score. Compared to those in the lowest quartile, survivors who consumed in the highest quartile of dark green vegetables (OR 0.77, 95% CI 0.61-0.97), legumes (OR 0.74, 95% CI 0.59-0.92), and whole grains (OR 0.75, 95% CI 0.60-0.95) were less likely to have a disease burden z-score &gt; 0, whereas those who consumed in the highest quartile of white potatoes (OR 1.31, 95% CI 1.05-1.64), refined grains (OR 1.26, 95% CI 1.01-1.58), and added sugars (OR: 1.27, 95% CI 1.01-1.56) were more likely to have a disease burden z-score &gt; 0. Conclusions: Specific components of diet are associated with chronic disease burden in long term survivors of cancer. Dietary interventions may have potential to decrease chronic disease burden in this population.
Does early palliative care reduce end-of-life hospital costs? A propensity-score matched, population-based, cohort study.
Authors: Hsien Seow, Rinku Sutradhar, Lisa Catherine Barbera, Dawn Guthrie, Kim McGrail, Fred Burge, Stuart Peacock, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2021)

12006 Background: Few studies describe how early versus late palliative care affects end-of-life health services costs. The aim of this study was to investigate the impact of early vs not-early palliative care among cancer decedents on the combined costs of receiving aggressive care (ED/hospitalization) and supportive care (home care/physician home visit). Methods: Using linked administrative databases, we created a retrospective cohort of cancer decedents between 2004 -2014 in Ontario, Canada. We identified those who received “early” palliative care (palliative care service used in the hospital or community 12 to 6 months before death [exposure]). We used propensity score matching to identify a control group of “not-early” palliative care, hard matched on age, sex, cancer type and stage. The propensity score included region, year, treatment, etc. We examined differences in median costs (including hospital, ED, physician, and home care costs) between pairs in the last month of life. Results: We identified 144,306 cancer decedents, of which 37% received early palliative care in the exposure period. After propensity score matching, we created 36,238 pairs of decedents who received early and not-early palliative care. After matching the early and not-early groups had equal distributions of age, sex, cancer type (24% lung cancer) and stage (25% stage 3 or 4). Among those who received early palliative care, 56.3% used hospital in-patient care in the last month, whereas 66.7% of the control group (not-early palliative care) used in-patient care; considering only inpatient hospital costs, those receiving early palliative care used a median of $2,894 in the last month of life compared to the control group of $5,311 (p &lt; 0.001). Overall median costs in the last month of life for patients in the early palliative care vs the control group was $11,129 vs. $10,598 (p &lt; 0.001). Conclusions: In our population-based, propensity-score matched, cohort study of cancer decedents, receiving early palliative care reduced the median overall health system costs, especially via avoiding hospitalizations in the last month of life.