tbuckley/cabot-search huggingface dataset:
Modeling the cost of immune checkpoint inhibitor-related toxicities.
Authors: Neil Thomas Mason, Nikhil I. Khushalani, Jeffrey S. Weber, Scott Joseph Antonia, Howard L. McLeod
Journal: Journal of Clinical Oncology (2016)

6627 Background: Recently approved immune checkpoint inhibitors targeting CTLA-4 (ipilimumab) and PD-1 (nivolumab and pembrolizumab) have gained a tremendous amount of attention for their efficacy, but also for their high cost and incidence of side effects. Most discussions of cost have focused on the price of the drugs themselves; however, this model estimates the total cost of treatment including the cost of managing toxicities. Methods: Drug costs were calculated utilizing Redbook average wholesale cost per dose and the average number of doses received by patients at H. Lee Moffitt Cancer Center (N=627). Major toxicities associated with each drug were identified from package inserts and peer-reviewed literature. Toxicity costs were obtained from peer-reviewed literature. Incidences of toxicities were obtained from patient data available in the Total Cancer Care database. The weighted average cost of managing toxicities associated with each drug was calculated and compared to the total anticipated cost of therapy. All cost estimates are in 2015 USD. Results: All three drugs have a similar estimated cost of managing toxicities with nivolumab estimated to be most costly (Table). Ipilimumab is estimated to cost the most per patient driven by the cost of drug. However, toxicities make up a much larger proportion of the cost of care for the PD-1 inhibitors. Conclusions: The cost of managing toxicities associated with immune checkpoint inhibitor therapy is not insignificant and could change the value-to-cost ratio between equally effective drugs, e.g. nivolumab and pembrolizumab. Treatment # of Patients Average # of Doses Estimated Cost of Therapy Estimated Average Cost of Toxicities Total Cost of Treatment % of Total Cost Re lated to Toxicity Ipilimumab 382 3.3 $101,290 $8,216 $109,506 6.3% Nivolumab 101 6.3 $38,078 $9,616 $47,686 17.6% Pembrolizumab 144 8.0 $58,008 $8,547 $66,555 16.0%
Prognostic value of the interval between the last neoadjuvant chemotherapy (CT) administration and breast surgery: Preliminary data of the NeoBracer international observational study.
Authors: Marika Cinausero, Giulia Galli, Debora Basile, Federica Martorana, Irene De Santo, Herman Andres Perroud, Nicoleta Zenovia Antone, Saul Campos Gomez, Lorenzo Gerratana, Alessandro Marco Minisini, Milena Sant, Secondo Folli, Karen Angelica Campos Gomez, Alexandru E. Eniu, Andrei Cismaru, Grazia Arpino, Paolo Giovanni Vigneri, Gianpiero Fasola, Serena Di Cosimo, Fabio Puglisi
Journal: Journal of Clinical Oncology (2018)

e12629 Background: Little is known about the timing-related effects of the interval between the last neoadjuvant CT administration and surgery (CTTS) in patients (pts) with early breast cancer (BC). Methods: The NeoBracer study analyzed a cohort of 683 consecutive BC pts treated with neoadjuvant CT in 7 Centers (4 in Italy, 1 in Argentina, 1 in Mexico and 1 in Romania), between 2004 and 2015. Cox regression was performed to evaluate the prognostic impact of CTTS in terms of relapse free survival (RFS) and overall survival (OS). The best cut-off was explored through median and ROC analysis. Results: Overall, 51.63% pts had a luminal-like, 30.70% HER2-positive and 17.67% triple negative (TN) BC. Median follow up was 59.64 months (mts), median OS and RFS were not reached. Median CTTS was 1.08 mts (25th-75th percentiles: 0.85-1.28 mts). On multivariate analysis, , T3-4, N2-N3 and grade 3 were associated with worse RFS (HR 1.43, 95%CI 1.05-1.94, P = 0.022; HR 1.71, 95%CI 1.25-2.35, P < 0.001; HR 1.72, 95%CI 1.01-2.95, P = 0.046; HR 3.70, 95%CI 2.09-6.52, P < 0.001, respectively). However, only T3-4 and N3 were associated with worse OS (HR 2.13, 95%CI 1.30-3.48, P = 0.002; HR 3.46, 95%CI 1.55-7.73, P = 0.002). No significant impact was observed in terms of OS (HR 1.37, 95%CI 0.93-2.03, P = 0.108) between CTTS > 1 vs < 1 mo. Notably, a marginally significant impact was observed in terms of RFS (HR 1.31, 95%CI 0.97-1.79, P = 0.076). ROC analysis highlighted overlapping but weak cut-offs for CTTS in respect to RFS (33 days, AUC 0.52) and 5-year OS (31 days, AUC 0.48). Subgroup analysis for CTTS showed no significant differences when stratification for the main clinico-pathological features was applied. Conversely, subgroup analysis for pCR highlighted an interaction for TNBC (HR 0.18, 95%CI 0.06-0.51, P for interaction = 0.026). Conclusions: The present study explored the impact of CTTS on RFS and OS. An interval higher than 1 months could be linked to a marginal detrimental effect on RFS, which is not transferd in terms of OS. Accrual is still open.
Abstract 18314: Adult Congenital Heart Failure Admissions in the United States: Trends, Resource Utilization & Mortality
Authors: Luke J Burchill, Lina Gao, Jessica Minnier, Adrienne H Kovacs, Abigail M Khan, Alexander Opotowsky, Craig S Broberg, Bryan G Maxwell
Journal: Circulation (2016)

Objectives: The primary objective of this study was to characterize temporal trends, health resource utilization, and outcomes in heart failure (HF) hospitalizations among adults with congenital he...
A phase II trial of total neoadjuvant treatment (TNT) (Capox plus radiotherapy) for local advanced rectal cancer patients with high risk factors.
Authors: Xin Wang, Yongyang Yu, Xiangbing Deng, Wenjian Meng, Hong Zhu, Dan Jiang, Hua Zhuang, Bing Wu, Zhiping Li, Meng Qiu, Hongfeng Gou, Feng Bi, Feng Xu, Ziqiang Wang, Zonggung Zhou
Journal: Journal of Clinical Oncology (2017)

e15025 Background: Standard neoadjuvant concurrent chemoradiotherapy didn't achieve improved overall survival in stage II-III rectal cancer. Total neoadjuvant treatment (TNT) might be a proper treatment option for patients with high risk factors. Therefore, this phase II trial was conducted to evaluate the safety and efficacy of TNT (Capox and IMRT/VMAT) in rectal cancer patients with high risk factors. Methods:Patients who were diagnosed stage II-III rectal cancer with at least one of the following high risk factors were recruited: cT4b, cN2, EMVI +, MRF+, lateral LN +. Three cycles of induction Capox were followed by pelvic IMRT/VMAT and two cycles of concurrent Capox. Three cycles of consolidation Capox were delivered after radiotherapy. Primary endpoints were pathological complete response (pCR) and R0 resection rate. Secondary endpoints were DFS, OS, toxicities and QOL. Here we present the initial results of this study. Results: From Jun 2015 to Jan 2017, 42 patients were evaluable. One patient (2.4%) who had acute intestinal obstruction after the first cycle of chemotheraoy underwent emergency TME. A total of 27 patients (64.3%) completed 8 cycles of chemotherapy. Forty-one patients (97.6%) completed the planned radiotherapy. 15 of 42 patients (35.7%) achieved a pCR or cCR, in which 12 patients (80%) completed 8 cycles of chemotherapy. Five patients refused the operation and selected Watch &amp; Wait. R0 resection rate of patients who underwent TME were 100%. The mean time of operation was 207 minutes (120-370 minutes). And the mean estimated blood loss was 89ml (10-500ml). The most common grade 3 or higher adverse events associated with the neoadjuvant administration were leucopenia (9.5%), diarrhea (4.8%), radiation dermatitis (4.8%) and thrombocytopenia (2.4%). The most common grade 3 or worse surgery-related complications were pelvic abscesses, anastomotic leaks and hemorrhage which were observed in one patient, respectively. Conclusions: Total neoadjuvant treatment (TNT) is effective and safe for local advanced rectal cancer patients with high risk factors. Long-term efficacies of TNT need to be evaluated.
Sensitivity of clinical <i>BRCA1 </i>testing compared with linkage analysis.
Authors: Payal D. Shah, Judy Ellen Garber, Jill Stopfer, Jacquelyn Powers, Katherine L. Nathanson, Susan M. Domchek
Journal: Journal of Clinical Oncology (2012)

1506 Background: Specific clinical interventions in BRCA mutation carriers reduces the risk of breast and ovarian cancers and may improve survival; thus,identification of mutation carriers is important. The sensitivity of current BRCA mutation testing is unclear as a “gold standard” test is lacking. We assessed the BRCA1 mutation detection rate with current comprehensive clinical testing using linkage analysis as the comparator. Methods: 26 families with linkage analyses results available were included in this analysis. BRCAPRO, BOADICEA, and other risk estimation models were applied. Maximum-likelihood linkage analyses were performed to compute two-point and multipoint LOD scores using previously described BRCA1 –linked genetic markers; scores were classified as linked, not linked, or suggestive. At least one individual from each family underwent comprehensive testing. Results: Of 26 families analyzed, 9 demonstrated linkage and 4 demonstrated suggestive linkage to BRCA1. Of these 13 families, 12 were found to have BRCA1 mutations: a detection rate of 92.3%. In 3 of these 12 families, genetic mutation testing performed prior to large genomic rearrangement (LGR) testing was negative, demonstrating an improved detection rate with LGR testing which in this series was 23%. The 12 families with higher LOD scores and positive mutation testing had high mean prior probabilities by all models. Families which were not linked and who tested negative for mutations had lower mean prior probabilities. In one family, disease demonstrated linkage with a two-point LOD score of 1.59 and multipoint LOD of 0.85 and all risk estimation models yielded high prior probabilities. Despite this, mutation testing was negative by full sequencing and MLPA analysis. Conclusions: When evaluated in a sample of families from high-risk clinics, current comprehensive testing compares well to linkage data. The inclusion of LGR testing has improved the mutation detection capability of clinical testing; however, some mutations may still be missed. Negative mutation testing results should be interpreted in the context of family history and prior probability during counseling. Despite recent advances, further improvements in genetic testing are warranted.
Rare bone sarcoma: A retrospective analysis of 149 adult patients from the French Sarcoma Group.
Authors: Pascaline Boudou-Rouquette, Elodie Martin, Emmanuelle Kempf, Nicolas Penel, Antoine Italiano, Florence Duffaud, Emmanuelle Bompas, Nelly Firmin, Francois Bertucci, jean Emmanuel Kurtz, Loic Chaigneau, Nicolas Isambert, Antoine Thyss, Jacques-Olivier Bay, Christine Chevreau, Jean-Yves Blay, Sophie Piperno-Neumann
Journal: Journal of Clinical Oncology (2018)

11523 Background: the benefit of neo-adjuvant/adjuvant chemotherapy (CT) in rare bone sarcoma is poorly documented. Methods: retrospective study from the French sarcoma network for bone tumors ResOs: 1) adult patients (pts) from 1976 to 2014, 2) Rare bone sarcoma: leiomyosarcoma, undifferentiated pleomorphic and radiation-associated bone sarcoma 3) with central pathological review. Clinical features, treatment modalities and outcome were recorded and analyzed. Results: we identified 149 pts from 14 centers. Of them, 109 (73%) presented with localized disease, the local treatment was associated or not with CT. In localized pts, median age was 53 (range 18-82) years (y), median tumor size was 7cm (range 3-18). Sites of disease were extremities (72%) or axial skeleton (28%). The most common histological subtypes were high-grade leiomyosarcoma (33%) and undifferentiated pleomorphic sarcoma (35%). Surgery was performed in 107 pts, conservative in 76.3%. R0 resection was achieved in 58 (82%) pts. Twenty-eight pts (26%) underwent upfront surgery or exclusive radiotherapy (RT)( > 50 Gy) without CT. Eighty-one pts (74%) received either neo-adjuvant CT (n = 13) or adjuvant CT (n = 23) or both (n = 45). The median duration of neo-adjuvant CT was 2.1 months (mo)(range: 0.1-5.7) and 2.4 mo for adjuvant CT (range: 0.7-6.4). Neo-adjuvant/adjuvant CT was mostly doxorubicin- (95%/85%) and cisplatin- (68%/63%) based, or methotrexate-based in 22%/21% of pts. Adjuvant RT was performed in 23 (22%) pts. An overall disease control rate (CR+PR+SD) of 86% was achieved after neo-adjuvant CT. Median follow-up was 5.6 y (95% CI 4.0-7.8). For patients with localized disease, the 3y and 5y-overall survival (OS) were 74.3% (95% CI: 64.1-82.0) and 62.4% (95% CI: 50.7-72.1). The 3y- and 5y-disease-free survival (DFS) were 52.5% (95% CI: 42.1-61.9) and 38.2% (27.7 and 48.5). In univariate analysis, age≤50y (p = 0.04) and neoadjuvant and adjuvant CT (p = 0.03) were associated with longer DFS, but no association was found with OS. Conclusions: in this retrospective study, patients with localized rare bone sarcoma treated according osteosarcoma standard of care, with pre- and post-operative chemotherapy, achieved better DFS.
Development of a benchmark tool for Comprehensive Cancer Centers: Results from a pilot exercise.
Authors: Anke Wind, Wineke van Lent, Peter Nagy, Wim H van Harten
Journal: Journal of Clinical Oncology (2016)

e18159 Background: The BENCH-CAN project is an international benchmarking project which aims to develop a tool for the benchmarking of comprehensive cancer care and yield good practice examples across the EU in a way that contributes to improve the quality of interdisciplinary patient treatment. The Joint Commission defines benchmarking as “a systematic, data-driven process of continuous improvement that involves internally and/or externally comparing performance to identify, achieve, and sustain good practice”. This paper describes the development and results of a pilot of an institutional tool at 5 cancer centers. Methods: The 13 step benchmarking process by Van Lent et.al. was used. A framework based on the European Foundation of Quality Management model and the Institute of Medicine domains of quality was developed to structure the indicators. Indicators were primarily derived from literature and secondary from expert opinion. Centers provided data and a site visit was performed to grasp the context and to clarify additional questions. Based on the results of the pilot good practices were defined. Results: The final indicator list contains 81 qualitative and 141 quantitative indicators. Centers reported the data in the same way which enables comparison.Differences between pilot sites are found in for example length of stay (5 to 9 days), and staff turnover rates (for nurses it varied from 0,46% to 25,5%). Another difference can be found in the domain of Resources such as IT (for example the storage of patient records which was done digitally in some centers, but on paper in others), and patient involvement both in their own care process, as in the strategy development of an institute. Conclusions: A benchmarking tool for Comprehensive Cancer Care has been developed that will become available in an open format. Variation of the results provided improvement opportunities for all centers. Reliability and validity of the tool are ensured by the pilot of the indicators at 5 cancer centers. The pilot showed that the sites all reported data in the same way and all provided the type of data that was required. Apart from this institutional benchmark, a pathway benchmark was developed as well as a consumer experience questionnaire.
LIHNCS: Lugol’s Iodine in Head and Neck Cancer Surgery—A multi-centre, randomised, controlled trial assessing the effectiveness of Lugol’s Iodine to assist excision of moderate dysplasia, severe dysplasia and carcinoma in-situ at mucosal resection margin of oral and oropharyngeal squamous cell carcinoma.
Authors: James Anthony McCaul, Jeremy McMahon McMahon, Jacqueline Quantrill, Kayleigh Gilbert, Hisham Mohamed Mehanna, Richard Shaw, Christopher C McConkey, David Gouldesbrough, Max Robinson, Janet Dunn
Journal: Journal of Clinical Oncology (2017)

6065 Background: Oral cavity and oropharynx cancer are increasing worldwide but survival has not significantly improved over the last thirty years. Presence of dysplasia or carcinoma in-situ at surgical margins following resection of squamous carcinoma (SCC) of the head and neck is associated with increased local recurrence and reduced survival. While carcinoma can usually be distinguished from normal mucosa, dysplasia is less readily distinguished at operation. We describe outcomes of LIHNCS, a RCT assessing effectiveness of Lugol’s iodine staining for visualization and excision of margin dysplasia at primary surgery. Methods: Patients planned for curative surgical resection of oral cavity/ oropharynx SCC were recruited. Participants were randomised 1:1 into either a standard surgical treatment arm or surgical treatment including Lugol’s iodine staining according to defined SOP. Randomisation was stratified by centre and surgeon using computer-generated random permuted blocks. Data monitors, pathologists and external reviewers were blinded to treatment allocations. Chief investigator, surgeons and other health care professionals were blinded to results. Primary endpoint is presence of carcinoma or dysplasia at mucosal margins. Results: Sixty-five surgeons in 24 centres recruited and LIHNCS was powered for 300 cases. Following successful recruitment, extension was granted for progression to 409, including 300 T1 and T2 cases. Patient acceptance was 89%. Median follow up is 36.5 months and 118 patients have died to date. Significantly fewer patients in the Lugols arm required further mucosal resection after primary surgery (p = 0.005). In as treated analysis dysplasia is reduced at resection margins for T1 and T2 tumours (p = 0.04). Conclusions: Lugol's iodine visualisation of dysplasia at curative surgical resection of oral and oropharynx SCC is associated with reduced requitement for further mucosal resection and appears to result in reduced dysplasia at mucosal resection margins. Clinical trial information: ISRCTN03712770.
Improvements in SOD mimic AEOL-10150, a potent broad-spectrum antioxidant
Authors: Xiao-rui Zhang, Wen-xia Zhou, Yong-xiang Zhang
Journal: Military Medical Research (2018)

AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase (SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard (SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome (ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM, chlorine gas and radiation exposure studies.
Preclinical evidence for management of thrombocytopenia associated with bromodomain extra-terminal (BET) inhibition therapy.
Authors: Srinivasa R Mantena, Minh Dinh, Scott Mittelstadt, Warren R Kati, Marcin Klapczynski, Keith McDaniel, Stormy Koeniger, Johannes E. Wolff
Journal: Journal of Clinical Oncology (2018)

e24207 Background: Thrombocytopenia is a potential dose-limiting toxicity associated with many oncology agents including BET inhibitors (BETi). Thrombocytopenia in rats closely mirrors clinical dose-limiting thrombocytopenia, enabling the use of this model to explore potential supportive care options. Methods: A pan-BETi molecule A-1550592 (1mg/kg) was administered by oral gavage for 4 days to Sprague Dawley rats and hematologic parameters measured on Day 5. Recombinant human erythropoietin (rhEPO 150 IU) was administered subcutaneously 4 days before and concomitantly with BETi. Folic Acid (FA, 3mg/kg and 30 mg/kg) was administered subcutaneously 4 days before and concomitantly with BETi. Romiplostim (30 micrograms) was administered prior to (2 doses) and concomitantly (1 dose) with BETi on days 2, 4 and 6. Results: rhEPO administration resulted in reticulocyte increases as compared to BETi alone (BETi, n = 3: 54x109; BETi + rhEPO, n = 3: 272x109; Control, n = 3: 346X109cells/mL). Interestingly, rhEPO administration was also associated with platelet increases in the rhEPO+ BETi group compared to BETi alone (BETi, n = 3: 465x109; BETi + EPO, n = 3: 808x109; Control, n = 3: 1175x109cells/mL). rhEPO was also noted to reverse the moderate decreased bone marrow cellularity seen with BETi administration. FA partially mitigated thrombocytopenia in the FA+ BETi group when compared with BETi alone (BETi, n = 3: 529x109; BETi + 3 mg FA, n = 3: 585x109; BETi + 30 mg FA, n = 3: 973x109; Control, n = 3: 1138x109). Romiplostim partially mitigated thrombocytopenia in the Romiplostim + BETi group when compared with BETi alone (BETi, n = 5: 808x109; Romiplostim, n = 5: 2678x109; BETi + Romiplostim, n = 5: 1150x109cells/mL). Conclusions: The observed hematologic responses in the rodent model to BET inhibition and various supportive care agents (rhEPO, FA, Romiplostim) suggests that these agents may be effective in mitigating clinical thrombocytopenia associated with BETi.
AB1018 Intravenous neridronate in the treatment of bone marrow oedema syndrome: efficacy and safety of two different treatment schedules
Authors: A. Lurati, A. Laria, P. Faggioli, M. Marrazza, D. Mazzocchi, A. Gilardi, A. Tamburello, L. Castelnovo, K.A. Re, A. Mazzone
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Bone Marrow Oedema Syndrome (BMES) is a severely disabling pain syndrome without a definite treatment well established. <h3>Objectives</h3> The aim of this monocentric prospective trial was to test the efficacy and the safety of the amino-bisphosphonate neridronate in patients with BMES administered in two different schedules. <h3>Methods</h3> one hundred seventy-three patients with BMES at various joints were consecutively assigned to I.V. infusion of 100 mg neridronate given four times over 10 days (Group A) or alternatively to I.V. infusion of 100 mg every 21 days over 63 days (Group B). At baseline (T0) and after 90 days from the first infusion we performed a MRI (T2). We assessed a 0–100 mm pain VAS in each patient at T0, at the day of the last infusion (T1: day 10 for group A and day 63 for group B) and at T2. Primary outcome was to evaluate the MRI changes, secondary endpoint was the VAS change. <h3>Results</h3> we observed a significant improvement in MRI with the resolution of bone marrow oedema present at T0 (p&lt;0.01), without a significant difference between Group A and Group B. Visual analogue scale (VAS) score decreased significantly during the study in both groups (p&lt;0.05) without a significant difference between the two treatment groups (p&gt;0.1). <h3>Conclusions</h3> In patients with BMES, the infusions of neridronate 100 mg every 21 days over 3 months or alternately every 3 days over 10 days are associated with clinically relevant and persistent benefits without significant differences between the two treatment-schedules. These results provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice BMES <h3>Disclosure of Interest</h3> None declared