tbuckley/cabot-search huggingface dataset:
Hearing evaluation of head and neck cancer patients (HNCP): Comparison of adverse event (AE) criteria.
Authors: A. Dimitrios Colevas, Ruth R Lira, Electra A Colevas, Philip W. Lavori, Kay W Chang
Journal: Journal of Clinical Oncology (2012)

5525 Background: The incidence and severity of baseline hearing abnormality in HNCP is poorly characterized, as is the subsequent CDDP associated hearing loss. While formal behavioral audiograms can characterize CDDP associated hearing loss in great detail, most oncologists either rely on subjective evaluation of hearing loss or grade hearing impairment using the CTCAE. Two new grading systems for grading cisplatin ototoxicity have been developed for use in pediatrics, the Brock and Chang systems. This report is the first evaluation of these 3 hearing loss criteria in an adult cancer patient population. Methods: We conducted an electronic medical records (EMR) search for all HNCP between 2004 and 2010 treated at the Stanford Cancer Institute (SCI) and identified which patients had audiograms in the EMR, and who had received CDDP. Three investigators (RL, ADC, KC) independently graded these audiograms using the CTCAE v3 and v4, Brock and Chang criteria. Baseline distributions, changes following CDDP dosing, and inter-observer variability were calculated for hearing impairment grading using all four criteria. Results: We evaluated 460 audiograms in 111 patients. Because 282/460 of the audiograms did not have threshold shifts measured at 1,2,3,4,6 and 8 kHz, CTCAE v4 could not be applied to them . We therefore limited all further comparisons to CTCv3, Brock and Chang criteria. The table below summarizes the analysis. Conclusions: The Brock and Chang ototoxity criteria scales deliver a distribution of hearing AE grades at baseline more compatible than the CTCAE v3 with respect to the expectation that most HNCP do not have severe baseline hearing loss. Both the Brock and Chang scales are more sensitive than the CTCv3 to CDDP associated hearing changes. The Brock scale, followed by the Chang scale, demonstrated highest inter-rater agreement. Additional data concerning performance characteristics and utility of these three grading systems will be presented. Replacement of the present hearing impairment criteria in the CTCAE with either the Brock or Chang scales should be considered. [Table: see text]
Repurposing Brigatinib for the Treatment of Colorectal Cancer Based on Inhibition of ER-phagy
Authors: Zhe Zhang, Wei Gao, Li Zhou, Yan Chen, Siyuan Qin, Lu Zhang, Jiayang Liu, Yujia He, Yunlong Lei, Hai-Ning Chen, Junhong Han, Zong-Guang Zhou, Edouard C Nice, Changlong Li, Canhua Huang, Xiawei Wei
Journal: Theranostics (2019)

Rationale: The sustained and severe endoplasmic reticulum (ER) stress in cancer cells may contribute to apoptotic cell death, thus representing a potential target for cancer therapy. Brigatinib is an anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive non-small-cell lung cancer (NSCLC). However, it remains unclear if brigatinib has alternative model of action to exert antitumor effect in ALK-negative cancers. Methods: ALK-positive NSCLC cells and various human ALK-negative cancer cells, especially human colorectal cancer (CRC) cells were used to examine the tumor suppression effect of brigatinib alone or in combination with autophagy inhibitors in vitro and in vivo. A variety of biochemical assays were conducted to elucidate the underlying mechanisms of brigatinib in CRC cells. Results: Here, we show the significant anti-cancer effect of brigatinib in CRC through induction of apoptosis by sustained ER stress. Mechanistically, brigatinib induces ER stress via promoting the interaction between ubiquitin-specific peptidase 5 (USP5), a deubiquitinase, and oxysterol-binding protein-related protein 8 (ORP8), leading to ORP8 deubiquitination, accumulation and growth inhibition. Furthermore, we find that brigatinib-mediated ER stress simultaneously induces autophagic response via ER-phagy that acts as a protective mechanism to relieve excessive ER stress. As such, combination of brigatinib with autophagy inhibitors significantly enhances the anti-CRC effect of brigatinib both in vitro and in vivo, supporting the repurposing of brigatinib in CRC, independently of ALK. Conclusion: The unearthed new molecular action of brigatinib suggests that therapeutic modulation of ER stress and autophagy might represent a valid strategy to treat CRC and perhaps other ALK-negative cancers.
Who Watches the Step-Watchers: The Ups and Downs of Turning Anecdotal Citizen Science into Actionable Clinical Data
Authors: Maya Sherman, Ziv Idan, Dov Greenbaum
Journal: The American Journal of Bioethics (2019)

Wiggins and Wilbanks (2019) raise a number of interesting concerns vis-a-vis citizen science and research. However, one area of innovation in citizen science that has seen significant advancements ...
Financial impact of an oncology medical home on participating providers.
Authors: Ram Swarup Trehan, Winston Wong, Daniel Winn, Joseph Cooper, Tim Olson, Jeffrey A. Scott, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2013)

e17581 Background: CareFirst BlueCross BlueShield (CFBCBS) partnered with Cardinal Health Specialty Solutions (CHSS) to launch the first cancer care clinical pathway in the United States in August 2008. Due to early success of the program with regard to savings and physician participation and compliance, CFBCBS and CHSS piloted an oncology medical home program in January 2011 with the hope of further decreasing cancer care costs while continuing consistency and quality of patient care. The medical home program offered a new physician reimbursement model that shifted the source of revenue from margin on drug sales to cognitive services. This would allow physicians to focus on optimal patient care without the financial incentive to prescribe chemotherapy. We analyzed the financial impact of the medical home program on participating physicians 1 year after implementation. Methods: Intravenous drug codes plus the evaluation and management codes for patient visits and chemotherapy administration were used in the analysis. We analyzed amounts paid to participating practices for chemotherapy, supportive care treatments, and nondrug services for year +1 to the amounts paid for the same services for year -1. We also analyzed the medical home fee schedule for year +1 when compared to the first-generation fee schedule applied to program year +1 utilization. This was calculated by repricing year +1 claims to the first-generation fee schedule and comparing that cost to what was actually paid under the medical home fee schedule. Results: Fourteen practices (31 physicians, 478 patients) joined the medical home program. Average amounts paid to physicians were 4.7% higher for year +1 compared to the prior year. The average cost difference for year +1 based on the medical home fee schedule versus the first-generation fee schedule was -5.7%. If physicians had chosen not to join the medical home program their revenues would have increased by 11%. Conclusions: Drug cost inflation was a significant contribution to savings in this model and directly impacts the observed lower average reimbursement to medical home participants versus their pathway program peers. Providers are likely to seek remedies for continued participation.
A novel microcurrent dressing for wound healing in a rat skin defect model
Authors: Chao Yu, Zhi-Xiu Xu, Yan-Hui Hao, Ya-Bing Gao, Bin-Wei Yao, Jing Zhang, Bing Wang, Zong-Qian Hu, Rui-Yun Peng
Journal: Military Medical Research (2019)

The exogenous application of low-intensity electric stimulation (ES) may mimic a natural endogenous bioelectric current and accelerate the repair process of skin wounds. This study designed a novel microcurrent dressing (MCD) and evaluated its potential effects on wound healing in a rat skin defect model.First, wireless ES was integrated into a medical cotton cushion to fabricate the MCD, and its electrical property was examined by using a universal power meter. Then, animal experiments were conducted to evaluate the MCD's effect. Forty-five rats were randomized into control (Con) group, Vaseline gauze (VG) group and MCD group. A full-thickness round skin incision 1.5 cm in diameter was made on the back of each animal. Apart from routine disinfection, the Con rats were untreated, whereas the other two groups were treated with VG or MCD. On days 3, 7 and 14 post injury, the wound areas were observed and measured using image analysis software following photography, and the skin samples were harvested from wound tissue. Then, histopathological morphology was observed routinely by hematoxylin and eosin (HE) staining; tumor necrosis factor α (TNF-α) and interleukin (IL)-1β expression were detected by Western blotting. Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) expression were detected with immunohistochemistry.The MCD generated a sf electric potential greater than 0.95 V. Animal experiments showed that the wound-healing rate in the MCD group was significantly increased compared with the Con and VG groups (P < 0.05 or P < 0.01). Histopathological observation revealed an alleviated inflammatory response, induced vascular proliferation and accelerated epithelization in the MCD group. Moreover, samples from the MCD group expressed reduced TNF-α and IL-1β levels and increased VEGF and EGF levels compared with those of the other two groups (P < 0.05 or P < 0.01). However, no significant difference was noted between the Con and VG groups at each time point.The MCD generates a stable and lasting ES and significantly promotes wound healing by reducing inflammation duration and increasing growth factors expression. Thus, MCD may act as a promising biomaterial device for skin wound healing.
Anaplastic lymphoma kinase (ALK): A potential oncogenic driver in triple-negative breast cancer?
Authors: Jasgit C. Sachdev, Pranitha Naini, Rafael Arteta-Bulos, Namratha Vontela, David Richard Hout, Fred R. Hirsch, Stephan Morris, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2013)

1067 Background: TNBC, a molecularly heterogeneous subset of breast cancer, has an aggressive clinical course and no established targets for therapy. Wild-type ALK gene amplification by fluorescence in situ hybridization (FISH) was noted in 6/9 inflammatory TNBC specimens (Robertson et al. SABCS, P3-01-18). The status of ALK, full-length or fused, in non-inflammatory TNBC has not been described. Identification of a biomarker such as ALK in TNBC would be clinically significant, given the ongoing development of multiple ALK inhibitors. We screened for ALK expression in TNBC specimens with a novel patented qRT-PCR assay (Insight ALK Screen). Methods: We tested archived formalin-fixed, paraffin-embedded blocks of TNBC tissue. Evaluable specimens had sufficient tumor material for 10 slides with 5-micron sections. Insight ALK Screen was performed using previously described methodology (Hout, et al. AACR 2011, Abstract 2220). We subjected ALK Screen positive specimens to ALK break-apart FISH (Vysis ) and direct sequencing analysis. Results: See clinical characteristics (Table). Insufficient RNA: 8/40 (20%). Insight ALK Screen-positive: 8/32 (25%). Break-apart FISH performed on these 8 specimens suggested 3/8 to be positive for ALK translocation and 2/8 to contain amplification of ALK without a translocation. The ALK-amplified specimens were subsequently confirmed with sequencing of RNA-PCR products to express full-length ALK. One additional ALK Screen-positive, FISH-negative specimen had full-length ALK expression confirmed on sequencing. Further analysis of the other 2 ALK Screen-positive cases is pending. Conclusions: ALK expression was seen in ~25% of TNBC specimens screened by Insight ALK Screen. We observed both ALK translocations and amplification/overexpression of full-length ALK. We are testing additional specimens by FISH and immunohistochemistry to evaluate the full spectrum of ALK alterations in TNBC. Updated data will be presented. [Table: see text]
The emerging, multifaceted role of mitophagy in cancer and cancer therapeutics
Authors: Debasna P. Panigrahi, Prakash P. Praharaj, Chandra S. Bhol, Kewal K. Mahapatra, Srimanta Patra, Bishnu P. Behera, Soumya R. Mishra, Sujit K. Bhutia
Journal: Seminars in Cancer Biology (2019)
John Lennard-Jones
Authors: Andrew Lennard-Jones
Journal: BMJ (2019)

John Edward Lennard-Jones was a pioneering gastroenterologist and an exceptional man in many ways. Known affectionately to his colleagues as “LJ,” he was a caring and astute physician, a gentle but inspirational teacher, and a prodigious clinical researcher. Colleagues recall that no one who worked with him ever had a bad word to say about him.

John was born in 1927 in Bristol into an academic environment; his father, Sir John Edward Lennard-Jones, was professor of theoretical physics. When John was 5, his father was appointed professor of theoretical chemistry at Cambridge, and the family moved. During John’s childhood his main interest was the natural world and this resulted in him undertaking a natural sciences tripos at Cambridge. After the war he was called up to do national service but was posted to the burns unit in Birmingham. While there he wrote two papers, one on the value of penicillin in finger pulp infections and the second on the importance of sensation in distinguishing partial thickness burns from full thickness burns. This entailed inflicting burns on himself, using different exposure to a 1 kg heated brass weight! His experiences there changed his life plan completely, and he decided to study medicine, returning to Cambridge.

He completed his clinical undergraduate training at University College Hospital, winning all the undergraduate prizes and going on to do professorial house jobs with …
Impact of comorbidities on overall survival of high-risk and advanced melanoma.
Authors: Prashanth Peddi, Jeong Hoon Oh, Kevin B. Kim, Jeffrey E. Gershenwald, Shana L. Palla, Christopher W Schacherer, Rakesh Jakkoju, Maria Suarez-Almazor
Journal: Journal of Clinical Oncology (2012)

8536 Background: Comorbidities have been shown to adversely affect survival among patients with cancer. Currently, the most important prognostic factor in patients with melanoma is AJCC stage. However, little is known regarding the impact of comorbidities on melanoma prognosis. The aim of our study was to determine the impact of the severity of concurrent comorbidities on the overall survival of patients with high-risk and advanced melanoma (defined as AJCC stages IIc, III and IV). Methods: We conducted a retrospective cohort study of eligible adult melanoma patients available in the MelCore prospective database at MD Anderson Cancer Center (MDACC) from 01-2003 to 12-2006 who were diagnosed and completed staging within 3 months of presentation to MDACC. Patients with ocular melanoma were excluded. Demographic, AJCC staging, and survival data were collected. The Adult Comorbidity Evaluation-27 (ACE-27) was utilized to collect comorbidity information and grade its severity. A Cox proportional hazards model was used. Results: Of 444 patients that met enrollment criteria, 176 (39.6%) had grade 0 (no comorbidities), 222 (50%) had grade 1 or 2 (mild or moderate comorbidities) and 46 (10.4%) had grade 3 (severe comorbidities). The median age of the entire cohort was 56.4 years (19.7-98.9), 141 (32%) were female, and 406 (91.4%) were white. The median overall survival after presentation to MDACC was 5.0 years for the entire cohort. Adjusted hazard ratios are shown in the table. Comorbidity and AJCC Stage were significantly associated with survival. Age, gender and race did not have a significant impact on overall survival. Conclusions: In our study, the presence of comorbidities at presentation were independent predictors of decreased survival, even when adjusted for AJCC stage. Our findings suggest that comorbidity should be incorporated into prognostic models and therapeutic decision-making for patients with high-risk or advanced melanoma. [Table: see text]
Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided cisplatin-based two-drug chemotherapy in unresectable non-small cell lung cancer
Authors: Y. W. Moon, Y. T. Kim, J. H. Sohn, J. Chang, S. K. Kim, M. S. Park, K. Y. Chung, S. H. Choi, J. Y. Yang, J. H. Kim
Journal: Journal of Clinical Oncology (2006)

7118 Background: Heterogeneity of tumor response to chemotherapy is a big obstacle in cancer treatment. The aim of this study was to investigate correlations of ATP-CRA and clinical outcome after ATP-TCA-guided cisplatin-based chemotherapy in unresectable NSCLC. Methods: From Sep. 2003 to Oct. 2005, ATP-CRA was done in tumor tissue specimen obtained from patients with suspected lung malignancy. ATP-CRA tested sensitivities of anticancer drugs used widely in advanced NSCLC such as cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabin, and vinorelbine. The cell death rate was determined by measuring the intracellular ATP levels of untreated controls and drug exposed cells. A sensitive drug was defined as a drug producing 30% or more reduction of ATP compared to untreated controls. Test-guided cisplatin-based two-drug chemotherapy was given to pathologically confirmed NSCLC. Results: 31 patients were enrolled and their median follow-up duration was 13.3 months. Response rate was 48.3%. Median progression-free and overall survivals were 4.4 months and 11.2 months, respectively. Patients were dichotomized into platinum-sensitive (S) and resistant (R) groups. S-group (19) contained cases sensitive to platinum alone (6) or both drugs (13). R-group (12) contained cases sensitive to none (9) or the other drug alone (3). Clinical response rate was higher in S-group (75.0% vs 35.3% in R-group; p = 0.0635). Considering correlations of test results and clinical response, positive/negative predictive values were 64.7% / 75.0% with the predictive accuracy of 69.0%. Although without significant differences in histology, stage, and performance status, S-group had longer progression-free (5.0 vs 2.4 months in R-group; p = 0.056) and overall (21.8 vs 9.7 months in R-group; p = 0.018) survivals. Conclusions: In vitro chemosensitivity test, ATP-CRA results and clinical outcome were correlated well after test-guided cisplatin-based two-drug chemotherapy in unresectable NSCLC, presenting favorable response and survival in platinum-sensitive versus resistant group. [Table: see text]
Masitinib in imatinib-naive advanced gastrointestinal stromal tumor (GIST): Five-year follow-up of the French Sarcoma Group phase II trial.
Authors: Axel Le Cesne, Jean-Yves Blay, Binh Bui Nguyen, Olivier Bouche, Julien Domont, Angela Cioffi, Julie Le Boulicaut, Alain Moussy, Olivier Hermine, Antoine Adenis
Journal: Journal of Clinical Oncology (2012)

10089 Background: Masitinib is a tyrosine kinase inhibitor that in vitro has greater activity and selectivity than imatinib against KIT. This multicenter, open label, phase 2 study evaluated efficacy and safety of masitinib as a first-line treatment of advanced GIST. Initial results with a median follow-up of 34 months, were previously reported in EJC 2010. We present here 5-year follow-up data from the same series with updated safety and survival data. Methods: Imatinib-naïve patients (pts) with inoperable, advanced GIST received oral masitinib (7.5 mg/kg/day) until progression, refusal or toxicity. Results: Thirty pts with a median age of 58 years (60% of males) were included from 06/2005 to 04/2007 in 5 institutions. At the cut-off date of 13/09/2011, 7/30 pts (23%) were still under treatment with median follow-up of 65 months and the median overall survival (OS) had not yet been reached (NR). The 5-year OS rate was 61.5% (95% CI [41.1;76.6]) (see Table). Among patients with confirmed KIT exon 11 mutation, 8/9 pts (89%) were still alive with one pt having died from non-treatment related causes (surgical complication) following a complete response while receiving masitinib. No additional progressions have been reported giving a total of 14 events (13 progressions and 1 death). Updated median PFS was 41.3 months (95% CI [17.5;53.8]).No additional grade 3/4 adverse events have been reported. Conclusions: Long term results of masitinib confirm an interesting activity with prolonged PFS and OS. The median PFS rate in masitinib compares very favorably to that of imatinib, which is reported as 18 months (JCO 26:626, 2008). The 5-year OS rates for masitinib in the overall and exon 11 populations also compare favorably to imatinib, both of which are reported at ≤50% for imatinib (JCO 26:626, 2008; JCO 28:1247, 2010). These results support the head to head comparison with imatinib in the currently ongoing phase 3 randomized clinical trial in first line advanced GIST pts. [Table: see text]
Impact of fosaprepitant use on dermal and vascular adverse events in anthracycline-based regimens administered through peripheral lines.
Authors: Takeo Fujii, Naoki Nishimura, Hisako Kanai, Hiromasa Ishimaru, Junko Kawano, Osamu Takahashi, Hideko Yamauchi, Teruo Yamauchi
Journal: Journal of Clinical Oncology (2013)

9629 Background: Fosaprepitant is effective in the prevention of chemotherapy-induced nausea and vomiting. In January 2012, we started using fosaprepitant in anthracycline- and cisplatin-based regimens and observed a tendency for an increase in dermal and vascular adverse events (AEs) at local infusion sites, particularly in the anthracycline group. In this study, we tested the hypothesis that fosaprepitant use is associated with dermal and vascular AEs differentially between anthracycline- and cisplatin-based regimens. Methods: We conducted a retrospective cohort study consisting of all patients who were administered anthracycline- or cisplatin- based regimens in 2011 and 2012 at St. Luke’s International Hospital, Tokyo. Aprepitant was used in 2011 and fosaprepitant was used in 2012. All other factors including pre- and post-hydration, premedication, and injection schedule were the same. Dermal and vascular AEs was defined as any grade pain or skin changes at local infusion sites or infusion veins. Factors we considered include fosaprepitant use, chemotherapy regimen, age, number of prior regimens, and body mass index. Interaction analysis using multivariate logistic regression was used to evaluate the association between treatment regimen, fosaprepitant, and risk of AEs. Results: A total of 268 patients (aged 54.3±12.3) were included, of which 120 (44.8%) used fosaprepitant. Among fosaprepitant users, 50 patients (41.7%) developed dermal and vascular AEs, whereas only 16 patients (10.8%) experienced AEs among non-users (P&lt; .001). When stratified by regimen, fosaprepitant was associated with a statistically significant increased risk of AEs (OR 12.10; 95% CI 5.45-26.93) in the anthracycline group. In contrast, no association was observed in the cisplatin group (OR 1.04; 95% CI 0.29-3.75). Statistically significant evidence of interaction was found (P&lt; .001) between regimen and fosaprepitant in the risk of AEs. Conclusions: Our results support the finding that using fosaprepitant in anthracycline-based regimens increases dermal and vascular AEs. In response, we discourage the use of fosaprepitant in anthracycline-based regimens through peripheral lines.