tbuckley/cabot-search huggingface dataset:
Patterns of recurrence in triple negative breast cancer patients (automated IHC) : An Indian Tertiary Care Center data.
Authors: Joydeep Ghosh, Sanjit Agarwal, Sandip Ganguly, Deepak Dabkara, Bivas Biswas, Shibarati Nandi, Santam Chakraborty, Soumitra Datta, Rosina Ahmed, Sanjoy Chatterjee
Journal: Journal of Clinical Oncology (2018)

e13128 Background: Contrary to earlier published data using manual IHC methods, we had reported Triple negative breast cancer (TNBC) rates of 11-15% as in western literature. Here we report the demographic characteristics, failure patterns, and survival outcomes and follow up. Methods: All TNBC patients were identified from a cohort of 2367 patients of non metastatic breast cancer between 2011 - 2017. Demographic and clinical information were collected. Patterns of recurrence were documented and simple statistical methods were used to report frequencies and proportions. Survival was calculated using Kaplan Meir method Results: A total of 351 TNBC patients were identified. The median age was 50yrs (range 20 to 84yrs) of whom 60% were post-menopausal. Post operative pathological staging (AJCC 7) revealed 18.5% stage I, 54.1 % stage II and 22.7 % stage III. Chemotherapy was administered in 93% cases, breast conservation surgery was done in 37% patients whilst radiotherapy was administered to 73% patients. With a median follow up of 22 months (IQR 11, 40), 16.1% recurred, out of which 22.8% had loco regional recurrence, and 77.2% had distant failure and 10.5% had both. The distribution were as follows: lungs and pleura 52.5%, liver 22.8%, bone 36.8%, nodes 26.3%, brain 17.5%. The estimated median disease free survival (DFS) was 66.4 months (95% CI – 21, 111) and median time to recurrence was 19.7 months. The estimated 5 year DFS is 60%. Conclusions: This is the first report of outcomes in Indian population after quality assured pathological evaluation. Results are similar to the west, thereby reducing the possibility varied geographic outcome and unsuitability of treatment. Genotypic comparison is now recommended to negate the hypothesis of a separate Äsian/Indian TNB cohort as have been reported earlier. Table 1:. Lin et al Sandhu et al Chatterjee et al Our study N 2569 7237 925 2376 % of TNBC 17% 31% 14.7% 14.7% IHC method Auto Manual Auto Auto Median DFS Not recorded (NR) NR NR 66.4 months 5yrs DFS NR by Lin et al (67% haffty et al) NR NR 60% Recurrence (overall) 26.6% (steward L et al) NR NR 16.1% Local 17.3% NR NR 22.8% Distant 63.6% NR NR 77.2% Both 19.1% NR NR 10.5%
Anlotinib for metastasis soft tissue sarcoma: A randomized, double-blind, placebo-controlled and multi-centered clinical trial.
Authors: Yihebali Chi, Yang Yao, Shusen Wang, Gang Huang, Qiqing Cai, Guanning Shang, Guowen Wang, Guofan Qu, Qiong Wu, Yu Jiang, Jianmin Song, Jing Chen, Xia Zhu, Zhengdong Cai, Chunmei Bai, Yongkui Lu, Zhihua Yu, Jingnan Shen, Jianqiang Cai
Journal: Journal of Clinical Oncology (2018)

11503 Background: No standard therapy is available in China for soft tissue sarcoma (STS) patients progressed after first-line chemotherapy. Anlotinib has shown single-agent activity in a phase II study presented orally at 2016 ASCO. This study aimed at confirming anlotinib’s efficacy and safety in advanced STS patients after failure of standard chemotherapy. Methods: Patients aged 18 years and older with angiogenesis inhibitor naive, histologically proven advanced STS, intolerance or failure to anthracycline-based chemotherapy, at least one measurable lesion according to RECIST 1.1, were eligible. Those patients were randomly assigned (2:1) to receive anlotinib (12 mg per day 2 weeks on and 1 week off) or placebo. The pathologic subtypes enrolled were: synovial sarcoma (SS), alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS) and others. Different pathologic subtypes were also randomly assigned (2:1) to each arm. The primary endpoint was progression-free survival (PFS). This trial was registered with ClinicalTrials.gov, number NCT02449343. Results: 233 patients were randomly assigned to either anlotinib (n = 158) or placebo (n = 75) and included in the final analysis. The median PFS was 6.27 months (95% CI: 4.30-8.40) for anlotinib compared with 1.47 months (95% CI: 1.43-1.57) for placebo (HR=0.33, p < 0.0001); objective response rate was 10.13% versus 1.33% (p = 0.0145); disease control rate was 55.7% versus 22.67% (p < 0.0001). For SS (n = 57), the median PFS was 5.73 months versus 1.43 months (HR = 0.2, p < 0.0001). For ASPS (n = 56), the median PFS was 18.23 months versus 3 months (HR = 0.14, p < 0.0001). For LMS (n = 41), the median PFS was 5.83 months versus 1.43 months (HR = 0.19, p < 0.0001). The most common grade 3 or higher adverse events were hypertension (18.99% with anlotinib vs 0 with placebo, p = 0.00), gamma glutamyl transferase elevation (4.43% vs 1.33%, p = 0.44), triglyceride increase (4.43% vs 0, p = 0.10), low density lipoprotein elevation (3.16% vs 2.67%, p = 1.00), hyponatremia (3.16% vs 1.33%, p = 0.67) and neutrophil count reduction (3.16% vs 0, p = 0.18). Conclusions: Anlotinib is a new treatment option for patients with advanced STS after failure of standard chemotherapy. Clinical trial information: NCT02449343.
Drug quantification in metastatic brain tumors in patients receiving bendamustine as a radiosensitizer for stereotactic radiotherapy.
Authors: Anees Dauki, He Lei, Ling Yonghua, Ashley Sekhon, Kari Lynn Kendra, Robert Cavaliere, Meng XU WELLIVER, John McGregor, Lai Wei, Ewa Mrozek, Thomas Olencki, Julie Thelen, Daniel Prevedello, William Thoman, Mani Matharbootham, Mario Ammirati, Christopher C Coss, John C. Grecula, Mitch A. Phelps
Journal: Journal of Clinical Oncology (2018)

e14017 Background: In this Phase I study, we evaluated the ability of the DNA alkylating agent, bendamustine (BD), to serve as a radiosensitizer in patients receiving stereotactic radiotherapy (SRT) to treat metastatic brain lesions. Prior studies in animals suggested BD crosses the blood-brain barrier, though we aimed to directly quantify BD in resected tissue to confirm the drug achieves active levels in metastatic tumors in human patients. Methods: Eligible patients with1- 4 brain metastases were enrolled on study. Patients eligible for surgical resection of brain metastases received 40 mg/m2 BD (30 min IV infusion) on days 1, 2, and 3 with resection on day 3 following BD. A full set of plasma samples for characterizing BD pharmacokinetics (PK) was obtained on day 1 or 2. As full PK could not be obtained on the day of surgery, one plasma sample was collected on day 3 immediately before, during, and after surgery. BD concentrations were measured using LC-MS/MS, and population modeling was used to estimate individual PK parameters. SRT combined with escalating doses of BD was initiated 4 weeks post-surgery or on day 1 in patients where resection was not indicated. Results: Eighteen patients with brain metastases were enrolled, and 14 patients underwent surgery and received preoperative BD. Plasma PK was determined in all of these 14 patients, and quantifiable BD levels were determined in tissues resected on day 3 from 8 patients. BD plasma concentrations at the precise time of surgical tumor resection on day 3 were simulated, and tumor/plasma ratios were calculated for each patient. Tumor concentrations ranged from 10.8 to 237 ng/gram of brain tissue, and tumor/plasma ratios ranged from 0.11 to 3.88 within the 8 patients with quantifiable BD levels in tumor samples. Conclusions: This was the first study to directly confirm BD penetration in metastatic brain lesions. BD at a dose of 50 mg/m2 IV given daily with 30 Gy in 5 fractions of SRT was well-tolerated, and is the RP2D of BD combined with 30 Gy/ 5 fractions of SRT. Clinical trial information: NCT00837928.
Meta-analysis of postprogression survival for first-line gemcitabine monotherapy in patients with advanced pancreatic cancer: Positive relationship between subsequent anti-cancer therapy and overall survival.
Authors: Akiyoshi Kasuga, Yasuo Hamamoto, Ayano Takeuchi, Kenta Kawasaki, Takeshi Suzuki, Kenro Hirata, Yasutaka Sukawa, Hiromasa Takaishi, Takanori Kanai
Journal: Journal of Clinical Oncology (2016)

e15687 Background: With the increasing number of drugs available for pancreatic cancer, the effect of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapy. We examined the relationship between postprogression survival (PPS) and OS in randomized trials of first-line gemcitabine (GEM) monotherapy for advanced unresectable pancreatic cancer. Methods: A literature search identified 56 randomized trials comparing GEM alone with other regimens. We partitioned OS into progression-free survival (PFS) and PPS and evaluated the relation between OS and either PFS or PPS. We also examined whether any association might be affected by the year of completion of trial enrollment. Results: For all 56 trials, PPS was strongly associated with OS (r = 0.858), whereas PFS was moderately associated with OS (r = 0.701). Average OS and PPS were significantly longer in recent trials than in older trials, (7.33 versus 6.15 months, p < 0.001) and (3.68 versus 2.86 months, p < 0.001), respectively. The correlation between OS and PPS in recent trials was much stronger than that in older trials (r = 0.912 versus 0.695). The percentage of patients with post-trial treatment was significantly higher in recent trials than in older trials (52.0% versus 39.7%, p < 0.001). The rate of post-trial anticancer therapy was significantly associated with OS (r = 0.877). Conclusions: We found an increase in median PPS in accordance with an increase in median OS in recent trials compared with older trials and that rate of post-trial anticancer therapy was strongly associated with median OS for patients with pancreatic cancer treated with GEM monotherapy.
MNGI-25. THE CAREGIVER BURDEN IN MENINGIOMA: LONG-TERM RESULTS AND ITS EFFECTS ON CAREGIVER’S HEALTH-RELATED QUALITY OF LIFE, ANXIETY AND DEPRESSION
Authors: Amir Zamanipoor Najafabadi, Pim van der Meer, Florien Boele, Rob Nabuurs, Johan Koekkoek, Frank Lagerwaard, Jaap Reijneveld, Wilco Peul, Martin Taphoorn, Martin Klein, Wouter van Furth, Linda Dirven, Saskia Peerdeman
Journal: Neuro-Oncology (2018)

Various studies in oncological/neurological patients highlight that informal caregivers suffer from a significant disease burden. We aimed to assess the meningioma caregiver burden, and its effects on caregivers health-related quality of life (HRQoL), and levels of anxiety and depression. In a multicentre cross-sectional study informal caregivers of intracranial meningioma patients at a median of 10 years after their last anti-tumour therapy were included. Informal caregivers were family members or close friends and completed the caregiver disease burden scale, SF-36 (HRQoL) and the Hospital Anxiety and Depression Scale. Caregiver burden was assessed as an independent determinant for caregivers HRQoL, and levels of anxiety and depression with multivariable analysis correcting for relevant confounders. Participant recruitment is still in progress. 110 informal caregivers were included (mean age: 64.5, female: 37.2%). Informal caregivers reported any caregiver burden in 35.2% of cases, and clinically relevant burden in 15.7%. More specifically, 20.4% of caregivers suffered from stress, 11.2% from social isolation, 13.0% from feelings of disappointment, 21.0% from emotional problems, and 12.0% from environmental factors complicating the care for the patient. The total caregiver burden score was significantly associated with decreased HRQoL on 6/8 scales and 2/2 component scores: physical function (=-6.53, p=0.071), role limitation due to physical problems (=-13.62, p=0.041), bodily pain (=-13.11, p=0.014), social function (=-11.87, p=0.001), mental health (=-14.32, p<0.001), vitality (=-14.24, p=0.001), physical component scale (=-4.40, p=0.022), and mental component scale (=-6.09, p<0.001). In addition, the total caregiver burden score was independently associated with higher anxiety (=3.11, p<0.001) and depression levels (=4.11, p<0.001). Caregiver burden in informal caregivers of meningioma patients is considerable, negatively affected their HRQoL, and levels of anxiety and depression. Paying more attention to meningioma patients caregivers seems therefore warranted, and effective support should be implemented if required.
Economic evaluation of diagnostic platforms for T790M detection in post EGFR-TKI NSCLC in Brazil.
Authors: Carlos G. M. Ferreira, Rosangela Caetano, Marcelo Custodio, Giuliana Montenegro, Luciene Schluckebier
Journal: Journal of Clinical Oncology (2018)

e21159 Background: Around 50% of all acquired resistance to first or second-generation EGFR-TKIs during the treatment of NSCLC can be attributed to T790M mutation. Clinical trial data demonstrated superior efficacy of Osimertinib after this progression. Nevertheless, the required molecular testing to identify the T790M mutation could be a challenge considering difficulties related to tissue re-biopsies. The availability of noninvasive techniques using cfDNA has permitted a safer and faster molecular diagnostic. Our objective was to compare the cost-effectiveness of current tests using T790M cfDNA. Methods: Population is NSCLC patients who had a progressive disease after treatment with first line EGFR-TKI. Decision tree model started with cfDNA evaluation (local commercially available tests are RT-PCR based kit, Digital Droplet PCR or NGS). Due to the intermediate sensitivity of cfDNA methods, a tumor sample analysis is recommended if plasma result is negative. In this case, the considered strategies were a combination of cfDNA tests and RT-PCR based kit or NGS for tumors re-biopsies. Prevalence of T790M mutation, test accuracy, proportion of unknown or unfeasible samples, complications and costs of tissue re-biopsies were also considered. The model was analyzed from a healthcare-payer perspective based on Brazilian private sector. Results: Strategy using ddPCR for plasma then NGS for tumor biopsy (if plasma negative) was the most effective with a cost-effective ratio of US$ 3,855.43 per positive T790M detected. Its cost was higher than the second most effective strategy (plasma-NGS + tissue NGS). The incremental cost-effectiveness ratio between both was US$ 21,193.66 per additional positive case detected. All strategies using RT-PCR based kit for plasma and/or tissue were dominated. Conclusions: In terms of costs and effectiveness, the best algorithms to detect more T790M positive cases are the combination of cfDNA based on ddPCR or NGS and NGS test for tumor re-biopsy. The use of ddPCR followed by NGS permits identification of 5% more T790M mutations than by dominated methods. This study is part of an effort to optimize expenditures and to integrate diagnostics discussions in Brazilian health system.
Economic impact of immune checkpoint inhibitor therapy in Brazil and strategies to improve access.
Authors: Pedro Nazareth Aguiar, Ramon Andrade De Mello, Hakaru Tadokoro, Gilberto Lopes
Journal: Journal of Clinical Oncology (2017)

6612 Background: Immunotherapy was elected by ASCO as the most important advance in Oncology for the last 2 consecutive years. Nevertheless, the costs of immune checkpoint inhibitors is a limitation to their incorporation in several countries, including Brazil. The objective of this study is to estimate the economic impact of immunotherapy and make suggestions in order to improve the access for patients who benefit the most from treatment. Methods: We assessed Brazilian cancer epidemiology data and the international literature to estimate the number of eligible patients each year. The authors estimated the economic impact according to the medication acquisition costs converted to US dollars. The median duration of the treatment was based upon the clinical trials. Results: We assessed 3 different agents (and one combo) for 7 indications. The results are summarized in the table below. Conclusions: The current cost of immune checkpoint inhibitors is prohibitive in the public health system in Brazil. While the country’s GDP per capita is 78% lower than that of the US, immune checkpoint inhibitors have similar prices in both. Biomarker selection, posology, and lower cost drugs help decrease the total economic impact of therapy. Price discrimination and volume discounts would help improve access. Further studies and discussion with all stakeholders is needed to identify patients who would benefit the most and to implement strategies to increase access to these potentially life-saving therapies. [Table: see text]
Clinical features and factors associated with survival in mucosal melanoma.
Authors: Karina Mayra Aliaga Llerena, Johana Muñiz, Henry Leonidas Gomez, Silvia P. Neciosup
Journal: Journal of Clinical Oncology (2017)

e21082 Background: Mucosal melanoma (MM) is a rare, aggressive and poorly prognostic neoplasm compared to cutaneous melanoma (MC), probably due to the lack of knowledge about its pathogenesis, biology, risk factors, staging and treatment not yet well established. Our objective is to identify the epidemiological, clinical and pathological characteristics of mm and ocular melanoma (OM) as well as its relation with survival. Methods: Observational, descriptive and retrospective study. We analyzed data from 219 patients who met the selection criteria. Overall survival (OS) was estimated using the Kaplan-Meier method and the differences were assessed using the log rank test. In the statistical analysis SPSS 19 software was used and a p &lt; 0.05 was considered statistically significant. Results: The mm represented 0.2% (219/98361) of the total number of patients diagnosed with cancer. MC represented 89% (N = 1598), mm 10% (N = 195) and MO only 1% (N = 24). mm predominated in females (N = 118 60%) with a median age of 63 years for both sexes. The most frequent sites were head and neck (N = 91 46.7%), anorectal (N = 68 34.9%) and vulva-vagina (N = 20 10.2%). The 5-year OS was 19.6% with a median of 21 months in the mm and 49.6%, with a median of 38 months in OM. Breslow &gt; 4mm (p = 0.004), location (p = 0.019), distant disease (p = 0.004) and treatment type (p = 0.003) were considered as factors associated with survival. Conclusions: The MM, in the era of immunotherapy, is still considered one of the neoplasias with poor prognosis and poorly studied. It is vital to incorporate these patients into clinical trials in order to obtain real information on treatment efficacy, given the limited data available at the time.
Financial ties to industry among national comprehensive cancer network guideline authors.
Authors: Aaron Philip Mitchell, Stacie Dusetzina, Ethan M. Basch
Journal: Journal of Clinical Oncology (2016)

6513 Background: Financial conflicts of interest (FCOIs) between physicians and industry include such things as meals, consulting fees, travel, and research funding. FCOIs have been shown to influence physicians’ appraisal of clinical trial results and preferences for specific drugs. If authors of clinical practice guidelines (CPGs) maintain such FCOIs, this may influence the recommendations that become standard of care. The goal of this study was to describe the prevalence of FCOIs among authors of recent National Comprehensive Cancer Network (NCCN) guidelines. Methods: The Open Payments provision of the Affordable Care Act recently made public all FCOIs between industry and US physicians. Using these data, we quantified the FCOIs among members of the NCCN guideline committees for four prevalent cancers (lung, breast, prostate, and colorectal) during 2014. Results: Of 125 guideline authors, 108 (86%) had at least one reported FCOI. FCOIs were described as research payments (RP), including funding associated with clinical trials, or general payments (GP), including consulting, meals, lodging, and other such transfers of value. Authors received an average of $10,011 in GP (range $0-$106,859) and $236,066 in RP (range $0-$2,756,713) (Table). 84% of authors received GP, with 56% receiving $1,000 or more in GP, while 47% received RP. Conclusions: Most NCCN guideline authors have reported FCOIs with industry. FCOIs involving research payments (RP) were of greater value, but GP were more prevalent. Although FCOIs may result from engaging in important scholarship, FCOIs have the potential to influence CPGs in counterproductive ways. More research is needed to understand how best to manage author FCOIs during guideline creation. General Payments Research Payments Number of authors receiving, N = 125 (%) 105 (84) 59 (47) Total received, all authors $1,251,422 $29,036,127 Mean per author (range) $10,011 ($0 - $106,859) $236,066 ($0 - $2,756,713) Mean number of companies from which each author received payment (range) 3.8 (0 – 19) 1.8 (0 – 13) Mean value of payments from single company to single author (range) $2,618 ($2 – $39,863) $123,047 ($17 – $1,823,352)
DNA damage with liposomal irinotecan (nal-IRI) in pancreatic cancer xenografts: Multimodal analysis of deposition characteristics.
Authors: Stephan G Klinz, Shannon C. Leonard, Nancy Paz, Daniel Gaddy, Helen Lee, Bart Hendricks, Jonathan B Fitzgerald
Journal: Journal of Clinical Oncology (2018)

e16205 Background: nal-IRI facilitates intratumoral drug deposition through enhanced permeability and retention, with pharmacokinetic and pharmacodynamic (PK/PD) analyses demonstrating an extended circulation of the liposome and its encapsulated payload. Here we investigate nal-IRI and non-liposomal irinotecan (IRI-HCl) in pancreatic tumor models. Methods: AsPC-1, BxPC-3 and CFPAC-1 tumors were grown in NOD-SCID mice, with animals dosed q7d with IRI-HCl (25‒50 mg/kg) or nal-IRI (5‒10 mg/kg) to evaluate efficacy under equivalent exposure. To assess PK/PD, samples were collected at multiple timepoints up to 72 h (IRI-HCl) and 168 h (nal-IRI) and evaluated for liposome localization, macrophage, tumor and vessel markers, DNA damage and apoptosis. Results: At equal dose levels, nal-IRI resulted in prolonged circulation and tumor exposure of IRI and active metabolite SN-38. Nal-IRI increased the duration of active metabolite above a hypothetical threshold compared with IRI-HCl, with an improved control of growth rates in pancreatic tumor models even at 5x lower doses. DNA damage in BxPC-3 tumors with IRI-HCl and nal-IRI was comparable, but maximal at 6 h after IRI-HCl (50 mg/kg) and 72 h after nal-IRI (10 mg/kg). Liposomes deposited in tumors heterogeneously around functional vessels. Accumulation peaked after 6–24 h, with similar deposition patterns in cell– or patient–derived xenografts. Liposomes were taken up by macrophages and to lesser extent by tumor or other stromal cells. Similar patterns were observed in a pancreatic PDX models. DNA damage was observed 24–72 h after treatment, mostly in tumor cells even without internalized liposomes. DNA damage and apoptosis were minimally seen in non-tumor cells. Induction of apoptosis was more prevalent in tumor cells even at lower liposomal uptake levels, while most non-tumor cells showing liposome uptake did not undergo apoptosis. Conclusions: Nal-IRI improved tumoral payload deposition in pancreatic models, with heterogeneous deposition restricted to perivascular areas. DNA damage patterns suggests sufficient intratumoral bioavailability of SN-38 outside of deposition areas. Effects of repeated dosing should be explored.