tbuckley/cabot-search huggingface dataset:
Cost of oncology drugs in the Middle-Eastern country of Lebanon: An update (2014-2016).
Authors: Ibrahim R. Bou-Orm, Fadia Elias, Salim Adib, Walid Ammar
Journal: Journal of Clinical Oncology (2018)

e18917 Background: Lebanon is facing a mounting burden from cancer with heavy financial consequences on the healthcare system. This study aims to evaluate increasing trends in the cost of oncology drugs procured by the Lebanese Ministry of Public Health (MOPH) between 2014 – 2016, and to assess the particular impact of the introduction of new immunotherapy drugs for treatment of lung cancer mid-2015 on the overall cost and the specific cost of lung cancer treatment. Methods: A secondary analysis was conducted of data from the MOPH Cancer Drug Scientific Committee (CDSC) with a total of 18,133 cancer files between 2014 and 2016. Results: Over the 3-year period, a total of about $140 million was spent on cancer drugs by the MOPH free dispensing program, with a 27% increase following the phasing-in of immunotherapy. The average drug cost per patient per year, measured across all cancer types, increased from $7000 in 2014 to $8,400 in 2016. Trastuzumab, approved for HER-2 positive breast cancer treatment ranked first in the total expenditures of 2014-2015. By 2016, two new immunotherapy drugs had topped the list: Pembrolizumab ranked first and Nivolumab ranked third, representing 64% of the total lung cancer treatment cost and about 19% of the total yearly budget, while beneficiaries were only 3% of all patients. Conclusions: This update documents the increasing financial impact of newer cancer drugs on the process of procurement in the middle-income country of Lebanon. The trend is aligned with the global financial burden of cancer drugs, calling for a collaborative global response to the crisis. Keywords: Health financing, cancer treatment, universal health coverage, global health, equity, Middle-East.
Patient (Pt) and oncologist (MD) discordance in goals of care in end of life (EOL) decision making.
Authors: Sara L Douglas, Barbara J Daly, Neal J. Meropol, Amy R Lipson
Journal: Journal of Clinical Oncology (2018)

10007 Background: Providing EOL care that is in accordance with Pt goals of care is an essential component of quality care. Because discordance between the attitudes of Pt and physician can undermine optimal EOL care, identification of disagreements regarding goals of care is important, particularly in the context of advanced disease. Methods: This was a longitudinal design study. Adult Pts with Stage IV gastrointestinal (GI) or lung cancer were eligible. Each Pt and MD were surveyed at study enrollment and every 3 months for 15 months or until the Pt died. The primary variables of interest were the Pt and MD identified goals of care and what the MD believed to be the Pt’s goal of care, using a visual analog scale (VAS). Scores on the VAS ranged from 0 (comfort, quality of life) to 100 (survival, length of life). Discordance was defined as an absolute difference > 40 on the VAS. Results: Between January 2015 and July 2017, 378 Pts were enrolled. Refusal rate was 27.5%; attrition rate 8.1%. 168 Pts (44%) died and their results are presented. Mean age was 64 years (range = 36-88 years); 66% had GI and 34% had lung cancer. Mean time from enrollment to death was 6.5 months (range = 3 - 15 months). At the last assessment prior to Pt death, 32% of the Pt-MD pairs had discordant goals ( > 40 points different). In 60% of these cases, the Pt had more survival focused goals while in 40% of cases the MD had more survival focused goals. Also, 77% of Pt-MD pairs with discord at enrollment still had discord at the last assessment before death (p < .001). In comparing what the MD believed to be the Pt’s goal of care with the Pt’s actual goal of care at death, there was discord in 27% of the pairs. The correlation between MDs’ own identified goals for Pts and what MDs identified as the Pts’ goals was large (r= .71, p < .001). Conclusions: These data suggest that communication between Pts and MDs is suboptimal regarding goals of care at the EOL. Interventions to improve the explicit discussion of mutual goals of care over time between MDs and Pts are needed in order to ensure that patients receive EOL care consistent with their goals.
Abstract 12168: Risk Stratification for Ventricular Tachyarrhythmias in Patients With Cardiac Sarcoidosis by Cardiac Magnetic Resonance Imaging
Authors: Masakazu Yasuda, Yoshitaka Iwanaga, Takao Kato, Toshiaki Izumi, Yasutaka Inuzuka, Takashi Nakamura, Takayuki Kawamura, Shigeru Ikeguchi, Moriaki Inoko, Takashi Kurita, Shunichi Miyazaki
Journal: Circulation (2015)

Introduction: Recently, late gadolinium-enhancement (LGE) cardiac magnetic resonance (CMR) imaging, which has been used to uniquely characterize the myocardial fibrosis, is reported to have a prognostic value in cardiac sarcoidosis (CS) Hypothesis: Not only fibrosis mass, but also its localization may help to identify the risk of ventricular tachyarrhythmias (VA) in patients with CS. Methods: 70 consecutive CS patients underwent CMR (cine and LGE imaging). Left ventricular (LV) mass and fibrosis mass were calculated and the localization was analyzed using 17 segment model. VA was defined as sustained ventricular beats ≥ 3 or ventricular fibrillation. The patients underwent prospective follow-up through 2015 from CMR examinations. Results: 33.3 % of the patients had a history of VA at the time of CMR examination. During a median follow-up of 15.5 months, 31.9 % had new-onset (11.6 %) or recurrent VA (20.3 %). Increased LV fibrosis mass (LVFM) was associated with the prevalence of VA (P &lt; 0.001) and receiver operating characteristics curve analysis indicated good predictive performance of LVFM for the combined VA (history of VA and new-onset VA) (AUC = 0.788, best cut-off value; 8.28 g). In addition, when localization score (LS) was defined as the summation of LGE enhancement in LV basal anterior, basal anteroseptal, or RV out-flow tract (RVOT) lesion, it was associated with the combined VA (P &lt; 0.001). Kaplan-Meier analysis showed that both LVFM and LS groupings were significantly associated with VA occurrence (Figure A). Furthermore, a combined analysis of LVFM and LS groups showed a better risk stratification for VA (Figure B). Conclusions: Not only fibrosis mass, but also its localization of basal anterior, anteroseptal, or RVOT was associated with the history of VA as well as the prognosis for VA in patients with CS. CMR may be a useful tool for risk stratification for ventricular tachyarrhythmias by detecting myocardial fibrosis and localization in CS patients.
Pneumocystis infection during first-line chemotherapy for solid tumours: Increased virulence or better diagnosis?
Authors: Alena Talia James, Alex James, Marcela Pinto do Nascimento, Domenic Higgs, Madeline Rogers-Seeley, Andrew Peter Dean
Journal: Journal of Clinical Oncology (2017)

e18277 Background: Pneumocystis Jirovecii (PJP, previously Pneumocystis Carinii) infection is typically seen in those with advanced immunodeficiency such as Acquired Immunodeficiency Syndrome, haematological malignancies, sustained chemotherapy with temozolomide or patients heavily pretreated with multiple lines of chemotherapy. PJP rarely presents early in the natural history of solid tumour malignancy. We observed a cluster of cases of PJP at our institution in patients undergoing first-line chemotherapy for solid tumours. Methods: An electronic database search was conducted to identify occurrences of PJP over a 3 month period. 4 patients were identified who developed Pneumocystis Jirovecii. The patients’ records, laboratory, radiology and pathology results were examined. Results: All 4 patients identified had developed PJP during first line chemotherapy for GI malignancy. In each case, the patient presented with dyspnoea, fever and hypoxia. All were noted to be lymphopenic with lymphocyte counts of 0.2 to 0.9 x10^9/L. All were HIV negative. Chest CT revealed new bilateral ground-glass changes associated with cyst formation. All cases were found to have positive PJP PCR on testing of induced sputum. On the basis of clinical presentation, positive PCR sputum cultures and CT findings, the patients were diagnosed with PJP and treated with high-dose sulphamethoxazole and trimethoprim. 3 patients recovered and 1 died despite best ICU management. Conclusions: The relatively high number of cases of PJP early in treatment is noteworthy. It raises the question as to whether PJP is becoming more potent or that better awareness leads to earlier and more accurate diagnosis. Coincidental clustering is also a possibility. Clinicians should be aware that pneumocystis infection can occur during first-line therapy in solid tumour malignancy. It should be considered as a differential in any patient on chemotherapy (regardless of line of therapy) presenting with acute respiratory illness.
P01.151 Gender differences in glioma - findings from the Swedish National Quality Registry for Primary Brain Tumors
Authors: A Malmström, L Åkesson, T Asklund, S Kinhult, K Werlenius, G Hesselager, S Hylin, R Henriksson
Journal: Neuro-Oncology (2018)

An often debated topic in neuro-oncology are the differences in incidence and survival between men and women with glioma. To the Swedish National Quality Registry for Primary Brain Tumors (SNQR) over 90% of all Swedish patients with primary brain tumor have been reported since 1999. We therefore conducted a study of clinical factors in relation to gender in patients registered with high grade glioma using data from the SNQR. The SNQR was searched for patients diagnosed with high grade glioma from 1999 through 2016 and clinical data were analyzed for gender differences regarding prognostic factors, tumor location and survival. In all 5470 patients were identified, 2268 women and 3202 men, giving a ratio of 1:1.4. We found a survival benefit for women when analyzing the whole time period. While there was no difference in median survival (315 versus 326 days for women versus men), there were significantly more long term survivors among women, with mean survival being 742 versus 628 days (p=0.03). The survival benefit for women was also only present in those being younger than 50 years at diagnosis. We looked at the prognostic factors age, performance status (PS) and surgery in relation to gender. We found that median age for being diagnosed with high grade glioma was significantly higher in women than men (63 versus 62 years, p=0.002) and the ratio of women in relation to men increases with increasing age, the ratios for younger than 50 years being 1:1.5 and over 50 years 1:1.39. A higher fraction of the women are over 60 years when diagnosed compared to men (57% vs 53%, p=0.002). For PS we identified that significantly more women were reported to have PS 3 and for men more PS 0 was registered. For type of surgery we found no gender differences. For tumor location more women had tumors in the frontal and less in the temporal lobe as compared to men. In the Swedish National Quality Registry for Primary Brain Tumors we identified differences in incidence and survival between men and women related to age and also a disparity regarding PS and tumor location. If the cause of these clinical differences is due to molecular background or has other causes warrants further study.
Effect of radium 223 on remission of bone metastases in androgen receptor-positive (AR+) salivary duct carcinoma (SDC) of the parotid.
Authors: Mario Airoldi, Fulvia Pedani, Elisa Bellini, Viviana Contu, Marcello Tucci, Valerio Podio, Luca Raimondo, Massimiliano Garzaro
Journal: Journal of Clinical Oncology (2016)

e17559 Background: SDC is a rare and highly aggressive disease. AR+ metastatic SDC can be successfully treated with a complete anti-androgen blockade (CAB) approach . In case of progression a second line with abiraterone or enzalutamide can be proposed. Herein we present a case of a third line therapy with radium 223 after very bulky bone metastases occurrence. Methods: A 66 -year-old man was treated with radical parotidectomy plus post-operative radiotherapy (66 Gy) for a SDC. After 2 yrs he presented parotid site swelling and cervical lymphadenopathy.A biopsy showed a 85% immunohistochemestry AR+ recurrent SDC. The patient was treated with CAB: monthly triptorelin (LHRH analogue) and bicalutamide 150 mg/day. The patient obtained a partial response of 18 months duration. After progression we started a treatment with Abiraterone Acetate (1000 mg/d) plus prednisone (10 mg/d) achieving a minimal response lasting 10 months. Then the patient had a very severe full vertebral and bilateral femoral pain with a total impairment of walking and standing up. A RMN showed dorsal-lumbar column and bilateral femoral diffuse osteolytic lesions. The patient had a superscan on bone scintigraphy. The patient received six injections of radium 223 (50 Kbq/Kg intravenously) given every 4 weeks. Results: No G3-4 toxicity was observed. At the end of treatment the patient had a full recovery of his functional impairments. After three months scintigraphy showed a complete remission. After 6 months the patient is asymptomatic and out of any treatment. Conclusions: AR+ recurrent SDC can be successfully treated with CAB as first line therapy; abiraterone acetate can obtain a palliative role. This is the first report of a Radium 223-induced complete remission of severe bone metastases due to SCD. This observation need more clinical data.
P01.067 Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma: the experience of the Italian Association of Neuro-Oncology
Authors: G Simonetti, A Silvani, E Biagioli, A Botturi, M Caroli, I de Simone, V Fregoni, P Gaviani, A Lanza, E Marchioni, A Pace, E Quaquarini, A Salmaggi, M D’Incalci
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) remains the most aggressive brain tumor; even with current standard of care for newly diagnosed GBM, the majority of patients recur within a year. Therapeutic options are lacking and the development of more effective therapeutic approaches is imperative. Ortataxel, another second-generation taxane, showed to be active in different tumor. It was hypothesize a potential therapeutic activity of ortataxel against glioblastoma and led us to design a phase two study in patients with glioblastoma recurring after surgery and first line treatment. A single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma was performed to evaluate the activity of ortataxel in in terms of PFS-6. PFS, overall survival at 9 months (OS-9) after the enrolment, objective response rate (ORR), compliance, tolerability and safety were evaluated as secondary endpoints. A total of 40 GBM patients were recruited. PFS-6 was 11.4 %: four patients were alive and progression free at 6 months after the enrolment. One additional patient progressed at 5.5 months with the appearance of a new lesion but his clinical status was considered stable and therefore the clinician decided to continue the treatment with ortataxel receiving up to 18 cycles until the further disease progression. All other patients progressed in a range from 1.0 to 5.5 months from the study entry. The median follow-up was 19.9 months (IQR 12.0–32.0). Median PFS was 1.7 months (IQR 1.4–3.8). Regarding the OS-9, 29 patients out of 35 (OS-9 %: 12.8; 95%CI: 21.8–53.8) died before 9 months from the enrolment, in a range from 0.99 to 7.70 months from study enrolment. The best response to treatment was PR in only one patient that was still on treatment when the analysis was performed and SD in 9 patients (29.0%). The most important toxicities were neutropenia, hepatotoxicity and leukopenia that occurred in 5 patients (13.2%), 5 patients (13.2%) and 6 patients (15.8%) respectively. The finding that two cases responded to the drug for a long time invite us to speculate that ortataxel might be effective in a limited fraction of GBM patients with some peculiar molecular features associated to high sensitivity to the drug.
A subgroup analysis of the East Asia population in RANGE: A randomized phase 3 study of docetaxel (DOC) with or without ramucirumab (RAM) in platinum-refractory advanced or metastatic urothelial carcinoma (UC).
Authors: Nobuaki Matsubara, Daniel Peter Petrylak, Hiroyuki Nishiyama, Wen-Pin Su, Jae-Lyun Lee, Jian-Ri Li, Richard A. Walgren, Oday Hamid, Annamaria Zimmermann, Katherine M Bell-McGuinn, Ling Gao, Gosuke Homma, Ikuo Yana, Thomas Powles
Journal: Journal of Clinical Oncology (2018)

4542 Background: RANGE (NCT02426125) is a global, randomized, double-blind, placebo-controlled, phase 3 study to evaluate the efficacy and safety of RAM in combination with DOC in patients (pts) with platinum-refractory advanced or metastatic UC. Here we report the results of RAM in combination with DOC in the East Asia population (EA). Methods: 530 pts were randomized (1:1) to DOC with either RAM 10 mg/kg or placebo (PL) on day 1 of a 21-day cycle (RAM/DOC or PL/DOC). EA pts (n = 110) received DOC 60 mg/m2; other pts received DOC 75 mg/m2. Primary endpoint was investigator-assessed progression free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival, safety, quality of life (QOL), and pharmacokinetics (PK). Results: PFS outcomes (investigator-assessed and blinded centrally reviewed) among EA remained consistent with the intention-to-treat population (ITT) (Table). Improvements in ORR and 6/12 month PFS rates for EA were in line with those for ITT. The most common grade ≥3 adverse events in EA, neutropenia and leukopenia, were observed at a similar frequency in both arms. Mean scores for global QOL in EA stayed largely stable over time without a clear difference between arms. Plasma concentrations of DOC for pts in the 60 mg/m2 group were similar to those for pts in the 75 mg/m2 group. Conclusions: The DOC PK profile for EA pts receiving 60 mg/m2 was consistent with non-EA pts receiving 75 mg/m2. Results in EA were consistent with the improved clinical outcomes and manageable safety profile observed with RAM/DOC in ITT. Clinical trial information: NCT02426125. ITT (first 437 pts) EA** RAM/DOC (N = 216) PL/DOC (N = 221) HR (95% CI)* RAM/DOC (N = 53) PL/DOC (N = 57) HR (95% CI)* Median PFS (month) (Investigator assessed) 4.07 2.76 0.757 (0.607-0.943) 3.02 2.99 0.928 (0.597-1.444) 6 month PFS rate (%) 28.5 18.9 30.6 24.8 12 month PFS rate (%) 11.9 4.5 14.9 7.1 Median PFS (month) (blinded centrally reviewed) 4.04 2.46 0.672 (0.536-0.842) 3.32 2.69 0.793 (0.513-1.225) ORR (%) 24.5 14.0 26.4 15.8 * Cox PH model (Stratified by ECOG PS at Baseline, Visceral Metastases, Geographical Region) ** All EA pts were included in the first 437 pts of ITT
Anti-PD-1 monoclonal antibody combined CD3-retronectin activated T cell in heavy-treated renal cell cancer.
Authors: Lingdi Zhao, Wei Li, Yonghao Yang, Yong Zhang, Xiubao Ren, Quanli Gao
Journal: Journal of Clinical Oncology (2017)

3047 Background: Metastatic renal cell carcinoma (MRCC) has a poor prognosis after failure of multitargeted tyrosine kinase inhibitors. New immunomodulators, such as anti-programmed death (PD)-1 antibody drugs, have made progress in the treatment of MRCC, but their objective response rate is only about 25%. Therefore, it is important to enhance the response rate of anti-PD-1 therapy. Methods: Patients with MRCC were eligible if they were failed to at least one kinase inhibitors, ECOG PS 0-2. Patients received nivolumab (2mg/kg, q2w) or keytruda ( 2mg/kg, q3w), followed by CD3-retronectin activated T cell, and the total number of CD3-retronectin activated T cell each time was about 5×10 9 /L. The primary objective was to determine the objective response rate, secondary objectives included time to symptom relief, time to efficacy, safety. Results: 8 pts were enrolled (median age 58 [31-79], male 6). Pts had received a median of 2 (1-4) prior regimens. To date there is 2 patients that the efficacy can not be evaluated. The other 6 pts got remission (3 complete remission and 3 partial remission), the median time to efficacy was 10 weeks (6-12 weeks) and the time to symptom relief was 4 weeks (3-6 weeks). There was no grade 3/4 adverse effects. family:'';font-size:12.0000pt;mso-font-kerning:1.0000pt;" &gt; 10 9 /L. The primary objective was to determine the objective response rate, secondary objectives included time to symptom relief, time to efficacy, safety. Conclusions: CD3-retronectin activated T cell might improve the efficacy of anti-PD-1 therapy without increasing the side effects. This combination therapy has many implications in the age of immunotherapy, and should be explored across cancer types. mily:'';font-size:12.0000pt;mso-font-kerning:1.0000pt;" &gt; 10 9 /L. The primary objective was to determine the objective response rate, secondary objectives included time to symptom relief, time to efficacy, safety.
Prognostic impact of <i>KRAS</i> mutation subtype and concurrent genetic mutations in non-small cell lung cancer.
Authors: Jacqueline Aredo, Sukhmani Kaur Padda, Christian Kunder, Summer S. Han, Heather A. Wakelee
Journal: Journal of Clinical Oncology (2018)

e21023 Background: KRAS mutations occur in ~25% of patients with non-small cell lung cancer (NSCLC), and concurrent genomic alterations may contribute to differences in patient survival. Therefore, we sought to characterize the effect of concurrent mutations on KRAS-mutant NSCLC patient outcomes. Methods: We identified patients with KRAS-mutant NSCLC who underwent next-generation sequencing of > 130 genes with the Solid Tumor Actionable Mutation Panel (STAMP) assay at the Stanford Cancer Institute between January 2015 and December 2017. Clinical and molecular data were abstracted from patients’ electronic health records. A multivariate Cox proportional hazards model was used to evaluate the association between concurrent mutations and overall survival from date of biopsy-proven diagnosis. Results: 186 patients were eligible for review, with median age 72 years (range 40-90), 57% female, and 94% adenocarcinoma. Staging ranged from local (n = 72, 38%), regional (n = 55, 30%), to distant (n = 59, 32%) disease. The most common KRAS mutation subtypes were G12C (n = 65, 35%), G12V (n = 37, 20%), and G12D (n = 32, 17%). Concurrent mutations were identified in TP53 (n = 72, 39%), STK11 (n = 22, 12%), KEAP1 (n = 15, 8%), CDKN2A (n = 10, 5%), and PIK3CA (n = 7, 4%). Median overall survival was 28 months (95% confidence interval [CI] 27 months-not reached). On multivariate analysis, KRAS G12D mutation subtype was significantly associated with poor survival (HR 3.07, 95% CI 1.47-6.39, p = 0.003). Concurrent mutations in STK11 were also associated with poor survival (HR 3.53, 95% CI 1.48-8.41, p = 0.005), whereas PIK3CA mutations were associated with improved survival (HR 0.25, 95% CI 0.06- 0.97, p = 0.045). Non-significant results were observed for all other concurrent mutated genes. Conclusions: KRAS G12D subtype and STK11 mutations confer poor prognoses for patients with KRAS-mutated NSCLC. Concurrent mutations may represent distinct subsets of KRAS-mutant NSCLC. Further investigation is warranted to elucidate the role of these molecular markers in guiding therapeutic intervention.