tbuckley/cabot-search huggingface dataset:
Enrollment in high-deductible health plans and access to care, out-of-pocket spending, and hospital emergency department use among cancer survivors.
Authors: Zhiyuan Zheng, Ahmedin Jemal, Matthew P. Banegas, Xuesong Han, K Robin Yabroff
Journal: Journal of Clinical Oncology (2018)

6582 Background: Little is known about the associations between enrollment in high-deductible health plans (HDHP) and access to care, spending, and health care utilization among working age cancer survivors. Methods: The 2010 to 2015 National Health Interview Survey was used to identify privately insured working age (18-64 years) cancer survivors (HDHP n = 1170; low-deductible health plan [LDHP] n = 2084) and those without a cancer history (HDHP n = 23,548; LDHP n = 50,251). We used multivariable logistic regression to examine associations between HDHP status, cancer history and three measures: reduced access to care for financial reasons, high out-of-pocket (OOP) spending, and hospital emergency department (ED) use. Predictive margins were generated to compare cancer survivors to those without a cancer history, stratified by HDHP status. Odds ratios (OR) were generated to compare HDHP to LDHP cancer survivors as well as the impact of health saving accounts (HSA) among HDHP enrollees. Analyses were also stratified by family income level (low, middle, or high). Results: Among low income HDHP enrollees, cancer survivors were more likely to report reduced access to care (24.8% vs 17.8%), high OOP spending (47.8% vs 34.5%), and ED use (30.1% vs 16.2%) than those without a cancer history (all p < .05). Compared to LDHP cancer survivors, HDHP cancer survivors were more likely to report reduced access to care (low income: OR = 2.18; high income: OR = 2.15), high OOP spending (low income: OR = 4.75; middle income: OR = 2.35; high income: OR = 2.05), and ED use (middle income: OR = 1.58, all p < .05). Among HDHP enrollees, HSA was associated with lower rates of reduced access to care (OR = .85) and ED use (OR = .88) and higher rate of high OOP spending (OR = 1.34, all p < .05), compared to HDHP enrollees without HSA. Conclusions: HDHP increases the risks of reduced access to care, high OOP spending, and ED use for cancer survivors, and the patterns vary by family income level. Future studies based on longitudinal data to investigate causal relationship is warranted, especially among low income working age cancer survivors enrolled in HDHPs.
A phase 1/2 study combining ipilimumab with abiraterone acetate plus prednisone in chemotherapy- and immunotherapy-naïve patients with progressive metastatic castration resistant prostate cancer (mCRPC).
Authors: Daniel Costin Danila, Timothy Kuzel, Jeremy Paul Cetnar, Dana E. Rathkopf, Michael J. Morris, Joshi J. Alumkal, Alex Butler, Tracy Curley, Melanie Hullings, Joshua R. Buddle, Julie Filipenko, Howard I. Scher
Journal: Journal of Clinical Oncology (2016)

e16507 Background: We hypothesized that combining abiraterone acetate (AA), an androgen biosynthesis inhibitor shown to induce prostate cancer apoptosis for patients (pts) with mCRPC, with Ipilimumab (IPI), an immune-stimulating agent designed to potentiate the host antitumor response, would be a rational novel approach for the treatment of pts with chemo-naive mCRPC. Methods: A typical 3+3 phase 1 trial was designed to enroll pts with chemo-naïve mCRPC to be treated with standard doses of AA 1000mg po daily + prednisone 5 mg po BID in combination with IPI once every 3 weeks for a total of 4 cycles. An escalation scheme for ipilimumab started at 3 mg/kg. The primary endpoint of this study was safety, with correlative studies including circulating tumor cell (CTC), FDG and FDHT-PET imaging and immunological studies of T cell subsets, effector to regulatory T cell ratio, absolute lymphocyte count and serum cytokines. Results: In a first cohort of three pts on concomitant AA and IPI, one pt experienced grade 3 transaminases, considered a dose limiting toxicity (DLT). In the expansion cohort, a second pt experienced grade 3 transaminases, and an additional pt experienced grade 3 fatigue and colitis. Due to these DLTs, the schedule was adjusted to allow for a lead in of AA (2 months) before initiating IPI. On the updated schedule, the first cohort with IPI at 3mg/kg required expansion to six patients due to grade 3 hypokalemia and dehydration. One additional pt experienced grade 3 transaminases, and our predefined Maximum Tolerable Dose (MTD) had been exceeded. Two of the four pts treated on the concomitant schedule experienced a PSA decline, one pt experienced a 92% decline, and one pt remained on treatment for 24 weeks. Two of the five pts treated on the lead-in schedule experienced a PSA decline, one pt experienced a 56% decline, and one pt remained on treatment for 41 weeks. Correlative immunological, radiological and CTC studies are ongoing. Conclusions: Concomitant or staggered AA 1000mg + prednisone 5mg BID with IPI at 3mg/kg resulted in toxicities that exceeded our predefined MTD. Support: DOD PC081610. Clinical trial information: NCT.
Metabolomic Changes in Mediastinal Lymph Node Samples Positive for Small Cell Lung Cancer.
Authors: Francisco Andres Socola, Daniel Sappington, Teka Bartter, Rosalind Penney, Thaddeus Bartter, Gunnar Boysen
Journal: Journal of Clinical Oncology (2016)

e23183 Background: The science of lung cancer is evolving towards increased understanding of metabolic pathways specific to cancer. We interrogated a library of lymph nodes (LN) aspirates from patients with small cell lung cancer (SCLC) and patients with non-malignant lung disease (NMLD) in an attempt to define metabolites that were specific to SCLC and predictive of patient survival. Methods: Endobronchial ultrasound-guided fine needle aspirates of mediastinal LN from patients with SCLC and NMLD were collected from 2011 to 2015. Metabolomic profiles were generated using liquid chromatography mass spectrometry. Metabolites were screened using multiple reaction monitoring of specific mass transitions. Analytes were confirmed using authentic standard compounds. Pathway-specific metabolite ratios were then examined for correlations with both diagnosis and survival data from the patients’ medical records. Mann Whitney and Kaplan-Meier analyses were used. Results: 49 LN aspirates were collected. 14 were positive for SCLC and 35 were from patients with NMLD. Diagnostic separation of SCLC from NMLD was observed with metabolites participating in glutamine utilization, glutamyl-cycle, and tryptophan catabolism pathways. With respect to survival, SCLC patients with lymph node aspirate anthranilic acid/tryptophan ratios above the median were associated with significantly shorter median-survival (15.2 months) than those patients with the metabolic ratio below the median (48.1 months) (HR = 0.28; 95% CI:0.03-0.68) Additionally, patients with arginine/glutamine below the median were moderately associated with shorter survival (16.2 months) versus those above the median (48.1 months) (HR = 2.88, 95% CI0.97-18.11) Conclusions: The metabolite activity of certain pathways are differed in aspirates of SCLC and NMLD patients. SCLC patients with anthranilic acid/tryptophan and arginine/glutamine ratios correlated with survival. This small study validates a mechanistic metabolic approach to SCLC, and can serve as a template for a larger population and for the application not only of metabolic but of proteomic and genomic analyses. The mechanistic approach has diagnostic, prognostic, and therapeutic potential.
A multi-center phase III study of carboplatin/paclitaxel versus oral uracil-tegafur as the adjuvant chemotherapy in resected non-small cell lung cancer
Authors: Shinichi Toyooka, Norihito Okumura, Hiroshige Nakamura, Masao Nakata, Motohiro Yamashita, Hirohito Tada, Shinsuke Kajiwara, Naoki Watanabe, Morihito Okada, Keitaro Matsuo, Motoi Aoe, Katsuyuki Hotta, Junichi Sakamoto, Shinichiro Miyoshi, Hiroshi Date
Journal: Journal of Clinical Oncology (2016)

8521 Background: Previous studies have reported that adjuvant chemotherapy provides a survival benefit in patients with resected non-small cell lung cancer (NSCLC). In Japan, uracil-tegafur (UFT) has been used for patients with completely resected NSCLC. We conducted a phase III study of carboplatin/paclitaxel versus UFT as the adjuvant chemotherapy in resected NSCLC. Methods: The patients with pathological stage IB-IIIA NSCLC, who underwent complete resection, were randomized 1:1 to carboplatin (AUC 5) /paclitaxel (175 mg/m2) every 3 week for 4 cycles (A arm) or oral administration of UFT (250 mg/m2) daily for 2 years (B arm). The primary endpoint was overall survival (OS) and secondary endpoints were relapse-free survival (RFS) and toxicity. The sample size was calculated on the basis of previous reports of an approximately 45% 5-year survival rate for the stage I-IIIA patients treated with UFT and the A arm was assumed to be 60% 5-year survival rate. A total of 200 patients for each arm were required to detect a difference with an α error of .05 and power of 80% Results: Between November 2004 and November 2010, 402 patients from 40 Japanese institutions were randomized. The median follow-up period for survivor was 6.5 years. Median age of A and B arms combined was 67 years (range; 44-82). There were 260 men and 142 women enrolled. Two-hundred sixty five patients had adenocarcinoma, 101 had squamous cell carcinoma, and 36 had other histologies. Pathological stage was IB in 195 and II-III in 207 patients. The 5-year OS rate was 70% (95% confidential interval [CI] 63 to 76%) in the patients with A arm, versus 73% (95% CI 66 to 78%) in the patients with B arm, indicating no significant difference (P = 0.69). Regarding RFS, there was no significant difference between A and B arms (P = 0.50). Toxicities were well tolerated and there were no deaths related to the treatments. Among Grade 3/4 toxicities, hematological toxicity was major and significantly frequent in A arm compared with B arm (P< 0.01). Conclusions: As adjuvant chemotherapy, carboplatin/paclitaxel does not improve the survival among completely resected NSCLC patients with stage IB-IIIA compared with UFT. Clinical trial information: UMIN000000810.
P05.02 Re-Radiation for progressive brain metastasis after previous whole brain radiation with VMAT (volumetric modulated arc therapy) technique in order to avoid Radionecrosis risk
Authors: M Theodorou
Journal: Neuro-Oncology (2018)

The risk for radionecrosis is a main problem in the radiotherapy oncology specially for Re-Radiation in the brain for brain tumors recurrence or brain metastasis progression. The whole brain radiotherapy is indicated by multiple brain metastasis more than 3 lesions. By the oligometastatic disease with brain metastasis (1- 3 lesions) a local radiotherapy such as radiosurgery or stereotactic radiotherapy is indicated. Many patients with multiple brain metastasis from breast cancer are radiated with Whole Brain radiotherapy and with the new target therapies they have a longer survival. By progression in the brain or new brain metastasis a local radiotherapy is indicated. With the advances in radiotherapy oncology with the new radiotherapy techniques a Re-radiation is possible with high dose and a good safety for the risk organs in order to avoid the radionecrosis risk. The VMAT-technique (volumetric modulated arc therapy) for Re-radiation in the brain for progressive brain metastasis after previous radiation specially whole brain radiotherapy is indicated due to the good safety for the Organ at Risk in order to avoid radionecrosis risk.
Re: Lepore et al.: Follow-up to age 4 years of treatment of type 1 retinopathy of prematurity intravitreal bevacizumab injection versus laser: fluorescein angiographic findings (Ophthalmology. 2018;125:218-226)
Authors: Michael P. Blair, Sarah Hilkert Rodriguez, R.V. Paul Chan, Michael J. Shapiro
Journal: Ophthalmology (2018)
Second-line avelumab treatment of patients (pts) with metastatic Merkel cell carcinoma (mMCC): Experience from a global expanded access program (EAP).
Authors: John Walker, Vijay Kasturi, Celeste Lebbe, Shahneen Kaur Sandhu, Giovanni Grignani, Meliessa G. Hennessy, Steven Hildemann, Josh Reed, Subramanian Hariharan
Journal: Journal of Clinical Oncology (2018)

9537 Background: Avelumab is a human anti–PD-L1 IgG1 antibody that showed a favorable efficacy and toxicity profile in pts with mMCC and progressive disease (PD) on or after chemotherapy (CT) in the phase 2 JAVELIN Merkel 200 trial (JM 200; NCT02155647), leading to accelerated approval in the US and Europe. We describe real-world experience with avelumab in a global EAP for pts with mMCC. Methods: Pts participating in the EAP (NCT03089658) had stage IV mMCC and PD on or after CT or were ineligible for CT. In contrast to JM 200, pts in the EAP could have ECOG performance status of 2, treated brain metastases, or immunosuppressive conditions with sponsor medical approval. Pts received avelumab 10 mg/kg IV Q2W until PD or unacceptable toxicity. A 3-mo supply of avelumab for approved pts was provided to treating physicians; additional re-supply was allowed for pts who had complete response (CR), partial response (PR), stable disease (SD), or clinical benefit per treating physician assessment. No central imaging was obtained. Results: Between Jan 2016 and Jan 2018, 460 requests for avelumab were received from 37 countries: 395 were approved, 45 were medically rejected for various reasons (eg, incorrect diagnosis, lack of appropriate prior therapy, incomplete information), and 37 were withdrawn. Most requests were from France (n = 97), Italy (n = 69), and Australia (n = 46). Median age was 74 y (range, 28-95), and 65.7% of pts were male. Among 131 response-evaluable pts, the objective response rate was 51.1%, including CR in 22.1% (n = 29) and PR in 29.0% (n = 38; including 1 pt with HIV); 19.1% (n = 25) had SD and 29.8% (n = 39) had PD. Durable responses were observed in immune-competent and immunosuppressed pts. Updated data will be presented. The safety profile was similar to that of JM 200. The EAP is ongoing but will close in 2018 (US closed in April 2017) with regulatory approval in multiple countries. Conclusions: The avelumab EAP rapidly enrolled many pts with mMCC and answered an unmet, urgent medical need for pts ineligible for clinical trials or for whom no approved alternative treatments were available. In a real-world setting, avelumab demonstrated safety and efficacy consistent with JM 200. Clinical trial information: NCT03089658.
P02.08 Visualizing tumor cell - lymphocyte interactions in the brain metastatic cascade using in vivo two photon microscopy
Authors: M Piechutta, A S Berghoff, M A Karreman, K Gunkel, W Wick, F Winkler
Journal: Neuro-Oncology (2018)

Despite high frequency of brain metastases (BM) in patients with advanced tumor stages and the process that immunotherapy becomes the treatment of choice in these cases, the activity and mechanisms of the adaptive immune response in BM is poorly understood. Current knowledge on the immunological tumor microenvironment is gained from in vitro- and ex vivo experiments, such as flow cytometry and immunohistochemistry. However, these methods fail to recapitulate the dynamic influx of lymphocytes and their interaction with tumor cells in the complex tumor microenvironment. A better understanding of lymphocyte recruitment, trafficking and activation in vivo is urgently needed to improve immunotherapeutic approaches. To characterize the adaptive immune response in BM at single cell resolution, we developed a unique model allowing us to monitor these processes in vivo over weeks using repetitive two photon intravital microscopy. Recipient mice with a chronic cranial window were introduced with fluorescent glycoprotein-100 (gp100) positive syngeneic melanoma cells via heart injection or stereotactic injection into the cortex. Next, these mice received adoptive cell transfer of tumor-specific, fluorescently labeled CD8+ T cells from pmel-1 donor mice. It was possible to establish the first long-term imaging method to study dynamic lymphocyte- tumor cell interactions in the event of BM in vivo on a single cell level. CD8+ T cells could be recognized not only by its fluorescence signal but also due to their size and typical lymphocytic movement. We observed tumor-specific T cells to cross the brain blood barrier within a couple of hours and reside at the site of tumor for several days. Notably, transferred T cells were found in the tumor margin and inside the tumor but not in healthy brain parenchyma. Taken together, this preclinical model provides insights into the underlying mechanisms driving the immuno-response in vivo at high resolution. Importantly, it enables to further investigate and improve immunotherapeutic approaches with respect to prevention and therapy of BM.
Comparison of clinical characteristics and prognoses of patients with T1 non-small cell lung cancer and small cell lung cancer in a Chinese real-world study.
Authors: Xu Jinming, Heng Zhao, Xiaofei Li, Yang Liu, Lunxu Liu, Xiangning Fu, Lin Xu, Yin Li, Xingpeng Han, Deruo Liu, Yihe Wu, Jinlin Cao, Haiying Yang, Jian HU
Journal: Journal of Clinical Oncology (2018)

e20527 Background: Radical resection is preferred for treatment of patients with T1 lung cancer, and patient prognoses could be significantly affected by tumor pathological types. Since the clinical data of patients with T1 non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) were rarely reported, the real-world study was proposed to explore clinical characteristics and prognoses of the target population in practice. Methods: The study was conducted based on a national collaborative lung cancer database (designed by LinkDoc Technology Co, Ltd.). The pathologically diagnosed T1 NSCLC and SCLC patients who received surgeries from 2014 to 2017 were enrolled to evaluate overall survival (OS) in the total population and in the subgroups. The OS were measured by the Kaplan-Meier method and the Log-rank test. Results: A total of 12,703 subjects with T1 NSCLC and 251 subjects with SCLC subjects were enrolled in the study. The one, two, and three-year OS rates of the NSCLC patients were 97.5%, 93.8%, and 89.0%, respectively while the OS rates of the SCLC patients were 90.5%, 77.6% and 72.1% individually. The patients with T1 SCLC presented significantly poorer OS than the NSCLC patients (hazard ratio, HR: 3.920, 95% confidential intervals, 95% CI, 2.723, 5.654, p < 0.05). In the subgroups of the patients categorized by age, gender, smoking/drinking history, body mass index (BMI), tumor size, modes of surgeries, poorer OS rate of the SCLC patients was observed compared to that of the NSCLC patients (p < 0.05). In the NSCLC subpopulation, OS in the elderly patients, patients with squamous cell carcinoma, patients with poor differentiated tumors, and patients with lymph metastases were poorer as demonstrated by multivariate analyses (p < 0.05). Conclusions: The real-world data offered clinical evidences on management of Chinese T1 NSCLC and SCLC patients. Poorer patient surival was observed in the T1 SCLC patients compared to the NSLCLC patients that could be references for design and data interpretation of the randomized clinical trials. Clinical trial information: ChiCTR1800014566.
Effect of local intervention on renal cell carcinoma metastases in patients treated with tyrosine kinase inhibitors (TKIs) stratified by IMDC risk groups.
Authors: James Ryan Mark, Caroline Arden Merwarth, Nicholas Brent Drury, Yimei Han, James Thomas Symanowski, Asim Amin, Kris E Gaston, Stephen Boyd Riggs
Journal: Journal of Clinical Oncology (2016)

e16101 Background: Local intervention (LI) with surgery or radiation may offer a benefit to patients with metastatic renal cell carcinoma (mRCC) treated with TKIs. The IMDC prognostic model has been shown to predict outcomes in patients with mRCC treated with TKIs. We assessed whether the IMDC prognostic model can be used to determine the impact of LI in patients with mRCC. Methods: Retrospective analysis was performed on patients diagnosed with mRCC who had previously undergone nephrectomy and received treatment with TKIs from 2006-2013. Patients were stratified into IMDC risk groups. Overall survival (OS) and progression free survival (PFS) were analyzed to compare patients receiving TKI with or without LI. Results: Of the 190 evaluable patients, 104 received TKIs and had complete data for stratification by IMDC. Median age was 57 years, and patients were predominantly male (75%). 79.78% of patients had clear cell mRCC. There were 12 (11.54%), 62 (59.62%), and 30 (28.85%) patients in favorable, intermediate, and poor risk IMDC groups, respectively. 66 patients were treated with LI. Favorable/ intermediate (pooled due to sample sizes) and poor risk patients treated with TKI + LI had an average of 3.2 and 2.8 metastatic sites vs 2.4 and 2.0 metastatic sites for favorable/ intermediate and poor risk patients treated with TKI alone. OS and PFS results are shown in Table 1. Conclusions: Patients with mRCC receiving TKIs in favorable/ intermediate IMDC risk group had significant improvement in OS and PFS from LI while the results for poor risk patients were inconclusive. These data suggest that IMDC stratification may be useful in selecting patients appropriate for LI. Overall survival (OS) and progression-free survival (PFS) by IMDC risk group and treatment modality. OS Risk Group N (events) Median (mos.) HR (95% CI) P-value Favorable/Intermediate pooled OS LI + targeted 48 (17) 94.2 0.28 (0.13, 0.59) <0.001 Targeted (ref) 26 (14) 31.5 -- PFS LI + targeted 48 (39) 21.7 0.29 (0.16, 0.51) <0.001 Targeted (ref) 26 (22) 5.7 -- OS Poor LI + targeted 18 (7) 50.2 0.41 (0.12, 1.35) 0.130 Targeted (ref) 12 (6) 20.0 -- PFS LI + targeted 18 (14) 9.2 0.74 (0.31, 1.75) 0.495 Targeted (ref) 12 (9) 7.4 --