bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding treatment patterns and outcomes in patients with metastatic NSCLC treated in a US community oncology network.
Authors: Nadler Eric S. , Espirito Janet L. , Pavilack Melissa , Boyd Marley , Vergara-Silva Andrea Leninka , Fernandes Ancilla 
Published: September 2018

e20643 Background: Multiple therapeutic options exist for metastatic non-small cell lung cancer (mNSCLC), including chemotherapy (CH), targeted therapy (T), and immunotherapy (IT). The first IT for mNSCLC was FDA approved in 2015 for use after progression on platinum-based CH and T in patients (pts) with EGFR or ALK mutations. The current study evaluates treatment (tx) patterns and outcomes in mNSCLC pts receiving first- (1L), 2nd- (2L), and 3rd-line (3L) therapy. Methods: This is a retrospective, observational cohort study of mNSCLC pts receiving initial tx from 1/2012–4/2016, with follow-up to 6/2016. Data were obtained from The US Oncology Network/McKesson Specialty Health electronic health records database. Demographics, clinical characteristics, and tx patterns were characterized. Overall survival (OS) was assessed using the Kaplan-Meier method. Results: 10,689 1L pts were identified during the study period. Median age was 68 y, and 54% were male. Most pts (59%) had an ECOG performance status of 1, 77% had nonsquamous histology, and 85% were former or current smokers. Initial tx was CH in 93% of pts. Among pts receiving initial T therapy, most were never smokers (48%) vs initial CH pts (12%; P< 0.0001). Median OS (mOS) for all pts at 1L was 12.3 mo (95% CI, 11.9–12.7), and mOS was significantly longer in pts who received T (24.3 vs 11.7 mo for T vs CH, p< 0.0001). Among pts who received 2L therapy in the study period (n = 4235), 66%, 17%, and 17% received CH, T, and IT respectively. Pemetrexed or docetaxel monotherapy was most commonly used for 2L CH, erlotinib was most used as 2L T, and nivolumab for 2L IT. mOS from start of 2L for CH, T, and IT was 9.2, 11.2, and 9.7 mo, respectively (log rank P= 0.01). In 3L pts (n = 1580), nivolumab was most frequently used (17%), and mOS from 3L for CH, T, and IT was 8.0, 7.4, and 11.3 mo, respectively ( P= 0.0187). Conclusions: These data demonstrate integration of novel therapies for mNSCLC in the community. Longer survival was observed in 2L and 3L patients treated with T and IT as compared with CH. This warrants additional randomized studies to investigate optimal sequencing of these agents.
Efficacy of PD-1/PD-L1 inhibitors in the front-line setting as compared to previously treated patients.
Authors: Jain Prantesh , Khunger Monica , Pasupuleti Vinay , Hernandez Adrian V , Velcheti Vamsidhar 
Published: September 2018

e20646 Background: Drugs targeting the PD-1/PD-L1 pathway show significant clinical activity in non-small cell lung carcinoma (NSCLC). Nivolumab, pembrolizumab and atezolizumab are currently approved for NSCLC patients who have progressed while on platinum-based chemotherapy. Recently, pembrolizumab received FDA approval for treatment naive NSCLC patients with tumor PD-L1 expression of ≥50%. However, there is relative lack of data on comparative efficacy of these drugs in the chemotherapy naive versus post-chemotherapy setting. In the current meta-analysis we compare the efficacy and toxicity of these drugs in chemotherapy naïve patients with those who receive them as subsequent therapy (after previous chemotherapy). Methods: A systematic search of electronic databases (PubMed-Medline, EMBASE, Scopus) and major conference proceedings was done for all clinical trials using PD1/PD-L1 inhibitors. Objective response rates (ORR) for patients determined to have positive tumor PD-L1 expression (Tumor Proportion Score ≥1%) from all phase I-III trials investigating nivolumab, pembrolizumab, atezolimumab, durvalumab and avelumab for NSCLC were collected. Only single agent PD-1/PDL-1 inhibitor trials were included. The ORR across trials was combined using DerSimonian-Laird random effects models. Higgins’ I2 statistic was used to assess heterogeneity. Results: 19 trials (7 with treatment naïve patients [n = 651]; 14 with chemotherapy treated patients [n = 2205]; 2 with separate treatment naïve and previously treated arms) were included. Treatment naïve patients were found to have statistically significant higher efficacy [ORR 28.27%(95% CI 20.70-36.52)] than those who received these drugs as subsequent therapy [ORR 20.13% (95%CI 17.53-22.85) (p = 0.02). Treatment naive patients had statistically significant higher rates of all grade pneumonitis as comapred to previously treated patients (4.9, 95%CI 3.4-6.7 vs 3.0 95% CI 2.0-4.1). Conclusions: PD1/PDL1 therapy for advanced NSCLC has a significantly improved efficacy (based on ORR) when used in treatment naïve patients as compared to its use in patients who have been previously treated with chemotherapy.
Impact of different timing of radiation therapy in patients with brain metastases from epidermal growth factor receptor-mutant non-small cell lung cancer.
Authors: Ying Xiaozhen , Han Shuiyun , Jiang Chenxue , Sun Xiaojiang , Xu Yaping , Mao Weimin 
Published: September 2018

e20667 Background: To perform a retrospective analysis of patients with brain metastases (BM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) to evaluate the preferred treatment timing of EGFR-tyrosine kinase inhibitors (TKIs) in this population. Methods: Of 94 initial or recurrent patients diagnosed BM from EGFR-mutant NSCLC between Jan 1, 2012, and Jun 31, 2016, 30 received upfront brain RT followed by EGFR-TKI, 39 EGFR-TKI combined with concurrent brain RT, and 25 upfront EGFR-TKI then brain RT. Disease-specific-graded prognostic assessment was similar among all 3 groups. The primary endpoint was overall survival (OS), and the second endpoint was intracranial progression-free survival. Results: Although the median OS was not significantly different among the upfront RT, concurrent treatment, and upfront EGFR-TKI groups (29.0 vs 24.0 vs 17.0 months; P = 0.186), however, it was longer in the upfront RT group compared with the upfront EGFR-TKI group (P = 0.035). On subgroup analysis, the exon 19 deletions patients had longer OS than the exon 21 mutations patients in upfront EGFR-TKI group (23.0 vs 15.0 months; P = 0.048), but the upfront RT (34.0 vs 23.0 months; P = 0.186) and the concurrent treatment groups (24.0 vs 13.0 months; P = 0.827) did not. According to multivariate COX analysis, KPS (≥ 70) and intracranial metastasis alone was associated with a longer OS. The median intracranial progression-free survival was significantly improved in patients receiving upfront RT compared with those receiving concurrent treatment or upfront EGFR-TKI (not reached vs 40.0 vs 9.0 months; P = 0.003). Conclusions: The present study suggests that the use of upfront brain radiotherapy, and the deferral of EGFR-TKI may result in superior OS in patients with brain metastases from EGFR-mutant NSCLC. Also, upfront brain radiotherapy management could significantly reduce the risk of intracranial progression. A prospective, multi-institutional, randomized trial of upfront EGFR-TKI then RT versus upfront RT followed by EGFR-TKI is urgently needed, especially based on different subgroup population.
Retrospective analysis of patients (pts) with metastatic melanoma (MM) showing long-term response (LTR) to vemurafenib (Vb).
Authors: Galli Giulia , Di Guardo Lorenza , Cimminiello Carolina , Cavalieri Stefano , Rodolfo Monica , Rivoltini Licia , Valeri Barbara , Bono Aldo , Tolomio Elena , Del Vecchio Michele 
Published: September 2018

e21001 Background: Efficacy of Vb in the treatment of mm has been established. We aimed to analyze characteristics of pts achieving LTR to Vb in order to identify potential predictive factors of prolonged benefit. Methods: We collected information about pts affected by BRAF V600 mutated mm treated with Vb at Medical Oncology Unit of Istituto Nazionale dei Tumori, Milan, Italy, from 09/2010 to 08/2014. LTR was defined as clinical or radiological benefit longer than 14 months (mos). Biological data about circulating lymphocyte subpopulations and CCL2 levels were also determined. Results: 46 pts (26 men, 20 women) were identified. Median age was 58 years. ECOG performance status was 0 in 44 pts. Disease stage was M1a in 14 pts, M1c in 20 pts. 8 pts had high serum LDH levels and 5 brain metastases at baseline. 41 pts harbored BRAF V600E mutation, 5 V600K. Median follow up was 47 mos. 5 pts had received adjuvant interferon; 9 pts had been treated with up to 3 lines for metastatic disease (either chemotx or ipilimumab). According to RECIST 1.1, 22% of pts showed complete response (CR), 50% partial response and 22% stable disease. Notably, all CRs were maintained for more than 2 years. 26 pts progressed, mostly (38%) with brain metastases; 16 of them continued tx beyond progression. Median duration of response was 33 mos, being significantly longer in M1a than in M1c (44 versus 28 mos). Median PFS was 32.5 mos; median OS was not reached. All pts experienced at least 1 adverse event (AE); the AEs were moderate or severe in 22% of cases. 19 pts underwent dose reduction, but no discontinuation due to AEs was observed. After 6 mos of tx, pts with LTRs had less myeloid derived suppressor cells (CD11b+ CD14+) and more memory Th1 cells (CD8+ CXCR3+) if compared with pts not bearing LTRs. The same pts after 1 mo of tx showed lower plasma levels of CCL2, a marker of acquired resistance to Vb. Conclusions: Vb can induce LTRs in a subset of pts with mm also in presence of unfavorable prognostic factors, though M1a pts are more likely to obtain prolonged benefit. Toxicity is frequent, but manageable with limited dose reductions. Exploratory biological analyses suggest an immunomodulatory effect of Vb and the existence of circulating biomarkers of LTR.
Efficacy of combined hypofractionated radiotherapy and anti-PD-1 monotherapy in patients with melanoma.
Authors: Roger Anissa , Finet Adeline , Boru Blandine , Mazeron Jean-Jacques , Otmezguine Yves , Blom Astrid , Longvert Christine , De Maleissye Marie-Florence , Beauchet Alain , Saiag Philippe 
Published: September 2018

e21008 Background: Information on the role and type of radiotherapy in melanoma pts treated with anti-PD1 is limited. We report a cohort of advanced melanoma pts having received simultaneous hypofractionated radiotherapy and anti-PD-1 monotherapy. Methods: Database search in the prospective database of a referral center with standardized radiotherapy procedures for all pts having received both treatments between 1/1/15-30/6/16. Radiologists performed independent tumor evaluations (RECIST 1.1) every 3 m, both on radiated and non-radiated lesions. Results: 25 pts with inoperable AJCC stage 3-4 melanoma, mean age 60.5 Y. Anti-PD-1 monotherapy was first systemic treatment in only 40% of pts. Median follow-up after onset of anti-PD-1 therapy (83% nivolumab, 17% pembrolizumab) was 13.3 m, with 48% of pts still alive at last follow-up. Radiotherapy was performed either early (within first 3 m of PD-1 blockade) in pts with rapidly progressing symptomatic lesion(s) (60% of pts) or late ( > 3 m) in pts with slow progression or dissociated response (40% of pts). It consisted of 1 weekly radiation during 4-5 w (84% of pts), or 1 gammaknife radiation for cerebral mets (16% of pts). Median delay between onset of PD-1 blockade and radiotherapy was 1.8 m (range 0.5-11 m). For radiated lesions, rates of complete (CR), partial (PR) responses, stabilization (S) or progression (P) were 24%, 8%, 44%, and 28%, respectively. For non-radiated lesions (84% of pts), rates of CR, PR, S, and P were 29%, 19%, 19%, and 33%, respectively. Among pts radiated late for insufficient response to anti-PD-1 monotherapy, CR or PR in non-radiated lesions (i.e. abscopal response) was observed in 56% of pts. Anti-PD-1 therapy could be discontinued in 4 pts with CR, without relapse to date. No unusual adverse event was recorded. Conclusions: Hypofractionated radiotherapy may enhance anti-PD1 monotherapy efficacy in difficult-to-treat pts. Controlled studies are needed.
Association of loss of nuclear BAP1 expression with prognosis in oral mucosal melanoma.
Authors: Guo Wei 
Published: September 2018

e21021 Background: The prognostic factors of oral mucosal melanoma (OMM),a rare and aggressive neoplasm, remain to be determined. BAP1 is a tumor suppressor that has been associated with the outcome of melanomas and other malignancies. In this study, we investigated the genetic alterations in BAP1 and the prognostic potential of BAP1 protein expression in oral mucosal melanoma. Methods: DNA sequence analysis of BAP1 from 12 OMM patient samples revealed missense mutations in the tissues from four patients. Results: Based on immunohistochemical staining, loss of nuclear BAP1 expression was associated with poor overall survival (P < 0.001, Log-rank = 21.308) and distant metastasis (P = 0.034, OR = 0.320). Multivariate analysis showed BAP1 to be an independent prognostic factor (P = 0.027, HR = 0.479). Conclusions: It thus appears that loss of nuclear BAP1 expression is an independent prognostic factor of poor overall survival and associated with distant metastasis in OMM.
Outcomes of melanoma brain metastases treated with stereotactic radiosurgery with and without concurrent immune checkpoint therapy.
Authors: Yang Jessica , Dercle Laurent , Yaeh Andrew M. , Yeh Randy , Manson Daniel K. , Saad Shumaila , Jeffrey Bruce N. , Sisti Michael B. , McKhann Guy M. , Wang Tony J. C. , Schwartz Lawrence H. , Carvajal Richard D. 
Published: September 2018

e21026 Background: Evidence supports a synergistic effect between immunotherapy and radiotherapy. In this single-institution study, we compared outcomes of patients (pts) with melanoma brain metastases (BMs) who received Gamma Knife Radiosurgery (GKRS) with and without concurrent immune checkpoint blockade (ICB). Methods: Using an IRB-approved protocol, we identified pts with melanoma BMs who received GKRS from 5/2000 to 8/2016. Treatment was deemed concurrent if patients had GKRS within 4 weeks of ICB. Irradiated lesion control, tumor growth rate (TGR; percent change in product diameters per month), distant brain control, overall response rate (ORR) by modified WHO criteria, best response, and overall survival (OS) were compared. Results: 28 pts were identified: 17 (34 BMs total) received GKRS alone; 11 (23 BMs total) received concurrent GKRS/ICB. ICB included: ipilimumab (n = 3), anti-programmed death-1 (anti-PD-1) therapy (n = 4), and combined ipilimumab + nivolumab (n = 4). In comparing baseline characteristics between the GKRS alone and GKRS/ICB groups: median age was 65 v. 59 years, proportion of males was 53% v. 73%, 41% v. 45% had prior neurosurgery, and median number of prior systemic therapies was 1 v. 0. There was no difference in irradiated lesion control (6-month control rate 86% v. 96%; n = 57; p = 0.65), median TGR (-14% [range -100% to +61%] v. -20% [range -71% to 0%]; n = 42 lesions, p = 0.38), or distant brain control (6-month control rate 68% v. 60%; p = 0.51; median follow-up 8.6 months v. 8.0 months) with GKRS/ICB v. GKRS alone. The ORR with GKRS alone v. GKRS/ICB was 61% v. 47% (p = 0.33), and the median maximum reduction in BM bidimensional measurement was -69% v. -45% (p = 0.43). Median OS from the date of GKRS was not reached for the GKRS/ICB group and was 16.6 months for the GKRS alone group (p = 0.03). Conclusions: There was no difference in local lesion control, TGR, or distant brain control with concurrent GKRS/ICB compared to GKRS alone, but the study was limited by small patient numbers and biased by closer follow-up in the GKRS/ICB group. OS was longer with concurrent ICB, likely reflecting the survival improvement with immune checkpoint inhibitors.
Frequency and outcomes of melanoma subtypes in a diverse population: The Los Angeles County – University of Southern California (LAC-USC) Medical Center experience.
Authors: In Gino Kim , Yang Dongyun , Thomas Jacob Stephen , Pham Anthony , Basu Arnab , Mehta Arjun Ajay , Miller Kimberly Ann , Cockburn Myles , Hu James 
Published: September 2018

e21063 Background: Melanoma is a biologically heterogeneous disease that varies by ethnicity and histology. While superficial spreading (SSM) histology is the most common subtype in non-Hispanic whites (NHW), acral lentiginous (ALM) and other subtypes occur more frequently in Hispanics, Asians and African Americans. There are no known risk factors for ALM, and further investigation is warranted. Methods: We retrospectively reviewed a database of melanoma patients diagnosed between 2001-2016 at LAC-USC. Overall survival (OS) was estimated using Kaplan-Meier methodology, and comparisons performed using log-rank testing. Fisher’s exact test was used to evaluate associations between relevant clinicopathological variables. A p-value < 0.05 was considered statistically significant. Results: Among 272 melanoma patients, there were 140 Hispanics (51.5%), 105 NHW (38.6%), 14 Asians, and 4 African Americans. The most frequent histology among Hispanics was ALM (30.7%), while SSM was the most frequent among NHW (33.3%). BRAF V600 mutations were found in 34.5% (10/29) and 58.8% (10/17) of Hispanics and NHW, respectively. A total of 52 patients with ALM were identified, including 43 Hispanics (82.7%). There was a significant association between no prior history of non-melanoma skin cancer (NMSC) and ALM (p < .0001). Median Breslow thickness for ALM was 4.2 mm, and 32.7% were ulcerated. The rate of BRAF V600 mutations among 13 ALM patients tested was 0%. NRAS mutations were found in 3 ALM patients; KIT amplification/mutations were found in 2 ALM patients. Conclusions: We identified a population enriched for Hispanic patients with ALM. We found an association between no prior NMSC and ALM, suggesting that UV exposure is not a causative risk factor. BRAF mutations are less common amongst Hispanics, and nearly absent in ALM. Survival differences were not statistically significant, but cannot be ruled out due to low number of patients in this early study. [Table: see text]
Retrospective analysis of ipilimumab-induced diarrhea and/or colitis: A single centre review.
Authors: Iafolla Marco Adelmo James , Pond Gregory Russell , McWhirter Elaine 
Published: September 2018

e21064 Background: Ipilimumab is an effective medication in advanced melanoma but can cause severe diarrhea and colitis. This study identified the rate of ipilimumab-induced diarrhea/colitis at the Juravinski Cancer Centre (JCC), its associated factors for development, overall survival (OS) and progression free survival (PFS). Methods: The Ontario Patient Information System was used to retrospectively identify all melanoma patients at the JCC who were treated with ipilimumab 3 mg/kg IV every 3 weeks (September 2012 to June 2016). Patient demographics, medical history, prior melanoma treatments, diagnosis of ipilimumab-induced diarrhea/colitis, interventions to treat the diarrhea/colitis, and OS and PFS were collected. Descriptive statistics summarized characteristics and outcomes. Kaplan-Meier methods estimated time to event outcomes. Cox regression evaluated whether markers were prognostic for time to diarrhea/colitis diagnosis. Results: 71 patients were treated with ipilimumab at the JCC, of which 22 patients (31%) developed diarrhea/colitis of any Grade; 4 patients developed Grade 1, 5 patients Grade 2, 6 patients Grade 3, 3 patients Grade 4, and 4 patients had unclear Grade. 11 patients required prednisone 1-2 mg/kg and 2 patients required anti-TNF treatment to treat their diarrhea/colitis; 1 patient required colectomy due to perforation. 10 patients required treatment discontinuation due to diarrhea/colitis. Whole cohort median OS and PFS was 340 days (95% CI 205, 519) and 110 days (95% CI 91, 138), respectively. Univariate analysis showed that only inadequate hematologic function at time of first ipilimumab application was prognostic of diarrhea/colitis (HR = 6.42, 95% CI 1.44, 28.62; p = 0.015). Conclusions: Our OS, PFS, and rate of all grade ipilimumab-induced diarrhea/colitis are similar to published data, however our rate of Grade > 2 is larger. Additional work is needed to identify risk factors for the development of this immune related adverse event.
Whole-body MRI (WB MRI) including diffusion weighted (DW) imaging for the surveillance of melanoma patients at high risk for recurrence following surgery or systemic therapy.
Authors: Jansen Yanina , Willekens Inneke , Brussaard Carola , Neyns Bart 
Published: September 2018

e21072 Background: Patients (pts) with locally advanced melanoma have a high risk of recurrence following complete surgical resection of macrometastases. Recent therapeutic progress has led to a growing number of stage IV pts achieving a durable complete remission (CR). For both populations no standards are established for surveillance with medical imaging. This prospective study explored the usefulness of surveillance by WB MRI for the early detection of melanoma recurrences. Methods: Pts with advanced melanoma (AJCC stages IIIb/-c or -IV) who were disease free following resection of macrometastases (cohort 1) and pts in CR following immunotherapy (cohort 2) were included. All pts underwent WB MRI, includingT1, Short Tau Inversion Recovery and DW imaging, Q4 mths the first 3 years of follow-up and Q6 mths in the following 2 years. Results: From Oct 2014 to Jan 2017, 43 pts were included (26 pts in cohort 1; 17 in cohort 2). 4 Pts were excluded (pacemaker [1pt], claustrophobia [1 pt], clinical recurrence before the first MRI [2 pt]). Mean follow-up was 103 wks (range 14–127). In total, 182 WB MRIs were performed (median number per pt: 4.5 [range 3-7]). A total of 16 pts were diagnosed with suspected lesions on WB MRI. Of these, 8 pts were diagnosed with melanoma recurrences (7 pts in cohort 1 and 1 pt in cohort 2). A total of 8 suspected lesions (8 Pts) identified on MRI (4 lymph node, 1 muscle, 1 bone, and 2 liver lesion) were considered to be of non-neoplastic origin based on additional diagnostic imaging and follow-up. No invasive procedures resulting in a false negative result were triggered by MRI. In 2 pts from cohort 2 a solitary subcutaneous metastasis was first detected by clinical examination (1 could be identified on MRI retrospectively, 1 was found in between MRIs). WB MRI was safe without any clinically meaningful ( > gr1) adverse event. Conclusions: Exploration of WB MRI for the surveillance of melanoma patients following resection of melanoma macrometastases or CR on systemic therapy indicates that it is a safe and sensitive imaging technique sparing patients cumulative exposure to x-rays and contrast media. Clinical trial information: NCT02907827.