bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGFR1 amplification in squamous cell lung cancers.
Authors: Cote Michele L , Bepler Gerold , Land Susan , Bollig-Fischer Aliccia , Schwartz Ann G. , Gadgeel Shirish M. 
Published: March 2020

7063 Background: Squamous cell carcinoma of the lung (SqCCL) is the second most common type of lung cancer. There are currently no established targeted therapies that take advantage of SqCCL-specific genetic abnormalities. Amplification of the fibroblast growth factor receptor type 1 gene (FGFR1) has been identified as a driver event in breast cancers and in SqCCL. The demographic characteristics and prognosis of patients with these tumors remains to be defined. Methods: DNA from 123 surgically resected, fresh frozen, and clinically annotated SqCCLs was extracted using a resin-based or phenol-based methodology. DNA quantity and quality was assessed using the Quantifiler kit (ABI). Specimen histology was validated, and the proportion of tumor cells was >60%. Copy number variation (CNV) analysis was performed using quantitative PCR with primers specific for exons 12 and 16 of FGFR1 and data analysis using CopyCaller (ABI). Samples with a predicted CNV of at 2 or greater in at least one exon were scored as amplified. Chi-squared tests were used to examine clinical and demographic differences between patients with and without amplification of FGFR1. Survival differences were examined by Kaplan Meier and Cox regression models. Results: Men comprised the majority of the population (n=91, 74%) and most cases were pathological stage I (n=75, 61%) or stage II (n=32, 26%). Thirty (24.4%) tumors showed amplification of FGFR1. There was no association between amplification and sex (p=0.18) or stage (p=0.37). The majority of the patients were white (n=114, 92.7%), but the proportion of tumors that were amplified was higher among non-whites (5/9, 55.5%) than whites (25/114, 21.9%, p=0.02). Overall, median survival was 32.2 months. In univariate survival analysis, amplification was associated with an increased hazard of death (HR=1.55, Wilcoxon p=0.03). Tumor stage at diagnosis was also associated with increased risk of death (HR=1.67, p=0.0009). Only stage remained a significant predictor of death in the multivariate survival models (HR=1.65, p=0.004). Conclusions: Somatic amplification of FGFR1 is a relatively common event in SqCCL and may be associated with race and overall survival.
Multicenter phase II study of concurrent high-dose (72Gy) three-dimensional conformal radiotherapy (3D-CRT) without elective nodal irradiation with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small cell lung cancer (NSCLC).
Authors: Horinouchi Hidehito , Sekine Ikuo , Sumi Minako , Satouchi Miyako , Isobe Hiroshi , Harada Masao , Niho Seiji , Mori Kiyoshi , Tamura Tomohide 
Published: March 2020

7070 Background: The optimal dose of radiotherapy remains unclear in concurrent chemoradiotherapy for unresectable stage III NSCLC. We previously concluded that the recommended dose for further trial was 72Gy in a phase I study (Sekine et al., Int J Radiat Oncol Biol Phys. 953-959, 2012). Methods: Eligible patients (unresectable stage III NSCLC, age between 20 and 74, PS 0-1, V20 ≤ 30%) received cisplatin (80 mg/m2 day 1) and vinorelbine (20 mg/m2 days 1 and 8) repeated every 4 weeks for 3-4 cycles. The 3D-CRT started at the first day of chemotherapy at a total dose of 72 Gy in 36 fractions. The primary endpoint was a 2-year survival rate and the planned sample size was 60 to reject the rate of 45% under the expectation of 65% with a power of 90% and an alpha error of 5%. Results: Thirty-one patients from 4 institutions were enrolled between May 2009 and March 2010. This trial was terminated early due to slow accrual and grade 5 pulmonary toxicities in 2 patients. There were 25 men and 6 women with a median (range) age of 59 (32-72) years. Of these, 23 had adenocarcinoma and 21 had stage IIIA disease. The median (range) V20 value was 20 (9-30). The full planned dose of radiotherapy could be administered in 30 (97%) patients, and 26 (84%) of the patients received 3-4 cycles of chemotherapy. During the chemoradiotherapy, grade 3-4 febrile neutropenia, infection and esophagitis were noted in 5, 4 and 1 of the 31 patients, respectively. After completion of the planned chemoradiotherapy, 5 patients had grade 3 or higher radiation pneumonitis, and 2 (6%) of these patients died at 6.6 and 7.3 months after the treatment started. The overall response rate was 97% (95% confidence interval: 83.3-99.9). Twenty-four patients are alive and thirteen patients experienced recurrence (2 had loco-regional recurrences, 7 had distant recurrence and 4 had mixed recurrence pattern) at a median follow up of 16.4 months. Conclusions: Concurrent high-dose (72Gy) 3D-CRT with chemotherapy using cisplatin and vinorelbine may have a too excessive incidence of pulmonary toxicities to warrant any further evaluation.
Size distribution and metastasis in discarded intrapulmonary lymph nodes (LN) after lung cancer resection.
Authors: Miller Laura Elizabeth , Ramirez Robert A. , Wang Christopher Gene , Adair Courtney A , Berry Allen , O'Brien Thomas , Osarogiagbon Raymond U 
Published: March 2020

7072^ Background: Lymph node (LN) status is the most important prognostic determinant after resection of lung cancer. 18% of a SEER cohort and 12% of a Memphis cohort had no LNs examined (pNx). Patients with pNx have inferior survival to T-category matched pN0 patients with at least 1 LN examined. The optimal number of LN needed to safely declare a patient pN0 may be >10. Less than 20% of resections in SEER achieve this. We hypothesized that a significant number of intrapulmonary LNs are left unexamined and some may harbor metastatic disease. We report the size characteristics of materials examined in a re-dissection protocol to test this hypothesis. Methods: Prospective study of lung resection specimens re-dissected after signout of the final pathology report. Remnant lung material was dissected with thin cuts and all LN-like material was retrieved for microscopic examination, irrespective of size or location. The size of non-LN tissue, LN without metastasis and LN with metastases were compared using the Wilcoxon-Mann-Whitney test. Results: 112 specimens were examined and 1,094 LN-like materials were retrieved. 749 (69%) proved to be LN tissue. 71 (10%) LNs retrieved had metastasis. Non-LN tissue was significantly smaller than LN tissue (p<0.0001). LNs with metastasis were significantly larger than those without metastasis (p <0.0001). 60% of materials >2cm were LNs with metastasis. 7% of materials <1cm were LN with metastasis. 52% of LNs with metastasis, and 55% of LNs without metastasis measured from 0.5 to 1.5cm (Table). Majority of LNs >2cm had metastatic disease, but 40% did not; a notable proportion of LNs with metastasis were small. Nearly equal percentages of LNs with and without metastasis were found in the range of 0.5-1.5cm. Conclusions: Statistical differences in size between lymph nodes with and without metastasis is clinically meaningless due to broad overlap. LN size alone is not an adequate predictor of LN metastasis. [Table: see text]
The Lung Cancer Symptom Scale (LCSS) as a prognostic indicator of overall survival in malignant pleural mesothelioma (MPM) patients: Post hoc analysis of a phase III study.
Authors: Wang Ping , Bowman Lee , Shen Wei , Winfree Katherine B. , Peterson Patrick , John William J. 
Published: March 2020

7075 Background: To determine the patients likely to benefit from therapy, clinicians seek factors associated with outcomes. This analysis investigates prognostic effect of baseline patient-reported symptoms on overall survival (OS) in the presence of demographic/clinical factors among MPM patients. Methods: Intent-to-treat patients (N=448) were included in the analysis. LCSS consists of 6 symptom items and 3 general items, each ranging from 0 (no symptoms) to 100 (worst). Average symptom burden index (ASBI) was the mean of 6 symptom items. Patients were classified into subgroups based on ASBI: low symptom burden (LSB; ASBI<25) and high symptom burden (HSB; ASBI ≥25). Univariate Cox models were used to determine the prognostic effect of 7 demographic/clinical factors, 9 LCSS items, and ASBI on OS. Multivariate Cox model was used to determine the prognostic effect of ASBI in the presence of 7 demographic/clinical factors. Kaplan-Meier curves of OS were generated for patients with LSB and HSB and compared using both univariate and multivariate Cox models. Results: In the univariate analysis, significant prognostic effects on OS were observed for baseline Karnofsky performance status (KPS; 90-100 vs. 70-80, hazard ratio [HR]=0.45, p<0.0001) and baseline stage (I/II/III vs. IV, HR=0.63, p<0.0001). In addition, significant prognostic effects were observed for 5 LCSS symptom items (anorexia, cough, dyspnea, fatigue, and pain), 3 LCSS general items (interference with activity level, symptom distress, and quality of life; HRs=1.08-1.20 for every 10 points worsening, all p<0.02), as well as ASBI (HR=1.32, p<0.0001). In the multivariate Cox model, ASBI remained a significant prognostic factor of OS (HR=1.22, p<0.0001), along with baseline KPS and stage. Patients with LSB (N=265) had significantly better OS than those with HSB (N=181) (12.9 vs. 6.9 months, HR=0.46, unadjusted p<0.0001; HR=0.59, p<0.0001 adjusted for the 7 demographic/clinical variables). Conclusions: The results suggest that baseline patient-reported symptoms as measured by LCSS provide distinct prognostic information in the presence of demographic and clinical measures in MPM.
Phase II study of bortezomib with cisplatin as first-line treatment of malignant pleural mesothelioma (MPM): EORTC 08052.
Authors: O'Brien Mary , Gaafar Rabab Mohamed , Popat Sanjaykumar , Grossi Francesco , Price Allan , Talbot Denis Charles , Cufer Tanja , Ottensmeier Christian H.H , Danson Sarah , Pallis Athanasios G. , Hasan Baktiar , Van Meerbeeck Jan P. , Baas Paul 
Published: March 2020

7081 Background: Cisplatin is one of the most active drugs available in MPM while bortezomib has shown some activity in single agent phase II studies against MPM. This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of MPM. Methods: Patients with histological proven MPM, with performance status (PS) 0/1, were eligible. The doses were cisplatin 75mg/m2 /3 wks and bortezomib 1.3mg/m2 day 1, 4, 8, 11 every 3 wks. The primary end-point was progression free survival rate at 18 wks (PFSR=18). The 2-stage Simon design (a=0.1; b = 0.05, P0=0.50 and P1=0.675) was used. In the first step of the study 37 eligible patients were planned. If more than 19 patients were alive and free of progression at 18 wks the total sample size was increased to 76 eligible patients. Results: Between 2007 and 2010 82 patients were entered. The median follow-up time is 32.3 months The median age was 55 years (range: 22-77yrs), male/female: 55/27 , PS 0/1: 9/73, Stage T1: 10%; T2: 42%, T3: 25%; T4: 23% and N0: 57%; N1: 4%; N2: 33%; N3: 6%. The median number of cycles received was 4 and 38% received 6 cycles. Cisplatin/ bortezomib dose intensity was 98/ 80%. Toxicity (grade 3/4): neutropenia 10%, thrombocytopenia 11%, anaemia 1%. Grade 3-4 hyponatraemia/ hypokalaemia occurred in 46/ and 17%. Grade 2 tinnitus, grade 3 fatigue occurred in 16%, and 12%, of patients. Motor/sensory/other neurotoxicity was grade 1: 6/28/7%, grade 2: 2/26/2% and grade 3: 1/7/2% respectively. There were 2 toxic deaths at 32 and 74 days due to acute pneumonitis and cardiac arrest. The PFRS-18 (including symptomatic progression) was 53% (80% confidence intervals, CI, 42-64%). The overall survival was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The PFS was 5.1 months (95% CI 3.3-6.5). Conclusions: On the basis of the PFRS-18, the null hypothesis could not be rejected, although CB gave predictable toxicity and was as active as other reported regimens in MPM.
NGR-hTNF and doxorubicin in relapsed small-cell lung cancer (SCLC).
Authors: Cavina Raffaele , Gregorc Vanesa , Novello Silvia , Grossi Francesco , Santoro Armando , Viganò Maria Grazia , Levra Matteo G. , Lambiase Antonio , Bordignon Claudio 
Published: March 2020

7085 Background: By selectively damaging tumor vasculature, NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is able to improve intratumoral uptake of doxorubicin (D). A phase I trial selected NGR-hTNF 0.8 µg/m2/day(d)1 and D 75 mg/m2/d1 every 3 weeks (q3w) for phase II. Methods: SCLC pts failing one or more platinum-based regimen received NGR-hTNF until progressive disease (PD) and D up to 550 mg/m2. This phase II trial (n=27 pts) had progression-free survival (PFS) as primary end point, with tumor response assessed q6w by RECIST, while secondary end points included adverse events (AEs), disease control rate (DCR), and overall survival (OS). Results: Among 28 pts enrolled (median age 63 years; M/F 19/9; PS 0/1-2 13/15; prior lines 1/2-3 20/8), 16 pts had platinum-resistant (R) disease (PD≤3 months) and 12 pts platinum-sensitive (S) disease (PD>3 months). At baseline, median neutrophil to lymphocyte ratio (NLR) was 4 (range 1-20). A total of 114 cycles were given (range 1-10), with 13 pts (46%) having ≥ 4 cycles and 9 pts (32%) ≥ 6 cycles. No grade 3/4 AEs related to NGR-hTNF were noted, while grade 1/2 AEs were transient chills (61%). NGR-hTNF did not apparently increase D-related AEs. Median PFS was 3.2 months (95% CI 2.6-3.8) and 1-year OS rate was 34%. Overall, DCR was 55% (95% CI 35-74), comprising 6 partial responses (22%; median duration: 6.3 months) and 9 stable diseases (33%; median duration: 4.1 months). Mean changes from baseline in target tumor size after 2, 4, and 6 cycles were -9%, -29%, and -32%, respectively for R disease and -11%, -20%, and -43%, respectively for S disease. In pts pretreated with ≥ 2 lines, DCR was 75%, median PFS was 5.1 months, and 1-year OS rate was 44%. In pts with R or S disease, DCR were 50% and 58% (p=.72), median PFS were 2.7 and 4.1 months (p=.07), and 1-year OS rates were 27% and 42% (p=.65), respectively. At multivariate analyses, PFS was not related to baseline characteristics, while an improved OS was associated only with a low NLR. The 1-year OS rate was 48% in pts with NLR ≤ 4 and 10% in pts with NLR > 4 (p=.007), while in pts with NLR ≤ 4, 1-year OS rate was 46% in R disease and 50% in S disease. Conclusions: This combination is well tolerated and active in platinum resistant and sensitive SCLC and further development is of interest.
Clinical trial design in small cell lung cancer: Surrogate endpoints and statistical evolution.
Authors: Nickolich Myles , Fu Pingfu , Babakoohi Shahab , Dowlati Afshin 
Published: March 2020

7087 Background: Small cell lung cancer (SCLC) is a devastating disease for which little recent therapeutic advance has been achieved. SCLC trial design and reporting may have an impact on the interpretation of studies conducted. Furthermore the use of surrogate endpoints in SCLC has not been explored. Methods: Through examining all phase II and III SCLC trials published in the Journal of Clinical Oncology (8,471 patients from 66 trials between 1983-2010), we examined how SCLC trial reporting and design has evolved, determining if the type I error, power, and sample size calculations were provided. We assessed primary endpoints for all trials and sought to discover if response rate (RR) or progression-free survival (PFS) correlated with overall survival (OS). We analyzed response and survival outcomes for associations using Pearson correlation coefficient and differences between data groups by ANOVA followed by Tukey’s multiple comparison procedure. Results: There were increased reporting trends of statistical design in power (16.7% in 1986-1996 to 77.8% of trials in 2006-2010 [p=0.001]) and type I error (22.2% in 1986-1996 to 72.2% in 2006-2010 [p=0.005]). 72.2% of trials published in 1986-1996 failed to report a primary endpoint whereas only 5.56% of trials in 2006-2010 failed to do so (p=0.004). Of phase II trials, primary endpoint was identified as RR in 65%, OS in 25%, and PFS in 10% (p<0.0001). There is a strong correlation between RR and both PFS (p=0.013) and OS (p=0.012) in extensive-stage disease (ED) but not limited-stage disease (LD) (p=0.978 for PFS, p=0.193 for OS). This correlation is for partial response rate (pRR) but not complete response rate. RR (p=0.029) exhibits a negative trend over time with a dramatic and significant decrease in RR across all studies starting in 2005. A strong positive correlation exists between PFS and OS for LD (p=0.036) and ED (p=0.058). We found no change in median overall survival (p=0.383). Conclusions: Over time there has been improvement in reporting the essential statistical data for proper interpretation of SCLC trials. No change in survival was seen over the past 28 years. RR should be evaluated as a surrogate endpoint for OS in ED but not LD. pRR correlates with OS and PFS in both LD and ED.
Phase II trial of huKS-IL2 with cyclophosphamide (CTX) in patients with extensive disease small-cell lung cancer (ED-SCLC).
Authors: Gladkov Oleg , Biakhov Mikhail , Ramlau Rodryg , Serwatowski Piotr , Milanowski Janusz , Tomeczko Janusz , Komarnitsky Philip B , Bernard Laurence , Kramer Daniel , Krzakowski Maciej Jerzy 
Published: March 2020

7090 Background: huKS-IL2 immunocytokine is a humanized antibody specific for EpCAM, fused at its Fc end to two molecules of IL2. Results of a phase 1b study of huKS-IL2 plus low-dose CTX, and preclinical data, provided a rationale to evaluate this combination in SCLC, which is often EpCAM-positive. Methods: Patients (pts) with ED-SCLC responding (PR/CR) to 4 cycles of first-line Pt-based chemotherapy were randomized 1,5:1 to receive huKS-IL2/CTX or best supportive care (BSC). Pts in the huKS-IL2/CTX arm received six 21-day cycles of CTX 300 mg/m2 on day (d) 1, and 1.5 mg/m2/d huKS-IL2 on d2–4, followed by 21-d cycles of CTX on d1 and huKS-IL2 on d2 until progression. Pts were stratified for prophylactic cranial irradiation (PCI) and response to chemotherapy. Primary endpoint was PFS rate at 6 months (mo). Secondary endpoints included OS rates at 12 and 18 mo from start of Pt-based chemotherapy, median PFS and OS, safety, and immunogenicity. Results: 108 pts (64 huKS-IL2/CTX arm, 44 BSC arm) were randomized and treated. Baseline characteristics were balanced between arms; however, higher % of males (75 vs 61.4%) and of ECOG PS 0 (45.3 vs 38.6%) were observed in the active arm. Median age was 61.7 (32; 81) and 59.2 (45; 74) years in the active and BSC arm, respectively. Most pts were in PR at randomization (2 pts – 1 in each arm – had CR). PCI was used in 15 (23.4%) and 11 (25%) pts in the active and BSC arm, respectively. No significant differences in PFS or OS were observed in the active vs BSC arm: PFS rate was 6.4 vs 12.2%; median PFS was 1.5 vs 1.4 mo; OS rates at 12 and 18 mo were 52 vs 61% and 24 vs 29%, respectively; median OS was 12.3 vs 14.1 mo. One PR (45% reduction vs randomization baseline) was observed in the active arm. In a subset of pts who received PCI, median PFS was 1.7 vs 1.5 mo, median OS 21.5 vs 14.3 mo in the active vs BSC arm, respectively. AEs observed more frequently in the active arm were flu-like symptoms, rash, hypotension, lymphopenia, LFT and creatinine elevations; all Grade 3/4 AEs related to huKS-IL2 were reversible/manageable. Conclusions: HuKS-IL2/CTX was well tolerated, but showed no benefit in pts with ED-SCLC in PR/CR after chemotherapy. A trend for improved PFS and OS was observed in pts who received prior PCI.
Circulating tumor cells (CTCs) in patients (pts) with small cell lung cancer (SCLC) as a marker of disease burden and therapeutic response, and predictor of disease relapse.
Authors: Ranganathan Anjana , Schwed-Lustgarten Daniel , Aggarwal Charu , Werner Lynn , Torigian Drew A. , Troxel Andrea B. , Evans Tracey L. , Stevenson James , Cohen Roger B. , Vaidya Bhavesh , Rao Chandra , Connelly Mark C. , Albelda Steven , Langer Corey J. 
Published: March 2020

7092 Background: Currently there are no validated biomarkers for assessment or prediction of disease burden or activity in SCLC. Enumeration of CTCs by CellSearch is FDA approved, highly reproducible and validated in other malignancies. Application as a prognostic and predictive marker in SCLC is limited due to a lack of studies documenting serial monitoring in pts on therapy. Methods: We are conducting a prospective study serially enumerating CTCs in pts with newly diagnosed SCLC. CTC number (per 7.5 ml peripheral blood) and percentage of CTCs demonstrating DNA damage and apoptosis based on γH2AX and M30 staining respectively, are being assessed prior to initiation of chemotherapy, during each cycle and at relapse. We are correlating CTC number with disease stage, number of metastatic sites, response to therapy, and time to progression (TTP). Results: 21 SCLC pts are evaluable. 9 pts with limited disease (LD) had median baseline CTC value of 1 (0-8); only 2 of 9 pts had >5 CTCs. 12 pts with extensive disease (ED) had median baseline CTC value of 80.5 (0-37780); 8 of 12 pts had >5 detectable CTCs (p value 0.02). Amongst the 12 pts with ED, median baseline CTC count was higher in pts with ≥3 (n=3) compared to 1-2 sites of metastatic disease (n=9) (2668 vs 71; p value 0.52). Median percentage of CTCs positive for γH2AX and M30 was also higher for pts with ≥3 compared to 1-2 metastatic sites (83, 164.5 vs. 2, 7.5) (p-value 0.40, 0.69). Serial CTC data are available on 3 pts with ED; all had responsive disease and reduction in CTC number to 0-1 after 2 cycles of chemotherapy. As this protocol is ongoing, correlation of CTCs with updated response status and TTP will be presented at the ASCO meeting. Conclusions: CTCs can be isolated and serially enumerated in pts with SCLC. Baseline CTCs correlate directly with disease stage. In pts with ≥ 3 metastatic sites, baseline CTCs tend to be greater and show higher levels of DNA damage and apoptosis compared to those with 1-2 metastatic sites. Reduction in CTCs is associated with radiographic response to therapy. Correlation between absolute number at baseline and TTP is not yet known.