bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of MAGE-A3 and PRAME gene expression in non-small-cell lung cancer (NSCLC).
Authors: Linder Albert , Budihardjo-Welim Henry , Velehorschi Wiorika , Coche Thierry , Gruselle Olivier , D'Agostino Diego , Louahed Jamila , Lehmann Frederic , Brichard Vincent G. 
Published: March 2020

7056 Background: We investigated the expression of some cancer–testis genes and their association with disease prognosis. Here we report our results for the expression, in resected NSCLC samples, of two tumor-specific antigens (Ags): MAGE‑A3 and PRAME, both under evaluation in clinical trials. Methods: We conducted a single-center, uncontrolled, retrospective study of tissue from resected stage I–III NSCLC patients (pts): 650 were in stage I, 215 in stage II and 395 in stage III. 1260 FFPE tumor tissue samples from the tumor tissue bank of the Department of Pathology, Lungenklinik Hemer (Germany), were tested for MAGE‑A3 and PRAME expression by specific qRT-PCR assays. The prognostic value of these Ags was determined by estimating the median overall survival (OS), disease-free interval (DFI) and disease-free survival (DFS). Results: Expression rates were 36% for MAGE‑A3 and 66% for PRAME. The co‑expression rate was 30%. Almost all tumors expressing MAGE‑A3 also expressed PRAME. We observed no difference overall in Ag expression according to stage, tumor size and pts’ age. Squamous tumors expressed MAGE‑A3 and PRAME more frequently than did adenocarcinomas (43 vs. 27 % and 80 vs. 44% respectively), and PRAME expression rates were higher in males than in females (70 vs. 53%). In the overall population, which included stages IA–IIIB, no prognostic value was detected for the expression of either Ag. In subset analyses, we found in 83 stage IIIB pts a trend to worse OS linked to MAGE‑A3 expression (HR=1.977, p=0.0312). In 395 stage IB pts, PRAME expression was associated with worse OS (HR=1.483, p=0.0344) and DFS (HR=1.492, p=0.0167). Conclusions: The MAGE‑A3 expression rate found is consistent with the results observed in the phase III MAGRIT trial (J‑H Kim et al., 2011). No prognostic value for either PRAME or MAGE‑A3 was observed in the overall population, in contrast to previous reports with smaller sample sizes (Gure et al., 2005, Boli et al., 2002) and in other tumors (Vourch’jourdain et al., 2009, Epping et al., 2008). We observed a trend toward poor prognostic value of MAGE‑A3 in stage IIIB pts and of PRAME in stage IB pts.
Prognostic value of pathologic complete response to preoperative chemotherapy in early-stage non small cell lung cancer: Combined analysis of two IFCT randomized trials.
Authors: Mouillet Guillaume , Monnet Elisabeth , Milleron Bernard , Puyraveau Marc , Quoix Elisabeth , David Philippe , Ducolone Alain , Molinier Oliver , Zalcman Gerard , Depierre Alain , Westeel Virginie 
Published: March 2020

7057 Background: Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non-small cell lung cancer (NSCLC) following neoadjuvant chemotherapy resulted in improved outcome and to determine predictive factors for pCR. Methods: Eligible patients with stage IB or II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique (IFCT) phase III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen. Results: Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival (OS) was 80.0% compared to 55.8% in the non-pCR group (p=0.0007). In multivariate analyses, pCR was a favorable prognostic factor of OS (RR=0.34; 95% CI=0.18-0.64) in addition to squamous cell carcinoma (SCC), weight loss ≤5%, and stage IB disease. Five-year disease-free survival (DFS) was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p<0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (OR=4.30; 95% CI=1.90-9.72). Conclusions: Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in Stage IB-II NSCLC. Our study is the largest published series evaluating pCRs following preoperative chemotherapy. The only factor predictive of pCR was SCC. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen.
Mediastinal lymph node examination and survival in resected early-stage non-small cell lung cancer in the Surveillance, Epidemiology, and End Results (SEER) database.
Authors: Osarogiagbon Raymond U , Yu Xinhua 
Published: March 2020

7069 Background: Pathologic nodal stage is a key prognostic factor in resectable non-small cell lung cancer (NSCLC). Mediastinal lymph node (MLN) metastasis connotes a poor prognosis. Yet, some NSCLC resections in the US do not include MLN examination. Methods: We analyzed SEER data from 1998 to 2002 to quantify the long-term survival impact of failure to examine MLN in resected NSCLC. We used Kaplan-Meier methods to compare the unadjusted survival difference between patients with, and without, MLN examination. We used Cox proportional hazards and competing risk models to serially adjust for the impact of risk factors on survival differences. Results: Sixty-two percent of patients with pathologic N0 or N1 NSCLC had no MLN examined. Men, African-Americans, patients with more advanced stage, and those who had less than pneumonectomy were less likely to have MLN examination. Five-year all-cause mortality (46.9% v 51.7%, p<.001), and lung cancer-specific mortality (31.5% v 36%, p<.001), rates were higher in those without MLN examination. After adjustment for potential confounders, MLN examination was associated with a 6% reduction in all-cause mortality (HR, 0.94; CI, 0.89-0.99; p=.014), and 10% reduction in lung cancer-specific mortality (HR, 0.90; 95% CI, 0.84-0.96; p=.002) rates. The excess risk in 1 year’s cohort of U.S. lung resections was 2,700 lives over 5 years. Conclusions: Failure to examine MLN was a common practice in "MLN-negative" NSCLC resections, which significantly impaired long-term survival. Efforts to understand the etiology of this quality gap, and measures to eliminate it, are warranted.
N0321: A phase II study of bortezomib, paclitaxel, carboplatin (CBCDA), and radiotherapy (RT) for locally advanced non-small cell lung cancer (NSCLC).
Authors: Schild Steven E. , Foster Nathan R. , Molina Julian R. , Dy Grace K. , Rowland Kendrith M. , Sarkaria Jann Nagina , Thomas Sachdev P. , Northfelt Donald W. , Kugler John William , Adjei Alex A. ,   North Central Cancer Treatment Group (NCCTG)
Published: March 2020

7073 Background: In preclinical studies, combinations of bortezomib and RT result in synergistic tumor killing (Cancer Chemother Pharmacol. 2007;59:207-15). Our group reported the results from the phase I portion of this study previously (J Clin Oncol. 200;28 (suppl; abstr 7085)). Based on these data, we undertook a phase II study of bortezomib in combination with paclitaxel/CBCDA and RT. Methods: Based on results from our previously reported phase I trial, systemic therapy included bortezomib (1.2 mg/m² IV days 1,4,8,11), paclitaxel (175 mg/m² IV day 2), and carboplatin (CBCDA; AUC=6 day 2) given every 3 weeks for 2 cycles. Thoracic radiotherapy (RT) included 60Gy/30 daily fractions starting day 1. The primary endpoint was the 12-month survival rate. If 41 or more of these 60 patients (68%) were alive at least 12 months after study entry, the trial would be deemed as positive and further study would be warranted. Results: 27 pts were enrolled to the phase II portion: M/F=17/10; stage IIIA/IIIB=13/14; ECOG PS 0/1=9/18; and median age: 58 (range 43-79). 18 pts (67%) completed therapy per protocol. At a planned interim analysis, 23 of 26 evaluable patients (88.5%, 95% CI: 70-98%) survived for at least 6 months, which exceeded the boundary of 21 or more needed to continue to full accrual. This trial could have continued per protocol, but was closed early due to slow accrual. With a median follow-up of 15.0 months in the 17 patients still alive, the 12-month survival rate was 71% (95% CI: 49 – 85). The median OS was 19 months (95% CI: 11 – no upper). Grade 3 or higher adverse events (regardless of attribution) were reported in 22 (82%) patients. Grade 4/5 adverse events were reported in 15 (56%) patients. There was one grade 5 event (pneumonitis). The most common (5 or more patients) grade 3/4 adverse events were fatigue (22%), leukopenia (63%), neutropenia (67%), and thrombocytopenia (44%). Conclusions: The addition of bortezomib resulted in high levels of severe hematologic toxicity, but also demonstrated evidence of activity with a 12-month survival rate of 71% and a median OS of 19 months. Further testing of this regimen in a larger study appears warranted.
Factors influencing recurrence following anatomic lung resection for non-small cell lung cancer.
Authors: Landreneau Rodney Jerome , Abbas Ghulam , Awais Omar , Pennathur Arjun , Siegfried Jill , Wilson David O , Luketich James D. , Schuchert Matthew J. 
Published: March 2020

7074 Background: Anatomic lung resection provides the patient with the best chance for cure in the setting of early-stage non-small cell lung cancer (NSCLC). Despite complete (R0) resection, up to 20-30% of patients will develop recurrent disease. In the current study, we analyze the impact of surgical and pathologic variables upon recurrence patterns following anatomic lung resection for clinical stage I NSCLC. Methods: A total of 1,192 patients (394 segmentectomies, 805 lobectomies) with clinical stage I NSCLC were evaluated. The primary outcome variable was recurrence. Multivariate analysis was performed based upon clinical (age, gender, comorbidities), surgical (operation, approach, surgical margin) and pathological (pleural invasion, tumor size and histology) variables. Predictors of recurrence were identified by proportional hazards regression. Differences in recurrence patterns between groups are illustrated by log rank tests applied to Kaplan-Maier estimates. Results: A total of 243 recurrences (20.3%) were recorded at a mean follow-up of 35.6 months (71 locoregional, 172 distant). There was no significant difference in recurrence patterns when comparing segmentectomy and lobectomy. Multivariate analysis demonstrated that a margin:tumor ratio < 1, angiolymphatic invasion and the presence of only mild-moderate tumor inflammation were predictors of recurrence risk. Conclusions: Recurrence following anatomic lung resection is influenced predominantly by pathological variables (tumor size, angiolymphatic invasion, tumor inflammation). Optimization of surgical margin in relation to tumor size may improve outcomes. Extent of resection (segmentectomy vs. lobectomy) does not appear to have an impact on recurrence-free survival when adequate margins are obtained. These data have implications regarding the potential use of adjuvant therapy in selected Stage I patients at high risk for recurrence. [Table: see text]
Phase II trial of BNC105P as second-line chemotherapy for advanced malignant pleural mesothelioma (MPM): Australasian Lung Cancer Trials Group and NHMRC Clinical Trials Centre Collaboration.
Authors: Nowak Anna K. , Brown Chris , Millward Michael , Hughes Brett Gordon Maxwell , Bibby David C. , Kremmidiotis Gabriel , Doolin Elizabeth E. , Mitchell Paul , Pavlakis Nick , Coskinas Xanthi , Sebastian Lucille T , Cummins Michelle M , Boyer Michael J. , Parnis Francis , Lavranos Tina C. , Stockler Martin R. 
Published: March 2020

7079^ Background: BNC105P is a tubulin polymerization inhibitor that acts as a Vascular Disrupting Agent (VDA), has direct cytotoxic effects, and had preclinical and phase I activity in MPM. This aim of this study was to determine activity and safety of BNC105P as second-line therapy after pemetrexed and a platin in MPM. Methods: Eligible patients had progressive MPM, prior pemetrexed and platinum, measurable disease by modified RECIST, ECOG 0-1, and adequate organ and cardiovascular function. Important exclusions included recent thromboembolic, cardiovascular or cerebrovascular disease, or therapeutic anticoagulation. Pts received BNC105P (16 mg/m2 IV) Day 1 + 8 q21d until progression or toxicity. The primary endpoint was centrally reviewed objective tumour response rate (RR); the Simon 2-stage design assumed a RR of interest of 20% and a RR of no interest of 5%, with α = β = 0.05. Continuation past first stage accrual required >1 objective response in 24 patients. Results: 30 subjects were accrued over 10 months (90% male; median age 65 (range 41-83); 77% ECOG PS 1; histology epithelioid (67%), biphasic (10%), sarcomatoid (7%), other/unspecified (17%)). All pts received at least one dose of study drug; pts received a median of 2 cycles and median dose intensity was 100%. No significant haematologic, biochemical, peripheral neurotoxic or cardiac adverse events (AEs) including hypertension were observed. Grade 3 or 4 AEs occurred in 10 pts (33%). There were 2 deaths on study: 1 due to stroke, the other due to pneumonia and respiratory failure. We observed 1 partial response (3%) and 13 pts with SD as their best response (43%). Median progression free survival was 1.5 mo (95% CI 1.4-2.4); median overall survival was 8.7 mo (95% CI 3.8-NR). Lung function and QOL data was collected. Biomarker analyses correlating to pharmacological changes induced by BNC105P are ongoing and will be presented. Conclusions: BNC105P was safe and tolerable but its single agent response rate failed to meet the pre-specified primary endpoint of interest.
Efficacy of rechallenge chemotherapy in patients with sensitive relapsed small cell lung cancer.
Authors: Wakuda Kazushige , Kenmotsu Hirotsugu , Naito Tateaki , Akamatsu Hiroaki , Ono Akira , Shukuya Takehito , Nakamura Yukiko , Tsuya Asuka , Murakami Haruyasu , Takahashi Toshiaki , Endo Masahiro , Nakajima Takashi , Yamamoto Nobuyuki 
Published: March 2020

7088 Background: Treatment efficacy of rechallenge chemotherapy recommended for patients with sensitive-relapse small cell lung cancer (SCLC) has not been fully clarified. Methods: We defined sensitive relapse as treatment-free interval (TFI) ≥ 90 days. Sixty-five sensitive-relapse SCLC patients who received second-line chemotherapy at the Shizuoka Cancer Center between September 2002 and May 2011 were separated into those treated with rechallenge chemotherapy (rechallenge group) and those treated with other regimens (other group) for comparison and analysis of treatment efficacy. Results: No significant differences in age, gender, ECOG performance status at relapse, disease extent at diagnosis, or response to first-line treatment were found between the two groups, but TFI was significantly longer in the rechallenge group, which included 19 sensitive-relapse patients. The other group included 46 sensitive-relapse patients, 21 of whom received amrubicin. There was no significant difference in overall survival (OS) between the two groups (median survival time (MST): rechallenge group 14.4 months, other group 13.1 months, p = 0.51). In the patients treated with amrubicin, MST was 12.6 months. Comparing the rechallenge group with the patients treated with amrubicin, there was also no significant difference in OS (p = 0.38). Both the rechallenge and other group included 11 patients with ex-sensitive relapse (TFI ≥ 180 days). There was no significant difference in OS between the two groups (MST 15.7 vs. 26.9 months, p = 0.46). Conclusions: Rechallenge chemotherapy did not prove superior to other chemotherapies, suggesting that monotherapy, such as amrubicin, might be reasonable as second-line chemotherapy for sensitive-relapse SCLC patients.
NCIC IND.190: A phase I trial of MK-0646 in combination with cisplatin and etoposide in extensive-stage small cell lung cancer (ES SCLC).
Authors: Ellis Peter Michael , Shepherd Frances A. , Laurie Scott Andrew , Goss Glenwood D. , Olivo Martin Sebastian , Powers Jean , Walsh Wendy , Seymour Lesley , Bradbury Penelope Ann 
Published: March 2020

7093 Background: Increased serum levels of insulin like growth factor (IGF), plus overexpression of the IGF-receptor (IGFR) are implicated in SCLC cell growth and proliferation, making suppression of the IGFR a potential therapeutic target. MK-0646 is a monoclonal antibody directed against the IGFR. The aim of this study was to determine the recommended phase II dose (RP2D) of cisplatin, etoposide plus MK-0646. Methods: We conducted a phase I study of two dose levels of MK-0646 (DL1 5mg/kg, DL2 10mg/kg IV weekly) in combination with cisplatin (25mg/m2) and etoposide (100mg/m2) IV D1-3, q21d, for patients with chemotherapy-naive ES SCLC, PS 0-2. Patients with treated stable brain metastases were eligible. Patients completing 4-6 cycles of combination therapy could continue single agent MK-0646 until disease progression. Primary outcome was determination of the RP2D. Secondary outcomes included ORR (RECIST 1.1), and toxicity (CTCAEv3). Results: A total of 12 patients were treated (DL1 – 3, DL2 – 9). The median age was 63 years (48-70), with 6 males and 6 females. Most subjects were good ECOG PS (PS 1 – 8, PS 2 – 4) and had 4 or more sites of disease (n=8). No DLTs were observed in DL1 or DL2. In an expanded DL2 cohort, 1 patient died from neutropenic sepsis during cycle 1. The median number of treatment cycles of chemotherapy was 4 (DL1) or 5 (DL2) and MK-0646 was 6 (DL1&2). Dose delays were observed for chemotherapy (DL1 - 2, DL2 – 6) and MK-0646 (DL1 – 3, DL2 – 7). The confirmed ORR was 72.7% (PR 8, SD 2, PD 1, non-evaluable 1). Grade ≥3 toxicities (any cycle) occurring in more than 1 patient included: neutropenia (92%); thrombocytopenia (25%); leukopenia (50%); anemia (17%); fatigue (33%); joint pain (17%); thrombosis (25%). Grade 2 or 3 hyperglycemia was observed in 1 of 3 (DL1) and 5 of 9 (DL2). Eight SAEs were observed in 3 patients (thrombosis, febrile neutropenia, infection, syncope, fatigue 2, dyspnea, back pain). Conclusions: MK-0646 can be combined at full dose with standard doses of cisplatin and etoposide (25mg/m2 and 100mg/m2 D1-3) with a RP2D of MK-0646 10mg/kg/week. The observed toxicities are consistent with that expected from cisplatin and etoposide except for hyperglycemia, which appears dose dependent.
Impact of PET staging in limited-stage SCLC.
Authors: Xanthopoulos Eric , Grover Surbhi , Corradetti Michael Nino , Fernandes Annemarie Therese , Kim Miranda , Simone Charles B. , Christodouleas John Paul , Evans Tracey L. , Stevenson James , Langer Corey J. , Apisarnthanarax Smith , Rengan Ramesh 
Published: March 2020

7098 Background: Although PET/CT has been established for the initial staging of NSCLC, it is still unproven for SCLC. This study examines clinical outcome in patients with limited-stage SCLC staged with and without PET/CT. Methods: An institutional database was reviewed to identify all patients that presented with limited-stage SCLC and treated definitively with concurrent chemoradiation. Overall survival and associations were assessed by the Kaplan-Meier approach, log-rank tests and Cox modeling. Results: From 01/04 – 08/10, 54 consecutive limited-stage SCLC patients were treated with concurrent chemoradiation at the University of Pennsylvania. 40 patients underwent PET staging; 14 underwent CT staging only; all had MR of the brain. Patient characteristics were well distributed, including age (p = 0.35), race (p = 0.21), sex (p = 0.93), dose (45 Gy, p = 0.89), and fractions per day (p = 0.89). PET-staged patients had median survival of 32 vs 15 months in patients without PET (p = 0.03). Survival rate was 57% vs 29% at 24 months. Median time to distant failure of 29 vs 11 months (p = 0.05). Median time to local failure was 41 vs 12 months (p = 0.03). Median followup was 38 months in the 19 surviving PET-staged patients and 40 in the 2 surviving non-PET patients (p = 0.59). Lack of PET-staging (OR = 0.92, p = 0.04) and race (OR = 1.02, p = 0.03) associated with increased distant failure on multivariate Cox analysis. Only PET-staging (OR = 0.93, p = 0.04) associated with increased overall survival on univariable Cox modeling. Conclusions: Median and overall survival of PET-staged SCLC patients compared favorably with those who were not. These findings are presumably due primarily to identification of CT-occult distant disease by PET. This study underscores the value of PET in staging patients with SCLC.
Amrubicin and carboplatin with pegfilgrastim in patients with extensive-stage small-cell lung cancer (ES-SCLC): A phase II study of the Sarah Cannon Research Institute (SCRI).
Authors: Shipley Dianna , Hainsworth John D. , Mekhail Tarek , Zubkus John D. , Flora Douglas B. , Daniel Davey B. , Waterhouse David Michael , Gravenor Donald , Burris Howard A. , Greco Frank A. , Spigel David R. 
Published: March 2020

7100 Background: Amrubicin is a novel anthracycline associated with high objective response rates (ORR) in patients (pts) with relapsed SCLC. Amrubicin improved the ORR and progression-free survival (PFS) in relapsed SCLC vs. topotecan, but not overall survival (OS) in a phase III study. Amrubicin with cisplatin/carboplatin for elderly Japanese pts was safe and active. We conducted a multicenter phase II study evaluating amrubicin and carboplatin in newly diagnosed ES-SCLC. Methods: Eligible pts had untreated ES-SCLC, measurable/evaluable disease (RECIST v. 1.1) and an ECOG PS <2. Pts received 4 cycles of amrubicin 30 mg/m2 on days 1-3 and carboplatin AUC=5 both IV day 1 every 21 days with restaging every 6 weeks. Pegfilgrastim 6 mg sq was administered on day 4 of each cycle. The primary endpoint was 1-year OS. Secondary endpoints included ORR, PFS, OS, and toxicity. Results: 78 pts were enrolled from 3/2010 to 7/2011. Baseline characteristics included: median age 65 yrs (range 45-84); 56% female. 64% completed 4 cycles of treatment. Eleven (14%) pts showed complete responses and 47 (60%) pts partial responses, for an ORR of 74% (95% confidence interval 65%-82%). Twelve (15%) pts had stable disease. Median PFS and OS were 5.3 and 9.5 months, respectively. The 1-year OS was 36%. Grade 3/4 myelosuppression was the most common toxicity (thrombocytopenia 44%, neutropenia 34%, febrile neutropenia 12%, anemia 26%), but was manageable. Severe non-hematologic toxicities (>5%) included hypokalemia 17%, fatigue 13%, dehydration 10%, hyponatremia 10%, pneumonia 9%, and nausea/vomiting 8%. 1 pt died from sepsis and another from aspiration pneumonia. Conclusions: First-line ES-SCLC treatment with amrubicin and carboplatin induced several complete responses and is considered highly active. Myelosuppression was managed effectively with growth factor support. These results are comparable to historical data with platinum-doublet chemotherapy. A larger randomized study would be required to best assess this regimen’s impact on survival.