bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, phase III study of mitomycin/vindesine/cisplatin (MVP) versus weekly irinotecan/carboplatin (IC) or weekly paclitaxel/carboplatin (PC) with concurrent thoracic radiotherapy (TRT) for unresectable stage III non-small cell lung cancer (NSCLC): WJTOG0105
Authors: Satouchi M. , Yamamoto N. , Chiba Y. , Kudoh S. , Hida T. , Kubo A. , Seto T. , Nishimura Y. , Nakagawa K. , Fukuoka M. 
Published: August 2020

7504 Background: Weekly chemotherapy with concurrent TRT displays acceptable toxicities and dependable efficacy. We conducted a randomized phase III trial to assess the efficacy and toxicity of weekly chemotherapy with concurrent TRT against MVP with concurrent TRT via a non-inferiority design. Methods: MVP: mitomycin (8 mg/m2 on days 1, 29), vindesine (3 mg/m2 on days 1, 8, 29, 36), and cisplatin (80 mg/m2 on days 1, 29) with concurrent TRT (60 Gy). Patients (pts) subsequently received 2 courses of consolidation chemotherapy with MVP; IC: weekly irinotecan (20 mg/m2)/carboplatin (AUC 2) for 6 weeks and TRT (60 Gy) followed by 2 courses of irinotecan (50 mg/m2)/carboplatin (AUC 5); PC: weekly paclitaxel (40 mg/m2)/carboplatin (AUC 2) for 6 weeks and TRT (60 Gy) followed by 2 courses of paclitaxel (200 mg/m2)/carboplatin (AUC 5). The primary endpoint was overall survival (OS), with secondary endpoints of progression free survival (PFS), response, and toxicity. Results: From Sep 2001 to Sep 2005, 456 pts were randomized. Pretreatment characteristics were well-balanced among 3 arms. Major toxicity incidences: The incidence of G3–4 neutropenia in the MVP, IC, and PC arms was 95.9, 72.1, and 46.9 % (p<0.001). The G3–4 non-hematologic toxicity incidences in terms of fatigue, febrile neutropenia, and gastrointestinal disorder were 13.0, 6.1, and 4.8 % (p<0.001), 37.0, 8.8, and 10.2 % (p<0.001), and 24.0, 8.2, and 9.5% (p<0.001) in the respective arms. The overall response rates were 66.4, 56.5, and 63.3 %, in the MVP, IC and PC arms, respectively. The median survival times were 20.5, 19.8 and 22.0 months and the median PFS (MPFS), 8.2, 8.0 and 9.5 months in MVP, IC and PC. Non-inferiority of the 2 experimental arms compared with MVP was not achieved, though no significant differences in OS and PFS were apparent among treatments. The PC arm displayed the most favorable MST, MPFS, and hematologic/non-hematologic toxicities. Conclusions: Weekly PC with TRT displays similar efficacy and more favorable toxicity profiles compared to MVP with TRT. Weekly PC with TRT warrants use as the reference regimen in forthcoming studies. [Table: see text]
A phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small cell lung cancer: Initial analysis of Radiation Therapy Oncology Group 0214
Authors: Gore E. M. , Bae K. , Wong S. , Bonner J. , Sun A. , Schild S. , Gaspar L. E. , Bogart J. , Werner-Wasik M. , Choy H. 
Published: August 2020

7506 Background: The incidence of central nervous system (CNS) metastases is high in patients with locally advanced non-small cell lung cancer. Brain as an only site of relapse appears increasingly common as loco-regional and extra-cranial systemic treatment improves. There is not standard agreement as to how to address this risk. Methods: Patients with stage III NSCLC without progression of disease after loco-regional treatment with surgery and/or radiation therapy with or without chemotherapy were eligible. Participants were randomized to prophylactic cranial irradiation (PCI) or observation and stratified by stage (IIIA or B), histology (non-squamous or squamous) and therapy (surgery or no surgery). PCI was delivered once daily at 2Gy per fraction to 30Gy. The primary endpoint of the study was overall survival (OS). Secondary endpoints were disease free survival (DFS) and the impact of PCI on incidence of CNS metastases, neuropsychological function, and quality of life (QoL). Kaplan- Meier estimation with the log-rank test was used for OS and DFS and the logistic regression model was used for calculating the incidence of CNS metastasis. Results: Total accrual was 356 patients of the targeted 1058 between 9/19/02 and 8/30/07. The study was closed early due to slow accrual. 340 patients were evaluable. One year OS (p=0.86, 75.6 % and 76.9% for PCI and observation) and one year DFS (p=0.11, 56.4% and 51.2% for PCI and observation) were not statistically significantly different. However, CNS metastatic rate at 1 year was statistically significantly different with CNS relapse 7.7% vs. 18% for PCI vs. observation (p=0.004). Logistic regression showed that the patients in the observation arm are 2.52 times more likely to develop CNS metastases than those in the PCI arm (odds ratio=2.52, 95% CI=(1.32–4.80)). Conclusions: PCI in patients without progressive disease after loco-regional therapy for III NSCLC significantly decreases the rate of CNS metastases. This study did not show a statistically significant difference in OS or DFS. Forthcoming analysis of the impact of PCI on neuropsychological function and QoL will influence the recommendations regarding the standard use of PCI. No significant financial relationships to disclose.
Randomized, multicenter phase III study of ranpirnase plus doxorubicin (DOX) versus DOX in patients with unresectable malignant mesothelioma (MM)
Authors: Reck M. , Krzakowski M. , Jassem J. , Eschbach C. , Kozielski J. , Costanzi J. J. , Gatzemeier U. , Shogen K. , von Pawel J. 
Published: August 2020

7507 Background: Ranpirnase (Onconase), a novel ribonuclease with preclinical activity against various tumors, has led to a median survival of 8.3 ms (one year survival: 42%) in a multicentre phase II trial in chemonaive and pretreated pts whom met the Cancer and Leukemia Group B (CALGB) prognostic criteria for group 1–4 (Mikulski, J Clin Oncol 20, 2001). Methods: This multicenter controlled phase III trial compared efficacy and safety of Dox (one of the most active single agents when the study was planned) with or without ranpirnase. Primary endpoint was overall survival (OS), secondary endpoints included progression-free survival, response rate, safety and disease related symptoms. Eligibility criteria: histologically proven unresectable MM; CALGB group 1–4, ECOG PS 0–1, adequate organ function. Stratification was performed according to CALGB group and histology (epitheloid vs. non-epitheloid). One line of prior therapy was permitted. Between 08/01 and 09/07 413 eligible pts were randomized to DOX 60 mg/m2 every 3 wks with or without ranpirnase 240 μg/m2 weekly (cycle 1) and 480 μg/m2 in subsequent cycles (maximum 6) if no severe toxicity had occurred. The study was designed to detect an increase of 4 ms (9 vs. 13) in median OS (MST) using a two-sided logrank test (α = 5%) with 90% power. Results: Both arms were well balanced (DOX + ranpirnase / DOX: 203/210 pts): Mean age 62.2/61.8 yrs; males 157/156; PS 0 52/60; PS 1 151/150; prior chemo 65/65 pts (pemetrexed 35/35; other chemo 30/30). CALGB groups 14/14 (1), 45/51 (2), 117/115 (3), 27/30 (4). In the intent to treat population (ITT) there was no significant difference in OS (MST: 11.1 vs 10.7 ms; HR 1.02, 95% CI 0.82–1.26) whilst in a preplanned analysis including 130 pretreated patients a significant advantage in survival in favor of DOX + ranpirnase was found (MST: 10.5 vs 9 ms; HR 1.49, 95% CI 1.02–2.17). The safety profile for both treatment arms was similar. Most frequent side effects reported for both treatment groups included nausea, fatigue and alopecia. Conclusions: Combination of ranpirnase and DOX is a safe and feasible treatment in unresectable MM and showed a significant impact on survival of pretreated patients compared to DOX alone. [Table: see text]
SWOG S0509: A phase II study of novel oral antiangiogenic agent AZD2171 (NSC-732208) in malignant pleural mesothelioma
Authors: Garland L. L. , Chansky K. , Wozniak A. , Tsao A. , Gadgeel S. , Vershraegen C. , Da Silva M. , Redman M. , Gandara D. 
Published: August 2020

7511 Background: Preclinical studies suggest the autocrine growth loop involving VEGF and its receptors is a relevant therapeutic target for malignant pleural mesothelioma (MPM). We evaluated AZD2171, a potent tyrosine kinase inhibitor (TKI) of VEGFR1/2 in MPM. Methods: MPM patients (pts) after platinum-based chemotherapy, with PS 0–2, measurable disease and adequate organ function were treated with oral daily dosing of AZD2171 45 mg. Study endpoints were response rate, progression free survival (PFS), overall survival (OS), frequency/severity of toxicities, and correlation of clinical outcomes with tumor and serum biomarkers. Results: 54 pts were registered between November 2005 and April 2008; 45 pts are eligible for response and 46 for toxicity analysis. Median age was 66.8 yrs; M/F: 37/9. Tumor response by RECIST was seen in 4/45 (9%) of pts; of these responders, 2 pts with bulky disease had 56% and 91% tumor shrinkage, respectively. 15/45 (33%) had SD; 21/45 (47%) had PD; 1/45 (2%) had early death. Thirty-five pts have died. For 46 pts, median PFS is estimated at 3 months; median OS is estimated at 10 months. For 46 pts, frequent grade 1–3 toxicities included anorexia (30%), diarrhea (63%), fatigue (60%), hypertension (67%), and proteinuria (28%). There were 8 grade 4 events: Cognitive disturbance, colitis, confusion, ileal perforation, hypertension, hyponatremia, hypotension, and renal failure. Conclusions: AZD2171 has antitumor activity in MPM, with a DCR (CR/PR/SD) of 42% by RECIST, which has limitations in measuring response in pleural tumors. Notably, 2 pt tumors were exquisitely sensitive to this drug. Toxicities were consistent with those of the anti-angiogenic TKI class of drugs. Studies correlating outcome measures with tumor hypoxia- and angiogenesis-related gene expression and circulating endothelial cells are underway. Based on these data, we are proceeding in SWOG with a study of pemetrexed/cisplatin ± AZD2171 (S0905). This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA14028, CA46441, CA105409, CA13612, CA45808, CA20319, CA86780, CA35090, CA67663, CA46282, CA42777, CA76448, CA04919, CA35176, CA63848, CA27057, CA16385. [Table: see text]
Outcome of surgical resection for pathologic Nx and N0 non-small cell lung cancer (NSCLC)
Authors: Osarogiagbon R. U. , Allen J. W. , Farooq A. , Ninan M. , Ratliff T. W. 
Published: August 2020

7513 Background: Metastasis to lymph nodes (LN) connotes poor prognosis in NSCLC. Sufficient LN must be examined to accurately determine LN negativity. Patients with no LN examined (pNx) may be incompletely staged and erroneously assigned to a low risk group. To evaluate this possibility, we compared the survival of patients with node negative disease and at least 1 LN examined (pN0) to those with pNx. Methods: Retrospective analysis of all resections for NSCLC from January 1, 2004 to December 31, 2007 identified through a search of pathology databases at hospitals in the Memphis Metropolitan Area. Benign and metastatic disease, pre-operative chemo/radio therapy, bronchoalveolar cell, small cell lung, carcinoid tumors and repeat lung resection were excluded. Date of death was obtained from a National Death Index search. Variables were compared by chi-squared test, survival estimates calculated by Kaplan Meier analysis, survival estimates compared by log-rank test. Results: 746 of 809 resections met inclusion criteria. 86 (11.5%) were pNx and 510 (68.4%) pN0. Demographic and histologic characteristics were similar ( Table 1 ). 55.8% of the pNx group had sublobar resection, compared to 5.7% of pN0 (p<0.0001). 179 pN0 patients (35.1%) had only hilar-intrapulmonary LN (stations 10–14), median 3 (range 1–18) examined. 46 patients (9.02%) had only mediastinal LN (stations 1–9), median 2 (1–13); 281 patients (55.1%) had both stations 10–14 and 1–9, median 7 (2–45). 85% of pN0 patients had <10 LNs examined. 3-year survival estimate for the T1NxM0 vs T1N0M0 patients was 69% vs 70% (p= 0.14); for T2NxM0 vs T2N0M0 it was 25% vs 65% (p <0.01). Conclusions: A high percentage of patients (11.5%) undergoing surgical resection for NSCLC had pNx. These patients were more likely to have sublobar resections. Most (85%) patients with pN0 had <10 nodes examined and a large proportion (35.1%) had no mediastinal LNs, raising the possibility of understaging. Patients with pT2NxM0 did significantly worse than those with pT2N0M0. [Table: see text] [Table: see text]
Impact of positive pleural lavage cytology on survival in patients undergoing lung resection for non-small cell lung cancer: An international multicenter study
Authors: Lim E. , Clough R. , Goldstraw P. 
Published: August 2020

7519 Background: Pleural lavage cytology (PLC) is the instillation of saline into the chest during surgery for non-small cell lung cancer (NSCLC). The aims of this study were to collate multi-institutional individual patient data to determine independence as a prognostic marker and characterise impact of positive results on stage adjusted survival. Methods: We identified 31 publications from 22 centers/research groups that performed pleural lavage cytology during surgery for NSCLC and invited submission of individual patient data. Actuarial survival was calculated using Kaplan Meier methods and comparisons were performed using the log-rank test. Cox proportional hazards regression was utilised to ascertain the covariates associated with survival. Results: By 1 January 2008, submissions were received internationally from 11 centers with individual data from 8763 patients. In total, 511 (5.8%) patients had a positive pleural lavage cytology result, and this was shown to be an independent predictor of adverse survival associated with a hazard ratio of 1.465 (1.290 - 1.665; P<0.001). On statistical modelling, the best adjustment for patients with a positive PLC result was a single increase in the T category assigned to the case, up to a maximum of T4. Correction for differences in survival were obtained in stage IB (P=0.315) and IIB (P=0.453), with a degree of correction in stage IIIA (P=0.07). Conclusions: Pleural lavage cytology should be considered in all patients with NSCLC suitable for resection. A positive result is an independent predictor of adverse survival and the impact on survival suggests that it may be appropriate to upstage patients by one T category. No significant financial relationships to disclose.
Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations
Authors: Janjigian Y. Y. , Park B. J. , Kris M. G. , Miller V. A. , Riely G. J. , Zheng J. , Dycoco J. P. , Shen R. , Azzoli C. G. 
Published: August 2020

7523 Background: Patients with stage IV adenocarcinoma whose tumors harbor EGFR mutations have high rates of response (∼ 75%) and prolonged progression free survival after EGFR tyrosine kinase inhibitor (TKI) treatment. Adjuvant cisplatin-based chemotherapy improves disease free survival (DFS) and overall survival (OS) in patients with resected stages IB-IIIA NSCLC. To see if adjuvant treatment with EGFR TKI (gefitinib or erlotinib) improves DFS in patients with EGFR mutation NSCLC, we conducted a retrospective review of patients with resected lung adenocarcinoma harboring EGFR mutations, some of whom received EGFR TKIs postoperatively. Methods: With Institutional Review Board approval, clinical information was obtained on all patients with stage I-III lung adenocarcinoma harboring EGFR exon 19 or 21 mutations that underwent resection at MSKCC between May 2002 and August 2008. Age, gender, type of surgery, histology, EGFR mutation status (exon 19 deletions and exon 21 L858R), stage, perioperative therapy and survival were recorded. Kaplan-Meier analysis and Cox regression analysis were performed. Results: We studied 150 patients (112 women, 38 men) with completely resected stage I-III lung adenocarcinoma whose resection specimens contained EGFR activating mutations in exon 19 or 21. Median age was 69. Forty two patients (28%) received cytotoxic chemotherapy. Forty eight (32%) received either erlotinib (n=26) or gefitinib (n=22) postoperatively. The median time on TKI was 16 months. The median DFS was 43 months in the group that received a TKI vs. 31 months for those that did not. After controlling for stage, individuals who received adjuvant gefitinib or erlotinib had a better DFS (HR=0.38, 95%CI: 0.16–0.90) than the non-TKI group (p=0.03). The median overall survival has not been reached. Conclusions: These data indicate that the adjuvant use of either gefitinib or erlotinib improves DFS in patients with completely resected stage I -III lung adenocarcinomas with mutations in EGFR exons 19 and 21. These data justify a randomized trial in similar patients. [Table: see text]
Analysis of IGF1R gene copy number by silver in situ hybridization (SISH) in non-small cell lung cancer (NSCLC)
Authors: Wynes M. W. , Singh S. , Dziadziuszko R. , Dziadziuszko K. , Jaskiewicz K. , Jassem J. , Aumen N. , Hirsch F. R. 
Published: August 2020

7525 Background: IGF1R is a potential biomarker for predicting outcome of NSCLC patients (pts) treated with therapeutics targeting the IGF1R signaling pathway. SISH can be expeditiously analyzed on a bright field microscope given that the morphology of the tissue is observed concurrent to the scoring of discrete gene signals. Methods: An experimental SISH probe designed by Ventana Medical Systems (Tucson, AZ) was used to evaluate IGF1R gene copy number on a tissue microarray containing triplicate samples from 189 pts surgically treated for NSCLC (median follow-up 4 years and 5-year survival probability of 40%). Valid results, at least one core with sufficient tumor content for assessment, were obtained for 166 patients. There were 128 males; 93 squamous cell carcinomas (SCC), 47 adenocarcinomas, 5 large cell carcinomas and 21 other histologies. The pathological stages were I: 68, II: 37 and III/IV: 60. The mean number of IGF1R gene copies/nuclei/core was determined by a board certified pathologist counting 50 nuclei in each core. The mean number of IGF1R gene copies/nuclei/patient was determined by using, within the triplicates, the core with the highest gene copy number/nuclei. Results: The mean number of IGF1R gene copies/nuclei per patient was 2.26 (range: 1.12 - 7.56; standard deviation 0.81). The median copy number was 2.11. The pts were divided into two groups, those with 2.1 genes/nuclei or less and those with greater than 2.1 genes/nuclei. There was no statistical difference related to gender (p=0.422) or between pathological stages, (p=0.221). However, there was a highly significant difference between the two categories when considering histological pattern. Among patients with SCC, 66.3% had high copy number compared to 33.7 % in non-SCC histologies (p=0.008). Analysis of overall survival comparing pts with low vs. high IGF1R gene copy number revealed no statistical difference in the median survival: 1.5 yrs (95% CI 0–3.7 yrs) vs. 3.3 yrs (2.0–4.5 yrs) or the 3-year survival: 46% (35–57%) vs. 52% (41–63%). Conclusions: IGF1R gene copy number detected by SISH is higher in SCC than in other histologies of NSCLC, but does not associate with gender, pathological stage or survival. IGF1R SISH should be further explored as a predictive biomarker for IGF1R therapeutics. [Table: see text]
A phase II study of accelerated high-dose thoracic radiation therapy (AHTRT) with concurrent chemotherapy for limited small cell lung cancer: RTOG 0239
Authors: Komaki R. , Paulus R. , Ettinger D. S. , Videtic G. M. , Bradley J. D. , Glisson B. S. , Choy H. 
Published: August 2020

7527 Background: Inter-group(IG) study 0096 showed that hyperfractionated and accelerated radiotherapy (HFXART) and concurrent etoposide/cisplatin(EP) improved 5-yr survival (26 %) for patients (pts) with limited small cell lung cancer (LSCLC) compared to daily treatment (TRT) with EP (16%), (p=0.04), HFXART/ EP still had high local failure (LF 40 %) and acute severe esophagitis (ASE) rate (27%). Radiation Therapy Oncology Group (RTOG) 0239 was developed to improve local control (LC) and overall survival (OS) without increasing ASE.Methods: Eligibility included limited stage SCLC, age ≥ 18; P.S. 0–1, with adequate hematologic, hepatic, and renal function. RT was given to large field to 28.8 Gy: 1.8 Gy/ fraction (Fx), 5 days (d) / wk for 16 Fx followed by BID with AP/PA fields in AM @ 1.8 Gy /Fx; boost with 2nd treatment in PM @ 1.8 Gy/Fx on d: 23–26; then off-cord boost, 1.8 Gy, BID, x last 5 days for a total dose of 61.2 Gy in 5 wks. EP was started on day 1 of TRT with P, 60 mg/m2 i.v; E, 120 mg/m2 i.v.; E, 240 mg/m2 p.o. d 2 and 3 or E 120 mg/m2 i.v. / d on d 2 or 3. Repeat cycle every 3 wks x 2 cycles with RT, followed by adjuvant EP alone x 2 cycles. CR pts were asked to participate in the prophylactic cranial irradiation (PCI) study RTOG 0212. RTOG 0239 was designed to detect an improvement in the 2-year survival rate from 47% to 60% with less than 30% of ASE.Results: RTOG 0239 accrued 72 pts (71 eligible) from June 20, 2003 to May 23, 2006. The median follow-up time is 19.0 months for all pts, and 30.4 months for pts still alive. The median age was 63, 52% female, 58% Zubrod PS 0. The 2 -year survival rate was 37 % [95% CI: 25.6, 47.7]. 13 pts (18 %) experienced severe esophagitis. 2 treatment related deaths (2.8%) were reported. Response rates 2 months post RX showed CR 41%, PR 39%, SD 10% and PD 6%. Locoregional control rate at two years was 80%. RT compliance was 95 %.Conclusions: RTOG 0239, AHTRT/EP for LSCLC resulted in 37% 2-year OS, 80% 2 year LC and 18% ASE. Compliance with treatment was high and treatment-related death rate was similar to other chemoradiation regimens. Although 2-year OS did not achieve 60%, excellent LC and low ASE were achieved by RTOG 0239 which became one of 3 arms in an ongoing randomized trial of LSCLC RTOG0538/CALGB30610. [Table: see text]