bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated survival analysis of JBR.10: A randomized phase III trial of vinorelbine/cisplatin versus observation in completely resected stage IB and II non-small cell lung cancer (NSCLC)
Authors: Vincent M. D. , Butts C. , Seymour L. , Ding K. , Graham B. , Twumasi-Ankrah P. , Gandara D. , Schiller J. , Green M. , Shepherd F. 
Published: August 2020

7501 Background: JBR.10 was one of a number of phase III trials that established adjuvant cisplatin based chemotherapy as a recommended treatment in completely resected NSCLC . Long-term follow-up of these trials is important to document persistent benefit and potential late toxicities of adjuvant therapy. We report the updated survival data for JBR.10 with more than 9 years median follow up. Methods: Patients with completely resected stage IB (T2N0) or II (T1–2N1) NSCLC were randomized to receive 4 cycles of vinorelbine/cisplatin or observation.. Kaplan-Meier curves were generated for overall (OS) and disease specific survival (DSS). Log-rank test was used to compare survival distribution and to test cause specific hazard. For the competing risk analysis, the Gray test was used to test the difference in cause specific incidences. All efficacy analyses were done on an ITT basis. Results: 482 patients were randomized. Data cut-off for this update was July 2008. Median follow-up is 9.3 years (3.2–13.8 y). 12 patients were lost to follow up, a median 4.9 years from randomization (1.5–12 years). 271 deaths have occurred, 73% due to lung cancer or its treatment. Survival analysis continues to show a benefit for chemotherapy: HR .78 (CI .61-.99, p=.04). The benefit appears to be confined to N1 patients: median OS 6.8 y versus 3.6 y, HR .68 (CI .5-.92, p=.01). N0 patients did not appear to benefit: HR 1.03 (CI .7–1.52, p=.87). Chemotherapy significantly prolonged DSS, HR.73 (CI .55-.97, p=.03) Competing risk analysis showed observation to be associated with significantly higher risk of death from lung cancer (p=.02) with no difference in incidences of death from other causes between arms (p=.62). Conclusions: Prolonged follow-up of patients in the JBR.10 trial continues to show a benefit in survival for adjuvant chemotherapy. This benefit appears to be confined to N1 patients. There was no increase in death from other causes in the chemotherapy arm. [Table: see text]
Relationship of thymidylate synthase levels to outcome of malignant pleural mesothelioma patients treated with pemetrexed-based chemotherapy
Authors: Selvaggi G. , Righi L. , Ceppi P. , Bacillo E. , Billè A. , Pandiscia S. , Ardissone F. , Scagliotti G. V. , Papotti M. 
Published: August 2020

7508 Background: Pemetrexed has shown activity in malignant pleural mesothelioma (MPM) but scanty data are available on the expression of thymidylate synthase (TS), its most important molecular target. Methods: From a database of 75 non-surgical, chemotherapy-naive MPM patients from our Institution in the period 2004–2008, 50 (male/female: 37/13, median age: 65 years) met the selection criteria i.e. epithelial type, availability of thoracoscopic tissue and outcome data. Pemetrexed was administered as single agent (14/50) or in combination with cisplatin or carboplatin (36/50). Retrospectively TS protein expression levels were evaluated by immunohistochemistry and quantified with H-score method. In addition, mRNA extraction was performed in 23 micro-dissected tissues and TS relative levels quantified by RT-PCR. Survival probability was assessed by Kaplan-Meier method and results compared by log-rank test. Cox multivariate analysis for survival was performed adjusting for clinical-pathological variables. Results: Thirty-two patients had progressive disease and 24 had died at the time of the analysis. Median time to progression (TTP) and median survival time (MST) were 11.6 and 20.9 months, respectively. Median TS H-score value was 90 (5–240). No correlation were found with sex, age, PS, stage and chemotherapy regimen. Patients with high TS H-score (4th quartile) had a significantly shorter MST (13.3 vs 21.1 months, p<0.01) and showed a trend for shorter TTP (8.3 vs 11.9 months, p=0.07). Median TS mRNA level was 1.88 (1–3.7 unit-less ratio) and a significant correlation between mRNA and protein expression (RS=0.67, p<0.0001) was found. Patients with high TS mRNA levels (4th quartile) had significantly shorter TTP (8.7 vs 14.7 months, p=0.019) and MST (11.7 vs 24.7, p=0.018). Multivariate analysis for survival indicated that TS protein levels were an independent prognostic factor (HR=2.17; CI 1.04–4.54; p=0.038). Conclusions: TS (protein and mRNA) levels predict outcome of epithelial MPM patients treated with pemetrexed-based chemotherapy. TS quantification, if confirmed in larger prospective studies, could be used to select those patients more likely to respond to chemotherapy. [Table: see text]
Quality of surgical resection for non-small cell lung cancer (NSCLC) in a U.S. metropolitan area
Authors: Allen J. W. , Osarogiagbon R. , Farooq A. , Ninan M. , O'Brien T. F. 
Published: August 2020

7512 Background: Curative treatment of early stage NSCLC requires good quality oncologic resection (GQR). For GQR, the National Comprehensive Cancer Network (NCCN) requires a minimum of segmentectomy, negative margins, lymph node (LN) sampling from stations 10–14 (level-1) and >2 mediastinal (level-2) stations. We reviewed details of consecutive resections for NSCLC to determine the proportion that met NCCN GQR criteria and the proportion who would have met eligibility for the RADIANT trial which requires >1 level-2 stations. Methods: Retrospective review of medical records of all patients who underwent curative- intent resection for NSCLC in the Memphis Metropolitan Area from 1/1/2004 to 12/31/2007. Resections for benign and metastatic disease were excluded. Death information was obtained from a national death index search. Categorical variables were compared by chi-square test or Fisher's exact test, survival curves by log-rank test. Results: 746 patients were eligible (Table). Median age was 67.7 (range, 36.5 - 89.4). 61/746 (8.2%) met NCCN GQR criteria. Black patients were more likely than whites to have GQR (P=0.022). No other patient demographic factor was associated with GQR. Three year survival was 72% in those with GQR versus 63% in those without GQR (P=0.50). There was a difference in achievement of GQR between the 3 major institutions where surgery was done (P=0.001) although it was low across the board. 77.9% of patients would have been disqualified from the RADIANT trial. Conclusions: Majority of surgical resections for NSCLC did not achieve GQR standards per RADIANT and NCCN. The greatest deficit is in surgical sampling of level-2 LNs, but evaluation of level-1 LNs is also frequently sub-optimal. Intervention is needed to improve current surgical and pathology practices in collection and examination of surgical specimens in order to achieve minimum standards for accurate staging, prognostication, determination of candidacy for post-operative adjuvant therapy, and eligibility for clinical trials. [Table: see text] [Table: see text]
Clinical impact of age on outcomes following anatomic lung resection for stage I non-small cell lung cancer
Authors: Schuchert M. J. , Pettiford B. , Kilic A. , Landreneau J. P. , Landreneau J. R. , Christie N. A. , Pennathur A. , Nason K. S. , Wilson D. O. , Luketich J. D. , Landreneau R. J. 
Published: August 2020

7515 Background: There is an increasing body of evidence that anatomic segmentectomy may represent an equivalent approach compared to lobectomy in the management of stage I NSCLC. Comorbidities associated with age may result in improved survival with sublobar resection for stage I cancer in the elderly. We report our single institution experience with segmentectomy vs. lobectomy for stage I non-small cell lung cancer stratified by age. Methods: A total of 232 consecutive anatomic segmentectomies were performed for stage IA (n=137) or IB (n=95) NSCLC from 2002–2007. Lobectomy was performed in 594 patients for stage IA (n=297) and IB (n=295) during the same period. Results of segmental resection were compared with lobectomy, stratified by the following age groups: <60, 60–69, 70–79 and = 80. Primary outcome variables included complications, mortality, recurrence patterns, and survival. Statistical analysis included t-test and Fisher's exact test. Results: Mean age (69.9 vs. 68.2), gender distribution and tumor histology were similar between the segmentectomy and lobectomy groups. There was no significant difference in complications, mortality, recurrence, and overall survival in the younger age groups (Table). Segmentectomy was associated with reduced mortality (7.8% vs. 2.8%) and improved overall 3-year survival (p=0.02) in patients >80 years old. Conclusions: Anatomic segmentectomy can be performed with similar morbidity, mortality, recurrence, and survival compared to lobectomy in stage I lung cancer. This approach may be particularly advantageous in the elderly age group, achieving comparable oncologic outcomes with less mortality and improved overall survival. [Table: see text] No significant financial relationships to disclose.
Survival predictors after surgical resection of synchronous bilateral non-small cell lung cancers (NSCLC)
Authors: Tanvetyanon T. , Robinson L. , Sommers E. , Altiok S. , Haura E. , Kim J. , Bepler G. 
Published: August 2020

7517 Background: Non-small cell lung cancer (NSCLC) that presents with bilateral lung lesions, but without extra-thoracic metastasis, is uncommon. Prognosis is typically poor: No long-term survivor is expected with systemic chemotherapy. However, small reports have suggested the feasibility of bilateral resections. To date, the predictors of survival following this treatment approach remain unknown. Methods: Our institutional tumor registry was searched for patients who underwent bilateral resections of NSCLC during 1998–2006. Patients with metachronous presentations (second lesion found ≥ 2 years afterward) were excluded. Kaplan-Meier survival estimate and Cox proportional hazards model were used to identify survival predictors. Results: Of the 2582 patients operated for NSCLC, 50 patients were included in this analysis. Median age was 69.2 years. Median tumor sizes were 2.0 cms; Adenocarcinomas were the most common (51%). Of 103 thoracotomies, pneumonectomy was performed in 3 patients. Overall peri-operative mortality was 1.9%. Median progression-free survival was 46.0 months (95% CI, 33.1–66.6); overall survival was 77.5 months (95% CI, 43.1–111.1). Performance status, presence of comorbidity, and pathological vascular invasion were important prognostic factors (Table). Risk score based on the sum of these factors (present =1; absent =0) was a strong predictor of survival. Patients with score ≥ 2 (N=11) had a median survival of 17.2 months, compared with 83.5 months among those with score ≤ 1 (HR 5.52, 95% CI 2.27–13.46; p=0.0002). Conclusions: In this largest series of surgery for synchronous bilateral NSCLC to date, the overall survival rate at 5 years is approximately 50%. Performance status, comorbidity, and vascular invasion are strong predictors of survival. Patients with vascular invasion are at an increased risk of progression or death and adjuvant therapy should be considered. [Table: see text] No significant financial relationships to disclose.
Baseline thymidylate synthase expression according to histological subtypes of non-small cell lung cancer
Authors: Scagliotti G. , Monica V. , Ceppi P. , Righi L. , Cambieri A. , Volante M. , Novello S. , Cappelletto E. , Papotti M. 
Published: August 2020

7521 Background: In non-small cell lung cancer (NSCLC) baseline thymidilate synthase (TS) levels are higher in squamous cell carcinoma (SCC) compared to adenocarcinoma (AC) and randomized clinical trials have shown a selective benefit for patients with non-squamous histology treated with pemetrexed, a TS-inhibiting agent. TS expression in undifferentiated large cell carcinoma (LCC) is unknown. Methods: TS expression at both mRNA (using tissue microdissection and qRT-PCR) and protein (through immunohistochemistry, IHC) levels was tested in 34 surgically resected LCC (stage I=20,II=6,IIIa=8) and compared with TS expression in surgical cases of SCC (n= 31) and AC (n=40). In addition other comparisons were made: a) TS protein expression with Ki-67 index; b) TS mRNA and E2F1 transcription factor mRNA; c) in all histotypes TS protein level with desmocollin-3 (DSC-3) immunostaining, a marker of squamous cell differentiation. TS expression level was assessed in a group of patients (n=22) with cytological diagnosis of NSCLC-NOS (not otherwise specified) and compared with TS data in tissue specimens obtained through subsequent bronchial biopsy or surgical resection. Results: Significantly higher median TS levels in LCC compared to AC (p<0.001 for both mRNA and protein values) and SCC compared to AC (p=0.002 mRNA, p<0.001 protein) were detected. A strong correlation between TS mRNA and protein levels were found (p<0.001) in SCC and AC, but not in LCC. TS and both Ki-67 and E2F1 were significantly correlated in AC and SCC (p=0.003 and p=0.05, respectively), but in LCC no correlation was found. In LCC, significantly higher TS levels were observed in DSC3-positive compared to DSC3-negative tumors (p=0.02). A significant correlation between TS IHC scores in matched cytological and corresponding tissue specimens was observed (p<0.001). Conclusions: This study demonstrates and confirms the: a) differential expression of TS among the NSCLC histotypes; b) lack of DSC-3 immunoreactivity in LCC is associated with lower TS expression; c) assessment of TS by IHC in cytological specimens correlates with the corresponding tissue TS expression. [Table: see text]
Prognostic significance of tumor size in patients with stage III non-small cell lung cancer: A SEER database survey
Authors: Waqar S. N. , Gao F. , Govindan R. , Morgensztern D. 
Published: August 2020

7529 Background: Although tumor size is a known predictor of stage I and II non-small cell lung cancer (NSCLC) treated with surgery or radiotherapy, there is limited information regarding its prognostic significance in patients with mediastinal lymph node involvement. Methods: The Surveillance Epidemiology and End Results (SEER) registry was queried for patients with unresected NSCLC stage III, without malignant pleural effusion, aged 21 or older, and diagnosed between 1998 and 2003. Tumor size was defined as S1 (0.1–3 cm), S2 (3.1–5 cm), S3 (5.1–7 cm) and S4 (7.1–20 cm). Demographic variables included age, gender, race and histology. The Kaplan-Meier method was used to estimate the overall survival (OS) and disease-specific survival (DSS), and the Cox proportional hazard model to evaluate whether tumor size remained an independent risk factor after adjusting for stage and other demographic variables. Results: A total of 12,205 patients met the eligibility criteria. Median age at diagnosis was 70 years and most patients were male (58.8%) and white (81.3%). Tumor size was a statistically significant predictor for both overall survival (p<0.0001) and disease-specific survival (p<0.0001) on multivariate analysis. Selected groups of patients with smaller stage IIIB disease had better OS compared to patients with stage IIIA, including; IIIBS1 vs. IIIAS3 (p=0.0005) or IIIA S4 (p<0.0001) and IIIBS2 vs. IIIAS4 (p=0.0001). Conclusions: Tumor size is an independent predictor for OS and DSS in patients with unresected stage III NSCLC and should be considered in the stratification of patients treated in this setting. [Table: see text] No significant financial relationships to disclose.
Clinical factors predictive of overall survival (OS) and the identification of prognostic groups in patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy on Cancer and Leukemia and Group B trial (CALGB) 39801
Authors: Stinchcombe T. E. , Hodgson L. , Herndon J. E. , Kelley M. J. , Cicchetti M. , Ramnath N. , Niell H. B. , Atkins J. N. , Green M. R. , Vokes E. E. 
Published: August 2020

7535 Background: CALGB 39801 was designed to test whether treatment with induction chemotherapy and concurrent chemoradiotherapy (arm B) would improve OS in comparison to identical chemoradiotherapy alone (arm A), and demonstrated no significant benefit in OS for induction therapy. The objective of this analysis was to identify factors predictive of OS, and to use relevant factors to dichotomize pts into prognostic groups. Methods: Between July 1998 and May 2002, 331 pts were studied and included in a Cox proportional hazard regression analysis investigating previously identified prognostic factors: age (< 70 vs. ≥ 70 years), gender, race/ethnicity, hemoglobin (hgb) (< 13 vs. ≥13), performance status (PS) (0 vs.1), pretreatment weight loss (wt loss) (<5% vs. ≥ 5%), and treatment arm. Results: Cox regression analysis identified weight loss ≥ 5%, age ≥ 70, PS of 1, and hgb < 13 as predictive of worse survival (p<0.05), but not treatment arm (p=0.55). The median survival for pts with 0 (n=66), 1 (n=100), 2 (n=100), or ≥ 3 (n=65) risk factors were 24, 18, 10, and 8 months, respectively (p=0.0001). The pts were dichotomized into “poor prognosis” (PP) defined as ≥2 factors (n=165) and “good prognosis” (GP) defined as ≤ 1 factors (n=166). The hazard ratio (HR) for overall survival for the PP in comparison GP was 1.88 (95% CI, 1.49 to 2.37; p-value < 0.0001); the median survival times (MST) observed were 9 and 18 months, respectively (p<0.0001). The reasons for discontinuing treatment, and the rates of hematologic and non-hematologic adverse events were similar between the two groups. In the PP group the OS was similar between arms A (n=82) and B (n=83) (HR=0.97, 95% CI, 0.70 to 1.4; p=0.34); MST of 8.7 and 9.5 months, respectively. In the GP the OS was similar between arms A (n=79) and B (n=87) (HR=0.86, 95% CI, 0.63 to 1.1; p=0.87); MST of 19.3 and 17.6 months, respectively. Conclusions: Factors predictive of OS can be used to dichotomize pts into prognostic groups. Induction chemotherapy was not beneficial in either prognostic group. No significant financial relationships to disclose.
Clinical outcomes of elective nodal irradiation (ENI) compared with involved field radiotherapy (IFRT) in NSCLC
Authors: Fernandes A. , Faerber J. , Finlay J. , Shen J. , Lin L. , Evans T. , Stevenson J. , Langer C. , Glatstein E. , Hahn S. , Rengan R. 
Published: August 2020

7541 Background: Local failure rates in patients treated with definitive radiotherapy for non-small cell lung cancer (NSCLC) remain high. IFRT allows higher radiation doses to the primary tumor with the goal of reducing local failure rates while minimizing toxicity. This approach, however, raises concern for increased nodal failures. Our retrospective analysis evaluates clinical outcomes of patients treated at our institution with ENI or IFRT. Methods: We assessed all patients (pts) with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy (RT) from January 1, 2003 to August 21, 2008. The decision to treat with ENI vs. IFRT was based on physician treatment philosophy. We compared baseline demographics in each group as well as toxicities and therapeutic outcomes. Involved nodal failures (INF) were defined as radiographic progression in lymph nodes that were initially involved at the time of treatment. Elective nodal failures (ENF) were defined as progression in initially uninvolved lymph nodes. Results: A total of 104 consecutive pts (56 ENI vs. 48 IFRT) were assessed. Pts in both groups had similar characteristics with respect to age, baseline KPS, and percentage receiving chemotherapy. The average RT dose was 6,345 cGy in the ENI group and 6988 cGy in the IFRT group. The median follow-up time was 8.4 mos (0.3–43.4) for all pts and 9.7 mos (1.5–40.1) for survivors. The results follow in the table below. Conclusions: Our data suggest that IFRT does not result in increased nodal failures or decreased survival compared to ENI, and may result in increased local control. The majority of patients who experienced a local failure also experienced nodal failure, suggesting that local relapse may be linked to subsequent nodal failure. This may explain the increased nodal failure rates in patients treated with ENI. Decreased esophagitis rates in patients treated with IFRT may allow the integration of concurrent, full dose systemic therapy in a greater proportion of patients, as well as higher RT doses. [Table: see text] No significant financial relationships to disclose.
S-1-based concomitant chemoradiotherapy for locally advanced non-small cell lung cancer: Two phase I trials from Okayama Lung Cancer Study Group (OLCSG)
Authors: Fujiwara Y. , Kiura K. , Takigawa N. , Hotta K. , Kishino D. , Nogami N. , Gemba K. , Takemoto M. , Tabata M. , Tanimoto M. 
Published: August 2020

7547 Background: Chemoradiotherapy (CRT) is a standard treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC), but the treatment outcomes have remained unsatisfied. Thus, more effective and feasible CRT is urgently needed to improve their survival. S-1 is a newly developed oral 5-fluorouracil derivative and has synergistic effects with radiation. However, the role of S-1 in CRT for LA-NSCLC has been undetermined. Methods: We conducted two phase I trials to define the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of S-1-based chemotherapy when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) for LA-NSCLC. OLCSG 0501 was designed to evaluate the two cycles of combination of S-1 (days 1–14) and cisplatin (days 1 and 8) for patients aged 75 or younger. S-1/cisplatin dosages (mg/m2) were escalated as follows: 60/30, 60/40, 70/40, 80/40, and 80/50. The other trial, OLCSG 0502, recruited patients aged 76 or older and evaluated S-1 alone. S-1 dosages (mg/m2) were increased as follows: 60, 70, and 80. Results: A total of 44 previously untreated LA-NSCLC patients were enrolled (22 in both trials). The MTDs for S-1/cisplatin and S-1 alone were determined to be 80 mg/m2/day / 50 mg/m2 and 80 mg/m2/day, respectively. In the OLCSG 0501, DLTs included febrile neutropenia, thrombocytopenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced grade 3 or more acute radiation pneumonitis and only one patient experienced grade 3 radiation esophagitis. In the OLCSG 0502, the DLTs were febrile neutropenia, stomatitis and delayed second cycle of chemotherapy. The overall response rates in OLCSG 0501 and OLCSG 0502 were 86.4% and 59.1%, respectively. Conclusions: These results indicate that S-1-based concomitant CRT would be a feasible treatment option and further phase II trials are currently under way. No significant financial relationships to disclose.