bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of annual screening of lung cancer with low dose computed tomography in 5,000 high-risk individuals
Authors: Veronesi G. , Bellomi M. , Spaggiari L. , Pelosi G. , Sonzogni A. , Paganelli G. , Preda L. , Solli P. , Maisonneuve P. , Leo F. , Veronesi U. 
Published: March 2020

7566 Background: Screening detected lung cancers are correlated with good prognosis however most of the reported cases were detected at baseline screening and little is known about the evolution of pulmonary nodules at annual screening. We report the results of the first and second year of a single centre screening trial focusing the attention on the evolution of pulmonary nodules. Methods: The Cosmos trial started in October 2004 and enrolled 5,202 asymptomatic persons at high risk for lung cancer in one year. Between October 2005 and October 2006, the participants of the study, have been recalled to undergo the annual low dose CT. New lesions were treated according to the baseline diagnostic work up protocol. Previously detected lesions grown at annual screening were investigated with repeated low dose CT and/or Pet scan. Surgical biopsy was scheduled in case of Pet positive or growing nodules. Stable lesions were sent to one year follow up. Results: 4,745 out of 5,202 underwent the annual screening (compliance 92%). Recall rate was 10.7% at baseline and 4% at annual screening. Rate of malignant disease was 1.03% at baseline and 0.7% at annual screening. Patients with stage I disease were 68% at baseline and 76% at annual screening. Of the 32 lung cancers diagnosed at annual screening 8 were new nodules, 1 nodules was stable and 23 nodules progressed from the previous year. Among these, 9 nodules were lower than 5 mm at baseline (out of 2,190 subjects = 0.4%) and 14 were larger than 5 mm (out of 560 subjects =2.5%). Conclusions: Screening low dose spiral CT is an effective tool for the early detection of lung cancer. At first annual screening malignancy rate decreased from 1% to 0.7% and stage distribution was more favourable. However the high rate of delayed diagnosis (2.5%) in cases of nodules larger than 5 mm at baseline CT may require a revision of our proposed diagnostic work up protocol to further anticipate detection of these cases. No significant financial relationships to disclose.
A multi-gene assay to predict long-term mortality in early stage lung adenocarcinoma
Authors: Raz D. J. , Kim J. Y. , Ray M. R. , Jablons D. M. 
Published: March 2020

7569 Background: The likelihood of long-term mortality for patients with early stage lung adenocarcinoma is poorly defined by clinical stage and histopathological findings. Our hypothesis was that a multigene quantitative polymerase chain reaction (PCR) assay can predict risk of mortality among patients with early stage lung adenocarcinoma. Methods: We identified 65 genes that were previously identified as prognostic for long-term mortality in early stage lung cancer in 3 published microarray studies and 2 PCR-based studies. RNA was extracted from 124 fresh-frozen tumor samples from consecutive patients with completely resected lung adenocarcinoma with at least 3 years of clinical follow-up. 80 samples were randomly assigned to a test group and the remainder assigned to a validation group. Real-time PCR of the 65 identified genes were run on the test set using Taq-man assays. A prediction model was created using a proportional hazards model of normalized gene expression levels using backwards model selection. A model score was calculated for each patient using model coefficients and individual gene expression levels. Patients were defined as high-risk if the model score was greater than the median score. Results: Adequate real-time PCR profiles were identified in all 80 patients. Eighteen genes were included in the final model. The proportion of patients identified as high-risk and low-risk was 52% and 48% percent, respectively. The Kaplan-Meier estimated five-year survival in the low-risk group was 82% and 5% in the high-risk group (P<0.001, log-rank test). Median survival was 22 months in the high-risk group and was not reached in the low-risk group. In multivariate survival analysis, the prognostic score predicted survival independent of tumor stage and size (P<0.001). Prognostic score predicted mortality better than clinical stage, based on model log-likelihood values (P<0.001). Conclusions: This multi- gene assay aids in predicting long-term mortality among patients with surgically resected early stage lung adenocarcinoma. We are currently validating this model in our test set of samples. No significant financial relationships to disclose.
The NATCH trial: Observations on the neoadjuvant arm
Authors: Felip E. , Rosell R. , Massuti B. , Alonso G. , González-Larriba J. L. , Camps C. , Isla D. , Mas C. , Sanchez J. J. , Maestre J. A. 
Published: March 2020

7578 Background: In early-stage NSCLC the neoadjuvant approach is a promising option since relatively low compliance rate with adjuvant therapy and incomplete recovery after surgery are commonly reported. The NATCH trial was therefore designed to address whether neoadjuvant or adjuvant paclitaxel (P)/carboplatin (C) improves disease-free survival compared to surgery alone in early-stage NSCLC. Patients randomized to the neoadjuvant arm have now undergone analyses of toxicity, radiographic response, resectability and surgical mortality. Methods: Consenting patients with clinical stage I (>2 cm), II, T3N1 NSCLC are randomized to surgery alone or 3 cycles of neoadjuvant PC (P: 200 mg/m2/ C:AUC=6 on day 1 every 3wk), or surgery followed by 3 cycles of adjuvant PC at the same schedule. Planned sample size of this prospective, randomized trial is 628 patients. Results: Since 2000, 616 patients have been accrued, 200 in the neoadjuvant arm, 208 in the adjuvant arm, and 208 in the surgery arm. Demographic data is now available for 162 patients in the neoadjuvant arm: 89% male; median age 64 years (range, 37–78); 45% PS 0; 53% squamous cell, 27% adenocarcinoma, 13% large cell; 7% stage IA, 64% IB, 2% IIA, 24% IIB, 2.5% T3N1. Neoadjuvant chemotherapy has been well tolerated with a median number of cycles per patient of 3. No unexpected toxicities have been seen with 12% of patients having grade 3–4 neutropenia and 43% grade 1–2 anemia. Major radiographic response has been observed in 59% of patients and progression during chemotherapy occurred in 6%. No patient characteristics were predictive for clinical response. Resection procedures at thoracotomy: lobectomy or bilobectomy in 70%, pneumonectomy in 26%, and explorative thoracotomy due to unresectable disease in 3% of patients. Post-operative mortality was 4%. Median tumor size was 4.5 cm at baseline CT-scan and 2.5 cm at surgery. At surgery, 9% patients had pathologic complete response, 75% N0–1 disease (with persistent T tumor), and 15% pathologic N2 disease. Conclusion: Neoadjuvant chemotherapy in early NSCLC has proven feasible and safe in this large multicenter sample. Chemotherapy compliance has been high and resectability rates as expected. Our findings are comparable with those of previous studies (BLOT and S9900). Mature survival results of the NATCH trial are expected in 2009. No significant financial relationships to disclose.
Triplets vs. doublets in the management of advanced non-small cell lung cancer (NSCLC) using third generation chemotherapeutic agents: A meta-analysis
Authors: Azim H. A. , Ganti A. K. , Elattar I. , Azim H. , Loberiza F. R. 
Published: March 2020

7580 Background: A platinum-based doublet is the current standard of care in the management of NSCLC. Addition of a third agent to the doublet has not shown to improve outcomes in a previous meta-analysis. Since one of the reasons for this may have been the inclusion of trials utilizing agents inferior to the currently used, we conducted a meta-analysis to evaluate the benefit of adding a third generation cytotoxic chemotherapeutic agent to a platinum doublet in terms of response rate, survival, and toxicity in patients with advanced NSCLC. Methods: Randomized controlled trials for advanced NSCLC, published as full papers in English, comparing doublets to triplets restricted to platinum salts and third-generation cytotoxic chemotherapeutic agents (vinorelbine, gemcitabine, docetaxel, paclitaxel) were analyzed. A Medline search was performed using the search terms “lung cancer” and “randomized trials”. Manual searches were also performed in the Journal of Clinical Oncology and Annals of Oncology. Pooled odds ratios (ORs) for the objective response and toxicity rates were calculated using the Mantel-Haenszel estimate. Pooled median ratios for median survival were calculated using the weighted sum of the log-ratio of median ratios of individual study. Results: Eight trials (2,107 patients) published between 2000 and 2006 were eligible. Patients receiving triplet therapy had a significantly increased response rate (OR 1.86; 95% CI, 1.53 –2.26; P<0.001) and median survival (41.9 weeks vs. 37.05 weeks; OR: 1.14, 95% CI: 1.00–1.31; P=0.047), at the expense of higher grade III/IV hematological and neurological toxicity (P<0.001) ( Table ). Conclusions: The addition of a third-generation cytotoxic agent to a platinum-based doublet was associated with improved response rate and survival, but with increased hematological and neurological toxicity. Thus, triplet therapy may be considered in selected good performance status patients with advanced NSCLC. No significant financial relationships to disclose. [Table: see text]
Skin rash as surrogate marker of efficacy in patients with non-small cell lung cancer treated with erlotinib
Authors: Cobo M. , Cardenal F. , Insa A. , Domine M. , Lianes P. , Guillot M. , Montesinos J. , Bover I. , Amador M. L. , Paz-Ares L. 
Published: March 2020

7602 Background: Erlotinib is an orally EGFR TKI approved for the treatment of advanced non-small-cell lung cancer. Its most frequent and specific toxicity is a rash which generally occurs in a dose-dependent manner. A relationship between rash and clinical outcome have been suggested. Methods: The TargeT trial was an open-label, non-randomized, phase II study carried out in 101 Spanish institutions. Patients (p) with confirmed NSCLC (stage IIIB-IV) were treated with 150 mg/day po until disease progression or unacceptable toxicity. Primary objective was time to progression. Here we report a retrospective analysis describing outcomes in terms of response and survival in the group of patients who developed rash and those who did not. Results: Data were available for 1,255 p. Key baseline characteristics were similar in p with and without rash. Median age 65y (range 26–95) Most p were male (75%); active/former smoker (82%) 51% adenocarcinoma histolog. ECOG PS 0/1/2 were (%) 20/53/27. The % p receiving erlotinib as 1st/2nd/3rd- line treatment were 26/39/35. 698 patients were evaluable for response. Objective response rate (ORR) 12.6% with 51% control disease rate. Skin rash of any grade was observed in 73.4% p, among these p, responses were observed in 14.3%. In p with no rash ORR was 8.1% (p=0.03). Control disease rate was significantly higher among p experiencing rash (56.6%) than those without rash (35.48%; p<0.0001). Median time to progression for p with rash were 3.8 mo (95% CI: 3.4–4.3), compared with 2.3 mo (95% CI: 2.1–2.6) in those with no rash (p<0.001). Similar trend was found in overall survival 6.5 mo (95% CI: 6.1–7.3) in p with rash versus 2.3 mo (95% CI: 2.3–2.7; p<0.001). In addition p who developed rash grade =2 had significantly longer TTP (4.2 m; 95% CI 3.6–4.8; p<0.001) and OS (7.9 mo; 95% CI 6.5–8.8). Conclusions: This retrospective analysis suggest a correlation between skin rash development and severity and treatment outcome. Skin rash seems to be a surrogate marker of efficacy. Studies to prospectively investigate the association between increased dosing of erlotinib, skin rash and optimal response are currently ongoing. However, data from our analysis indicate that skin toxicity is neither sufficient nor necessary condition for an optimal outcome. No significant financial relationships to disclose.
Concomitant chemoradiation plus induction (I) or consolidation (C) chemotherapy (CT) with docetaxel (D) and gemcitabine (G) for unresectable stage III non-small cell lung cancer (NSCLC) patients (p). Results of the randomized SLCG 0008 phase II trial
Authors: Garrido P. , Massutí T. , Morán T. , Cardenal F. , Juan O. , Dómine M. , Cobo M. , García R. , Maestu I. , Isla D. 
Published: March 2020

7620 Background: Neither the optimal sequence of treatment nor the best combination CT is yet well-defined in p receiving concomitant therapy Methods: P with unresectable stage III NSCLC with IK ≥ 70 and weight loss < 5% were initially randomized to sequential treatment (arm A), concurrent CT/TRT followed by consolidation CT (arm B) or induction CT followed by CT/TRT (arm C). Based on RTOG 9410 results, arm A was closed and the study continues with two concomitant arms (B, C). All p receive 2 cycles of D 40 mg/m2 d1, 8 plus G 1,200 mg/m2 d1, 8 as I or C therapy. Concomitant treatment includes D 20 mg/m2 and carboplatin (Cb) AUC 2 weekly plus 60 Gy TRT. Results: From May 01 to Jun 06, 151 p were included (A: 19, B: 66, C: 66). Due to the early closing of arm A, only data of evaluable arms B and C p are shown: toxicity 127 p (B: 63, C: 64) and response 110 p (B: 53, C: 57). All groups are well-matched for baseline disease characteristics. Toxicity grade 3–4 by CTC and RTOG criteria was: esophagitis 19.5% (arm B) and 14.2% (arm C); pneumonitis 8.8 % (arm B) and 10% (arm C). Neutropenia during I or C therapy: 22% (B) and 6.2% (C). Thrombocytopenia 8% (B) and 3% (C). Neutropenia during concomitant therapy: 6.3% (B) and 6% (C). No thrombocytopenia or severe anemia was found during CT/TRT. The reduction CT rate was superior in consolidation (35%) than in induction (15%) and in arm C during concomitant therapy (22.4% C, 6.5% B). Delay of CT dose was similar in B and C arms during I or C (22% B, 20% C) but superior in arm C during concurrent treatment (19.6% B, 30.6% C). The final response rates were 57% (B) and 56.9% (C). A trend for longer time to progression (TTP) was found (B: 7.6 months (m) and C: 9.2 m; p= 0.12) but with similar overall survival (B: 14.3 m and C: 14.7 m; p=0.38). Conclusions: Non- platinum CT plus concomitant chemoradiation offer similar response rate and a favorable hematological toxicity profile in unresectable stage III NSCLC p. No differences in OS but a trend for longer TTP in the arm C (I followed by concurrent approach) has been found. Final data are pending in order to select the best sequence for further studies. No significant financial relationships to disclose.
Stereotactic bradiotherapy (SRT) for operable stage I non-small cell lung cancer: Is SRT comparable to surgery?
Authors: Onishi H. , Shirato H. , Nagata Y. , Hiraoka M. , Kotaro G. , Karasawa K. , Niibe Y. , Hayakawa K. , Takai Y. , Kimura T. 
Published: March 2020

7623 Background: Stereotactic radiotherapy (SRT) has been aggressively performed as a radical treatment for stage I non-small cell lung cancer (NSCLC) in Japan, however most cases were medically inoperable. In a large Japanese multi-institutional experience, we reviewed the treatment outcome of SRT for medically operable stage I NSCLC cases with the patients’ refusal to surgery. Methods: In 1995–2004, 86 medically operable patients with stage I NSCLC (median age, 74 years; 62 T1N0M0; 24 T2N0M0) were treated with SRT alone in 14 reliable institutions. Stereotactic three-dimensional treatment was performed using non-coplanar dynamic arcs or multiple static ports. A total dose of 20 to 72.5 Gy at the isocenter was administered in 1 to 10 fractions. Median calculated biological effective dose (BED) was 115 Gy (range, 100–153 Gy). The data was collected and analyzed in a retrospective manner. Results: During follow-up (median, 43 months), pulmonary complications of above grade 2 arose in 4 patients (5.8%). Local control rates at 3 and 5-year post SRT were 88.1% and 85.5%, respectively. Three and 5-year overall survival rates were 80.7% and 71.3%, respectively. Five-year overall survival rate for patients whose age was over 70 years (n=27) and under 70 years (n=58) were 74.3% and 69.6%, respectively. Five-year overall survival rate for stage IA (n=62) and IB (n=24) cases were 72.3% and 68.4%, respectively. Conclusions: SRT is safe and promising as a radical treatment for operable stage I NSCLC. The survival rate of SRT is potentially comparable to that of surgery. No significant financial relationships to disclose.
Activated c-Met[pY1003]: A potential marker of intrinsic resistance and therapy target to restore sensitivity to gefitinib
Authors: Zucali P. A. , Gallegos Ruiz M. , Giovannetti E. , Destro A. , Floor K. , Ceresoli G. L. , Rodriguez J. A. , Roncalli M. , Santoro A. , Giaccone G. 
Published: March 2020

7624 Background: Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) show anti-tumor activity in only 10% of Caucasian non-small cell lung cancer (NSCLC) patients. Aim of this study was to evaluate several biological parameters potentially related to EGFR, including c-Met activation, as potential markers of intrinsic resistance to EGFR-TKIs in NSCLC. Methods: P-Akt, p-Erk, c-Src, E-Cadherin, c-Met[pY1003] and c-Met[pY1230/1234/1235] status was immunohistochemically determined on a tissue micro-array of tumor samples from 51 NSCLC patients treated with gefitinib. EGFR, k-ras, and c-Met mutation analysis was also carried out. A panel of NSCLC cell lines expressing c-Met[pY1003] were treated with gefitinib (0.01–100μ M) alone or in combination with hepatocyte growth factor (40 ng/ml) and the c-Met-agonistic antibody DN-30 (80 μg/ml) for 72 hours in 0.5% FCS medium. Drug interaction between gefitinib and DN-30 was assessed, at a non-constant concentration ratio, using the combination index (CI) method. Results: There was no association between p-Erk, c-Src, E-Cadherin, c-Met[pY1230/1234/1235], and k-ras status and response or survival. EGFR exon 19 deletion and p-Akt nuclear staining were significantly associated with response (P<0.0001; Fisher's exact test) and longer time to progression (TTP) (P=0.007; log-rank test), respectively. High c-Met[pY1003] membrane staining was significantly associated with progressive disease (P=0.019; Fisher's exact test) and shorter TTP (P=0.0416; log-rank test), but not with survival. Multivariate analysis confirmed a significant relationship between c-Met[pY1003] and increased risk of disease progression (HR=2.464, 95% CI 1.293–4.696, P=0.006). No c-Met mutations were found. In vitro, the combination with DN- 30 synergistically (CI<1) enhanced gefitinib-induced growth inhibition in all c-Met[pY1003]-expressing NSCLC cells studied (H460, SW1573, A549 and H292). Conclusions: Activation of c-MET may be a biological marker of intrinsic resistance to gefitinib in NSCLC patients, and combined inhibition of c-Met and EGFR may be a suitable therapeutic approach in patients with activated c-Met[pY1003] tumors. No significant financial relationships to disclose.
Bevacizumab: Analysis of clinical benefit in females across trials in colorectal cancer and non-small cell lung cancer
Authors: Ramies D. A. , Sandler A. , Gray R. , Giantonio B. , Brahmer J. , Lyons B. , Schiller J. 
Published: March 2020

7634 Background: Bevacizumab (Bv) has demonstrated significant improvement in overall survival (OS) in randomized trials in first- and second-line (FL and SL) metastatic CRC (mCRC), FL NSCLC, and progression-free survival (PFS) in metastatic breast cancer (mBC). However, in FL metastatic non-squamous NSCLC, OS benefit was less robust in females treated with Bv + chemotherapy (CTx). In order to examine whether there is a gender effect upon efficacy in other trials, an analysis of results from randomized ph II and open-label ph III trials with Bv in mCRC (and a randomized ph II trial in SL NSCLC) was conducted for females. Methods: RR, PFS and OS are summarized for females in the following trials (primary endpoint): 1] ph II FL mCRC (PFS); 2] ph III: FL mCRC (OS); 3] ph III SL mCRC (OS); 4] ph II SL NSCLC (PFS); 5] ph III FL NSCLC (OS). Results: Table 1 presents results of Studies 1 - 5. RR is presented as the difference in RR between Bv and respective control arms. Conclusions: Clinical benefit with Bv + CTx compared to CTx-alone was observed in OS for females in studies which included Bv in treatment of mCRC. OS observed in females in Study 5 (FL NSCLC) is inconsistent with findings in mCRC, mBC and SL NSCLC, and the improvement for PFS and RR for females in Study 5. As such, there is no compelling evidence to suggest lack of benefit with Bv in females. [Table: see text] [Table: see text]
Vaccination of patients with advanced non-small cell lung cancer with an optimized cryptic hTERT peptide (Vx-001)
Authors: Kosmatopoulos K. , Bolonaki E. , Kotsakis A. , Papadimitraki E. , Agouraki D. , Kosnoslakis G. , Vagia A. , Christophylakis C. , Georgoulias V. , Mavroudis D. 
Published: March 2020

7642 Background: To evaluate the immunological and clinical efficacy of the optimized peptide TERT572Y (Vx-001) presented by HLA-A*0201 in patients with advanced non-small cell lung cancer (NSCLC). Methods: Twenty-two patients with residual (n=8) or progressive (n=14) advanced NSCLC following chemotherapy and/or radiotherapy received two subcutaneous injections of the optimized TERT572Y peptide followed by four injections of the native TERT572 peptide given every 3 weeks. Peptide-specific immune responses were monitored by Elispot assay and/or TERT572Y pentamer staining. Clinical outcome was compared with that of 22 case-matched historical control patients. Results: Thirteen (59%) out of 22 patients completed the vaccination program. Toxicity consisted primarily of local skin reactions. TERT572-specific CD8+ cells were detected in 16 (76.2%) out of 21 patients after the 2nd vaccination and 10 (90.9%) out of 11 patients after the 6th vaccination. Stable disease occurred in 8 (36.4%) patients with a median duration of 11.2 months. Patients with an early immunological response (n=16) had a significantly longer time to disease progression and overall survival than non-responders (n=5) (log-rank tests p=0.046 and p=0.012, respectively). The estimated median overall survival was 30.0 (range, 2.8–40.0) and 4.1 (range, 2.4–10.9) months for immunological responders and non-responders, respectively. Moreover, median overall survival was 30.6 months (95% CI:10.9–48.9) and 6.1 months (95% CI:4.4–7.8) for the vaccinated and case-matched historical control patients, respectively (p=0.074). Conclusions: TERT572Y peptide vaccine is well tolerated and effective in eliciting a specific T-cell immunity which seems to be associated with prolonged patients’ survival. No significant financial relationships to disclose.