bluuebunny/crossref_metadata_2025_split huggingface dataset:
Staging 18FDG-PET in newly diagnosed small cell lung cancer (SCLC): 15-year institutional experience
Authors: Azad A. , Chionh F. , Scott A. , White S. , Mitchell P. L. 
Published: August 2020

e19044 Background: 18FDG-PET is not routinely used in the initial staging of SCLC despite evidence that it alters stage classification and management. Furthermore, the association between stage classification by PET and prognosis of newly diagnosed SCLC has not previously been directly assessed. We aimed to evaluate whether PET altered stage classification, management and prognosis when used to stage newly diagnosed SCLC. Methods: We retrospectively reviewed the medical records of 46 consecutive patients undergoing PET during initial staging for SCLC at Austin Health from 1993 to 2008 inclusive. Data collected included patient demographics, stage classification before and after PET, treatment history and date of death. Statistical analysis included estimation of overall survival (OS) by the Kaplan-Meier method using the log-rank test. Results: PET altered stage classification in 12 of 46 (26%) of patients. Stage alteration led to a change in treatment modality in 9 of these 12 patients. In addition, PET altered the target radiation field in another three patients. Therefore, PET had a significant impact on management in 12 of 46 (26%) of patients. Patients with limited disease (LD) on both conventional imaging and PET had significantly longer OS than patients with LD on conventional imaging that was upstaged to extensive disease (ED) on PET (median 557 days versus 172 days; log-rank p<0.0001). Patients with ED on conventional imaging that was downstaged to LD on PET had significantly longer OS than patients with ED on both conventional imaging and PET (median 328 days versus 177 days; log-rank p=0.037). Conclusions: The use of 18FDG-PET during staging for SCLC had a major impact on stage classification, management and prognostic stratification. The use of staging PET should be considered in patients with newly diagnosed SCLC. No significant financial relationships to disclose.
Comparison of incidence and pattern of interstitial lung disease (ILD) during erlotinib and gefitinib treatment in Japanese pts with NSCLC
Authors: Hotta K. , Kiura K. , Takigawa N. , Yoshioka H. , Harita S. , Yonei Y. , Fujiwara K. , Maeda T. , Tabata M. , Tanimoto M. 
Published: August 2020

e19056 Background: Erlotinib was approved in Dec 2007 in Japan, and incidence and pattern of ILD during its therapy for Japanese pts with NSCLC has not still been determined, although we had previously reported the frequency of ILD through the gefitinib treatment [PASCO2004, #7063]. In this study, we intended to elucidate this issue in pts receiving erlotinib therapy. Methods: We reviewed the clinical records of 159 pts who had initiated erlotinib therapy last year (cohort A), and of 330 pts receiving gefitinib between 2000 and 2003 (cohort B) for comparing the incidence and pattern of ILD during the both TKI treatments. Toxicity data during the first months after the initiation of TKIs were obtained. Results: The demographics of 489 pts were as follows; M:63%, Ad:75%, and PS 0–1:69%. None of pts in the cohort B received erlotinib therapy before the gefitinib treatment, whereas 66 of the 159 cohort A pts (42%) were given gefitinib before the erlotinib therapy. In 23% and 28% of the pts in the cohorts A and B, erlotinib and gefitinb treatments were discontinued within 1 month after the initiation of TKI therapy, respectively. Two pts (1.3%) developed ILD in the cohort A during the first month of erlotinib treatment, while 8 ILD-events (2.4%) were observed in the gefitinib therapy (cohort B) during the same treatment period. Both 2 pts who developed ILD during the erlotinib therapy had not had a history of prior gefitinib treatment. The toxicity grades of ILD were as follows: grades 1 and 2 in 1 each (cohort A) and grades 3, 4 and 5 in 1, 1 and 6 pts, respectively (cohort B). Statistically significant factors affecting the occurrence of ILD by multivariate analysis were presence of prior pulmonary fibrosis (OR=37.3, p<0.01) and poor PS (OR=6.4, p=0.02), but type of TKIs was not a significant risk factor for ILD. Conclusions: In this setting, the type of TKIs did not affect the incidence of ILD although its incidence after the initiation of erlotinib was somewhat low as compared with that during gefitinib therapy. In addition, the grade of ILD was less severe in the cohort A. These might be partly due to a patient selection based on the recent awareness of Japanese physicians regarding the risk factors for ILD events who learned it through the gefitinib treatment. No significant financial relationships to disclose.
Docetaxel-carboplatin chemotherapy in combination with cetuximab in patients with locally advanced or metastasized non-small cell lung cancer (NSCLC): Interim results of the nonrandomized phase II study TaxErb
Authors: Fischer J. R. , Griesinger F. , Fink T. , Buchholz E. , Salm T. , Marseille A. , Wolf M. 
Published: August 2020

e19062 Background: Combination chemotherapy with carboplatin-docetaxel has been shown to be effective and safe for patients with locally advanced or metastasized NSCLC. The monoclonal anti-EGRF antibody cetuximab has the potential to improve response rates and survival without a substantial increase in toxicity when given in combination with chemotherapy. Methods: Open, non-controlled phase II study with a planned sample size of 70 pts. Pts with locally advanced or metastasized NSCLC, ECOG performance status ≤ 2 and no prior systemic chemotherapy were treated with carboplatin AUC5 (d 1) q4w for 4–6 cycles and docetaxel 35 mg/m2 (d1, 8, 15) q4w; cetuximab 400 / 250 mg/m2 (d 1) q1w until progression or intolerable toxicity (12 month max.). The primary endpoint was response rate defined as complete or partial remission according to RECIST. Secondary endpoints were toxicity, 1 year survival, median and progression free survival. Results: Subject of the interims analysis were 27 pts (25 stage IV, 2 stage IIIb). ECOG 0/1/2 was 33.3%/59.3%/3.7% (1 no data). 63% had prior surgery, 93% prior radiotherapy and all had adjuvant or inductive chemotherapy. Pts received a mean of 3 ± 1.4 cycles docetaxel-carboplatin-cetuximab. 49 adverse events were grade 1–2 and 12 grade 3–5. Skin toxicity (49%; 95%CI: 30%-68%; 41% G1/2, 8% G3/4), dyspnoea (35%; 95%CI: 17%-53%) and diarrhoea (23%; 95%CI: 7 %-39%; 19% G1/2, 4% G3) were most frequent. 11 pts (41%) had toxicity leading to dose reduction. 0 pts had complete and 11 pts had partial remission resulting in a response rate of 40.7% (95%CI: 22%-59%) based on intention to treat. 6 pts had stable disease (22.2%; 95%CI: 7%-38%). 5 pts were not evaluable for response. Conclusions: The combination of carboplatin-docetaxel-cetuximab has an overall acceptable tolerability. With a preliminary response rate of 40.7% the benefit risk assessment was found to be favourable and the study was continued. [Table: see text]
A phase I trial of intravenous therapy with tumor suppressor FUS1-nanoparticles for recurrent/metastatic lung cancer
Authors: Lu C. , Stewart D. J. , Ji L. , Ramesh R. , Jayachandran G. , Erasmus J. , Lee J. J. , Templeton N. S. , McMannis J. D. , Roth J. A. 
Published: August 2020

e19065 Background: The tumor suppressor gene FUS1 is frequently inactivated early in lung cancer development. FUS1 mediates apoptosis in cancer cells but not normal cells through its interaction with Apaf1. DOTAP:cholesterol nanoparticles encapsulating a FUS1 expression plasmid showed selective uptake by cancer cells and activity in mouse xenograft metastatic lung cancer models. Methods: Patients with recurrent/metastatic lung cancer previously treated with platinum-based chemotherapy were treated with escalating doses of intravenous DOTAP:cholesterol FUS1 nanoparticles. Nanoparticle-DNA complexes were manufactured in GMP facilities to meet specifications of OD400, size, appearance, and transfection efficiency. Results: Patients have received doses ranging from 0.01–0.09 mg/kg at 3 week intervals. To date 23 patients have been entered on study at 6 dose levels, with 21 patients currently evaluable for the primary endpoint of cycle 1 toxicity. 70% of subjects had received 2 or more prior chemotherapy regimens. Among 4 patients treated without premedications, all 4 developed grade 2 or higher fevers within 24 hours of treatment. Among the 17 patients premedicated with dexamethasone and diphenhydramine, 4 developed grade 1 fever. There have been no other grade 2 or higher drug-related toxicities. Four patients received only one dose because of rapidly progressing disease at a site requiring local treatment. Fifteen patients received two or more doses and are evaluable for response, with 4 patients achieving stable disease and 11 patients progressing. Median survival time for all patients is 10.3 months. A maximum tolerated dose (MTD) has not been reached. Pre and 24 hour posttreatment tumor biopsies were obtained from 4 patients. A quantitative real time reverse transcriptase PCR (RT-PCR) analysis using a plasmid FUS1 sequence-specific probe have been performed on 3 paired-samples blinded to time of biopsy. A high level of plasmid FUS1 expression was detected in all 3 posttreatment samples but not in three pretreatment samples and negative controls by RT-PCR. Conclusions: DOTAP:cholesterol FUS1 nanoparticles can be safely administered intravenously in lung cancer patients with demonstrable gene expression in posttreatement tumor biopsies. [Table: see text]
The correlation between the expression of ABH and Lewis A histo-blood group antigens and the biological behavior of primary pulmonary adenocarcinoma
Authors: LI J. , Zhou X. , Liu Q. , Wang Z. , LI Y. , LI Y. 
Published: August 2020

e19066 Objective: To investigate the correlation between the expression of ABH and Lewis A histo-blood group antigens and the differentiation, tumorigenesis, progression, metastasis and prognosis of primary pulmonary adenocarcinoma. Methods: The expression of ABH and Lewis A histo-blood group antigens were detected in normal tissue (n=30), primary adenocarcinoma (n=103) and corresponding metastatic lesion (n=41) with immunohistochemistry S-P method. Results: The positive expression of A, B, H antigens was found in normal corresponding pulmonary tissue. While in cancer tissue, such expression was absent. The absence in poorly differentiated tumor was significantly higher than in moderate and highly differentiated cell (P<0.001). And the absent expression was statistically higher in tumor with metastasis than in without metastasis (P=0.036),higher in N2 than in N1 group, higher in secondary tumor in than primary focus(P=0.008).There was significantly statistical difference on the absent expression rates among normal pulmonary tissue, primary tumor and metastatic tumor (P<0.001), and having a tendency of increased absence rate. The expression of Lewis A antigen was markedly higher in pulmonary adenocarcinoma than in normal tissue (P=0.024). Concerning Lewis A expression, the significant difference was found in Stage I,II and III+IV cancers (P=0.001), while the positive expression rate in advanced cancer (StageII+III+IV) was remarkably higher than in early cancer (Stage I) . The 5-year survival of positive expression of ABH antigen was 25%, higher than that in negative expression group (P<0.0001). The 5-year survival in positive expression of Lewis A antigen was 7%, lower than in negative group (P=0.0002). Conclusions: The absence of ABH antigen is closely correlated with tumorigenesis, poor differentiation, and metastasis of primary adenocarcinoma. The detection of ABH, Lewis A antigen may be of vital significance for the prognosis. No significant financial relationships to disclose.
A phase II study of S-1 for previously treated small cell lung cancer (SCLC)
Authors: Kudo K. , Ohyanagi F. , Horiike A. , Miyauchi E. , Motokawa I. , Horai T. , Mun M. , Sakao Y. , Okumura S. , Nakagawa K. , Nishio M. 
Published: August 2020

e19074 Background: S-1 is a novel oral 5-fluorouracil derivative that exhibits obvious activity against various tumor types including NSCLC. However, the effects of S-1 against SCLC have not been reported. The present phase II trial assesses the efficacy and safety of S-1 in previously treated SCLC patients. Methods: Eligible patients had pathologically documented SCLC that relapsed after platinum-based chemotherapy, ECOG performance status (PS) 0–2, and adequate bone marrow, kidney and liver function. Patients with untreated or symptomatic brain metastasis were excluded. Treatment comprised the oral administration of S-1 at 40 mg/m2 twice each day for 28 days every 6 weeks. The primary end point was the objective tumor response rate (RECIST). Secondary endpoints included progression-free survival and overall survival. Results: Twenty-six evaluable patients were enrolled (Simon's two-stage optimal design; α = 0.1; β = 0.1; P0 = 0.05; P1 = 0.25) with the following characteristics: male: female, 22/4; median age, 68 (33 - 79) y; PS0–1, n = 21; PS2, n = 5. The median number of prior treatment regimens was 2 (1–3). S-1 was administered for a mean of 1.3 cycles (1 - 5). One patient (3.8%) partially responded, 10 (38.5%) had stable and 15 (57.7%) had progressive disease. The overall response rate was 3.8% and the disease control rate was 42.3%. The median time to progression was 33 days. The median survival time was 8.0 months and the 1-year survival rate was 23%. This regimen was well tolerated. The common grade 3/4 toxicities included neutropenia (7.7%), leukopenia (7.7%), anemia (7.7%), hyponatremia (7.7%), rush (7.7%), infection (7.7%), and diarrhea (3.8%). None of the patients developed febrile neutropenia and no deaths were attributed to treatment. Conclusions: S-1 is well tolerated but has low activity as a single agent in previously treated patients with SCLC. No significant financial relationships to disclose.
Outcomes of small cell lung cancer (SCLC) patients treated with second-line chemotherapy (SL): A retrospective analysis of 166 patients
Authors: Garassino M. C. , Michetti G. , Lo Dico M. , Califano R. , Aglione S. , Borgonovo K. , Mancuso A. , Galetta D. , Gallerani E. , Collovà E. , Torri V. 
Published: August 2020

e19093 Background: Patients with SCLC progressed after first-line chemotherapy (FL) have a poor prognosis and the evidence of a benefit of SL is still limited.This retrospective analysis evaluates the clinical outcomes of patients who received a SL treatment after failure of a FL for SCLC Methods: Retrospectively we reviewed 166 consecutive patients who failed a FL and received a second or third-line treatment, between 1993 and 2008 in 17 institutions. We divided patients for analysis in four subgroups, according to the type of SL administered: 1) Platinum-based (P) rechallenge 2) Non-platinum-based polichemotherapy 3) Non-topotecan monochemotherapy 4) topotecan monochemotherapy. Our endpoints were Overall survival (OS), Progression free survival (PFS) and Response Rate. Survival curves were designed with Kaplan-Meier method and Cox proportional hazard model was used for investigating factors which influence survival Results: Median age was 63 (range 25–86). Median OS from the SL was 6.2 months and PFS 2.9. 163 patients received a platinum based chemotherapy as FL, among them 67% obtained a response (CR=14%, PR=53.7%) and 19% had a progressive disease. 74% of patients had a PS 0–1 when started on SL. Moreover, 50 patients underwent also a third-line chemotherapy. Of the 23 CR at FL, 7 patients achieved a response in SL(30%), of the 85 PR only 19 (22%) and of the PD+SD only 6 (16%) (test for trend p=.03). No statistical differences among regimens groups were found; however, patients rechallenged with P went better then others when a long PFS in FL was demonstrated (p=.02) Conclusions: The clinical benefit of SL therapy for SCLC is poor and strictly dependent on response and on duration of response with FL treatment. Our retrospective analysis confirms that median OS for patients receiving SL is about 6 months and median PFS 2.9 months. A rechallenge with platinum should be the best options in patients with a long PFS in FL. Single agent topotecan, the most investigated agent in the literature, did not show evidence of superiority against other chemotherapy regimens No significant financial relationships to disclose.
Rituximab maintenance after R-CHOP in the first-line treatment of follicular lymphoma: A GOTEL phase II trial
Authors: Rueda A. , Provencio M. , Abrio M. , Gómez-Codina J. , Llanos M. , Delgado J. , Rifá J. , Sabin P. , Vélez de Mendizabal E. ,   Grupo Oncológico para el Tratamiento y Estudio delos Linfomas, Baz V. 
Published: August 2020

e19502 Background: Rituximab maintenance have demonstrated improvements in progression-free and overall survival in relapsed patients with follicular lymphoma (FL). Ongoing trials are evaluating the benefit of rituximab maintenance following treatment of therapy-naive patients (pts) treated with rituximab-containing chemoinmunotherapy induction regimens. Methods: The current study evaluated the activity and toxicity of rituximab maintenance after chemoinmunotherapy in the first line treatment of advanced-stage FL. Pts with advanced stage FL were eligible. The induction treatment consisted in 8 courses of chemoinmunotherapy with R-CHOP (rituximab 375 mg/m2; cyclophosphamide 750 mg/m2; doxorubicin 50 mg/m2 and vincristine 2 mg). Pts entering a complete (CR) or partial remission (PR) received maintenance with 6 doses of rituximab (375 mg/m2/d) to be given every two months after the end of induction therapy. Results: From December 2004 to November 2006, 52 pts were included. Median age was 52 years (range, 36–85) and 26 pts were women. At baseline 32 (62%) pts had stage IV and 20 (38%) stage III. According to the Follicular Lymphoma International Prognostic Index (FLIPI), 8 pts (15%) had low risk disease, 24 pts (46%) intermediate risk, and 20 pts (39%) high risk disease. Six (12%) pts did not receive maintenance (3 pts progressed during induction, 2 pts refused maintenance and 1 pt had severe toxicity to induction). Of the 46 pts included in the maintenance phase, 32 (69%) were in CR/CRu and 14 pts (31%) in PR after induction therapy. Rituximab was well tolerated in the maintenance phase. Only 5 pts didn´t receive the 6 scheduled courses (toxicity: 1; progressive disease: 2; cardiovascular events: 2). Grade 3–4 toxicity occurred as follow: neutropenia in 4 pts (9%), and fever in 1 pt (2%). No severe infections were seen. After maintenance, 40 (87%) pts were in CR/CRu, 4 pts (9%) in PR and 2 (4%) progressed. With a median follow-up of 27 months, progression-free and overall survival at 30 months were 82% and 92%, respectively. Conclusions: Rituximab maintenance after first-line R-CHOP is safe and increase the complete remission rate obtained in the induction phase. No significant financial relationships to disclose.
A phase II trial of sorafenib in patients with relapsing and resistant multiple myeloma (MM) previously treated with bortezomib (S0434)
Authors: Srkalovic G. , Hussein M. , Bolejack V. , Hoering A. , Zonder J. , Barlogie B. 
Published: August 2020

e19517 Background: The multikinase inhibitor sorafenib targets several serine/threonine and receptor tyrosine kinases by blocking RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway regulated by the Ras oncogene, which is mutated both in primary patient samples and in human MM lines (35–50%). As the frequency of these mutations increases with advancing disease and increasing drug resistance, inhibition of the RAF/MEK/ERK signaling pathway, as well the angiogenic VEGFR-2/PDGFR beta cascade by sorafenib may be a useful new approach for the treatment of MM. Methods: SWOG evaluated the effect of sorafenib as a single agent in relapsed/refractory MM patients. In this phase II study we assessed response rate, overall (OS) and progression-free survival (PFS) as well as toxicities associated with this treatment. Twenty-three heavily pretreated MM patients were enrolled in the study. Sorafenib was started at oral dose of 400 mg daily until progression or toxicity. This dose was based on the label for metastatic renal cell carcinoma. Results: The study was closed as planned due to lack of efficacy in first 18 patients who were assessable for toxicity and response. Three patients experienced Grade 4 toxicity consisting of thrombocytopenia, anemia and renal failure. 8 cases suffered Grade 3 toxicities including thrombocytopenia, neutropenia, anemia, hand-foot syndrome, diarrhea and dyspnea. No responses were observed. 3 patients had stable disease (2.4–15.9 months) and the remainder progressed. Median PFS is one month, and OS at 12 months is 50%. Conclusions: Thus, single agent sorafenib did not show activity in this group of heavily pretreated MM patients previously exposed to bortezomib. As the frequency of RAS oncogene mutations increases resulting in resistance to traditional chemotherapeutic agents as well as possibly supporting cytokine resistance to immune modulators, sorafenib might have a supportive role in combination therapy with bortezomib, lenalidomide or everolimus in relapsed/refractory MM which is currently being evaluated in ongoing studies. No significant financial relationships to disclose.
Prognostic role of interim 18FDG-PET in Hodgkin lymphoma: A single-center experience
Authors: Cocorocchio E. , Vanazzi A. , Botteri E. , Alietti A. , Negri M. , Bassi S. , Preda L. , Travaini L. , Peccatori F. A. 
Published: August 2020

e19520 Background: The role of FDG-PET for staging and response assessment in Hodgkin lymphoma (HL) is still evolving. We report our experience with the intent of evaluate prognostic role of 18FDG-PET in terms of long term complete remission (CR). Methods: We retrospectively analysed 65 consecutive pts affected by newly diagnosed HL. Median age was 36 yrs. Histology included 50 classical and 10 lymphocyte predominance HL. According to Hasenclever index, 58 out of 65 pts were considered at low risk, 5 at intermediate and 2 at high risk. 30/65 pts showed good prognosis (defined as IA-IIA, < 3 nodal sites, ERS < 50) and received 4 cycles of VBM followed by involved field (IF) radiotherapy (RT); the remaining 35 pts received hybrid ChlVPP/ABVVP for 6 cycles followed by IF RT in case of bulky disease. All patients underwent 18FDG-PET scans at diagnosis, after the fourth cycle in the VBM group, after the third cycle in the ChlVPP/ABVVP (interim 18FDG-PET), at the end of treatment in all patients. Fisher exact test was used to compare percentages between groups. Results: CR was recorded in 60 (92%) pts. Interim 18FDG-PET was negative in 52 out of 65 pts (80%), all in CR at the end of treatment. Eight out of 13 pts with positive interim 18FDG-PET obtained a CR at the end of treatment (100% versus 62%, Fisher exact text p<0.01). Six out of 65 pts relapsed: interim 18FDG-PET was negative in 5 of them, positive in 1 case. Two deaths occurred, one among pts with negative and one with positive interim 18FDG-PET. After a median follow-up of 30 months, 3-year freedom from treatment failure was 83% and 62% in pts with negative and positive interim 18FDG-PET, respectively (Log-rank test p<0.01, Hazard Ratio 4.9 (95%CI 1.4–16.1)). Conclusions: In our experience interim 18FDG-PET demonstrate a predictive role regarding the achievement of CR and treatment failure, at least as relevant as Hasenclever index, but failed to predict clinical result in 12 (18%) pts. Its role in defining the best therapeutical approach in HL pts must be further investigated in randomized clinical trials. No significant financial relationships to disclose.