bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of smoking dose on the outcome of Japanse patients with non-small cell lung cancer who had gefitinib treatment
Authors: Asami K. , Kawahara M. , Atagi S. , Kawaguchi T. , Kubo A. , Okishio K. , Yagi Y. , Matsuda Y. , Kagawa T. , Kitaichi M. 
Published: August 2020

e19004 Background: Non-smoking history and epidermal growth factor receptor (EGFR) mutation are associated with increased sensitivity to gefitinib in non-small cell lung cancer (NSCLC). However, it is still unclear how much smoking dose is associated with survival and response to gefitinib among smokers. Methods: NSCLC patients (pts) with detailed smoking history who received gefitinib at our institution between 9/02 and 9/04 were reviewed. An analysis was conducted to the pts for association between smoking dose, EGFR mutations, performance status (PS), response and overall survival using multivariate analysis. Results: Data were available for 100 pts including 30 females and 70males. We expressed smoking dose as pack year (Py).The median dose of smoking was 32 Py (0.1–100 Py). We defined the group of <10 Py as light smokers(17 pts) and the other group of 10 Py or more as heavy smokers(83 pts). We detected 31(31%) EGFR mutation (median 14 Py 0.1–75 Py) with exon 18 / 19 /21 mutation;3/17/11 pts .Cox survival analysis showed that overall survival was preferably associated with small dose of smoking(<10 Py)(HR=0.505; [95% CI 0.277–0.921; P=0.013]), EGFR mutation(HR=0.452[95% CI 0.235–0.87;P=0.035])and PS;0–1(HR=0.347 [95% CI 0.207–0.583 P<0.001]). EGFR mutations were significantly more frequently observed in light (12/17:71%) than heavy smokers(19/83:23%) (p<0.001). Disease control rate(DCR) was significantly higher in light (13/17;76%;PR 6, SD 7) than heavy smokers(29/83;35%;PR 15, SD 14)(P=0.002), but there was not significant difference between those groups in terms of response rate (RR)(P=0.187). There were significant differences between pts with EGFR mutations (PR 13 SD 14; RR 42%,DCR 87%) and pts without EGFR mutations (PR 8 SD 15; RR 12%, DCR 33%) in terms of RR(P<0.001) and DCR(P<0.001). In pts with EGFR mutation, there was no significant difference between light and heavy smokers in terms of RR (light smokers 5/10, heavy smokers 8/21; P=0.701) and DCR (light smokers 10/10, heavy smokers17/21; P= 0.277). Conclusions: EGFR mutations were predictive factor and prognostic factor. Small dose of smoking (< 10 Py) was prognostic factor, however it was not a predictive factor of smokers with NSCLC. No significant financial relationships to disclose.
A phase II first-line study of gemcitabine, carboplatin, and bevacizumab (GCB) in advanced (adv) stage non-squamous non-small cell lung cancer (NSCLC)
Authors: Krupitskaya Y. , Ganjoo K. , Lavori P. W. , Kumar A. , Clement-Duchene C. , Zhao G. , Padda S. , San Pedro- Salcedo M. , Wakelee H. A. 
Published: August 2020

e19024 Background: B adds to 1st-line paclitaxel/carboplatin (PC) for pts with adv NSq-NSCLC. Gemcitabine/carboplatin (GC) has equivalent efficacy to PC with a different toxicity profile. This study was designed to evaluate toxicities (AEs) of GCB and to estimate survival. Methods: Patients (pts) with untreated adv NSq-NSCLC, with no evidence of CNS metastases were eligible. Pts received G 1000 mg/m2 on d1, 8; C AUC 5 d1; and B 15 mg/kg d1 q21d for up to 6 cycles. B was then continued q21d until disease progression or unacceptable toxicity. Chemo dose reductions were mandated for significant cytopenias. Imaging was every 2 cycles. Results: From 07/06 to 12/08, 48 pts enrolled (accrual complete): 23(48%) men, 19(40%) never smokers, median age 59yo (35–81). One pt died prior to receiving therapy and is not included in the analysis. Median cycle number is 6(0–37). To date, 35 pts (74%) completed ≥ 4 cycles of 3 drugs. Dose reductions occurred in 29(62%) of pts. G3/4 AEs included: neutropenia (47%/17%), thrombocytopenia (11%/15%), and anemia (6%/0%). No pts were hospitalized for neutropenic fever. G3/G4 non-hematologic AEs included dyspnea (6%/2%), bacterial pneumonia (4%/0) hypertension (4%/2%), 1G3 wound dehiscence, 1G4 MI, 1G3 transaminitis and hyperbilirubinemia, 1G3 proteinuria and 1G3 leucocyturia. 1 pt died from hemoptysis with untreated aspergillosis found post-mortem. Other bleeding included 1 case each with G3 epistaxis, hemorrhoidal bleeding and ecchymosis. Common G1/2 AEs included fatigue, hypertension, anemia, constipation, nausea, headaches, transaminitis and epistaxis. In 42 evaluable pts: we saw 7(17%) PRs, and 31(74%) SDs at 1st f/up. 44/47 pts were followed for a median of 10.5mo (3 recently enrolled pts with f/u < 20d - excluded). Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4mo [95%CI 4.6–8.6mo]. 17/44 (38.6%) pts have died with median overall survival (mOS) not reached but preliminarily estimated at 16.7mo [95%CI 13.4mo-inf]. Estimated OS is 73% at 1yr and 32% at 2yrs. Conclusions: Treatment with GCB has an acceptable toxicity profile with promising mOS despite a low RR and frequent dose reductions in a population with a high proportion of non-smokers and women. No significant financial relationships to disclose.
Baseline quality of life as a prognostic factor for overall survival in lung cancer patients
Authors: Zhao X. , Sloan J. , Yang P. , Sargent D. , Wampfler J. , Shao Y. 
Published: August 2020

e19031 Background: Useful predictors of survival in cancer patients have been found including such as gender, race, age, marital status, state of disease and tumor location. We set to explore the prognostic value of baseline QOL assessments on overall survival in lung cancer patients. Methods: A total of 1,319 lung cancer patients were followed at Mayo Clinic between 1997 and 2007. Overall QOL was assessed by either Lung Cancer Symptom Scale (LCSS) or a single-item Linear Analogue Self Assessment (LASA) with comparable wording. QOL scores were transformed to a 0–100 scale with higher scores representing better status. Patients QOL scores assessed within the first 6 months of follow-up were dichotomized using a priori definition for clinically deficiency score (CDS, ≤50 vs. >50). The Kaplan-Meier method was used to estimate the distribution of survival times by QOL clinical deficient categorization. Cox Proportional Hazards Models were used to evaluate the prognostic importance of QOL on OS alone and in the presence of age, smoking category, gender, treatment, stage of disease, smoking cessation and years of consuming a pack every day. Results: Baseline QOL was significantly associated with OS univariately (HR=0.46 with p<0.0001 based on the CDS categorization). After controlling for all these other factors, the indication of a clinically deficient baseline QOL contributed significantly to the prediction of patient survival (p=0.0002; HR=0.67). Age, treatment, disease stage, smoking cessation and smoking category were also significant predictors of OS multivariately. The median survival for patients that had an overall QOL score less than the CDS (≤50) was 1.6 versus 4.6 years for patients with QOL >50. Conclusions: Baseline overall QOL measured by LCSS or LASA is a significant and independent prognostic factor for OS in lung cancer patients. A meaningful next step in this research is to investigate interventions to improve lung cancer patient QOL and thereby increase their likelihood of survival as well. No significant financial relationships to disclose.
Prescribing plans (PP) of American Oncologists for first-line therapy (Rx) for patients with stage III (wet)/IV non-small cell lung cancer (NSCLC) and PS 2: Overall selection and impact of gender and smoking status
Authors: Shabbir M. , Daniels L. , Shirai K. , Cole S. , Willey J. , Iovino L. , Labarre K. , Green M. R. 
Published: August 2020

e19046 Background: Selection of oral EGFR inhibitors or chemotherapy as 2nd line in patients with NSCLC may be influenced by patients’ performance status (PS), smoking status, gender; tumor histology; tolerance/response to 1st-line Rx; and patient expectations/desires. Methods: Between February ’07 and October ’08, we used a core case scenario of stage IV mucin positive adenocarcinoma (Adeno ca) of lung in a 68-year-old former smoker (FS; stopped 6 years ago) with PS 2, to study patient related variations in PP of almost 800 American medical oncologists during 10 live research events [393 MDs/5 events during 2008]. Impact of gender or/and smoking history on 1st-line Rx selection was assessed. Results: In 2007–08, 97%/97%% MDs planned anti-tumor Rx: 53%/63% combination; 44%/34% single agent. PP for 2008 is shown in the table . [2007 PP data for erlotinb use included]. PP for erlotinib in these 4 scenarios are stable over the 2007 - 08 testing interval. Impact of smoking status dominates over gender. For a female NS with Adeno ca /PS2, ≥2/3 of MDs plan erlotinib 1st-line. In the absence of testing results for EGFR expression by IHC, EGFR gene copy number by FISH, EGFR gene mutation testing, or kras mutation testing, our data show a direct correlation of patient “phenotype” and PP for erlotinib as 1st-line Rx, a setting not specifically an approved indications for this agent. The impact of recently reported progression free survival data from an Asian phase III trial (IPASS: gefitinib or chemotherapy or as 1st-line therapy in non or former light-smoking patients with lung adenoca) on future prescribing plans in this clinical setting will be of great interest. Conclusions: By our observations, smoking status dominates over gender in PP of oncologists when treating wet IIIB/IV Adeno ca of lung. Therefore we plan to continue to assess American oncologists’ PP for this NSCLC setting during 2009. [Table: see text] [Table: see text]
Impact of dose reductions of platinum compounds on survival in stage IIIB/IV non-small cell lung cancer (NSCLC)
Authors: Yumuk P. F. , Teomete M. , Dane F. , Cabuk D. , Basaran G. , Turhal N. S. 
Published: August 2020

e19055 Background: Platinum compounds are the main component of the CT in NSCLC. Standard recommended doses of cisplatin/carboplatin is usually couldn’t be administered and dose reductions are necessary because of side effects. We aimed to determine the effect of dose reductions of platinums on outcome of stage IIIB/IV NSCLC. Methods: Data of 420 patients were retrospectively reviewed. A platinum analogue was used in combination with vinorelbine, gemcitabine, paclitaxel, docetaxel or etoposide as first line treatment in 85% patients. Cumulative platinum doses and dose reduction ratios compared to standard doses were calculated. Patients with decreased GFR were excluded from the analysis. Results: Median age was 60 years (range: 28-87), 79% of patients were male, 31% were 65 yearsold/older, 55% had PS of 0, and 27% had stage IIIB disease. Histological subtypes were squamous cell in 32%, adenocarcinoma in 34%, and NSCLC in 31%. Median dose of cisplatin used per cycle was 67mg/m2 and carboplatin was 287mg/m2. 51% of the patients received standard or less than 10% reducted doses of platinum, while dose reductions were 10–20% in 19%, 21–30% in 24% of patients, and more than 31% in 6%. Median overall survival (OS) was 11 months, 1- year and 2-year OS ratios were 56% and 25%, respectively. Median time to progression was 5 months; 1-year progression free survival ratio was 18%. Gender, age, histologic subtype, and treatment with lower dose of platinum didn’t have any statistically significant impact on survival in univariate analysis. Patients with PS of 0, no weight loss, stage IIIB disease, receiving combination CT with docetaxel-cisplatin, and having partial response to treatment lived significantly longer. On multivariate analysis weight loss, stage and type of response to treatment had an impact on OS. Conclusions: Using lower doses of platinum compounds in combination chemotherapy for stage IIIB/IV non-small cell lung cancer might not have a negative impact on survival and definitely have a better toxicity profile. No significant financial relationships to disclose.
Results from short-term CT assessments in patients (pts) with advanced poor performance status non-small cell lung cancer (NSCLC) receiving pemetrexed in a phase II trial
Authors: Zinner R. , Herbst R. S. , Fossella F. V. , Johnson F. M. , Karp D. D. , Kies M. S. , Heymach J. V. , Price J. S. , Lippman S. M. , Erasmus J. 
Published: August 2020

e19069 Background: Early determination of therapeutic failure can potentially spare a pt ineffective and toxic treatment. We previously reported in a retrospective study the use of CT within 4 weeks of initiation of chemotherapy in advanced NSCLC to assess response and progression by RECIST (Bruzzi et al. JTO 2006). Here, we prospectively assess whether CT imaging after the first cycle of pemetrexed in advanced NSCLC has a role in evaluating response and management. Methods: We accrued pts with PS 2 or 3 advanced NSCLC receiving at least one dose of 1st or 2nd line pemetrexed. A repeat CT prior to a 2nd course was required. Pts with progression by RECIST were to come off study. CT scans were done using multislice CT technology (GE Lightspeed Plus), and images were reconstructed with slice thicknesses of 3.75mm or less. All images were reviewed using a PACs workstation (Stentor iSite) and measurements were done with electronic calipers. RECIST criteria: progression, an increase in the tumor's longest dimension by 20%, response, a decrease by 30%. Results: Thirty pts had a median age of 68 years (45 - 81). PS 2/3, 1st/2nd line, and F/M were 16/14, 17/13, and 12/18 respectively. Pts received 1–8 cycles (median 2). Twelve pts received only 1 course of whom 7 pts had f/u CTs at a median of 20 days (12–25) after 1st chemo dose. Of these pts, 5/7 had progression by RECIST and the other 2/7 pts had stable disease with 1 pt who came off due to serial PEs and 1 pt who opted off for reasons of travel. Two of the 5 pts who had progression by CT had no detectable change by CXR. Of 5/12 pts treated with only 1 course without f/u CT, 2 pts died, 2 pts had progression by CXR, and 1 pt stopped after treatment for pneumonia. All 18 pts receiving ≥2 cycles had a repeat CT prior to their 2nd course. Conclusions: The results of this prospective trial support earlier retrospective findings that short-term follow-up using CT in pts with advanced NSCLC can detect tumor progression and impact patient management. We will also present f/u CTs in pts who received ≥ 1course to determine whether early signs of progression predict later RECIST determined progression. [Table: see text]
Phase II trial of second-line erlotinib and digoxin in patients with non-small cell lung cancer (NSCLC)
Authors: Kayali F. , Janjua M. A. , Laber D. A. , Miller D. M. , Day J. M. , Kloecker G. H. 
Published: August 2020

e19077 Background: There is laboratory evidence that digoxin sensitizes cancer cells to the induction of apoptosis by chemotherapy. Inhibition of the Na/K-ATPase enzyme by ouabain disturbs the intracellular ion composition of cancer cells, altering cellular homeostasis. This suggests that inhibition of the Na/K pump results in cellular sensitization of malignant, but not benign cells to induction of apoptosis. Epidemiologic studies also have shown beneficial effects of digitalis in breast cancer incidence. At ASCO 2007 our group presented a phase II study showing encouraging results by adding digoxin to bio-chemotherapy for melanoma. Erlotinib is one of the standard second-line treatments for NSCLC with a response rate (RR) of 10%. This study hypothesized, that adding digoxin to erlotinib may improve the RR and time to progression (TTP) in NSCLC. Methods: This was a phase II trial using daily 150 mg erlotinib and digoxin 0.25 mg. The digoxin dose was adjusted to keep levels between 1–2 ng/ml. Patients with progressive disease (PD) after chemotherapy were enrolled, if they had an ECOG 0–2 and good organ function. CT scans were done every 6 weeks. Treatment continued until PD or significant toxicity occurred. Results: Patient accrual lasted from 3/06–8/08 and was stopped early at time of interim analysis. Twenty eight patients were enrolled and 24, who completed at least 6 weeks of therapy, are presented here. All patients had unresectable stage III/IV at diagnosis. Median age was 61 (34–78), 14 were female, 17 had prior radiation (not involving the target lesions), 23 had one prior chemotherapy and 1 subject had two. Only one patient was a never smoker. Histologies were 50% adenocarcinoma, 30% squamous and 20% unspecified. One patient had a PR, 9 SD, and 14 PD. The median TTP was 61 days (9–366) and median survival 157 days (9–844). Side effects were similar to erlotinib single agent with no treatment related mortality. There were no unexpected or increased adverse events related to digoxin. Conclusions: Digoxin did not increase the response rate of erlotinib in the treatment of progressive NSCLC. TTP and survival seen in this study were similar to the published results with erlotinib alone. This combination does not warrant further clinical studies in NSCLC. No significant financial relationships to disclose.
The efficacy of chemotherapy in the advanced NSCLC patients who failed with the treatment of EGFR-TKI
Authors: Zhou S. , Ren S. , Zhang L. , Sun H. , Zhou C. 
Published: August 2020

e19078 Background: EGFR-TKI such as gefitinib and erlotinib were used as standard 2nd/3rd line therapy in previously treated NSCLC. However, those who benefit from EGFR-TKI will inevitably progress from the disease. We reported the efficacy of chemotherapy(CT) in the advanced NSCLC pts failed with the previously 2nd/3rd line treatment of EGFR-TKIs. Methods: Eligibility criteria included advanced NSCLC pts who got disease control(included CR, PR or SD) initially from TKI therapy and then progressed, PS = 0–2, and normal fatal organ function. Pts received systemic CT (docetaxal, pemetrexed, gemicitabine, novelbine or combined with platinum agent) until disease progression or unacceptable toxicity. Results: 32 pts were enrolled from Oct 15 2007 to Nov 30 2008. Demographics: M 56.3%/F 43.7%; median age 56 y [range 34–72]; stage IV 100%; PS 0/1/2: 3 (9.4%)/22(68.8%)/7(21.8%); adenocarcinoma/non-adenocarcinoma 29(90.6%)/3(9.4%); EGFR-TKI treatment duration >6 m 20(62.5%) /< 6 m 12(37.5%); monotherapy 16 (50%)/ doublets 16 (50%). All pts were evaluable for efficacy; partial response in 5 cases (15.6%), stable disease in 21 cases(37.5%), progressive disease in 15 (46.9%) ( Table ). The response of CT was not related with gender, age, regimens, but these with TKI treatment > 6 m achieved a significantly better response than those < 6 m(p=0.01) and these with PS 0–1 got a marginally significantly better response than PS 2(p=0.095). The toxicity was acceptable. Median progression free survival was 3.4 months and it was not correlated with the gender, age and regimens, but PFS were significant longer in the pts received > 6 m of TKI (median 4.8 vs 1.9, p=0.009) and with PS 0–1 (median 4.7 vs 1.9, p=0.002). Conclusions: Pts benefited from TKI therapy and developed progressive disease could also benefit from CT. The response duration of EGFR-TKI and performance status could be predictive for the better efficacy of CT. [Table: see text] No significant financial relationships to disclose.
ERCC1 expression and survival in small cell lung cancer
Authors: Hennemann M. , Sostruznik M. H. , Gaiger A. M. , Barrios C. H. 
Published: August 2020

e19080 Background: The excision repair cross-complementation group 1 (ERCC1) protein expression has been suggested as both predictive or prognostic according to the administration or not of cisplatin-based chemotherapy in non-small cell lung cancer. It's role in small cell lung cancer (SCLC) is still uncertain. Methods: Forty four patients (pts) with diagnosis of SCLC were retrospectively analyzed. Paraffin blocks were reviewed to reconfirm a SCLC diagnosis and submitted to semi-quantitative immunohistochemical (ICH) method to detect the ERCC1 protein. The criteria for ERCC1 IHC evaluation was based on the percentage of cells with positive staining. Medical charts were reviewed and findings correlated to the IHC expression. All pts were treated with standard cisplatin-based chemotherapy and concomitant radiotherapy when appropriate according to stage. We report the correlation of ERCC1 expression with the overall survival of the population. Results: The group of pts had 59% (n=26) men with a median age of 60,8 years (±10). Staging revealed limited disease (LD) in 41% (n=18), extensive disease (ED) in 55% (n=24) and was not available from the chart review in 7% (n=3). The median survival time (MST) was 15.84 (±9.73) months (mo) in LD; 8.39 (±8.53) mo in ED. ERCC1 was positive in 50% (n=22) of the pts. From these, 54% (n=12) had ≥50% of the cells with positive staining. The overall median survival of this group was 10.8 (±8.6) mo. The 45% (n=10) of cases presenting with <50% of cells with positive staining had an overall survival of 13 (±10) mo. In the group with positive ERCC1 expression, 45%(n=10) had LD and median survival of 17.1 (±7.8) mo [≥50% staining (n=6): median survival 12.1 (±3.9) mo; <50% staining (n=4): median survival 24.4 (±6.1) mo]. The 11 pts with ERCC1 expression and ED had a median survival of 7.9 (±8.7) mo. [≥50% staining (n=6): median survival 9.4 (±12) mo; <50% staining (n=5): median survival 6.1 (±1.5) mo]. The group with no ERCC1 expression (n=22)] had an overall survival of 9.7 (±10.1) mo. Of these pts 7 had LD and a median survival of 14.03 (±12.4) mo, while 13 pts had ED and a median survival of 8.76 (±8.73) mo. Conclusions: In this group of SCLC pts ERCC1 expression by IHC does not seem to correlate with survival. No significant financial relationships to disclose.