bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency and clinical correlations of epidermal growth factor receptor (EGFR) mutations in a large cohort of Italian non-small cell lung cancer (NSCLC) patients (pts) within the EGFR FASTnet program.
Authors: Normanno Nicola , Pinto Carmine , Taddei Gian Luigi , Troncone Giancarlo , Graziano Paolo , De Maglio Giovanna , Mottolese Marcella , Ludovini Vienna , Zupo Simonetta , Larocca Luigi Maria , Roz Elena , Russo Antonio , Palmieri Giuseppe , Perrone Giuseppe , Di Maio Massimo , Ardizzoni Andrea , Crino Lucio , Perrone Francesco , Clemente Claudio , Marchetti Antonio
Published: March 2020

e18021

Background: Gefitinib was approved in Italy for treatment of pts with advanced NSCLC carrying mutant EGFR in May 2010. Methods: The EGFR FASTnet program was designed to facilitate the exchange of biological material, clinico-pathological data and reports between medical oncologists, primary pathologists and referral laboratories. EGFR mutational analysis was carried by Sanger sequencing, Real Time PCR, Pyrosequencing, Fragment Analysis and High resolution melting. The Italian Association of Medical Oncology (AIOM) and the Italian Society of Surgical Pathology and Cytopathology (SIAPEC-IAP) have full access to the anonymous EGFR FASTnet database. Results: As of December 31, 2011, 503 oncologists, 135 pathologists and 38 referral laboratories joined the EGFR FASTnet program. The enrolled cohort of 3819 pts with advanced NSCLC was significantly enriched for adenocarcinoma histology (3172 [83%]), female sex (1361 [36%]) and smoking history (never smoker 911 [24%], former smoker>15 yrs 880 [23%], light smoker 194 [5%]). Mutational analysis was feasible in 3567 pts (93%). At registration, 72% of the pts had not received yet treatment for advanced disease. Mutational analysis was carried by Sanger sequencing in 2021 cases (57%), Real Time PCR in 174 (5%), Pyrosequencing in 636 (18%) and other techniques in 736 (21%). EGFR mutations were found in 520 cases (14.6%): 334 in exon 19 (9.4%), 163 in exon 21 (4.6%), 7 in exon 18 (0.2%) and 16 in exon 20 (0.4%). Proportion of mutated cases was slightly higher with Real time PCR compared to other techniques: Sanger 14.8%, Real time PCR 21.3%, Pyrosequencing 13.5%, other 13.3% (p = 0.049). A higher mutation rate was found in never smokers (32.0%), light smokers (18.7%) and former smokers >15 yrs (12.4%), as well as in adenocarcinoma (15.7%) and females (25.2%). Conclusions: The pts for EGFR mutational screening are spontaneously selected by medical oncologists according to known predictive factors. The results of the mutational analysis from clinical practice in Italy are consistent with data from literature.
Failure pattern after response to reversible tyrosine kinase inhibitors in advanced non-small cell lung cancer.
Authors: Serra Olbia , Peralta Sergi , Heras Lucia , Garcia Alicia , Plana Maria , Villanueva Rafael , Martin Montse , Losa Ferran
Published: March 2020

e18030

Background: Reversible tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) significantly increase survival for patients with previously treated advanced non-small cell lung cancer (NSCLC). Some studies have shown that most of responders to TKIs failed due to the appearance of new lesions without progression of the pre-existing target lesions. Methods: We retrospectively reviewed patients with advanced NSCLC diagnosed from 2005 to 2010 at two different hospitals in Catalonia (Spain) to identify those treated with TKIs. Patients with a clinical objective benefit as defined by Jackman were included. We analyzed both the clinical features of patients and their failure pattern. Results: There were 34 patients, 14 were women, with a median age of 64 years (range: 38 -81 years). Twenty-seven cases were adenocarcinoma while only 3 were squamous cell carcinoma. Eleven patients had never smoked. Previously to TKI, all patients received at least one line of chemotherapy except nine patients who received TKI as first-line treatment. Median time to progression after initiation of TKI was 8.7 months (1.9 - 38.9 months). Radiological TKI response was CR/PR/SD: 1/15/17 (1 not available). Rash and diarrhea were the most common toxic effects. No grade 3 or 4 toxicities were observed. TKI was discontinued in all patients after disease progression; 12 patients were unable to receive further therapy due to symptomatic deterioration. In 19 patients, PD was due to the appearance of new lesions and not to progression of the pre-existing lesions. Results of mutations of EGFR were available in 7 patients (ratio of mutant/wild status was 5/2). In all patients with known EGFR mutation, only new lesions leaded to progression. Conclusions: In spite of our series’ heterogeneity, results are consistent with previous data and suggest that a wide range of patients can benefit from TKIs. Furthermore, more than half of progressions were due to new lesions. Patients with known EGFR mutation strictly followed this failure pattern, though larger studies in EGFR mutated patients are needed to assess both failure patterns and benefits of continuing TKIs after progression when pre-existing lesions are stable.
Usefulness of serial measurement of serum N-telopeptides of type I collogen (NTx) in patients with lung cancer who developed bone metastasis: A prospective study.
Authors: Tamiya Motohiro , Okada Hideaki , Kobayashi Masashi , Suzuki Hidekazu , Okamoto Norio , Sasada Shinji , Morishita Naoko , Matsuura Yuka , Daga Haruko , Tokunaga Shinya , Taira Koichi , Hattori Michiyo , Miyamoto Natsuko , Takeda Koji , Hirashima Tomonori
Published: March 2020

e18036

Background: The bone resorption biomarkers urinary NTx (uNTx) and serum NTx (sNTx) have been shown to aid in the diagnosis of bone metastasis in patients with lung cancer. Patients with metastatic bone disease from lung cancer (MBDLC) are often treated with zoledronic acid. Zoledronic acid reduces the levels of bone resorption biomarkers and also the risk of skeletal adverse events in patients with MBDLC. We studied the effects of treatments including zoledronic acid on levels of sNTx during disease progression. Methods: Patients with MBDLC at the initial diagnosis were entered to this study. sNTx was measured once a month using the sNTx assay OSTEOMARK serum NTx (Alere Medical). MBDLC was characterized by monthly physical examination and by bone scintigraphy every 3 months for 12 months. All patients were required to provide written informed consent. Results: Twenty patients were enrolled between June and December 2010. The mean +/- 1 SD of the sNTx concentrations was 19.8 +/- 5.8 nM BCE/L at baseline. In the 16 patients receiving zoledronic acid, the levels of sNTx showed a significant decrease in the first month of treatment (baseline: 21.3 +/- 5.5 nM BCE/L; one month later: 13.6 +/- 2.7 nM BCE/L; p<0.01). During follow-up period, 12 of the patients treated with zoledronic acid experienced worsening MBDLC or had died from lung cancer, and there were statistically significant differences in the levels of sNTx at baseline (19.7 +/- 4.47 nM BCE/L), at the lowest levels after the administration of zoledronic acid (11.5 +/- 2.73 nM BCE/L) and at the point of measurable disease progression or death (13.0 +/- 2.07 nM BCE/L). Conclusions: Serial measurements of sNTx in patients with MBDLC treated with zoledronic acid might predict disease progression of bone metastasis. Administration of zoledronic acid significantly decreased the level of sNTx from baseline within one month and maintained the level of sNTx lower than baseline during study periods.
Combination chemotherapy of intermittent erlotinib with pemetrexed for pretreated patients with advanced non-small cell lung cancer: A phase I dose-finding study.
Authors: Takahashi Ryo , Minami Seigo , Kijima Takashi , Kida Hiroshi , Nakatani Takeshi , Hamaguchi Masanari , Takeuchi Yoshiko , Nagatomo Izumi , Yamamoto Suguru , Tachibana Isao , Komuta Kiyoshi , Kawase Ichiro
Published: March 2020

e18056

Background: Erlotinib and pemetrexed have been approved in second-line treatment for non-small cell lung cancer (NSCLC) and have different mechanisms of action. Their combination could potentially augment the antitumor activity brought by either agent alone. We investigated the safety in combination of erlotinib and pemetrexed in pretreated NSCLC patients. Methods: A phase I dose-finding study was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. This study was registered as UMIN000002900. Patients received 500 mg/m2 of pemetrexed intravenously every 21 days and erlotinib (100 mg in Level 1, 150 mg in Level 2) orally on days 2-16. Results: Twelve patients were recruited. Patient characteristics included median age of 66 (range, 48-78), 9 males, 9 stage IV, 7 adenocarcinoma, and 2 activating mutation-positives in the gene of epidermal growth factor receptor. Treatment was well-tolerated and the recommended dose of erlotinib was fixed on 150 mg. Dose-limiting toxicities were experienced in 3 patients: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required the second dose reduction of pemetrexed, and grade 3 diarrhea. None experienced drug-induced interstitial lung disease. Three patients achieved partial response and 5 kept stable disease. Conclusions: Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated with promising efficacy against pretreated advanced nonsquamous NSCLC.
Effect of germline polymorphisms of DNA repair genes on chemotherapy outcome in advanced non-small cell lung cancer (NSCLC) patients.
Authors: Sullivan Ivana , Majem Margarita , Páez David , Pallares Cinta , Paré Laia , Del Rio Elisabeth , Ramon Y Cajal Teresa , Barnadas Agust , Baiget Montserrat
Published: March 2020

e18057

Background: The identification of predictors of efficacy of chemotherapy in NSCLC could help in the selection of patients who are more likely to benefit from a particular scheme and the avoidance of undue toxicity in poor responders. We examined the role of several polymorphisms in DNA repair and DNA synthesis genes as pharmacogenetic markers in the outcome of NSCLC patients. Methods: A blood sample was collected from 117 patients with NSCLC and genomic DNA was isolated from the peripheral blood nucleated cells. Polymorphisms were analyzed by polymerase chain reaction amplification and automated sequencing techniques or using a 48.48 dynamic array on the BioMark system. The germline polymorphisms studied were excision repair cross-complementing-1 (ERCC1 Asn118Asn), xeroderma pigmentosum group D (XPD Lys751Gln), thymidylate synthase (TS) (VNTR/5’UTR, 2R G>C SNP, 3R G>C SNP) and Methylenetetrahydrofolate reductase (MTHFR) (C677T, A1298C). Progression-free survival (PFS) and overall survival (OS) were evaluated according to each genotype. Results: 103 patients with stage III-IV NSCLC (47% adenocarcinoma, 41% squamous cell carcinoma, 12% NOS) receiving platinum-based chemotherapy were eligible (14 patients with stage I-II were excluded). The median PFS was significantly longer in patients with C/T or T/T genotypes in codon 118 in ERCC1: 13 months (m) and 10 m, respectively, as compared to 6 m for the C/C patients (p=0.034). Patients with ERCC1 C/T or T/T genotypes had a trend to longer median OS (20 m) than those C/C (10.5 m; p=0.1). Subgroup analysis revealed that ERCC1 C/T or T/T genotypes were associated with increased PFS in male (p=0.005), smokers (p=0.036) and age <70 years (p=0.012). Patients with A/A or A/C genotypes in codon 751 in XPD had a trend to longer median OS than those C/C (p=0.09). No differences in median PFS were observed. No association between TS and MTHFR polymorphisms and outcome was found in overall population. Conclusions: ERCC1 C/T or T/T genotype in codon 118 might be useful for predicting the outcome of NSCLC patients treated with platinum-based chemotherapy specially in male, smokers and age <70 subgroups.
Final result of phase II study of irinotecan (CPT-11) plus oral S-1 for previously treated advanced NSCLC patients.
Authors: Arai Daisuke , Soejima Kenzo , Naoki Katsuhiko , Ikemura Shinnosuke , Terai Hideki , Sato Takashi , Satomi Ryousuke , Nakayama Souhei , Yoda Satoshi , Ishioka Kouta , Ohgino Keiko , Miyata Jun , Kabata Hiroki , Miyazaki Masaki , Betsuyaku Tomoko
Published: March 2020

e18058

Background: Both CPT-11 and S-1, which contains a prodrug of 5-FU, have moderate activity against NSCLC as a single agent and the combination of these agents have been reported to possess marked synergistic effects and tolerability in several gastrointestinal cancers. So the combination of CPT-11 and S-1 will be a promising alternative for the second line treatment of NSCLC patients. We have previously reported the phase I study of this combination and determined the recommended doses of these agents. This study was conducted as a phase II trial to evaluate the efficacy and safety of CPT-11 and S-1 for NSCLC patients who had previously treated. Methods: :This trial was open-label, multicenter study. NSCLC patients who had received one prior chemotherapy with performance status 0-1 were enrolled. Primary endopoint was response rate and secondary endpoints were progression free survival, overall survival, 1-year survival rate and adverse events. CPT-11 (60mg/m2 on days1, 8) and oral S-1 (80mg/m2/day on days1-14) was administered on every 21 days, maximally 6 cycles. Results: By October 2011, 31 patients were enrolled. Nineteen were adenocarcinoma and 12 were non-adenocarcinoma. The median age was 60 y/o (range 35-74) and the median number of treatment cycles was 4 (range 1-6). The objective response rates were PR 7.7%, SD 61.5% and PD 30.8%. Median PFS, median OS and 1-year survival rate were 2.8 month, 12.6 month and 55%, respectively. Grade 3-4 hematologic toxicities comprised neutropenia (15%), anemia (11%) and thrombocytopenia (3%). Other grade 3-4 non-hematologic toxicities comprised pneumonitis (7%), diarrhea (3%), anorexia (3%), liver dysfunction (3%) and mucosal disability (3%). No treatment related death was observed. Conclusions: Combination of CPT-11 and oral S-1 was moderately effective with acceptable toxicities as a second line treatment for advanced NSCLC patients.
The influence of gastric secretion inhibitors on gefitinib therapy in patients with non-small cell lung cancer harboring epidermal growth factor receptor activating mutations.
Authors: Saeki Sho , Sasaki Jiichiro , Morioka Junko , Sato Ryo , Sakata Shinya , Ichiyasu Hidenori , Fujii Kazuhiko , Saita Naoki , Kohrogi Hirotsugu
Published: March 2020

e18059

Background: Gefitinib is orally available, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in patients with non-small cell lung cancer (NSCLC), especially harboring EGFR activating mutations. Pharmacokinetic study revealed absorption of gefitinib was affected by the gastric pH. However, cancer patients in advanced stage are frequently administered gastric secretion inhibitors, such as proton pump inhibitors (PPIs) and H2 blockers (H2Bs) for various reasons. We hypothesized that gastric secretion inhibitors might suppress the efficacy of gefitinib therapy in NSCLC patients with EGFR activating mutations. The purpose of this study is to investigate the influence of PPIs/H2Bs on the efficacy of gefitinib therapy in the patients with NSCLC harboring EGFR activating mutations. Methods: From Apr 2004 to Aug 2011, we retrospectively analyzed the correlation between administration of PPIs/H2Bs and efficacy of gefitinib therapy in the patients with NSCLC harboring EGFR mutations. Results: Forty-three patients with EGFR mutations received gefitinib therapy in our hospital. 65.1% (28/43) patients administered PPIs/H2Bs simultaneously. Patients who received PPIs/H2Bs (PPIs/H2Bs group) had similar response rate compared with patients who didn’t receive PPIs/H2Bs (non-PPIs/H2Bs group) (77.8% vs 73.3%, p=1.00). Median progression free survival was 291 days in PPIs/H2Bs group and 353 days in non-PPIs/H2Bs group ( HR 1.23, Log-rank trest, p=0.578), respectively. Median overall survival was 718 days in PPIs/H2Bs group and not reached in non-PPIs/H2Bs group ( HR 1.53, Log-rank trest, p=0.403), respectively. Conclusions: Gastric secretion inhibitors didn’t affect the efficacy of gefitinib treatment in patients with NSCLC harboring EGFR activating mutations.
First-line cisplatin-fractionated doublet for unfit patients with advanced/metastatic non-small cell lung cancer.
Authors: Mansueto Giovanni , Narducci Filomena , Quadrini Silvia , Mancini Maria Laura , Sperduti Isabella , Gamucci Teresa
Published: March 2020

e18072

Background: standard treatment for unfit patients (pts) with stage IIIB-IV non-small cell lung cancer (NSCLC) is single-agent chemotherapy. Such pts are usually not suitable for cisplatin (CDDP)-based chemotherapy due to poor performance status (PS) and/or significant comorbidity that could enhance toxicity of high-dose CDDP. They also are not able to tolerate hydric load that is recommended for CDDP at high doses. We investigated a schedule of fractionated CDDP as first-line treatment in unfit pts with stage IIIB/IV NSCLC. Methods: 42 consecutive unfit pts with advanced/metastatic NSCLC were treated. They all had ECOG PS 2 and/or significant comorbidity and were not eligible for a standard CDDP-based doublet. Median age was 65,6 years (range 46-77), stage IIIB/IV=15/27 pts. Histology: squamous 62,4%, adenocarcinoma 37,5%, other/NOS 0,1%. All pts received q3w CDDP 35 mg/mq d1-8 plus Gemcitabine 1000 mg/mq d1-8 or Pemetrexed 500 mg/mq d1 according to histology, for a maximum of 6 cycles. Maintenance Pemetrexed was allowed in pts with non-squamous histology. Progression-free survival (PFS), clinical benefit rate (CBR) and toxicity were evaluated. Results: 33 pts are evaluable for efficacy and 35 for toxicity. Mean number of cycles per patient was 5,03 (total 211). Maintenance with q3w Pemetrexed was performed in 10 pts (23,8%)(mean 4,3 cycles per patient). Five pts in response after CDDP received thoracic RT. A partial response was observed in 42,5% of pts and a stable disease in 35,4% of pts, for an overall CBR of 77,9%. Median PFS was 10,1 months (Kaplan-Meier); 31,9% of pts were progression-free at 1 year. Pts with adenocarcinoma had significantly better PFS than those with squamous histology (11 vs 8 months, p=0.03). G3-G4 haematological toxicity: neutropenia 48,4% (3% febrile), thrombocytopenia 27,2% and anaemia 9,0%. A 25% dose reduction was required in 39,3% of patients. One patient died for cardiac failure during treatment. Conclusions: fractionated CDDP seems to be effective in our patients population with advanced NSCLC. Adequate supportive care help to manage severe hematological toxicity. A randomized phase II trial of fractionated CDDP-doublet versus monotherapy has been planned.
Customized first-line chemotherapy according to ERCC1 and RRM1 SNPs in advanced NSCLC patients: A phase II study.
Authors: Mazzoni Francesca , Cecere Fabiana Letizia , Meoni Giulia , Giuliani Costanza , Camerini Andrea , Allegrini Giacomo , Amoroso Domenico , Boni Luca , Martella Francesca , Ranchicchio Prabha , Giommoni Elisa , Torricelli Francesca , Di Costanzo Francesco
Published: March 2020

e18074

Background: Excision repair cross complementing group 1 (ERCC1) and ribonucleotide reductase1 (RRM1) expression levels are predictive of CT efficacy in some malignancies. “Customized” CT has several advantages: (1) pts are more likely to be treated with agents that they will respond to, (2) pts can be spared the toxicity of agents that they are resistant to, (3) effective treatment can be delivered early in the course of disease. Methods: We planned a phase II multicentric open label study in two steps (based on Simon design) to evaluate ERCC1 SNPs (T118C and C8092A) and RRM1 SNPs (-37C>A and -524T>C) in advanced NSCLC pts. Here we report the first step for futility. Pts received first line CT according to the assessed ERCC1 and RRM1 SNPs status and the correlated expression levels: treatment A (low ERCC1 and low RRM1) Cisplatin plus Gemcitabine; treatment B (low ERCC1 and high RRM1) Cisplatin plus Docetaxel; treatment C (high ERCC1 and low RRM1) Gemcitabine plus Docetaxel; treatment D (high ERCC1 and high RRM1) Docetaxel plus Vinorelbine. Results: 42 pts were enrolled from Jan. 2010 to Oct. 201, 40 pts received at least 1 cycle of CT; median age was 66 yrs (range 47-73); 33 pts were males; 23(55%) pts were ECOG PS 0, 19(45%) PS 1; all pts had stage IV; 23(55%) pts had adenoca, 13(31%) squamous, 6(14%) other types; 25(62%) pts received treatment A, 3(8%) treatment B, 11(27%) treatment C, 1(3%) treatment D. As primary end-point we assessed the overall best response: 18(45%) pts achieved PR, 12(30%) SD, 8(20%) PD, 2(5%) pts were not evaluable. Updated information on OS and PFS will be presented. CT was well tolerated, there were no treatment related deaths. Conclusions: We observed an improved RR in this setting of NSCLC pts treated with CT according to ERCC1 and RRM1 SNPs status. We are planning to continue the second step of this trial (total 110 pts).
The role of serum carcinoembryonic antigen in predicting objective responses to chemotherapy and overall survival in patients with non-small cell lung cancer.
Authors: Liu Hongbing
Published: March 2020

e18084

Background: Previous studies indicated the carcinoembryonic antigen (CEA) could predict the therapeutic objective response (OR) and overall survival (OS) of patients with cancers, including non-small cell lung cancer (NSCLC). However, the role it could play in evaluating therapeutic responses and OS in patients with NSCLC requires further elucidation. Herein, we investigated the potential role of CEA in predicting OR and OS in patients with NSCLC. Methods: 689 patients with NSCLC were enrolled between January 2000 and August 2011. The correlations between the CEA levels and OR or OS were examined via statistical analyses including the chi-squared test, logistical regression, paired-samples t-test, receiver operator characteristic curve, Kaplan-Meier survival analysis, log-rank test and Cox regression model. Results: The calculated cut-off for predicting an OR to chemotherapy in patients with NSCLC was a reduction of 5.28% in serum CEA. This value demonstrated a sensitivity of 61.3% and a specificity of 62.4%. Serum CEA levels significantly decreased after two cycles of chemotherapy in NSCLC patients (t = 2.196, P = 0.031). The Kaplan-Meier survival analysis indicated no significant correlation between baseline CEA and OS (log rank test =0.079). However, according to the Cox regression analysis the number of distant metastatic organs (=1 and ≥2) was the independent risk factor of the OS (P = 0.026; P =0.003), and the cycle numbers of chemotherapy was the protective factor for OS in patients with NSCLC (P=0.011).More importantly, baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes (P = 0.014; P = 0.017, respectively). Conclusions: Our study shows that baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes. While the baseline level of serum CEA was not a prognostic factor, the post-treatment reduction of serum CEA level can predict the OR in patients with NSCLC,. The number of chemotherapy cycles was the independent protective factor, while the numbers of distant metastatic organs was the independent risk factor for NSCLC patients’ OS.
ERCC1, class III β-tubulin, p53, and RRM1-tailored selection of personalized chemotherapy for stage IV NSCLC patients: A prospective study.
Authors: Guo Huiqin , Zhao Yu , Lu Jiangyang , Li Zejian
Published: March 2020

e18087

Background: ERCC1, class III β-tubulin, p53, and RRM1 are predictive molecular biomarkers of platinum agents, taxel, vinorelbine and gemcitabine respectively in personalized therapies of NSCLC. Tailored therapy with several of these markers suggested patient benefit was reported previously. But there was no report about prospective study involving all of these biomarkers. Here we report a prospective study that patients were treated with the personalized therapy tailored by these 4 markers to assess this new therapy approach. Methods: From Feb. 2009 to Feb. 2011, in our single group at the thoracic surgical department of PUMC hospital, we identified 48 patients with previously untreated stage IV NSCLC, ECOG PS of 0-2, and at least 2 of the 4 low expression level markers were eligible. The expression level of ERCC1, class III β-tubulin, p53, and RRM1 was assayed by immunohistochemical (IHC) staining with the tissue samples obtained from bronchoscopy biopsy, percutaneous lung biopsy or operation. Patients with low ERCC1/low class III β-tubulin expression received cisplatin/taxel, patients with high ERCC1/low class III β-tubulin expression received gemcitabine(with low RRM1 level) or vinorelbine (with low p53 level)/taxel, patients with low ERCC1/high class III β-tubulin expression received cisplatin/gemcitabine(low RRM1) or vinorelbine (low p53), and patients with high ERCC1/high class IIIβ-tubulin expression received gemcitabine/vinorelbine. A follow-up CT was performed after every 2 cycles chemotherapy and every 3 months after chemotherapy. PFS and OS were estimated by the Kaplan-Meier method. Results: Follow-up period was 35 months till Jan. 2012. 16(33.3%) patients died within follow-up period, 32(66.7%) patients are still alive. The overall response(CR+PR) rate is 85.4% with 10CR, 31 PR, 5 SD and 2 PD. Median PFS is 14 months and median OS was 27 months. And 1-year OS was 88.3% Conclusions: Our study suggest ERCC1, class III β-tubulin, p53, and RRM1-tailored selection of personalized chemotherapy of NSCLC could dramatically raise response rate and improve survival over standard chemotherapy. It might be a promising treatment option in the future..
A multicenter, randomized phase II study of sequential vinorelbine (V)/cisplatin (C)/bevacizumab (B) followed by docetaxel (D)/gemcitabine (G)/B versus D/C/B as a first-line therapy for advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC).
Authors: Kotsakis Athanasios Panayotis , Kontopodis Emmanouil , Vardakis Nikolaos , Kalbakis Kostas , Kentepozidis Nikolaos K. , Xyrafas Alexandros , Christophyllakis Charalampos , Mavroudis Dimitrios , Georgoulias Vassilis
Published: March 2020

e18105

Background: The combination of D with G has been shown equally active compared to the platinum-based doublets, which is considered the cornerstone for the treatment of NSCLC, with a more favorable toxicity profile (Georgoulias V. Lancet 2001 357: 1478-84). Sequential therapy with four active drugs (two doublets) in NSCLC, including C, was recently investigated and attributed a promising response rate (Pallis A. Lung Cancer, 2006, 52(2): 165-71). Incorporation of B to the standard platinum-based regimen improved its clinical outcome. Aim of this trial was to compare the efficacy of sequential four drug treatment in combination with B to the standard non platinum-based regimen combined with B. Methods: Seventy-seven treatment naïve patients (pts) with stage IIIB and IV non-squamous NSCLC were randomized to receive V 60 mg/m2 PO on day 1 and 8, C 80mg/m2 IV on day 1 and B 15 mg/kg IVon day 1, for 3 cycles followed by D 75 mg/m2 IV, G 1100 mg/m2 IV and B 15 mg/kg IV, all on day 1 (Arm A) or D 75 mg/m2 IV, C 80mg/m2 IV and B 15 mg/kg IV on day. The cycles were repeated every 3 weeks for a total of 6 cycles. The primary endpoint of the study was response rate (RR) and the secondary outcome measures were overall survival (OS) and progression free survival (PFS). Results: Thirty-nine pts were randomized to the control arm (Arm B) and 38 pts to the sequential arm. Pt demographics were balanced in both the arms. The overall RR was 36.8% and 46.2% in arm A and B, respectively (p= 0.49). There were 3 complete responses, one in arm A. Median PFS was 6.87 and 5.53 months in arm A and B, respectively (p= 0.368). Median OS was 19.6 and 10.33, respectively (p= 0.239). The estimated 1 and 2-year survival for arm A versus B were 71.1% and 36% versus 45.3% and 28%, respectively. No statistically significant difference in the toxicity profile was observed between the 2 arms. Conclusions: Sequential treatment with four active drugs is feasible and safe. The combination attributes encouraging results compared to the standard platinum-based regimen.
Pulmonary blastoma: A clinical study of three cases.
Authors: Sandoval-Sus Jose D , Hansra Damien Mikael , Ochoa Roberto Enrique , Ponce Mario , Santos Edgardo S.
Published: March 2020

e18109

Background: Pulmonary blastoma (PB) is a rare biphasic neoplasm composed of both immature mesenchymal and epithelial cells representing 0.2-0.5% of pulmonary malignancies. Initial presentation ranges from asymptomatic to classical symptoms of advanced pulmonary tumors. Surgical resection is the preferred treatment with no consensus on the role of other adjuvant therapies. Methods: We report the clinical features of PB in 3 patients (pts). Retrospective review of medical records of pts diagnosed with pulmonary blastoma at Jackson Memorial Hospital, Miami, FL since 2009. Staging was done using the 2009 AJCC staging system for NSCLC. All cases required to have confirmed pathological diagnosis before inclusion. Variables analyzed were demographics, clinical presentation, treatments and outcomes. Results: Mean age at diagnosis was 53 years old; two were male; 2 were Hispanic and one African American. Two of them were heavy smokers (80 and 45 packs year, respectively). At diagnosis, all cases where symptomatic; one had mild hypercalcemia of 12.9 mg/dL and two where stage IV with confirmed metastatic disease (bone and thyroid gland). Two of the cases where treated with surgical resection and both achieved complete remission (CR); one pt still remains on CR after 8 months post-surgery and the other one relapsed after 22 months post-surgery. This pt was placed on palliative chemotherapy (3 cycles of cisplatin/docetaxel) with no response. Further palliation was radiotherapy (37 Gy) with no response. The other case was treated with chemotherapy alone (6 cycles of cisplatin/docetaxel) and attained partial remission. All 3 patients remain alive. Conclusions: In our case series, all pts were symptomatic at diagnosis and two presented with metastatic disease. Surgery was the most beneficial intervention in regard to CR and disease-free interval as in previous reports. Chemotherapy has shown mixed responses, thus, larger studies are needed to define the role of chemotherapy in the adjuvant and palliative settings.
Epidermal growth factor receptor tyrosine kinase inhibitor in treatment of brain metastasis from non-small cell lung cancer.
Authors: Zhang Lan-jun , Cai Ling , Zhu Jian-fei , Rong Tie-hua , Wu Shao-xiong , Chen Zhong-pin , Liu Meng-zhong
Published: March 2020

e18121

Background: Brain metastasis (BM) presents 20-25% of patients with non-small cell lung cancer (NSCLC). Whole brain radiation therapy (WBRT) along with stereotactic radiosurgery (SRS), or surgical resection (SR) or chemotherapy (CXT) were usually used alone or in a combination modality for the treatment. In this study, we purposed to determine the outcome of patients with BM from non-small cell lung cancer treated with EGFR-TKI in combination with conventional therapy. Methods: A total of 201 BM patients with NSCLC were treated sequentially using EGFR-TKI combined with WBRT, or SRS, or SR, or CXT between Jan, 1999 and Nov, 2011 according to our institutional protocol. The median age was 56 yrs (range: 25-80). The histopathological type was predominantly adenocarcinoma (88%) and squamouscell carcinoma (9%), adenosquamous carcinoma (3%). Median follow-up was 28 months (range: 5-80). In addition to the treatment regimen, twelve potential prognostic factors were evaluated including age, gender, smoking status, primary tumor type, tumor size, expression of carcinoembryonic antigen (CEA), intracranial symptoms, lymph nodes metastasis (LNM), number of intracranial metastases, extracerebral metastases, time of taking EGFR-TKI, and TKI-related rash. Results: Median overall survival (OS) for the entire cohort was 29 months (95% CI: 25-34). The OS rate at 1, 2, 3 year were 61%, 38%, and 29%, respectively. On univariate analyses, improved OS was found to be significantly associated with age < 56 yrs (P=0.027), non-expression of CEA (P=0.016), absence of intracranial symptoms (P=0.018), no lymph nodes metastases (P=0.000), number of intracranial metastases < 3 (P=0.003), absence of extracerebral metastases (P=0.000), time of taking medicine ≥ 5 months (P=0.000), and appearance of acneiform rash (P=0.001). On multivariate analysis, time of taking medicine (P=0.000), age (P=0.046), absence of intracranial symptoms (P=0.002) and absence of extracerebral metastases (P=0.000) retained statistical significance. Conclusions: Patients with NSCLC and brain metastasis might benefit from treatment of EGFR-TKI in combination with conventional treatment.
Lymphopenia: Is it a prognostic factor in metastatic non-small cell lung cancer?
Authors: El Mekkeoui Zineb Benbrahim , Arifi Samia , Amaadour Lamiae , Abda Naima , Nejjari Chakib , Nawfel Mellas , El Mesbahi Omar
Published: March 2020

e18124

Background: Lymphopenia is frequent in advanced cancers and predicts the toxicity of chemotherapy. It is known as a poor prognostic marker in solid tumors such as metastatic breast cancer and sarcomas. However, its impact on relapse and survival in metastatic non small cell lung cancer is unknown. The aim of our study was to establish the correlation between lymphopenia and survival (disease-free survival (DFS) and overall survival (OS)) in metastatic non small cell lung cancer. Methods: We reviewed retrospectively 115 cases of metastatic non small cell lung carcinomas diagnosed between January 2007 to June 2011 at the Medical Oncology Department at Hassan II University Hospital. Complete blood counts were performed at the time of diagnosis and prior to treatment. Lymphopenia was defined as an absolute lymphocyte count (ALC) < 1000 /µL. We used the Kaplan-Meier method and Cox model to estimate OS and DFS. Results: Median age was 57 ± 10 years. 83.5% of patients were men. 81% of patients were treated with platinum based chemotherapy. Twelve patients (13%) had a low ALC at diagnosis with a mean of 854 (± 100)/µL. Lymphopenia was frequent in men patients (p=0.03) and non squamous cell carcinomas (p= 0.04). However, it was not correlated to age, performance status, body mass index, number of metastatic sites involved, pleural effusion, liver metastasis, hypercalcemia, anemia and hypoalbuminemia. The median duration of follow-up was 7.4 months (range: 1-99 months). In the univariate analysis, the medians of OS and DFS were shorter but not significantly different in lymphopenic patients (OS: 7.5 versus 9 months p= 0.07 and DFS: 5 versus 6 months p= 0.12). In multivariate analysis, lymphopenia was not significantly associated with OS and DFS. Conclusions: In this study, the association between lymphopenia and unfavorable OS and DFS was not clearly demonstrated in patients with metastatic non small cell lung carcinoma. Prospective clinical trials are needed to confirm or deny the prognostic role of lymphopenia in this cancer.
MCPH1 (BRIT1) and outcome to erlotinib in non-small cell lung cancer (NSCLC) patients (p) harboring EGFR mutations.
Authors: Garcia-Campelo M. Rosario , Taron Miquel , Benlloch Susana , Sanchez Jose Javier , Costa Carlota , Gimenez Capitan Ana , Bertran-Alamillo Jordi , Mayo Clara , Molina-Vila Miguel Angel , Majem Margarita , Moran Teresa , Massuti Bartomeu , Camps Carlos , Isla Dolores , Cobo Manuel , Cros Sara , Capdevila Laia , Carcereny Costa Enric , Viteri Ramirez Santiago , Rosell Rafael
Published: March 2020

e18131

Background: Progression-free survival (PFS) in EGFR-mutant NSCLC p treated with erlotinib can range from a few months (m) to more than two years, but genetic influences on the duration of response remain unclear. The cytotoxic effect of erlotinib has been related to several proteins that regulate DNA damage response (eg, BRCA1, BRCA2). MCPH1 contains 3 BRCT domains which are conserved in important molecules involved in DNA damage signaling, including BRCA1, MDC1 and 53BP1. MCPH1 binds to BRCA2 and regulates the localization of BRCA2 and Rad51 at sites of DNA damage. MCPH1 also regulates the ATP-dependent SWI-SNF chromatin remodeling complex during DNA repair. Methods: We used the NanoString nCounter gene expression system, which captures and counts individual mRNA transcripts, to analyze the expression of 44 selected genes, many of which are involved in DNA damage response, in 55 erlotinib-treated NSCLC p. We identified MCPH1 and correlated expression levels with clinical outcomes. Results: p characteristics: 16 males, 39 females (70.9%); 39 never-smokers (70.9%), 12 former smokers, 4 current smokers; 34 with EGFR deletion in exon 19 (61.8%), 21 with L858R mutation (38.2%). PFS was not reached for patients with high MCPH1, while it was 19 m for those with intermediate levels and 9 m for those with low levels (P=0.01). Median survival was 31 m for p with high levels, not reached for p with intermediate levels and 17 m for p with low levels (P=0.004). Conclusions: The enhanced effect of erlotinib in the presence of elevated MCPH1 could be due to the fact that MCPH1 can interfere with the function of MDC1 and 53BP1. The role of MCPH1 merits validation as a predictive marker of erlotinib response.
The use of primary radiation for ocular adnexal MALTomas.
Authors: Russell Wesley Alan , Gessert David , Cohen Jack A. , Rubenstein Jonathan B. , Herskovic Arnold M. , Gregory Stephanie A.
Published: March 2020

e18502

Background: Ocular adnexal mucosal associated lymphoid tissue lymphomas (MALTomas) are rare with no phase III trials to guide treatment. Typical management has been primary radiation therapy. This retrospective series aims to report the experience of a single institution and add to the current literature. Methods: Using our electronic medical record systems and available paper charts, we identified patients with MALTomas of the lacrimal gland or sac, conjunctiva, and posterior orbital structures. Records were reviewed to determine pathology, staging, treatment information, local and distant control, salvage treatments, and late toxicity. Results: Sixteen patients with ocular adnexal MALTomas had local radiation between 1992 and 2011 for primary or recurrent disease. 50% had lymphoma in the conjunctiva, 25% in the lacrimal sac/gland, and 25% in the posterior orbit. 75% had stage IAE disease, 6% had stage IIAE, and 19% had a positive bone marrow biopsy. One patient received chemotherapy as part of his initial therapy. The median radiation dose was 30 Gy (25.5-36 Gy) delivered with electrons (31%) or photons (69%). After a median follow-up of 34.78 months, two patients had residual/progressive disease, two had contralateral recurrence, and 1 had a distant failure, for local control of 87.5% and overall disease control of 68.75%. Recurrence/progression occurred at a median of 35.45 months. Two patients with residual/progressive disease and one with a contralateral recurrence were followed, successfully salvaged, and are NED. Fourteen patients are still alive and there were no disease-related/toxicity deaths. Seven patients developed cataracts in the treated eye, 2 had radiation retinopathy, 2 had permanent dry eye syndrome, and 1 had severe keratopathy requiring enucleation. Six patients (3.75%) had worsening visual acuity of unclear etiology. Conclusions: Primary radiation therapy for ocular adnexal MALTomas with a median dose of 30 Gy led to excellent local control. Those patients who did recur were successfully salvaged. Radiation was generally well-tolerated with expected cataractogenesis given the dose required to achieve local control with only one patient developing severe keratopathy after receiving the highest dose in this series.
R-ICE versus R-ESHAP for salvage therapy in aggressive B-cell non-Hodgkin lymphoma.
Authors: Freyer Craig , George Timothy , Price Samantha , Shah Bijal Dinesh , Bello Celeste M. , Sokol Lubomir , Sotomayor Eduardo M. , Cultrera Jennifer L.
Published: March 2020

e18509

Background: Standard therapy for aggressive Non-Hodgkin’s lymphoma (NHL) consists of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), however the 5 year relapse rate is 20%. Patients with relapsed/refractory (RR) NHL are offered autologous stem cell transplantation (SCT) after salvage chemotherapy demonstrates chemosensitivity and reduces tumor burden. No standard salvage regimen for RR-NHL exists. Frequently used regimens include R-ICE (rituximab, ifosfamide, carboplatin, etoposide) and R-ESHAP (rituximab, etoposide, methylprednisolone, cytarabine, cisplatin). Which regimen provides the greatest efficacy with least toxicity remains unclear. Methods: Patients diagnosed with RR aggressive NHL who received R-ICE or R-ESHAP between 1/1/2000 and 9/30/2011 were identified. Patients may have received either regimen after failure of initial therapy. The primary objective was to determine the overall response rate (ORR) for each regimen. Secondary objectives included determination of overall survival (OS), and proportion of patients able to receive SCT. OS for each regimen was compared using Kaplan-Meier survival curves. Continuous data was compared using the student’s T-test. Results: The median age was 59 years, 27% were female and 90% were described as Caucasian. 78% were diagnosed with diffuse large B cell lymphoma (DLBCL), 13% with transformed follicular lymphoma, 9% with related aggressive NHL subtypes. 55% had a revised International Prognosis Score of 2. Conclusions: No standard of care exists for management of RR-NHL. No regimen has shown superior efficacy or long term outcomes over another. Our trial suggests similar ORR and OS between two commonly used regimens. Although toxicity profiles differ between these regimens, discontinuation rates due to toxicity were similar. The choice of salvage regimen may be determined by ease of administration, toxicity profile and patient/physician preference rather than improved efficacy between R-ICE and R-ESHAP. [Table: see text]
Comparison of clinical parameters and survival in Vietnam era (V) versus non-Vietnam era (non-V) veterans with non-Hodgkin lymphoma (NHL).
Authors: Srinivas Shanthi , Chang Victor T , Floyd Leroy Cordero , Kasimis Basil , Gonzalez Melanie L. , McPherson Monica , Cogswell Janet , Crump Barbara , Duque Lourdes , Paz-Querubin Emma R
Published: March 2020

e18516

Background: The incidence of NHL has been increasing in the US population. Agent Orange exposure has been implicated in the development of B cell lymphoproliferative disorders including NHL. We explored possible differences in the clinical and lab parameters and predictors of survival in V versus Non-V veterans with diagnosis of NHL at the VAHCSNJ. Methods: In an IRB-approved protocol, the records of veterans diagnosed with NHL from January 1997 to December 2011 were reviewed for demographic, clinical, and pathology data, including HIV, Hep B, Hep C titers, Vietnam Veteran status and survival. We tabulated the ECOG Performance Status (PS), International Prognosis Index (IPI)/ Follicular Lymphoma International Prognostic Index (FLIPI), Charlson Comorbidity Index (CMI), the Kaplan-Feinstein Index (KFI), the Cumulative Illness Rating Scale (CIRS) and Vietnam status. Cox regression analyses were performed to determine predictors of survival. Results: There were 152 veterans who met the eligibility criteria; 78 V and 74 non-V; the groups did not differ by PS, stage, beta 2microglobulin (b2m), and HIV status, IPI/FLIPI. Differences in their clinical features are summarized (Table). The proportion of V vets with high grade lymphomas was greater than non V vets (p .036). Survival predictors for both the V and non-V veterans were the age, PS, hemoglobin, LDH, albumin, grade, IPI/FLIPI. However, in V veterans, b2m (p< 0.001) and stage were additional predictors of survival. Median survival for V veterans was 1454 days (95%CI 864-3377) and Non-V was 1824 days (95% CI 560-2075). Conclusions: The V veterans were younger with higher grade disease compared to the Non-V veterans. While their stage and PS were not different, survival was shorter. These should be studied further in a larger sample. [Table: see text]
Outcome of patients treated with a single-fraction dose of radiation for lymphomatoid papulosis.
Authors: Gentile Michelle Sara , Thomas Tarita O. , Agrawal Priya , Guitart Joan , Rosen Steven T. , Kuzel Timothy , Mittal Bharat Bhushan
Published: March 2020

e18523

Background: Lymphomatoid Papulosis (LYP) is a primary cutaneous CD30+ lymphoproliferative disorder and a radiosensitive tumor. Treatment with radiation is typically given in multiple fractions for patients presenting with symptomatic unilesional or multilesional disease. However, a single fraction of radiation is more convenient to the patient. The purpose of this retrospective review was to evaluate the clinical response to a single fraction of radiation for palliation of symptomatic LYP lesions. Methods: The records of 8 (5 female, 3 male) patients with LYP, treated with a single or multi-fractionated palliative radiation therapy between 10/2001 and 9/2011, were reviewed. All patients had received multiple previous treatments such as chemotherapy, PUVA, topical nitrogen mustard, and UVB. A total of 19 sites with disease were given the following single doses: 700 (n=3) and 800 (n=16). In the earlier years, a total of 6 sites with disease were given 250 cGy in 18 fractions for a total dose of 4500 cGy. Radiation therapy was administered with electrons to 20 sites and with photons to 5. A bolus was used in most cases to increase the radiation dosage to the skin. Results: Minimum and median follow-up were 1 and 43 months (range, 1 - 120), respectively. Median age of the patients was 65 (range, 24 - 83). For disease sites receiving a single fraction therapy, a complete response (CR) was seen in 17 of the 19 sites (89.5%), and a partial response (PR) was seen in an additional 2 of the 19 sites (10.5%). Therefore, the overall response rate was 100%. For the disease sites receiving multi-fractionated therapy, a CR was seen in 6 of the 6 sites (100%). Evaluation of patient characteristics and treatment did not reveal any differences between patients achieving a CR or PR. Conclusions: For previously treated, radiation-naıve LYP lesions, palliative radiation therapy with single fractions of 700 - 800 cGy is associated with an excellent CR and is a convenient and cost effective strategy.