Lung Cancer

Editorial Board

2010-09-01

Surgical treatment of oligometastatic non-small cell lung cancer

Joachim Pfannschmidt, Hendrik Dienemann — 2010-05-31

Abstract: Patients with stage IV metastatic non-small cell lung cancer (NSCLC) are generally believed to have an incurable disease. Patients with oligometastatic disease represent a distinct subset of patients among those with metastatic disease.There is evidence that these patients have synchronous or metachronous satellite nodules in different pulmonary lobes or have solitary extrapulmonary metastases. In these cases, evidence has shown that surgical resection may provide patients with survival benefit. This article discusses the biology of the oligometastatic state in patients with lung cancer and the selection of patients for surgery, as well as the prognostic factors that influence survival of the patient. To properly select patients for an aggressive local treatment regime, accurate clinical staging is of prime importance. The use of FDG-PET should be considered for restaging if oligometastatic disease is suspected based on a patient's CT scan.A limitation of retrospective clinical studies for oligometastatic disease is that it is difficult to summarize and evaluate the available evidence for the effectiveness of surgical resection due to selection bias, and to a high degree of variability among different clinical studies. Nevertheless, we can certainly learn from the clinical experience acquired from retrospective case series to identify prognostic factors. Following surgical resection, the overall 5-year actuarial survival rate is about 28% for patients with satellite nodules and 21% for patients with ipsilateral nodules. Patients with resected brain metastasis achieve 5-year survival rates between 11% and 30%, and those with adrenalectomy for adrenal metastasis achieve 5-year survival rates of 26%.

Lessons learnt from gefitinib and erlotinib: Key insights into small-molecule EGFR-targeted kinase inhibitors in non-small cell lung cancer

Eckart Laack, Guido Sauter, Carsten Bokemeyer — 2010-06-21

Abstract: Improving treatment options and patient outcomes for those with non-small cell lung cancer (NSCLC) represents a significant worldwide challenge. Although traditional treatment strategies are widely accepted and initially successful, many tumors still fail to respond to available drugs. Therapeutic options for patients with NSCLC are therefore moving towards more individual and personalized treatment strategies. The first-generation tyrosine kinase inhibitors (TKIs), designed to target specific molecular pathways within the tumor, have paved the way towards tailored therapy. Promising experience with these agents has opened the door to a sudden surge of new drug advances. The development of these second-generation treatments offer the potential to further maximize patient benefit and provide greater therapeutic options for patients with advanced NSCLC. As the number of second-generation TKIs continues to grow, the efficacy and safety of new members of this class continue to be established in ongoing clinical trials.

Rationale of a relaunch of gefitinib in Caucasian non-small cell lung cancer patients

Andreas Pircher, Ferdinand Ploner, Helmut Popper, Wolfgang Hilbe — 2010-02-19

Abstract: In 2002 results of two-phase II studies with the new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib showed not only promising efficacy in second and third line non-small cell lung cancer (NSCLC) therapies but also an excellent tolerability. Since then, thousands of patients have been treated in one of the largest expanded access programs ever performed and the successful application in daily routine led to a preliminary approval of the drug by the U.S. Food and Drug Administration in 2003. In the light of the negative results of a subsequent phase III trial comparing gefitinib with best supportive care, the approval was withdrawn. In 2009 gefitinib was relaunched for Caucasian patients in the US and Europe based on new data and on the re-interpretation of previous studies. The approval is now recommended exclusively for patients with an activating EGFR mutation. For the first time in lung cancer, molecular work-up is of clinical relevance and will change the diagnostic and therapeutic algorithms. The present review summarizes these data, presents the rationale for this development and proposes a diagnostic work-up.

KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: A meta-analysis of 22 studies

2009-12-23

Abstract: Epidemiologic studies have evaluated the association between KRAS mutations and resistance to the treatment of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, results were inconclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic computerized searches of the PubMed and Medline databases (up to Jun 30, 2009) were performed. A total of 22 studies were included in the final meta-analysis, consisting of 1470 NSCLC patients, of whom 231 had KRAS mutations (16%). Current or former smokers had a higher frequency of KRAS mutations than never smokers (25% versus 6%; OR=4.36; P<0.01). Mutations were more common among adenocarcinoma than other histologies (26% versus 16%; OR=1.98; P<0.01). The objective response rate (ORR) of NSCLC patients with mutant KRAS was 3% (6/210), whereas the ORR of NSCLC patients with wild-type KRAS was 26% (287/1125). The overall pooled RR for ORR was 0.29 (95% CI: 0.18–0.47; P<0.01). Subgroup analyses were conducted on the basis of ethnicity and study treatment, all the results were not materially altered and did not draw different conclusions, indicating that our results were robust. In summary, this meta-analysis suggests that KRAS mutations may represent negative predictive biomarkers for tumor response in NSCLC patients treated with EGFR-TKIs. However, due to a mutually exclusive relationship between KRAS and EGFR mutation and no difference in survival between KRAS mutant/EGFR wild-type and KRAS wild-type/EGFR wild-type NSCLC, the clinical usefulness of KRAS mutation as a selection marker for EGFR-TKIs sensitivity in NSCLC is limited.

PTEN mutations and relationship to EGFR, ERBB2, KRAS, and TP53 mutations in non-small cell lung cancers

2009-12-17

Abstract: Somatic mutations of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in non-small cell lung cancers (NSCLCs) have been investigated in but a small number of cases. In addition, the relationship between PTEN mutations and epidermal growth factor receptor (EGFR), KRAS, and TP53 mutations has not been investigated. Therefore, we investigated the frequency of PTEN mutations in 176 surgically resected NSCLCs and analyzed the relationship between PTEN mutations and EGFR, ERBB2, KRAS, and TP53 mutations. Mutations of PTEN (exons 1–9), EGFR (exons 18–21), ERBB2 (exons 19 and 20), KRAS (exon 1), and TP53 (exons 2–11) were determined by polymerase chain reaction and direct sequencing. PTEN mutations were present in 8 (4.5%) of the 176 tumors. PTEN mutations were only found in ever-smokers and were significantly more frequent in squamous cell carcinoma than in adenocarcinoma (10.2% vs 1.7%, P=0.02). Mutations of EGFR, ERBB2, KRAS, and TP53 genes were found in 36 (20.5%), 2 (1.1%), 11 (6.3%), and 66 (37.5%) cases, respectively. Of the 8 tumors with PTEN mutations, 1 case concurrently had an EGFR mutation and 4 cases had TP53 mutations. However, PTEN mutations were not found in the tumors with KRAS mutation. Our findings indicate that PTEN mutations are relatively common in NSCLC, and thus analysis of PTEN mutations may facilitate a comprehensive understanding of the genetic alterations related to the EGFR signaling pathway.

Usefulness of melanoma antigen (MAGE) gene analysis in tissue samples from percutaneous needle aspiration biopsy of suspected lung cancer lesions

2010-01-11

Abstract: Background: As mortality from lung cancer is still very high, early detection prior to metastasis is important in clinical settings. We prospectively evaluated the clinical usefulness of a reverse transcription-nested polymerase chain reaction (RT-nested PCR) using melanoma antigen (MAGE) A1-6 genes with tissue samples obtained from the percutaneous needle aspiration (PCNA) biopsies used in the diagnosis of lung cancer.Methods: We enrolled 53 patients with suspected lung cancer based on CT scan (M:F, 39:14; mean age 61 years). A PCNA biopsy was performed twice and lung cancer was diagnosed by a pathological examination. The MAGE genes were analyzed using RT-nested PCR from tissue samples obtained from the PCNA biopsy of the lesion. We compared the results from the RT-nested PCR and the pathologic diagnosis. We also analyzed the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV).Results: Of the 53 patients, 39 were diagnosed with lung cancer. Six patients had tuberculosis and 8 were confirmed with chronic inflammation or benign lesion. Based on the RT-nested PCR examination, 41 of 53 patients were positive for the MAGE gene: 34 of 39 patients had lung cancer; 5 of 6 patients had tuberculosis; and 2 of 8 patients had chronic inflammation or benign lesion. The sensitivity, specificity, accuracy, PPV and NPV were 83%, 58%, 77%, 87% and 55%, respectively.Conclusion: MAGE gene analysis by RT-nested PCR may be a useful method for the diagnosis of lung cancer, but it is still limited in patients with tuberculosis.

Snail nuclear expression parallels higher malignancy potential in neuroendocrine lung tumors

J.A. Galván, M.V. González, G. Crespo, M.V. Folgueras, A. Astudillo — 2010-01-21

Abstract: Introduction: The aim of our study was to determine the integrity of the cell–cell adhesion E-cadherin–β-catenin complex in neuroendocrine lung tumors (NELTs) and the possible involvement of Snail in its deregulation.Methods: The studied series consisted of formalin-fixed-paraffin-embedded tissue samples from 70 patients diagnosed with NELT (2000–2006) including tumors of low malignacy potential (3 tumorlets, 33 typical carcinoids), intermediate malignancy potential (3 atypical carcinoids) and tumors of high malignancy potential (10 large cell neuroendocrine carcinomas—LCNEC and 21 small cell carcinoma—SCLC). E-cadherin, β-catenin and Snail expression were immunohistochemically evaluated and mRNA levels were assessed by Q-RT-PCR for E-cadherin and Snail.Results: Nuclear Snail signal was high in 46% tumors with the strongest level observed in high malignancy tumors. Furthermore, Snail levels correlated with tumor size, lymph node involvement and tobacco consumption. E-cadherin expression was downregulated in 24% cases and it was absent from the membrane in 31%, all of them cases of high malignancy potential. High E-cadherin levels and a membrane pattern were associated with tumor-free lymph node patients and inversely proportional to Snail protein expression. β-catenin levels were weak in 43% and absent from the membrane in 59% cases. Interestingly, among high malignancy potential tumors, β-catenin levels were significantly higher in LCNEC than in SCLC. The integrity of the E-cadherin–β-catenin complex was retained in 37% cases, most of them carcinoid tumors, and correlated with low Snail levels, low malignancy potential and free lymph nodes.Conclusion: Snail nuclear expression and loss of integrity of cell adhesion complex E-cadherin/β-catenin parallels higher malignancy potential in NELTs.

Stereotactic body radiotherapy using real-time tumor tracking in octogenarians with non-small cell lung cancer

2010-01-08

Abstract: As the incidence of stage I non-small cell lung cancer (NSCLC) increases among octogenarians and only selected patients are surgical candidates, an alternative treatment is necessary. This manuscript evaluates the overall survival, local tumor control rate, and treatment-related toxicity after stereotactic body radiotherapy (SBRT) in 38 octogenarians with stage I NSCLC. Treatment consisted of 45Gy (n=4) or 60Gy (n=25) in 3 fractions for patients with peripheral tumors. A risk adaptive schedule of 45–60Gy in 3–6 fractions was used for central (n=7) or large peripheral tumors (n=2).An overall survival rate of 65% at 1 year and 44% at 2 years was achieved in octogenarians after SBRT. The local tumor control rate was excellent (100% at 2 years) and no grade 4 or 5 treatment-related toxicity occurred. Despite the high incidence of comorbidity in these octogenarians (Charlson score ≥5 in 16% of patients), an approach that merely provides supportive care cannot always be justified. SBRT offers octogenarians with stage I NSCLC a good treatment alternative.

Pemetrexed and cisplatin with concurrent radiotherapy for locally advanced non-small cell and limited disease small cell lung cancer: Results from 2 phase I studies

2010-01-25

Abstract: Background: The objectives were to determine the maximum tolerated dose (MTD) of pemetrexed and cisplatin with concurrent radiotherapy. Secondary objectives include incidence and nature of acute and late toxicities, tumor response and overall survival.Patients and methods: Treatment naïve patients received 1 cycle of cisplatin 80mg/m2 in study I (stage III NSCLC), 75mg/m2 in study II (LD-SCLC) and pemetrexed 500mg/m2 before the phase I part. In study I, patients were treated in cohorts with escalating cisplatin doses (60–80mg/m2), pemetrexed doses (400–500mg/m2) and concurrent escalating radiotherapy doses (66Gy in 33–27 fractions). In study II, patients were treated with cisplatin 75mg/m2 and escalating pemetrexed doses (400–500mg/m2) with concurrent escalating radiotherapy doses (50–62Gy).Results: The trials closed prematurely: study I because of poor accrual, study II because of sponsor decision. Thirteen patients were treated: 4 with NSCLC, 9 with LD-SCLC. No dose-limiting toxicity was observed. There was no grade 4 toxicity, grade 3 hematological toxicity was mild. One patient developed grade 3 acute esophagitis, but was able to complete radiotherapy without delay. Two patients experienced grade 2 late pulmonary toxicity, 1 complete response, 6 partial responses and 1 progressive disease were observed.Conclusions: Although the studies stopped too early to assess MTD, we have demonstrated that the combination of cisplatin and pemetrexed with concurrent radiotherapy up to 66Gy (33×2Gy) is well tolerated and this new combination shows activity in NSCLC. Pemetrexed is the first 3rd generation cytotoxic found to be tolerable at full dose with concurrent radiotherapy.

Estimation of an optimal chemotherapy utilisation rate for lung cancer: An evidence-based benchmark for cancer care

2010-01-18

Abstract: Background: Optimal chemotherapy utilisation rates can serve as benchmarks to assess the quality of cancer service delivery. This study aims to determine the optimal proportion of patients with lung cancer that should receive chemotherapy at least once during the course of their illness, based on the best available evidence.Methods: An optimal chemotherapy utilisation tree was constructed using indications for chemotherapy identified from evidence-based treatment guidelines. Data on the proportion of patient and tumour-related attributes for which chemotherapy was indicated were obtained and merged with the treatment indications to calculate an optimal chemotherapy utilisation rate. This optimal rate was compared with reported actual rates of chemotherapy utilisation.Results: Chemotherapy is recommended at least once in 73% of all patients with lung cancer (93% of small cell lung cancer (SCLC) patients and 69% of non-small cell lung cancer (NSCLC) patients). Comparison of these benchmark rates with international reported actual chemotherapy utilisation rates reveals under-utilisation of chemotherapy in all newly diagnosed lung cancer patients, regardless of histological type and stage, with the exception of stage I NSCLC.Conclusion: The optimal chemotherapy utilisation rate can serve as a feasible, evidence-based measure of the quality of cancer care. Chemotherapy may be under-utilised in the initial management of lung cancer.

Re-challenge chemotherapy for relapsed non-small-cell lung cancer

2010-01-13

Abstract: There has been no report about re-challenge chemotherapy (RC) consisting of the same regimen as first-line chemotherapy in non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the efficacy of RC as second-line chemotherapy in patients with relapsed NSCLC. We conducted a retrospective review of 28 consecutive NSCLC patients who were treated with RC and compared their clinical outcomes with those of 38 consecutive NSCLC patients who were treated with docetaxel (DOC) at our hospital between July 1992 and December 2003. The RC group consisted of 21 men and 7 women, with a median age of 62 years (range, 42–76 years). Most first-line regimens were platinum-based and the median administered course was 3 (range, 2–7). All patients had responded to the first-line chemotherapy and had performance status (PS) 1 at relapse. The median interval from the end of first-line chemotherapy to relapse was 5.0 months (range, 1.6–36.1 months). The overall response rate of RC was 29%. The median survival time from the beginning of RC was 17.0 months and the 1-year survival rate was 60%. RC led to a significantly better overall survival rate than DOC (p=0.0342). RC could be an active second-line regimen in patients with relapsed NSCLC who responded to first-line chemotherapy.

Second-line weekly paclitaxel in resistant or relapsed non-small cell lung cancer treated with docetaxel and carboplatin: A multi-center phase II study

2010-01-06

Abstract: We conducted a phase II trial to evaluate the safety and efficacy of weekly paclitaxel in patients with resistant or relapsed non-small cell lung cancer (NSCLC) treated with docetaxel and carboplatin. Thirty-two NSCLC patients at a median age of 58.0 years (range 33–75) were enrolled. The Eastern Cooperative Oncology Group performance status scores (0/1/2) were 18/9/5, respectively. The majority of patients had adenocarcinoma (84%) and stage IV disease (81%). The response rate for the first-line chemotherapy was 28%. Paclitaxel was administered at a dose of 80mg/m2 as an intravenous infusion 60min weekly for 6 consecutive weeks of an 8-week cycle. All patients were assessable for response and toxicity. The median number of cycles administered was two (range 1–8), and the overall response rate was 15.6%. The median survival time (MST) was 10.6 months (95% CI=8.2–12.5), while the 1-year survival rate was 37.5%, and the median progression-free survival was 4.9 months (95% CI=3.0–7.1). Hematological toxicities (grade 3 or 4) were observed in 15 patients (46.9%) with leukopenia, and in 4 (12.5%) with anemia. Non-hematological toxicity was generally mild, though grade 3 anorexia was observed in 3 patients (9.3%). No treatment-related deaths were observed. In conclusion, second-line weekly paclitaxel is effective in NSCLC patients treated with docetaxel plus carboplatin and is associated with a tolerable toxicity profile.

The efficacy of pemetrexed as a third- or fourth-line therapy and the significance of thymidylate synthase expression in patients with advanced non-small cell lung cancer

2010-01-11

Abstract: Background: Pemetrexed is one of the standard second-line therapies in advanced non-small cell lung cancer (NSCLC). Currently, there are no standard cytotoxic treatments beyond second-line therapy. We evaluated the efficacy and safety of pemetrexed as a salvage regimen in heavily pretreated NSCLC patients. We also analyzed thymidylate synthase (TS) expression in tumor tissues to determine whether TS expression is correlated with the clinical efficacy of pemetrexed.Methods: One hundred and ten NSCLC patients who received pemetrexed as third- or fourth-line therapy at the Samsung Medical Center between June 2006 and June 2008 were retrospectively reviewed. TS expression was analyzed by immunohistochemical staining in 55 NSCLC tissue specimens. The relationships between TS expression and clinicopathological factors were evaluated. Univariate and multivariate analyses were performed to define the predictive factors and prognostic significances.Results: The median age of patients in this study was 59 years (range: 24–84), 50.9% were men, and 27 (24.6%) were smokers or previous smokers. Sixty-five patients (59.1%) received pemetrexed as third-line treatment, and 95 (86.4%) had non-squamous cell carcinoma. Platinum-based chemotherapy (84.6%) was the most common first-line therapy, and EGFR TKIs [erlotinib (17.3%) or gefitinib (43.6%)] were a common second-line therapy. The median time from date of diagnosis to the date of the first pemetrexed treatment was 12.8 months (range: 1.8–62.2 months) and the median number of pemetrexed treatments was 4 (range 1–22). Eighteen patients achieved PR (16.3%), 41 patients SD (37.3%), and 43 patients PD (39.1%), with a disease control rate of 53.6%. The median follow-up duration was 16.1 months, the median progression-free survival (PFS) was 3.2 months (95% CI: 1.9–4.5 months), and the median overall survival (OS) was 11.6 months (95% CI: 9.0–14.1 months). Male gender was the only independent variable for poor PFS (HR=1.673, 95% CI: 1.103–2.535), with poor performance status (HR=2.454, 95% CI: 1.405–4.287) and history of smoking (HR=1.856, 95% CI: 1.087–3.168) being independent adverse factors for OS. Thirteen of 55 tumor tissues (23.6%) showed TS expression; however, there were no significant correlations between TS expression and the clinicopathological factors.Conclusion: Pemetrexed was suggested as a third- or fourth-line therapy due to its favorable efficacy and tolerable toxicity. Further studies are warranted to define the adequate sequence of salvage treatments, especially in patients with adenocarcinoma lung cancer.

Unsuspected pulmonary emboli in lung cancer patients: The impact on survival and the significance of anticoagulation therapy

2009-12-15

Abstract: Background: Many pulmonary emboli (PE) are detected unsuspectedly in lung cancer patients. The purpose of our study was to retrospectively evaluate the role of anticoagulation therapy for unsuspected PE in lung cancer patients. We also aimed to evaluate risk factors associated with the development of PE as well as the prognostic power of PE in lung cancer patients.Patients and methods: The Samsung Medical Information System was used to evaluate predictors and prognosis of PE in lung cancer patients. We found patients with PE using the Radiation Interpretation Registry and reviewed their medical records.Results: Among 8014 lung cancer patients, PE developed in 180 patients (cumulative incidence rates=2.2%). Metastasis and prior history of chemotherapy were significant predictors of the development of PE. Pulmonary embolism detected within 3 months after diagnosis of lung cancer was a significant poor prognostic factor (hazard ratio [HR], 1.5; 95% CI, 1.1–2.0) in the complete lung cancer cohort. One hundred thirteen (63%) out of total 180 PE patients were incidentally found to have PE. Among the 113 patients with unsuspected PE, 62 patients (55%) did not receive anticoagulation therapy, and died sooner than those who received anticoagulation therapy for unsuspected PE (HR, 4.1; 95% CI, 2.3–7.6).Conclusion: Anticoagulation therapy for unsuspected PE is associated with increased overall survival in lung cancer patients.

VeriStrat® classifier for survival and time to progression in non-small cell lung cancer (NSCLC) patients treated with erlotinib and bevacizumab

2009-12-28

Abstract: We applied an established and commercially available serum proteomic classifier for survival after treatment with erlotinib (VeriStrat®) in a blinded manner to pretreatment sera obtained from recurrent advanced NSCLC patients before treatment with the combination of erlotinib plus bevacizumab. We found that VeriStrat® could classify these patients into two groups with significantly better or worse outcomes and may enable rational selection of patients more likely to benefit from this costly and potentially toxic regimen.

Prognostic significance of matrix metalloproteinase-1 levels in peripheral plasma and tumour tissues of lung cancer patients

2010-01-08

Abstract: Matrix metalloproteinase-1 (MMP-1) participates in a variety of physiological and pathological processes. We previously found that MMP-1 was one of the lung cancer-related proteins detectable in peripheral blood. To validate our preliminary observations and explore the clinical significance of MMP-1 for lung cancer further, we carried out the present study. The concentrations of MMP-1 in circulating plasma specimens of 170 lung cancer patients and 70 healthy individuals were measured by an enzyme-linked immunosorbance assay. The expression status of the MMP-1 in archival tissue samples from 122 lung cancer patients was examined by immunohistochemical analysis. The correlation between the MMP-1 levels and prognosis of the lung cancer patients was then assessed statistically. Protein levels of MMP-1 were considerably raised in the plasma from lung cancer patients relative to those in healthy controls. The high plasma MMP-1 levels were associated with advanced-stage of the disease and significantly lower overall survival rate of the patients. Coincidently, MMP-1 protein extraordinarily overexpressed in the tumour tissues of lung cancer; and the up-regulated MMP-1 was associated with the progression (including tumour size, staging and lymphatic invasion), especially with decreased survival rate of the patients. Statistic analysis revealed that MMP-1 protein levels had an independent influence on survival. MMP-1 levels were elevated in both tumour tissue and blood; the latter may serve as an independent predictor for survival of lung cancer patients. MMP-1 protein levels in plasma/serum thus represent a potential and clinically relevant biomarker for the prognosis of patients with lung cancers.

Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients

2009-12-18

Abstract: The presence of IL-17-positive cells is observed in a variety of inflammatory associated cancers and IL-17 has been found to be involved in angiogenesis. The aim of this study is to determine the prognostic significance of IL-17 in NSCLC patients and to examine the correlation between IL-17 expression and lymphatic vessel density in NSCLC tissues. The expression of IL-17 was measured by immunohistochemistry in 52 paraffin-embedded tissues with non-small cell lung cancer. The χ2 test was used to analyze the correlation between IL-17 expression and clinical parameters and lymphatic vessel density (LVD). The Kaplan–Meier method, univariate and multivariate regression analysis was used to analyze the correlation between IL-17 expression and overall survival and disease-free survival. High expression of IL-17 was observed in 25 of 52 lung cancer patients and was associated with smoking status, TNM stage, LVD, overall survival and disease-free survival. Univariate and multivariate analysis showed that IL-17 was an independent prognostic factor for overall survival and disease-free survival. Our results indicate that IL-17 may play a role in the metastasis of lung cancer by promoting lymphangiogenesis. IL-17 expression is an independent prognostic factor in both overall and disease-free survival in NSCLC.

CD8+ T cells expressing IL-10 are associated with a favourable prognosis in lung cancer

2010-01-20

Abstract: The dual role of tumour-infiltrating macrophages and lymphocytes on nonsmall cell lung cancer (NSCLC) progression and prognosis may be due to the differential activity of their phenotypes. To investigate the impact of inflammatory cells on NSCLC, we first quantified the number of macrophages (CD68+) and lymphocytes (CD8+ and CD4+) and the percentage of CD8+ cells expressing IL-10 (CD8+/IL-10+) in tumour stroma and epithelium. Then, we evaluated the possible relationships between the numbers of these cells and the clinicopathological features and the overall survival of patients.Paraffin-embedded sections of surgical specimens from 64 patients who had undergone surgery for NSCLC were immunostained with antibodies directed against CD68, CD4, CD8 and IL-10.The percentage of CD8+/IL-10+ cells was higher in cancer stroma of patients with stage I NSCLC than in those with stages II, III, and IV. High percentages of stromal CD8+/IL-10+ cells were associated with longer overall patient survival. In contrast, the number of CD68+, CD8+ and CD4+ cells did not differ between stage I NSCLC and stages II, III, and IV.In conclusion, the survival advantage of patients with stage I NSCLC may be related to the anti-tumour activity of the CD8+/IL-10+ cell phenotype.

Recurrent EML4–ALK-associated lung adenocarcinoma with a slow clinical course

2010-06-18

Abstract: The fusion gene EML4–ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) was recently identified as a novel genetic alteration in non-small-cell lung cancer. The clinicopathological features of EML4–ALK-positive adenocarcinoma are reported to include its high incidence in young, non-smoking patients, tumors that show distinct solid or acinar growth patterns with or without signet-ring cell histology, and its mutually exclusive occurrence with mutations in EGFR and KRAS. However, the clinical findings have not been well described. Here, we report a case of EML4–ALK-positive lung adenocarcinoma that showed multiple metachronous lesions on the pleura and pulmonary field, suspected to be a recurrence of lung adenocarcinoma after a 20-year disease-free interval. The slow clinical course may be characteristic of EML4–ALK-positive lung adenocarcinoma. Therefore, long-term observation of patients with EML4–ALK-positive lung adenocarcinomas is required after surgery.

The value of day 8 blood count in treatment decisions when using oral vinorelbine in non-small cell lung cancer

J.S. Myerson, A. Faria, M. Puglisi, N. Starling, S. Popat, M.E.R. O’Brien — 2010-09-01

We read with interest the manuscript from Provencio et al. published in volume 68 issue 3 of this journal, regarding the use of blood parameters on day 8 of cisplatin plus vinorelbine in metastatic non-small-cell lung cancer patients. We have looked at the same question when giving the oral form of vinorelbine (the preferred formulation at our institution).

Corrigendum to “Emerging profile of cetuximab in non-small cell lung cancer” [Lung Cancer 68 (2010) 332–337]

David S. Ettinger — 2010-07-12

The author apologizes that the conflict of interest statement of this article, which was published in the June issue of Lung Cancer, was incorrect. It should read as follows: