Stereotactic body radiotherapy (SBRT) for the treatment of inoperable stage I non-small cell lung cancer patients

Introduction

Lung cancer is the most frequent neoplasm in humans. Surgery is considered the best therapeutic approach for stage I non-small lung cell cancer (NSCLC). However, a remarkable amount of patients are considered as inoperable. Stereotactic body radiotherapy (SBRT) has risen as an option for those patients, rendering excellent results in quality of life and survival.

Materials and methods

We analyzed clinical studies published between 2002 and 2015 which included SBRT as a treatment modality. Our own clinical series was analyzed as well. The patterns of failure following SBRT were investigated, together with the outcomes and the toxicity observed.

Results

SBRT has proven to maintain an excellent local control. The analysis showed the tumor size and the histology as determinant factors for the response to treatment.

Conclusion

According to the published evidence as well as our own experience, SBRT is a safe and feasible approach for early NSCLC. Its results may be comparable with surgery treatment.

     

A SUV<Subscript>max</Subscript>-based propensity matched analysis of stereotactic body radiotherapy versus surgery in stage I non-small cell lung cancer: unveiling the role of 18F-FDG PET/CT in clinical decision-making

Background

The value of maximum standard uptake value (SUV_max) was overlooked in current studies comparing stereotactic body radiotherapy (SBRT) versus surgery for stage I non-small cell lung cancer (NSCLC). Herein, we aimed to compare the 3-year outcomes based on patients for whom SUV_max were available, and to explore the role of SUV_max in clinical decision-making.

Methods

From January 2010 to June 2016, data of eligible patients were collected. Patient variables and clinical outcomes were compared in both unmatched and matched groups using propensity score matching (PSM). Multivariate analysis was performed for predictors of poor outcome. The relationship between treatment approach and survival outcome was also evaluated in subgroup patients stratified by SUV_max level.

Results

A total of 425 patients treated with either surgery (325) or SBRT (100) were included. Patients receiving SBRT were significantly older, had a higher level of SUV_max and were more likely to have tumor of centrally located. Multivariate analysis showed that SUV_max and tumor size were significant predictors for 3-year OS, LRC, and PFS, while better PFS was also related to peripheral tumor and surgery. The result of PSM analysis also showed that compared to SBRT, surgery could only achieve better PFS. Subgroup analysis indicated that surgery had added advantage of 3-year LRC and PFS for patients in high SUV_max group (SUV_max > 8), but not in low SUV_max group.

Conclusions

The study found a superior PFS after surgery while OS and LRC did not differ between SBRT and surgery. Surgery should be recommended for tumor of high SUV_max.

     

A novel peptide (Thx) homing to non-small cell lung cancer identified by ex vivo phage display

Aim

To identify linear peptide homing to non-small cell lung cancer (NSCLC) tumor cells using ex vivo phage display method.

Materials and methods

Twenty-six clinical patient samples were used to identify linear homing peptide, which was exposed to NSCLC cell cultures and control cell lines to determine cell binding affinity and cell localization. Also, ex vivo biodistribution was analyzed using tumor-bearing mice.

Results

The panning yielded peptide enrichment with a core motif ^A/_SRXPXXX. Based on this, an amino acid sequence, ARRPKLD, was selected for characterization and named Thx-peptide. The in vitro binding properties of Thx-peptide demonstrated selectivity toward NSCLC. Internalization assays showed that Thx-Alexa and fluorescein conjugates were located in a subset of perinuclearly located lysosomes of tumor cells. Thx-peptide appeared with fluorescein-labeled peptide and peptide-DTPA-chelator complex in adenocarcinoma xenografts in mice.

Conclusion

Thx shows promise for targeted imaging and drug delivery.     

Effect and mechanism of 125I radioactive particles interposed radiotherapy between organizations on lung cancer

Objective

The aim of this study was to evaluate effect and mechanism of ¹²⁵I radioactive particles interposed radiotherapy between organizations on lung cancer.

Methods

Fourteen cases of patients diagnosed with non-small cell lung cancer (NSCLC), the use of the B-, CT-guided, according to preoperative imaging and treatment planning system (TPS) program for radioactive particles interposed ¹²⁵I interstitial radiotherapy.

Results

All patients were successfully ¹²⁵I interstitial radioactive particles interposed radiotherapy. Postoperative local complete tumor remission in 9 cases, partial remission in 5 cases, the efficiency of 100%. No case of serious complications. After 3 to 4 weeks of chemotherapy after 11 cases. 4 cases of lung cancer with bone metastases, pain completely disappeared after treatment. Up to now, five cases have died due to tumor progression, survival time of 12 to 16 months. Nine cases still under follow-up observation and treatment.

Conclusion

¹²⁵I radioactive particles interposed radiotherapy between organizations of lung cancer, simple operation, trauma, fewer complications, conformal high, high local tumor dose, efficacy, and is a supplement of modern radiotherapy techniques for the treatment of lung cancer provides a comprehensive line of the method of effective.     

Expanded risk groups help determine which prostate radiotherapy sub-group may benefit from adjuvant androgen deprivation therapy

Purpose

To investigate the influence of inhomogeneity corrections on stereotactic treatment plans for non-small cell lung cancer and determine the dose delivered to the PTV and OARs.

Materials and methods

For 26 patients with stage-I NSCLC treatment plans were optimized with unit density (UD), an equivalent pathlength algorithm (EPL), and a collapsed-cone (CC) algorithm, prescribing 60 Gy to the PTV. After optimization the first two plans were recalculated with the more accurate CC algorithm. Dose parameters were compared for the three different optimized plans. Dose to the target and OARs was evaluated for the recalculated plans and compared with the planned values.

Results

For the CC algorithm dose constraints for the ratio of the 50% isodose volume and the PTV, and the V_{20 Gy} are harder to fulfill. After recalculation of the UD and EPL plans large variations in the dose to the PTV were observed. For the unit density plans, the dose to the PTV varied from 42.1 to 63.4 Gy for individual patients. The EPL plans all overestimated the PTV dose (average 48.0 Gy). For the lungs, the recalculated V_{20 Gy} was highly correlated to the planned value, and was 12% higher for the UD plans (R² = 0.99), and 15% lower for the EPL plans (R² = 0.96).

Conclusion

Inhomogeneity corrections have a large influence on the dose delivered to the PTV and OARs for SBRT of lung tumors. A simple rescaling of the dose to the PTV is not possible, implicating that accurate dose calculations are necessary for these treatment plans in order to prevent large discrepancies between planned and actually delivered doses to individual patients.     

Analysis of factors influencing skip lymphatic metastasis in pN2 non-small cell lung cancer

Objective:Although many clinical studies on skip lymphatic metastasis in non-small cell lung cancer have been reported,the risk factors for skip lymphatic metastasis are still controversy and debatable.This study investigated,by multivariate logistic regression analysis,the clinical features of skip metastasis to mediastinal lymph nodes(N2) in non-small cell lung cancer(NSCLC) patients.Methods:We collected the clinicopathological data of 256 pN2-NSCLC patients who underwent lobectomy plus systemic lymph node dissection in Fujian Medical University Union Hospital.The cases in the present study were divided into two groups:skip metastasis(N2 skip+) and non-skip metastasis(N2 skip-).A retrospective analysis of clinical pathological features of two groups was performed.To determine an independent factor,multivariate logistic regression analysis was used to identify possible risk factors.Results:A total of 256 pN2-NSCLC patients were recruited.The analysis results showed that gender,pathologic types,surgery,pleural involvement,smoking history,age,tumor stages,and differentiation were not statistical significant factors impacting on skip metastasis in pN2-NSCLC(P>0.05),whereas tumor size was an independent factor for skip metastasis(P=0.02).Conclusions:The rate of skip lymphatic metastasis increases in pN2-NSCLC patients,in accompany with an increased tumor size.     

Pathologie als Gatekeeper

Background

Lung cancer is the cancer type with the highest number of cancer deaths and non-small cell lung cancer (NSCLC) is the most frequent subtype. In the last years the knowledge on this tumor type has developed rapidly and fortunately this has led to an improvement in diagnostic stratification and new therapeutic opportunities.

Objectives

This review represents a selective overview on recent results of the tumor pathology of NSCLC and highlights the importance of the interaction between pathology and clinical disciplines. The main focus is laid on novel aspects of morphological and molecular tumor classification.

Material and methods

This overview is based on recent publications and the involvement of the authors in committees and panels that are related to the classification and therapy of lung cancer patients.

Results and conclusion

The report provides on the one hand a short outlook on the new WHO classification of lung tumors that is currently in preparation. On the other hand it reviews molecular changes of lung cancer with a special emphasis on those alterations that may have potential therapeutic relevance.     

A retrospective, deformable registration analysis of the impact of PET-CT planning on patterns of failure in stereotactic body radiation therapy for recurrent head and neck cancer

Background

Stereotactic body radiation therapy (SBRT) has seen increasing use as a salvage strategy for selected patients with recurrent, previously-irradiated squamous cell carcinoma of the head and neck (rSCCHN). PET-CT may be advantageous for tumor delineation and evaluation of treatment failures in SBRT. We analyzed the patterns of failure following SBRT for rSCCHN and assessed the impact of PET-CT treatment planning on these patterns of failure.

Methods

We retrospectively reviewed 96 patients with rSCCHN treated with SBRT. Seven patients (7%) were treated after surgical resection of rSCCHN and 89 patients (93%) were treated definitively. PET-CT treatment planning was used for 45 patients whereas non-PET-CT planning was used for 51 patients. Categories of failure were assigned by comparing recurrences on post-treatment scans to the planning target volume (PTV) from planning scans using the deformable registration function of VelocityAI?. Failures were defined: In-field (>75% inside PTV), Overlap (20-75% inside PTV), Marginal (<20% inside PTV but closest edge within 1cm of PTV), or Regional/Distant (more than 1cm from PTV).

Results

Median follow-up was 7.4?months (range, 2.6–52?months). Of 96 patients, 47 (49%) developed post-SBRT failure. Failure distribution was: In-field–12.3%, Overlap–24.6%, Marginal–36.8%, Regional/Distant–26.3%. There was a significant improvement in overall failure-free survival (log rank p?=?0.037) and combined Overlap/Marginal failure-free survival (log rank p?=?0.037) for those receiving PET-CT planning vs. non-PET-CT planning in the overall cohort (n?=?96). Analysis of the definitive SBRT subgroup (n?=?89) increased the significance of these findings (overall failure: p?=?0.008, Overlap/Marginal failure: p?=?0.009). There were no significant differences in age, gender, time from prior radiation, dose, use of cetuximab with SBRT, tumor differentiation, and tumor volume between the PET-CT and non-PET-CT groups.

Conclusions

Most failures after SBRT treatment for rSCCHN were near misses, i.e. Overlap/Marginal failures (61.4%), suggesting an opportunity to improve outcomes with more sensitive imaging. PET-CT treatment planning showed the lowest rate of overall and near miss failures and is beneficial for SBRT treatment planning.     

Stereotactic body radiation therapy and intensity modulated radiation therapy induce different plasmatic cytokine changes in non-small cell lung cancer patients: a pilot study

Purpose

To assess kinetics of plasmatic cytokines during radiation therapy (RT) for locally advanced and early-stage non-small cell lung cancer (NSCLC).

Methods

This prospective study was conducted on 15 early-stage NSCLC underwent to extreme hypofractionated regimen (52 Gy in 8 fractions) with stereotactic body RT (SBRT), and 13 locally advanced NSCLC underwent to radical moderated hypofractionated regimen (60 Gy in 25 fractions) with intensity modulated RT (IMRT). For patients undergoing SBRT, peripheral blood samples were collected on the first day of SBRT (TFd), the last day (TLd) and 45 days (T45d) after the end of SBRT. For patients undergoing IMRT, blood samples were collected at: TFd, 2 weeks (T2w), 4 weeks (T4w), TLd, and T45d. The following cytokines were measured: IL-1, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17A, EGF, FGF-2, INF-γ, MIP-1α, MIP-1β, TGF-α, TNF-α, and VEGF. Cytokine levels measured in different RT time and compared.

Results

No difference in baseline levels of cytokines was documented between patient radiation approaches (except for MIP-1α). For SBRT patients, a mean reduction of IL-10 and IL-17 plasma level was documented between TLd and TFd, respectively (p < 0.05). For IMRT patients, a statistically significant (p < 0.05) mean plasma level reduction was documented between T4w and TFd for all the following cytokines: IL-1, IL-1ra, IL-2, IL-12, FGF-2, MIP-1α, MIP-1β, TGF-α, TNF-α, VEGF.

Conclusions

SBRT and IMRT induce different plasmatic cytokine changes in NSCLC patients, supporting hypothesis that RT regimes of dose schedules and techniques have different impacts on the host immune response.

     

肿瘤药敏指导下的化疗对非小细胞肺癌并恶性胸水治疗的有效性(英文)

Objective:The aim of the study was to investigate the clinical value and application of ATP based bioluminescence tumor chemosensitivity assay (ATP-TCA) in the chemotherapy for hydrothorax caused by non-small cell lung cancer (NSCLC). Methods:Hydrothorax specimens from 120 NSCLC patients were analyzed by ATP-TCA and the most sensitive chemotherapeutic drugs were used in NSCLC patients (treatment group). At the same time, 56 NSCLC patients with hydrothorax were admitted in our Hospital (Department of Oncology, The No. 2 People’s Hospital of Yibin, China) and given chemotherapy without guidance of the ATP-TCA (control group). Before the third chemotherapeutic cycle, clinical outcomes were analyzed in the two groups. Results:Effective rate of hydrothorax in treatment group was 67%, while 46% in control group (P < 0.05). In refractory hydrothorax patients, they were 69% and 40% (P < 0.05), respectively. In vitro results correlated well with clinical outcomes (P < 0.01). Conclusion:Effective rate of chemotherapy for hydrothorax in NSCLC is higher in treatment group than that in control group. ATP-TCA is especially helpful for refractory hydrothorax.     

CUG-binding protein 1 (CUGBP1) expression and prognosis of non-small cell lung cancer

Background and aims

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. As CUGBP1 may also play a great role in tumor genesis and deterioration, the purpose of this study was to detect the expression of CUGBP1 mRNA and CUGBP1 and assess the prognostic significance of CUGBP1 in NSCLC.

Methods

Expression of CUGBP1 mRNA and CUGBP was detected by Semi-quantitative PCR and Immunohistochemistry, respectively, from 57 NSCLC patients. The percentage of CUGBP1 mRNA and CUGBP1 expression was correlated with clinical characteristics using χ ² test. The prognostic significance was assessed by univariate and multivariate analyses in the Cox hazard model.

Results

The expression of CUGBP1 mRNA and CUGBP1 was over-expressed in cancer group and was correlated with TNM stage and Differentiation. By both univariate and multivariate survival analyses, CUGBP1 expression (P = 0.0074, HR = 3.701, 95 % CI 1.420–9.648), TNM-stage (HR = 4.043, 95 % CI 2.098–7.794) and age (HR = 3.207, 95 % CI 1.544–6.664) were noted to be independent indicators of a shorter postsurgical survival.

Conclusions

The expression of CUGBP1 independently predicted a shorter postsurgical survival in NSCLC.     

A Novel Neoadjuvant Therapy for Operable Locally Invasive Non–Small-Cell Lung Cancer. Phase I Study of Neoadjuvant Stereotactic Body Radiotherapy. LINNEARRE I (NCT02433574)

Background

Despite improved staging and surgical techniques, the rate of incomplete resection (R1) of non–small-cell lung cancer (NSCLC) has not significantly decreased. Patients with R1 resection have worse survival compared with those with complete resection (R0). Stereotactic body radiotherapy (SBRT) is a rapid and convenient radiotherapy treatment that delivers high-dose radiotherapy to tumors with high precision while sparing normal organs. Although its efficacy in treating small lung tumors is documented, its use as neoadjuvant therapy for locally advanced (LA) NSCLC has not been examined. We hypothesized that a short course of preoperative SBRT is feasible and can be delivered safely as a neoadjuvant therapy in patients at risk for incomplete resection.

Stereotactic Body Radiotherapy for Large (> 5 cm) Non–Small-Cell Lung Cancer

Background

Stereotactic body radiotherapy (SBRT) is a well-established treatment option for early stage non–small-cell lung cancer (NSCLC) tumors < 5 cm. There is limited information on tumors > 5 cm.

Mechanisms of enhanced tumoricidal efficacy of multiple small dosages of ranpirnase, the novel cytotoxic ribonuclease, on lung cancer

Purpose

The effect of multiple small dosages of the cytotoxic RNase, ranpirnase (ONCONASE^®, ONC), on lung cancer was studied. The possible mechanisms for the enhanced tumoricidal efficacy of multiple small dosages of ONC were also investigated.

Methods

Hematoxylin and eosin staining, TUNEL labeling, and caspase-3-antibody labeling were used for in vivo analysis of apoptosis. A growth-delay assay was applied to detect the therapeutic potential of small and multiple dosages of ONC in vivo. ONC-induced changes in blood flow in A549 tumors and the kidney were measured non-invasively by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).

Results

In cell culture studies, ONC significantly inhibited tumor growth of A549 human NSCLC cells without damaging non-cancerous cells (HLF-1 human lung fibroblast). Multiple small dosages of ONC significantly prolonged tumor growth delay of A549 tumors, with increased apoptosis in vivo from 0.5 ± 0.3 to 70.1 ± 1.1% (by TUNEL labeling, N = 3, P < 0.05). Interestingly, multiple small doses of ONC were more effective than a single large dose for the inhibition of tumor growth with reduced side effect. Using non-invasive DCE-MRI methods, we found that the mean of the K ^trans median values increased to 49.3 ± 7.5% from the pre-ONC values by ONC (N = 4 mice, P < 0.05). A subsequent T ₁ map of the kidney showed that T ₁ values were temporarily decreased for up to 2 days (however, fully recovered ～4 days post-treatment).

Conclusions

Multiple small dosages of ONC significantly inhibited tumor growth of A549 NSCLC cells in vivo, with markedly increased apoptosis. This investigation suggests important potential clinical uses of ONC for the treatment of NSCLC cancer patients.     

Expressions of osteopontin (OPN), ανβ3 and Pim-1 associated with poor prognosis in non-small cell lung cancer (NSCLC)

Objective: To examine the expressions of osteopontin (OPN), αVβ3 and Pim‐1 in non‐small cell lung cancer (NSCLC), and investigate their potential pathogenic roles in the development of NSCLC. Methods: Immunohistochemistry was used to examine the expressions of OPN, αVβ3 and Pim‐1 in cohort (136 cases) of NSCLC samples and their adjacent normal lung tissue specimens. Statistical analysis was performed to evaluate the relationships among expressions of OPN, αVβ3 and Pim‐1 and their associations with patients clinico‐pathological parameters. Results: The expressions of OPN and Pim‐1 were predominantly observed in cytoplasm. The expression of αVβ 3 was mostly detected in cytoplasm and/or membrane. In NSCLC samples, the positive rates of OPN, αVβ3 and Pim‐1 expressions were 68.4% (93/136), 77.2% (105/136) and 57.4% (78/136), respectively. In normal lung tissues, in contrast, the positive rates of OPN, αVβ3 and Pim‐1 were 24.0% (12/50), 26.0% (13/50) and 16.0% (8/50), respectively. There were significant differences of the positive expression rates of OPN, αVβ3 and Pim‐1 between NSCLCs samples and normal lung tissues (P<0.01). In addition, the positive expression of OPN, α Vβ3 and Pim‐1 in NSCLCs samples was significantly associated with increased pathological grade, lymph node metastasis and advanced clinical stage (P<0.01), and they were independent of other clinicopathological parameters (P>0.05). Furthermore, a significantly positive correlation between the expression of OPN and αVβ3 (r=0.38, P<0.01), OPN and Pim‐1 (r=0.37, P<0.01), or αVβ3 and Pim‐1 (r=0.20, P<0.05) was evaluated in our NSCLC cohort. Conclusion: OPN, αVβ3 and Pim‐1 proteins are frequently overexpressed in NSCLC, and they may play important roles in the development and/or progression of NSCLC.     

Pharmacokinetics of single-agent axitinib across multiple solid tumor types

Purpose

Axitinib, a potent and selective inhibitor of vascular endothelial growth factor receptors, showed antitumor activity as a single agent against several solid tumor types in Phase II and III trials. This study was conducted to evaluate axitinib pharmacokinetics across a variety of solid tumors.

Methods

The current study analyzed the pharmacokinetics of axitinib in 110 patients with non-small cell lung cancer (NSCLC), thyroid cancer, or melanoma from three Phase II trials plus 127 healthy volunteers, using nonlinear mixed-effects modeling. Boxplots of maximum observed plasma concentration (C _max) and area under the plasma concentration–time curve (AUC) of data from these tumor populations was compared to C _max and AUC from the final population pharmacokinetic model developed for metastatic renal cell carcinoma (mRCC) to compare axitinib pharmacokinetics across different tumor types.

Results

Axitinib disposition based on data from 237 subjects was best described using a two-compartment model with first-order absorption and lag time. Population estimates for systemic clearance, central volume of distribution, absorption rate constant, absolute bioavailability, and lag time were 20.1 L/h, 56.2 L, 1.26/h^?1, 0.663, and 0.448 h, respectively. Statistically significant covariates included gender on clearance, and body weight on central volume of distribution. However, predicted changes due to gender and body weight were found not clinically meaningful. The final analysis indicated that the pharmacokinetic model for mRCC was able to successfully describe axitinib pharmacokinetics in patients with NSCLC, thyroid cancer, and melanoma.

Conclusion

The pharmacokinetics of axitinib appears to be similar across a variety of tumor types.     

T1-Tumoren

Context

Local tumor control in stage I non-small cell lung cancer (NSCLC) will cure many patients. Risk-adapted screening procedures will probably increase the frequency of earlier tumor stages.

Methode

Research and analysis of the current literature and clinical trials.

Results

Advanced age and comorbidities, however, complicate treatment in this patient population. Both surgery and stereotactic ablative radiotherapy (SART) provide similar rates of local efficacy in early stage lung cancer. The curative potential of an oncological radical tumor resection has been documented for many years. In clearly operable patients the advantage of complete histological staging, definitive removal and risk estimate for adjuvant treatment have been confirmed. The SART is less invasive and also offers definitive treatment for frail patients.

Conclusion

Presently, interdisciplinary counselling with consideration of age, comorbidities and patient preference seems mandatory for optimal patient care.     

Stereotactic body radiation therapy for stage I non-small cell lung cancer: The importance of treatment planning algorithm and evaluation of a tumor control probability model

Background

Stereotactic body radiation therapy (SBRT) is increasingly used to treat early-stage non-small cell lung cancer (NSCLC). A previous report introduced the term size-adjusted biologically effective dose (sBED), which accounts for tumor diameter and biologically effective dose (BED) and may be used to predict the likelihood of local control following SBRT. Here we seek to replicate those findings using a separate dataset.

Does the extent of lymph nodes dissection affect the prognosis of resected stage IA non-small cell lung cancer?

Purpose

Curative surgery remains the priority for treatment of stage IA non-small cell lung cancer (NSCLC). The purpose of this study is to investigate if the extent of lymph node (LN) dissections affect the prognosis of resected stage IA NSCLC.

Methods

A total of 110 stage IA NSCLC patients who underwent curative resections were reviewed. The patients were classified according to the number of lymph nodes dissected (N) and levels sampled (NL, N₂). The tumor residuals of 2,251 LNs were detected by immunohistochemistry (IHC). The Flow Cytometry (FACS) of the peripheral blood (PB) and LNs was used to evaluate patients’ immunity. The relationship between the studied factors and the correlation with disease-free survival (DFS) was analyzed.

Results

Disease free survival was improved as the extent of dissections increased in terms of N, NL and N₂ (p = 0.005, <0.001, <0.001). Multivariate tests suggested N, N₂ and NL (p = 0.001, 0.001, <0.001) were independent risk factors. However, the detection of tumor residuals also increased with the extent of dissection (p = 0.023, <0.001) while the presence of micrometastasis (MM) correlated with poor DFS (p = 0.028). Increased N represented weakened innate immunity (p = 0.048). Multivariate tests did not indicate a correlation between immunity and patients’ DFS (p = 0.074).

Conclusion

The more extensive lymph node dissections achieved better disease control for stage IA NSCLC. Greater retrieval of LNs did not imply enhanced innate immunity; nor did their immunity level affect survival.     

Clinical significance of human leukocyte antigen loss and melanoma-associated antigen 4 expression in smokers of non-small cell lung cancer patients

Background

Melanoma-associated antigen-A4 (MAGE-A4) is one of the candidates for a target of immunotherapy and is expressed in non-small cell lung cancer (NSCLC). However, tumors sometimes lose human leukocyte antigen (HLA) class I expression, and tumor-specific T cells cannot eliminate the tumor with loss of HLA. However, the relationship between MAGE-A4 expression and HLA loss has remained unclear.

Methods

Among 363 NSCLC patients who consecutively underwent curative surgery, 187 cases whose material could be analyzed were reviewed. The expression of HLA class I molecules was assessed by immunohistochemical staining. The expression of MAGE-A4 was analyzed by RT-PCR.

Results

Seventy-seven tumors expressed HLA normally; however, 110 tumors lost HLA. The proportion of patients with a smoking habit and expressing the MAGE-A4 gene in patients with HLA loss was higher than those with HLA expression (p = 0.04 and 0.028, respectively). Five-year overall survival (OS) rate in the patients expressing MAGE-A4 but with loss of HLA was 52.4 %, and OS was significantly poorer than their counterparts (74.0 %, p = 0.036). Multivariate analysis indicated that advanced stage or history of smoking and HLA loss was an independently poor prognostic predictor of OS in NSCLC (p < 0.01 and p = 0.04, respectively).

Conclusion

HLA class I loss in NSCLC was related to smoking history and MAGE-A4 expression of tumors. HLA class I loss in smokers or patients with the MAGE-A4 gene was a prognostic factors in NSCLC.