Differential gene expression in peripheral blood lymphocytes of cancer patients treated with whole body hyperthermia and chemotherapy: A pilot study

Purpose: The effect of whole body hyperthermia (WBH) at 41.8–42°C on the cellular immune system is still poorly investigated. The aim of this study was to identify genes that become upregulated in peripheral blood lymphocytes (PBLs) of cancer patients during a combined treatment with WBH and chemotherapy by generating complex arrays of cDNA.

Methods: PBLs were obtained from four patients with different malignancies treated with WBH and varying cytostatic schedules before treatment and immediately thereafter. After constructing subtracted cDNA libraries, clones were screened for cDNA induction by dot-blot and semi-quantitative RT-PCR (sq-RT-PCR).

Results: Among 192 clones, 39 cDNAs were significantly upregulated. Sequencing revealed three groups of genes for which upregulation of mRNA was confirmed by sq-RT-PCR. The first group consisted of genes encoding for various heat shock proteins (HSP 60, 90a, 90b, 105). Further sq-RT-PCR demonstrated differential expression of HSP27 and HSP70 as well. The second group (calcyclin-binding-protein, haemoglobin-beta-chain) comprised genes without pre-specified association to hyperthermia. The cDNA encoding macrophage-inflammatory-protein-1-beta was also observed and may be associated with the pre-described activation of lymphocyte sub-populations during WBH.

Conclusion: Treatment with WBH and chemotherapy elicits significant short-term effects on the expression of a variety of genes responsible for cellular integrity, stimulation and migration of immune effector cells. Further investigation is warranted to more clearly define the role of those genes for the clinical effect of WBH.     

A pilot study of whole body hyperthermia and carboplatin in platinum-resistant ovarian cancer

The aim of this study was to determine whether the addition of whole body hyperthermia (WBH) to carboplatin (CBDCA) can induce responses in patients with platinum-resistant ovarian cancer. 16 pretreated patients with platinum-resistant ovarian cancer were entered on a Systemic Hyperthermia Oncological Working Group (SHOWG) study; (14 patients were eligible with 14 evaluable for toxicity and 12 for response). The patients were treated with WBH (Aquatherm) 41.8 degrees C x 60 min in combination with carboplatin (CBDCA) (area under the curve (AUC) of 8) every 4 weeks. Disease status was evaluated every two cycles. Patients were treated for a maximum of six cycles. One patient had a complete response (CR) and 4 had a partial response (PR). 4 patients had stable disease (SD). 3 patients had progressive disease (PD). 2 patients were unevaluable: 1 had a bowel obstruction shortly after her first treatment; the second patient achieved a CR, but only had one treatment secondary to an idiosyncratic reaction to sedative drugs. 2 patients entered on study were ineligible, as they did not meet criteria for platinum resistance; 1 entered a CR and 1 had SD. Dose-limiting toxicity, which required CBDCA dose reductions, was grade 4 thrombocytopenia. Other toxicities included neutropenia (grade 3/4), and nausea and/or vomiting. Consistent with preclinical modelling, these results suggests that 41.8 degrees C WBH can overcome platinum resistance in ovarian cancer. These observations suggest further investigation of the therapeutic potential of WBH in a group of patients who historically fail to respond to salvage therapies is warranted.     

T-cell receptor gene expression in tumour-infiltrating lymphocytes and peripheral blood lymphocytes of patients with nasopharyngeal carcinoma.

The T-cell receptor (TCR) repertoire expression of tumour-infiltrating lymphocytes (TILs) from 19 nasopharyngeal carcinoma (NPC) biopsies was compared with those of lymphocytes from 18 control nasopharyngeal biopsies. mRNA was extracted from these lymphocytes and the cDNA transcribed. A panel of 18 V alpha- and 21 V beta-specific primers was used to detect the TCR gene use from cDNA. The use of V alpha and V beta genes was restricted in TILs compared with lymphocytes from biopsies. The frequencies of V alpha 2, V alpha 3, V alpha 9, V alpha 10, V alpha 11, V alpha 13, V alpha 14, V alpha 15, V beta 11, V beta 15 and V beta 20 were decreased and the frequencies of V alpha 10 [Pc = 0.04; relative risk (RR) = 0.05], V alpha 11 (Pc = 0.02; RR = 0.07), V alpha 13 (Pc = 0.002; RR = 0), V alpha 14 (Pc = 0.04; RR = 0.05), V beta 14 (Pc = 0.001; RR = 0.03) and V beta 20 (Pc = 0.001; RR = 0.03) remained significantly reduced after correction for the number of families typed. The frequency of V alpha 17 was higher in NPC biopsies than in NPC PBLs (P = 0.05), and the frequency of V beta 15 was lower in NPC biopsies than in NPC PBLs (P = 0.02). The frequencies of V alpha 17 and V alpha 18 in HLA-B46+ patients were significantly lower (P = 0.009; P = 0.044) than in B46+ controls. The results suggest that the restriction of TCR gene use in NPC patients may be important in NPC pathogenesis.     

肺癌患者外周血中MDR-1及MRP基因在化疗前后的表达及意义

目的 探讨肺癌患者化疗前后外周血淋巴细胞中多药耐药基因(MDR-1)和多药耐药相关蛋白(MRP)的表达及意义。方法 分别于化疗开始前及化疗周期结束后第3周收集肺癌患者外周血标本。采用逆转录聚合酶链反应(RT-PCR)法检测39例肺癌患者外周血中MDR-1mRNA和MRP mRNA的表达情况,并与20例健康体检者进行对比。结果 病例组化疗前MDR-1mRNA和MRP mRNA的阳性表达率与健康对照组相比差异没有统计学意义(P＞0.05);各种病理类型的肺癌患者外周血MDR-1mRNA和MRP mRNA的阳性表达水平随着化疗次数的增多而增强,其中小细胞肺癌患者化疗后MDR-1 mRNA和MRP mRNA的表达水平均高于化疗前,差异具有统计学意义。结论 化疗可诱导肺癌患者外周血淋巴细胞MDR-1mRNA和MRP mRNA的表达水平增强;应用外周血评估MDR-1mRNA和MRP mRNA的方法简单可靠,创伤性小,可能成为预估肺癌患者化疗疗效的有效指标。     

化疗联合全身热疗治疗中晚期卵巢癌疗效观察

目的：观察并评价TP化疗方案联合全身热疗对中晚期卵巢癌的治疗作用。方法：采用TP双途径化疗联合全身热疗治疗26例中晚期卵巢癌患者,观察近期疗效及毒副反应。结果：26例患者卡氏评分提高20—40分。CR21例,PR3例,SD1例,PD1例;有效率为92．3％。1年无瘤生存率为88．5％。结论：TP双途径化疗联合全身热疗治疗中晚期卵巢癌疗效肯定,毒副反应小,值得推广应用。     

微波热疗合并化疗对晚期肺癌的初步应用

目的　对微波区域性加温合并化疗治疗晚期肺癌 ,初步观察疗效、全身温度情况和毒副作用。方法　以UHR 915MHz微波热疗机进行胸部区域加温联合化疗对 2 4例肺癌患者进行 47次治疗 ,加温治疗中对患者的食管、鼓膜和直肠测温。结果　UHR 915MHz微波热疗机对胸部区域性加温可使体温升高。大多数在加温后温度达 40℃以上。47次治疗中鼓膜温度达 40℃以上 3 9次。食管及直肠温度达 40℃以上 42次。联合化疗治疗晚期肺癌近期总有效率达79.17%。毒副作用主要为心率增快 ,皮肤烧伤和皮下硬结 ,以及化疗所致的毒副反应。对肝肾功能和神经系统无明显影响。结论　UHR 915MHz微波热疗机可以籍区域性加温进行全身热疗 ,联合化疗治疗晚期肺癌仍然有效。对心血管系统有较轻且可逆的影响 ,可能不增加化疗药物的毒副反应。     

DNA damage and repair in peripheral blood lymphocytes from healthy individuals and cancer patients: a pilot study on the implications in the clinical response to chemotherapy

Drug resistance is considered the main impediment to successful cancer chemotherapy. The quest for a method useful to predict individual responses to chemotherapy prior to treatment is highly desired. This study was designed to determine the individual influences of doxorubicin and cisplatin on the degree of DNA damage, DNA repair and hMSH2 and the hMLH1 protein expression in peripheral blood lymphocytes (PBL) and their correlations with the clinical response. PBL were obtained from 25 cancer patients (pre- and post-chemotherapy) and from 10 healthy persons, cultured and exposed to doxorubicin or cisplatin. Cells were collected at T0 (immediately after drug treatment) and 24h after damage (T24). The alkaline comet assay was employed to assess the DNA damage and repair function, and immunocytochemistry to study hMLH1 and hMSH2 expression. Clinical response was evaluated after three cycles of chemotherapy. Pre-chemotherapy PBL from cancer patients showed significantly higher levels of basal DNA damage than healthy persons, with appreciable interindividual variations between them. The in vivo administration of antineoplasic drugs was accompanied by significant DNA damage, and an increased in the number of apoptotic cells. Cancer patients with complete response showed a high number of apoptotic cells. The DNA migration increased at T0 and at T24 in cisplatin-treated patients, reflecting a decreased rate of cisplatin adducts repair than that observed in healthy individuals. The ability to repair DNA lesions in doxorubicin-damaged cells was very similar between healthy individuals and cancer patients. Cisplatin-treated patients that died by the disease showed lower DNA migration than the mean value. The expression of hMLH1 and hMSH2 was practically identical between healthy individuals and cancer patients. Nevertheless, chemotherapy induced a depletion mostly of hMLH1. In 83% of cisplatin-treated patients with CR the hMLH1 and hMSH2 expression at T24 was higher than the mean. In this pilot study the alkaline comet assay offered information about the amount of DNA damage and the DNA repair status in PBL from individual patients and this seems useful in predicting the response to chemotherapy.     

化疗联合全身微波治疗晚期非小细胞肺癌的临床观察

目的:评价化疗联合全身微波热疗治疗晚期非小细胞肺癌(non-small cell lung cancer, NSCIC)的近期疗效及毒副反应.方法:64例不能手术的Ⅲ、Ⅳ期NSCLC患者随机分成两组,治疗组31例,采用健择(GEM)联合顺铂(DDP)化疗(GP方案),同时联合全身微波热疗;对照组33例,仅采用GP方案化疗,化疗2个周期后评价疗效.结果:治疗组近期有效率为45.2%,对照组近期有效率为30.3%.两组比较差异有统计学意义,P<0.05;主要毒副反应为骨髓抑制以及恶心、呕吐反应,两组比较差异无统计学意义,P>0.05.结论:化疗联合全身微波热疗可提高晚期NSCLC疗效,且毒副反应可以耐受.     

Weekly dose-intensive chemotherapy in patients with small-cell lung cancer: a pilot study.

The study was aimed to evaluate the feasibility of dose-intensive chemotherapy given on a weekly basis for 12 weeks. Seventeen [7 with limited disease (LD) and 10 with extensive disease (ED)] previously untreated patients with small-cell lung cancer (SCLC) were treated with the cisplatin, vincristine, doxorubicin, and etoposide (CODE) regimen. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was given to eight patients for the purpose of increasing the dose intensity. Overall response rate was 88%, with a 29% complete response. The median survival times were greater than 20.5 months for LD patients and 8.1 months for ED patients. Overall actual dose intensity was 88% of planned protocol. The major toxicity was myelosuppression. Fifteen patients (88%) had grade 3 or 4 leukopenia. Other problems were weight loss and worsening of performance status during the treatment. RhG-CSF significantly reduced leukopenic nadirs and shortened the neutropenic period. Our preliminary results indicate that 12 cycles of the CODE regimen on a weekly schedule is effective for SCLC, but is also associated with significant toxicity.     

肺癌患者外周血淋巴细胞与癌细胞耐药基因表达的相关性研究

目的：探讨肺癌患者外周血淋巴细胞和癌细胞耐药基因表达的相关性。方法：采用RT—PCR法检测40例肺癌患者外周血淋巴细胞耐药基因MDR-1的表达,免疫组化法检测肺癌组织原代培养癌细胞耐药基因蛋白P—gp和MRP的表达。结果：肺癌患者外周血淋巴细胞耐药基因MDR-1的表达率37．5％（15／40）,与肺癌细胞耐药基因蛋白P—gp和MRP的表达具有相关性（P〈0．05）,与肺癌患者的年龄、分期、病理类型及性别无关（P〉0．05）。结论：外周血淋巴细胞耐药基因MDR-1的表达率较高,与癌细胞耐药基因蛋白P—gp和MRP的表达具有相关性,对肺癌临床化疗药物的选择具有重要的参考价值。     

大肠癌患者外周血与肿瘤组织中浸润淋巴细胞Fas及FasL表达的意义

目的 :探讨Fas/FasL在大肠癌患者外周血淋巴细胞及肿瘤浸润淋巴细胞的表达变化的意义。方法 :用流式细胞仪对 3 6例大肠癌患者外周血淋巴细胞与肿瘤浸润淋巴细胞(tumorinfiltratinglymphocyte ,TIL)的Fas及FasL进行定量分析。结果 :大肠癌患者外周血淋巴细胞上Fas/FasL表达明显高于正常对照 ,TIL上Fas/FasL表达高于外周血淋巴细胞上表达。结论 :Fas/FasL在大肠癌患者外周血淋巴细胞与TIL的不同分布说明 ,Fas/FasL不仅在肿瘤浸润区域而且在全身参与了免疫系统与肿瘤的相互斗争。     

Chromosomal aberrations in peripheral blood lymphocytes of prostate cancer patients treated with IMRT and carbon ions

Background and purpose

To investigate the cytogenetic damage in blood lymphocytes of patients treated for prostate cancer with different radiation qualities and target volumes.

Materials and methods

Twenty patients receiving carbon-ion boost irradiation followed by IMRT or IMRT alone for the treatment of prostate cancer entered the study. Cytogenetic damage induced in peripheral blood lymphocytes of these patients was investigated at different times during the radiotherapy course using Giemsa staining and mFISH. A blood sample from each patient was taken before initiation of radiation therapy and irradiated in vitro to test for individual radiosensitivity. In addition, in vitro dose-effect curves for the induction of chromosomal exchanges by X-rays and carbon ions of different energies were measured.

Results

The yield of chromosome aberrations increased during the therapy course, and the frequency was lower in patients irradiated with carbon ions as compared to patients treated with IMRT with similar target volumes. A higher frequency of aberrations was measured by increasing the target volume. In vitro, high-LET carbon ions were more effective than X-rays in inducing aberrations and yielded a higher fraction of complex exchanges. The yield of complex aberrations observed in vivo was very low.

Conclusion

The investigation showed no higher aberration yield induced by treatment with a carbon-ion boost. In contrast, the reduced integral dose to the normal tissue is reflected in a lower chromosomal aberration yield when a carbon-ion boost is used instead of IMRT alone. No cytogenetic “signature” of exposure to densely ionizing carbon ions could be detected in vivo.     

A study of ovarian cancer patients treated with dose-intensive chemotherapy supported with peripheral blood progenitor cells mobilised by filgrastim and cyclophosphamide.

We have shown that large numbers of haemopoietic progenitor cells are mobilised into the blood after filgrastim [granulocyte colony-stimulating factor (G-CSF)] alone and filgrastim following cyclophosphamide chemotherapy in previously untreated patients with ovarian cancer. These cells may be used to provide safe and effective haemopoietic rescue following dose-intensive chemotherapy. Using filgrastim alone (10 micrograms kg-1), the apheresis harvest contained a median CFU-GM count of 45 x 10(4) kg-1 and 2 x 10(6) kg-1 CD34+ cells. Treatment with filgrastim (5 micrograms kg-1) following cyclophosphamide (3 g m-2) resulted in a harvest containing 66 x 10(4) kg-1 CFU-GM and 2.4 x 10(6) kg-1 CD34+ cells. There was no statistically significant difference between these two mobilising regimens. We have also demonstrated that dose-intensive carboplatin and cyclophosphamide chemotherapy can be delivered safely to patients with ovarian cancer when supported by peripheral blood progenitor cells and filgrastim. Carboplatin (AUC 7.5) and cyclophosphamide (900 mg m-2) given at 3 weekly intervals with progenitor cell and growth factor support was well tolerated in terms of haematological and systemic side-effects. Double the dose intensity of chemotherapy was delivered compared with our standard dose regimen when the treatment was given at 3 weekly intervals. Median dose intensity could be further escalated to 2.33 compared with our standard regimen by decreasing the interval between treatment cycles to 2 weeks. However, at this dose intensity less than a third of patients received their planned treatment on time. All the delays were due to thrombocytopenia.     

Tumour cell kinetics as predictors of response in canine lymphoma treated with chemotherapy alone or combined with whole body hyperthermia.

Kinetic parameters including potential doubling time (Tpot), duration of S phase (Ts), labelling index (LI), and DNA index (DI) were obtained from 42 dogs with previously untreated lymphoma. Standard flow cytometric techniques using BrdUrd were employed. All dogs were treated with L-asparaginase and remission was induced in 26 dogs, which were then randomized to receive chemotherapy only (doxorubicin [DOX] alone or with lonidamine) or chemotherapy plus whole body hyperthermia (WBH). Dogs were treated every 3 weeks for up to five treatments and evaluated every 3 weeks for evidence of tumour recurrence. Within this subset of animals there was no difference in outcome based on treatment group. Median values for Tpot, Ts and LI were 3.4 days, 7.23 h and 12.49%, respectively. Dogs that had tumours with LI > or = 20% had a shorter time until recurrence than dogs with tumours characterized by LI < 20%. In dogs treated only with chemotherapy, dogs bearing tumours with longer than median Tpot and Ts values and lower than median LI had significantly longer remission duration than dogs with more rapidly proliferating tumours. Dogs treated only with chemotherapy, which had longer than median Tpot and Ts values and lower than median LI, had significantly longer remission duration than all other dogs in the study. The mechanisms in which kinetics are associated with response to chemotherapy are not clear and vary depending on tumour type and treatment regimen. More work is needed to understand factors involved in cell killing during in vivo hyperthermia.     

Gene expression profiles of diabetic mice treated with whole body hyperthermia: A high-density DNA microarray analysis

Previously we have demonstrated that whole body hyperthermia (WBH) improves insulin resistance in diabetic mice. The aim of the present study was to perform a gene expression analysis of the liver and adipose tissue of obesity-induced insulin resistant diabetic mice (db/db mice) after WBH and to define the molecules that play the important role in improvement of insulin resistance by WBH. Male db/db mice were treated with WBH 3 times per week for 12 weeks. Total RNA was extracted from the liver and adipose tissue of db/db mice, and differences in the gene expression profiles among db/+ mice, untreated db/db mice, and WBH-treated db/db mice were investigated using a high-density DNA microarray. WBH directly targets liver and adipose tissue, resulting in modifications in NF-κB and IL-6 signalling pathways, as well as lipid metabolism. Although the mechanisms have not yet been completely investigated, we can conclude that WBH may provide a new therapeutic or preventive modality against type 2 diabetes mellitus and metabolic or insulin resistance syndrome through the modification of several signalling pathways.     

Topotecan chemotherapy in patients with breast cancer and brain metastases: results of a pilot study.

BACKGROUND: Symptomatic brain metastases occur in approximately 10-15% of patients suffering from breast cancer and are linked to a clear deterioration of the patient's condition. Although radiotherapy is recommended as a primary therapy, the optimal management remains controversial. To evaluate the role of topotecan as a primary chemotherapy for brain metastases, we performed a pilot study in patients with metastatic breast cancer. PATIENTS AND METHODS: 24 patients with newly diagnosed, bidimensionally measurable brain metastases received topotecan, 1.5 mg/m(2) day, 30-min infusion for 5 days every 3 weeks. A total of 93 courses of therapy were administered (range 1-11, median 3 courses per patient). Prior radiotherapy was excluded. Most of the patients had received prior adjuvant or palliative chemotherapy. RESULTS: 3/24 patients were withdrawn from the study for various reasons, 16/24 patients could be evaluated in terms of their response to therapy; 1 and 5 patients showed complete and partial response to therapy, respectively, and 5 patients had a stable condition. The median time of survival was 6.25 months. Hematologic toxicity was the major side effect, nonhematologic side effects occurred rarely and were tolerable. CONCLUSIONS: Our results demonstrate that primary chemotherapy with topotecan is an effective and well-tolerated treatment for patients with breast cancer and CNS metastases. Based on this pilot study, future clinical protocols should be developed including multimodal treatment strategies (i.e. radiotherapy).     

N-acetyl-beta-glucosaminidase of peripheral blood lymphocytes in patients with cancer of the larynx.

In 20 men, age 35 to 55 years, with cancer of the larynx of N-acetyl-beta-glucosaminidase in peripheral blood lymphocytes was determined cytochemically according to Hayashi's method. Numbers of enzyme-positive cells were counted with regard to the type of cytochemical reaction (granular, granular-diffuse, or diffuse), and to the number of enzyme-positive lysosomal granules within a single cell. In comparison to 20 healthy men, age 20 to 30 years, the following changes were noted in the patients: 1) the decrease of the total count of enzyme-negative lymphocytes; 2) the decrease of the total count of lymphocytes with granular type of reaction; 3) the increase of the counts of lymphocytes with granular-diffuse and diffuse type of reaction. The authors suggest that these changes could be related to the immune reaction of specific tumor antigens.     

Regional abdominal hyperthermia combined with systemic chemotherapy for the treatment of patients with ovarian cancer relapse: Results of a pilot study

Purpose: Due to the poor prognosis of patients with ovarian cancer relapse (OCR), newer strategies are warranted to improve the therapeutic index. We performed a prospective phase I/II-study of regional abdominal hyperthermia (RHT) combined with systemic chemotherapy in OCR patients in order to evaluate outcome, efficacy and tolerance.

Materials and methods: OCR patients with an Eastern Cooperative Oncology Group status <2, without any thromboembolic disease or severe cardiovascular co-morbidities, and pre-treated with at least one systemic chemotherapy regimen due to epithelial ovarian cancer were enrolled into the present study. RHT was applied using a SIGMA 60 applicator and a Hybrid-System SIGMA-Eye/MRT composed of a 1.5T-MRT and a Sigma-Eye-applicator.

Results: Overall, 36 OCR patients were enrolled. The majority of the patients (>80%) were classified as platinum resistant. The most common chemotherapeutic agent applied was pegylated-liposomal-doxorubicin (47.2%) followed by carboplatin (16.6%) and topotecan (13.9%). One patient (2.8%) achieved a complete remission (CR), 12 patients (33.3%) yielded a partial remission (PR) and 16 patients (44.4%) developed a progressive disease (PD). In platinum-sensitive patients we observed higher response (57.1% versus 31%) and lower progression rates (28.6% versus 48.3%) than in platinum-resistant patients. Eleven patients (30.5%) discontinued treatment due to toxicity. The main toxicity was a haematological one with grade 3/4 anaemia, leucopenia and thrombocytopenia occurring in 13.9%, 5.6% and 8.3%, respectively. Median overall survival was 12 months (range: 1–48), while median progression-free survival was 5 months (range: 0.5–34).

Conclusions: Our results demonstrate the feasibility of RHT combined with systemic treatment. Prospective phase III trials are warranted to evaluate the benefit and efficacy in heavily pre-treated patients with OCR.     

High mutagen sensitivity in peripheral blood lymphocytes predicts poor overall and disease-specific survival in patients with stage III non-small cell lung cancer treated with radiotherapy and chemotherapy.

PURPOSE: To investigate whether the bleomycin sensitivity assay, an in vitro peripheral blood lymphocyte assay, can predict outcome in patients with inoperable stage III non-small-cell lung cancer (NSCLC) treated with definitive radiotherapy and chemotherapy. EXPERIMENTAL DESIGN: We identified 102 patients with inoperable stage III NSCLC cell lung cancer treated with definitive radiotherapy and chemotherapy. The patients' pretreatment peripheral blood lymphocyte cultures were treated with the radiomimetic mutagen bleomycin. An index of bleomycin sensitivity was determined by counting the number of chromatid breaks in 50 metaphases. The correlation between bleomycin sensitivity (expressed as mean breaks per cell) and clinical outcome was analyzed. RESULTS: High bleomycin sensitivity (defined as a mean of >1.02 chromatid breaks/cell, representing the third quartile of bleomycin sensitivity) predicted poor disease-specific survival and overall survival. The 6-year disease-specific survival was 27% in patients with high bleomycin sensitivity compared with 46% in patients without such sensitivity (P = 0.0094). The association remained statistically significant when adjusted for smoking status, age, and radiation dose. The 6-year overall survival was 19% for patients with high bleomycin sensitivity and 29% for those without (P = 0.0193). There was a trend toward worse local regional control and worse disease-free survival among patients with high bleomycin sensitivity. There was no difference between the two groups in distant metastasis-free survival or radiation treatment-related complications. CONCLUSIONS: High bleomycin sensitivity correlated with poor overall survival and disease-specific survival in these patients with stage III NSCLC treated with radiotherapy and chemotherapy. Bleomycin sensitivity may function as a biomarker for poor clinical outcome for this group of patients.