Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: a nationwide population-based study in Sweden.

BACKGROUND: A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden. METHODS: We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010. RESULTS: The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I=1.6; 95% confidence interval (CI)=1.5-1.7. OR stage III-IV versus I=2.3; 95% CI=1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high=2.02; 95% CI=1.80-2.26; p<0.0001) and intermediate (HR intermediate versus high=1.35; 95% CI=1.20-1.51; p<0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR=1.13; 95% CI=1.01-1.27; p=0.04) but not for intermediate versus high (HR=1.11; 95% CI=0.99-1.24; p=0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55 years, patients with truncal tumours and during the first 5 years after diagnosis. CONCLUSION: Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies.

Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark's level of invasion: results of a population-based study from the Swedish Melanoma Register.

BACKGROUND: Survival and prognostic factors for thin melanomas have been studied relatively little in population-based settings. This patient group accounts for the majority of melanomas diagnosed in western countries today, and better prognostic information is needed. OBJECTIVES: The aim of this study was to use established prognostic factors such as ulceration, tumour thickness and Clark's level of invasion for risk stratification of T1 cutaneous melanoma. METHODS: From 1990 to 2008, the Swedish Melanoma Register included 97% of all melanomas diagnosed in Sweden. Altogether, 13,026 patients with T1 melanomas in clinical stage I were used for estimating melanoma-specific 10- and 15-year mortality rates. The Cox regression model was used for further survival analysis on 11,165 patients with complete data. RESULTS: Ulceration, tumour thickness and Clark's level of invasion all showed significant, independent, long-term prognostic information. By combining these factors the patients could be subdivided into three risk groups: a low-risk group (67·9% of T1 cases) with a 10-year melanoma-specific mortality rate of 1·5% (1·2-1·9%); an intermediate-risk group (28·6% of T1 cases) with a 10-year mortality rate of 6·1% (5·0-7·3%); and a high-risk group (3·5% of T1 cases) with a 10-year mortality rate of 15·6% (11·2-21·4%). The high- and intermediate-risk groups accounted for 66% of melanoma deaths within T1. CONCLUSIONS: Using a population-based melanoma register, and combining ulceration, tumour thickness and Clark's level of invasion, three distinct prognostic subgroups were identified.

Concurrent cetuximab and radiotherapy after docetaxel-cisplatin induction chemotherapy in stage III NSCLC: satellite--a phase II study from the Swedish Lung Cancer Study Group.

BACKGROUND: Several attempts to increase the locoregional control in locally advanced lung cancer including concurrent chemotherapy, accelerated fractionation and dose escalation have been made during the last years. As the EGFR directed antibody cetuximab has shown activity concurrent with radiotherapy in squamous cell carcinoma of the head and neck, as well as in stage IV NSCLC combined with chemotherapy, we wanted to investigate radiotherapy with concurrent cetuximab in locally advanced NSCLC, a tumour type often over expressing the EGF-receptor. METHODS: Between February 2006 and August 2007 75 patients in stage III NSCLC with good performance status (PS 0 or 1) and adequate lung function (FEV1>1.0) were enrolled in this phase II study at eight institutions. Treatment consisted of 2 cycles of induction chemotherapy, docetaxel 75 mg/m² and cisplatin 75 mg/m² with 3 weeks interval. An initial dose of cetuximab 400 mg/m² was given before start of 3D-CRT to 68 Gy with 2 Gy per fraction in 7 weeks concurrent with weekly cetuximab 250 mg/m². TOXICITY was scored weekly during radiotherapy (CTC 3.0), and after treatment the patients were followed every third month with CT-scans, toxicity scoring and QLQ. RESULTS: Seventy-one patients were eligible for analysis as four were incorrectly enrolled. HISTOLOGY: adenocarcinoma 49%, squamous cell carcinoma 39% and other NSCLC 12%. The majority had PS 0 (62.5%), median age 62.2 (42-81), 50% were women and 37% had a pre-treatment weight loss>5%. TOXICITY: esophagitis grade 1-2: 72%; grade 3: 1.4%. Hypersensitivity reactions grade 3-4: 5.6%. Febrile neutropenia grade 3-4: 15.4%. Skin reactions grade 1-2: 74%; grade 3: 4.2%. Diarrhoea grade 1-2: 38%; grade 3: 11.3%. Pneumonitis grade 1-2: 26.8%; grade 3: 4.2%; grade 5: 1.4%. The median follow-up was 39 months for patients alive and the median survival was 17 months with a 1-, 2- and 3-year OS of 66%, 37% and 29% respectively. Until now local or regional failure has occurred in 20 patients and 22 patients have developed distant metastases. Weight loss, PS and stage were predictive for survival in univariate as well as in multivariate analysis. CONCLUSION: Induction chemotherapy followed by concurrent cetuximab and RT to 68 Gy is clearly feasible with promising survival. TOXICITY, e.g. pneumonitis and esophagitis is low compared to most schedules with concurrent chemotherapy. This treatment strategy should be evaluated in a randomised manner vs. concurrent chemoradiotherapy to find out if it is a valid treatment option.

How to improve loco-regional control in stages IIIa-b NSCLC? Results of a three-armed randomized trial from the Swedish Lung Cancer Study Group.

BACKGROUND: A combination of chemotherapy and radiotherapy is the treatment base for locally advanced non-small cell lung cancer (NSCLC). However, both loco-regional and distant failure is frequent. Attempts to improve the loco-regional control were made in three separate phase II studies in Swedish University Hospitals, where accelerated radiotherapy or concurrent daily or weekly chemotherapy with conventional radiotherapy were tested. Comparatively good results from these studies lead to this national randomized phase II study, the RAKET-study, where the different concepts were investigated on a wider basis for further phase III studies. METHODS: Inoperable stage III non-small cell lung cancer patients in good performance status (PS<2) were equally randomized to either of three arms in eight institutions. All arms started with two cycles of induction chemotherapy: paclitaxel 200 mg/m2 and carboplatin AUC6. Arm A: a third identical cycle was given concomitant with start of accelerated radiotherapy, 1.7 Gy BID to 64.6 Gy in 4.5 weeks. Arm B consisted of daily concomitant paclitaxel 12 mg/m2 with conventionally fractionated radiotherapy: 2 Gy to 60 Gy in 6 weeks. Arm C: weekly concomitant paclitaxel 60 mg/m2 and identical radiotherapy to 60 Gy. Primary endpoint: TTP. Secondary: OS, toxicity, QL and relapse pattern. RESULTS: Between June 2002 and May 2005 152 patients were randomized and of them 151 were evaluable: 78 men and 73 women, median age 62 years (43-78), 55% had performance status 0 and 45% PS 1. Thirty-four percent had stage IIIa and 66% IIIb. HISTOLOGY: adenocarcinoma 48%, squamous cell carcinoma 32% and 20% non-small cell carcinoma. The three arms were well balanced. Toxicity was manageable with 12% grades 3-4 esophagitis, 1% grades 3-4 pneumonitis and there was no clear difference between the arms. The QL data did not differ either. Median time to progression was 9.8 (8.3-12.7) months (8.8, 10.3 and 9.3 months for arms A, B and C, respectively). Median survival was 17.8 (14.4-23.7) months (17.7, 17.7 and 20.6 months for A, B and C, respectively). The 1-, 3- and 5-year overall survival was 63, 31 and 24%. Sixty-nine percent of the patients relapsed with distant metastases initially and 31% had loco-regional tumor progression, without significant differences between treatment arms. Thirty-four percent developed brain metastases. CONCLUSIONS: Treatment results are quite equal by intensifying the loco-regional treatment either by accelerated fractionated radiotherapy or daily or weekly concomitant chemo-radiotherapy both in terms of survival, toxicity and quality of life. The optimal treatment schedule for patients with locally advanced NSCLC is still to be decided and investigated in future clinical studies. Relapse pattern with distant metastases and especially brain metastases is a great problem and need further research for better therapy options and higher cure rate for this patient group.

Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer.

BACKGROUND: The purpose of these studies was to compare efficacy and toxicity of docetaxel alone with the combination of gemcitabine and docetaxel for treatment of metastatic esophageal carcinoma. PATIENTS AND METHODS: These studies enrolled patients with histopathologically verified squamous cell carcinoma or adenocarcinoma of the esophagus or cardia. Between March 1997 and June 1999, 52 patients were enrolled in the initial Phase II study (Study 1). They were scheduled for treatment with docetaxel 100 mg/m2 every third week as a 1-h infusion. The second Phase II study between September 2000 and March 2003 included 65 patients (Study II). They were given docetaxel 30 mg/m2, administered as a 30-min i.v. infusion weekly for four times, followed by 2 weeks of rest, and gemcitabine starting with a dose of 750 mg/m2 (if well-tolerated 1,000 mg/m2) on days 1 and 15, followed by 3 weeks of rest. A new cycle began on day 36. Patients were premedicated with betamethasone 8 mg p.o. on the evening before, and 8 mg i.v. 30-60 min before the docetaxel infusion. Response was confirmed by computed tomography and assessed at 12 and 24 weeks. Toxicity was assessed according to WHO scales. RESULTS: In study I, 38 out of the 52 enrolled patients were valuable. Two patients experienced complete remission (CR) (5%), 10 patients partial remission (PR) (26%), nine patients stable disease (SD) (24%), and 17 patients showed progressive disease (PD) (45%). Toxicity mainly involved leukopenia, which in some cases required hospitalization and treatment with antibiotics. In Study II, 46 out of the 65 enrolled patients (70%) were assessable. Out of these, three patients (7%) had CR, eight patients (17%) had PR, 10 patients (22%) had SD, and 25 (54%) PD. Overall response was 24% while an additional 22% showed stable disease. Toxicity mainly consisted of leucopenia and pain. CONCLUSION: Docetaxel as a single agent is active in esophageal cancer, both in treatment naive and in previously treated patients with recurrent disease. The overall response rate was 31%, with a good-safety profile. The addition of gemcitabine is well tolerated, but adds no efficacy. Weekly administration of docetaxel may be less effective. It demonstrates moderate efficacy and the doses used provide an acceptable safety profile.

HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival.

The incidence of esophageal carcinoma is increasing worldwide. In Sweden, approximately 400 patients are diagnosed each year. The present study retrospectively investigates survival in 97 patients with esophageal carcinoma in regard to their HER-2 status as examined by immunohistochemistry (IHC) and chromogen in situ hybridization (CISH). Sixty-eight patients had localised disease and 29 patients had advanced disease. Seventy patients had squamous cell carcinoma, and nine of these patients (13%) had HER-2 overexpression (3+). Eight (30%) of 27 adenocarcinoma patients overexpressed (3+) HER-2. In patients overexpressing (3+) HER-2 a statistical trend towards poorer survival was observed (P = 0.057). In squamous cell carcinoma patients, HER-2 overexpression (3+) correlated with poorer survival (P = 0.035), whereas in adenocarcinoma patients, HER-2 status (3+) did not. HER-2 amplification according to CISH was present in five (two squamous cell carcinomas and three adenocarcinomas) out of 17 HER-2 overexpressing (3+) tumours. In conclusion, HER-2 overexpression (3+) seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma.

Role of circulating cytokeratin fragments and angiogenic factors in NSCLC patients stage IIIa-IIIb receiving curatively intended treatment.

Non-small cell lung cancer (NSCLC) is derived from epithelial cells and accounts for approximately 80% of all lung cancers. Cytokeratins are specific for epithelial cells and during malignant transformation the cytokeratin profile usually remains constant. Angiogenesis is the formation of new blood vessels out of the existing vascular bed. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are potent circulating angiogenic factors. The aim of the present study was to determine if increased levels of a new cytokeratin assay (MonoTotal, which in comparison with TPAcyk detects not only fragments of cytokeratins 8 and 18 but also of cytokeratin 19) is correlated with circulating angiogenic factors (VEGF and bFGF) and the secondary aim was to investigate if increased levels of these circulating markers are associated with survival. In the present study, a total of 45 NSCLC patients (26 patients stage IIIa and 19 patients stage IIIb) receiving only curatively intended treatment for advanced NSCLC were included. These patients donated a total of 291 serum samples during follow-up which was investigated for the presence of MonoTotal, VEGF and bFGF. MonoTotal was statistically significantly correlated with bFGF (R=0.26, p=0.00049) and VEGF (R=0.26, p=0.00007). From the time of histological diagnosis until time of death, MonoTotal increased by 603 U/l (p<0.0001). VEGF increased by 430 pg/ml (p=0.0004) whereas the corresponding value for bFGF was 5.93 pg/ml (p=0.018). MonoTotal, a newly developed commercial cytokeratin assay, seems to be a potentially very interesting serum marker that, in conjunction with other clinical data, might be used for monitoring of patients with NSCLC.

Genes associated with telomerase activity levels in esophageal carcinoma cell lines.

Telomerase activity levels have been shown to correlate with tumor progression in several malignancies. However, the genetic regulation of telomerase activity levels is not fully understood. The aim of the present study has been to identify a gene expression profile, predicting correlation with the telomerase-activity test. Ten human esophageal carcinoma cell lines were investigated using the telomerase activity assay (TRAPeze) Telomerase Detection Kit), followed by further characterization using the GeneChip Human Genome U133A 2.0 Array (Affymetrics Inc., USA), including 14 500 human genes. Telomerase activity levels were detected in all cell lines with a broad range of activity levels. Using a high correlation coefficient, r > 0.90, the following genes were found to be positively correlated with telomerase activity levels: N-myristoyltransferase 2; ribosomal protein L3; retinoblastoma-like 2 (pRb2/p130); and cyclin G2. Only one gene was negatively correlated with telomerase activity levels, zinc finger protein 207. In conclusion, the present microarray data provide primary validation data indicating possible candidates for prognostic and prediction factors in esophageal cancer in relation to telomerase activity.

Newly developed assay measuring cytokeratins 8, 18 and 19 in serum is correlated to survival and tumor volume in patients with esophageal carcinoma.

Esophageal carcinoma is the seventh most common cause of cancer-related death in the Western world. In Sweden, approximately 400 new esophageal carcinomas are diagnosed yearly. Cytokeratins (CK) are specific for epithelial cells and the expression profile usually remains unchanged even when the epithelium undergoes malignant transformation. In the present study, MonoTotal, a newly developed RIA-assay detecting circulating CK 8, 18 and 19 fragments, was investigated in sera from patients with esophageal carcinoma. Serum samples from 40 patients with esophageal carcinoma were collected. The median value of circulating CK 8, 18 and 19 measured with MonoTotal was 378 U/L (range 53-6843) and with regard to the defined cut-off (< 75 U/L), 39/40 (98%) patients were shown to have elevated levels of circulating CK 8, 18 and 19. Patients with localized disease had a median value of circulating CK 8, 18 and 19 of 305 U/L (mean: 500 U/L), whereas the corresponding value for metastatic disease was 771 U/L (mean: 1506 U/L). This difference was statistically significant (P = 0.016). Circulating CK 8, 18 and 19, according to cut-off, were not associated with survival in univariate analysis (P = 0.34). However, continuous values of circulating levels of CK 8, 18 and 19 were associated with survival (P = 0.000083) in univariate as well as in the multivariate analysis (P = 0.03). In conclusion, circulating CK 8, 18 and 19 correlates with increased tumor burden and might, in conjunction with other clinical parameters, aid the clinician in estimating the prognosis of the individual patient.

Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumour angiogenesis. In the present retrospective study, serum VEGF and bFGF from patients with locally advanced non-small cell lung cancer (NSCLC) were analysed before, during and after treatment. Seventy-three patients and a total of 460 serum samples were analysed for VEGF and 443 serum samples were analysed for bFGF. Pre-treatment bFGF levels in patients with normal platelet counts, were correlated to poorer survival, P-value = 0.047. During chemotherapy, each rise of one unit bFGF corresponded to a hazard ratio of 4.06 (P=0.022). In patients with normal platelet counts, VEGF levels after radiotherapy significantly correlated to good prognosis (P=0.023), during radiotherapy VEGF levels indicated the same correlation (P=0.085). We conclude that serum VEGF and especially bFGF are of clinical interest as prognostic factors, especially in patients presenting with normal platelet counts.

Elevated preoperative serum levels of angiogenic cytokines correlate to larger primary tumours and poorer survival in non-small cell lung cancer patients.

We have analysed the predictive and prognostic information in preoperatively collected serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients clinically evaluated as operable non-small cell lung cancer (NSCLC). Fifty-eight patients with operable NSCLC were included. VEGF and bFGF levels in serum were analysed using enzyme linked immunosorbent assays (Quantikine human VEGF and Quantikine HS human FGF basic, R&D Systems). Univariate analysis demonstrated that tumour volume, platelet counts, VEGF and bFGF were significant prognostic factors. However, only bFGF remained significant in the multivariate analysis (P=0.014). Significant correlation's were demonstrated between VEGF levels and tumour volume (r=0.33; P=0.012) and platelet count (r=0.43; P=0.001). bFGF levels correlated significant with recurrent disease (r=0.34; P=0.01), platelet count (r=0.53, P<0.001) and performance status (r=0.29; P=0.029). Furthermore, bFGF levels and VEGF levels correlated significantly (r=0.44; P<0.001). We conclude that elevated circulating angiogenic cytokines correlate with tumour volume, higher relapse risk and poorer survival in patients with operable non-small cell lung cancer.

A Swedish study of chemoradiation in squamous cell carcinoma of the esophagus.

This multicenter study describes the development of a chemoradiation protocol for the treatment of non-metastatic squamous cell carcinoma of the esophagus. Eighty patients were treated with three courses of chemotherapy (cisplatinum and 5-fluorouracil) with concomitant radiotherapy (40 Gy) during the last two courses of chemotherapy. Esophagectomy was performed, when feasible. If no operation was performed, patients were planned to receive a target dose of 64 Gy. Toxicity was mainly attributable to hematological impairment and led to two adjustments of the treatment protocol (addition of filgrastim and lowering of the 5-fluorouracil dose). These changes made it possible to administer the planned treatment in a gradually higher proportion of patients (13/23 [57%] before changes of treatment compared with 30/36 [83%] after changes). Treatment-related mortality was 3.75% (3 patients, associated with leucopenic septicemia after chemotherapy). Fifty-four patients were resected. No per- or postoperative mortality was encountered. The complete response (pathological CR) rate in operated patients was 46% (27/59 patients) after chemoradiation. In the whole series the CR rate (including clinical CR for non-resected patients) was 44%. With a minimum follow-up of 37 months, the 3-year survival for the whole group was 31% compared with 57% for the CR patients. Total 5-year survival thus far (July 1999) is 26%.

Trends in lung cancer incidence in Sweden with special reference to period and birth cohorts.

OBJECTIVE: Sweden has one of the largest population-based cancer registers in the world that provides an opportunity to examine the trend of lung cancer incidence during a 35-year period. The primary aim of the present study was to estimate the effects of birth cohort, year of diagnosis (period), and age on the time trends of lung cancer incidence rates, and to analyze the gender-specific incidence of different histopathological types of lung cancer. RESULTS: Among men the age-standardized incidence rate increased steadily up to 1982, when a peak of 49 cases per 100,000 person-years was reached. Among women the incidence rate was lower and showed a monotonic increase throughout the observation period. The fastest rate of increase was noted among the youngest women. In women, but not in men, there was a steady increase in risk with each successive birth cohort. For both sexes there were large changes in the histopathological distributions of cases. The most notable was a major increase in adenocarcinomas. CONCLUSIONS: The overall age-adjusted incidence rate of lung cancer in Sweden has stabilized in men during the past two decades while rates are still increasing in women. In view of the continued high prevalence of smoking among young women, a future definite increase in the overall number of lung cancer cases in women can be expected.

The frequency of micronuclei in lung cancer cell lines and their correlation to intrinsic radiation sensitivity.

BACKGROUND: Micronuclei arise from chromosomal, acentric, fragments or whole chromosomes that are not incorporated into the daughter nuclei at mitosis. The micronuclei assay is technically simple and requires only one mitosis in order to obtain information concerning the amount of micronuclei. This study was performed to investigate whether the formation of micronuclei could be used as a marker for intrinsic radiation sensitivity in lung cancer patients. MATERIALS AND METHODS: Two human lung cancer cell lines, a non-small cell lung cancer (NSCLC) cell line (U-1810) and a small cell lung cancer (SCLC) cell line (U-1906L), were used. Radiosensitivity data on the survival fraction at 2 Gy were obtained from the clonogenic assay. Radiation was delivered as one-fraction doses: 0, 1, 2, 4, 10 and 20 Gy. After irradiation, the cells were incubated for 0, 24, 48, 60, 72 and 96 hours before fixation and staining. RESULTS: The frequency of micronuclei in U-1906L was clearly elevated after 96 hours in the 20 Gy fraction. The frequency of micronuclei reached 5.5%. For U-1810 the micronuclei had a peak clearly different than the other settings after 48 hours in the 10 Gy fraction. The frequency of micronuclei was 1.2%. CONCLUSION: Counting micronuclei is not sensitive enough for estimation of radiosensitivity in clinical doses. However, our results demonstrated a distinct difference between NSCLC and SCLC cell lines at higher doses. This difference might be due to different repair fidelity, so future studies with this assay should aim to investigate this hypothesis.

Radiation responsiveness of human lung cancer cell lines measured with a short term semiautomatic assay.

BACKGROUND: Fluorometric microculture cytotoxicity assay (FMCA) is a short-term semi-automatic method, based on dye-inclusion of surviving cells. The assay was developed for investigations of drug resistance on tumour cells from biopsy material. In the present study, this short-term assay was evaluated, regarding usefulness in determining radio-sensitivity. MATERIALS AND METHODS: Eight human lung cancer cell lines were used. There were five small cell lung cancer (SCLC and three non-small cell lung cancer (NSCLC cell lines. Results were compared with the corresponding data derived from the clonogenic assay and/or the extrapolation method. RESULTS: The surviving fraction (SF) after 2, 5 and 10 Gy compared with data from the clonogenic assay were not in accordance for 5 of the 8 cell lines. The FMCA assay overestimated SF- values for the SCLC cell lines. CONCLUSION: The FMCA assay is not useful as a quick screening method for the radioresponsiveness in vitro of human tumour cell lines.

Serum p53 autoantibodies as prognostic marker in patients with oesophageal carcinoma.

BACKGROUND: Oesophageal carcinoma is one of the more aggressive cancers and the patients usually seek medical attention only when the disease is already advanced. Therefore it is important to have a tool, which is simple and fast, to measure and to predict the prognosis for these patients. Mutations in the p53 gene are among the most common genetic abnormalities in oesophageal carcinoma. The present study is the first study, to our knowledge, in which the relationship between the presence of p53 autoantibodies in the serum and survival has been investigated in patients with oesophageal carcinoma. PATIENTS AND METHODS: Serum from patients with oesophagal carcinoma was collected between 1996 and 1999 at the Department of Oncology, Uppsala University Hospital, Sweden. The serum samples were analysed for the presence of p53 autoantibodies using a sandwich ELISA. RESULTS: In a multivariate analysis, the presence of p53 autoantibodies was associated with decreased survival (p=0.047). Patients with extensive disease had a poor prognosis and time to death was decreased in these patients (p=0.000022). The one-year survival was 0% for these patients if they had p53 autoantibodies compared to 36% for patients with no p53 autoantibodies and extensive disease. CONCLUSION: We conclude that the presence of serum p53 autoantibodies is associated with decreased survival for patients with oesophageal carcinoma.

Different fraction schedules and combinations with chemotherapy in radiation treatment of non-small cell lung cancer.

BACKGROUND: In locally advanced non-small cell lung cancer (NSCLC), studies demonstrating advantages with hyperfractionated accelerated radiotherapy versus conventional radiotherapy have been published, so have studies demonstrating the value of chemotherapy concomitantly with radiotherapy. However, the value of non-conventional fractionation together with concomitant chemotherapy has not been investigated. MATERIALS AND METHODS: Consecutive patients from a single institution were studied in a retrospective non-randomised fashion. Inclusion criteria were stage III NSCLC, treatment with curative intent and a total dose above 50 Gy. RESULTS: Eighty-two patients were included and further divided into four different treatment groups. Multivariate analysis indicated a survival advantage with non-conventional radiotherapy (NCRT), especially if combined with concomitant chemotherapy. Toxicity was feasible, however there was a trend towards higher toxicity, mainly esophagitis, in patients given concomitant chemotherapy with NCRT. CONCLUSION: Our results suggest that accelerated hyperfractionated radiotherapy with concomitant chemotherapy could be an interesting test-arm in a future prospective study.

Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer.

This randomized study was designed to determine the response rates, survival and toxicities of single-agent gemcitabine (GEMZAR) and a combination of cisplatin/etoposide in chemonaive patients with non-resectable, locally advanced or metastatic non-small cell lung cancer (NSCLC). Gemcitabine 1000 mg/m2 was given as a 30-min intravenous infusion on days 1, 8, 15 of a 28-day cycle, cisplatin 100 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1 (following cisplatin), 2 and 3. Major eligibility criteria included histologically confirmed non-small cell lung cancer, measurable disease, Zubrod performance status 0-2, no prior chemotherapy, no prior radiation of the measured lesion, and no CNS metastases. One hundred and forty-seven patients were enrolled, 72 in the gemcitabine and 75 in the cisplatin/etoposide arm. Patient characteristics were well-matched across both arms. Sixty-seven gemcitabine and 72 cisplatin/etoposide patients were qualified for efficacy analysis. There were no complete responses, but 12 partial responses in the gemcitabine arm and 11 in the cisplatin/etoposide arm, for protocol-qualified response but 12 partial responses in the gemcitabine arm and 11 in the cisplatin/etoposide arm, for protocol-qualified response rates of 17.9% (95%, CI: 9.6-29.2%,) and 15.3% (95% CI: 7.9-25.7%,), respectively. Median survival times were 6.6 months (95% CI: 4.9-7.3 months) for gemcitabine and 7.6 months (95% CI: 5.4-9.3 months) for cisplatin/etoposide. The 1-year survival probability estimate was 26% for gemcitabine and 24% for cisplatin/etoposide. There were no statistically significant between-group differences in time-to-event measures, but patients in the gemcitabine arm had a greater probability of achieving a tumour response after 2 months (probability estimate: 8 vs. 0%,) and of the response lasting at least 6 months (73 vs. 45%,). Clinical and haematologic toxicity was more pronounced in the cisplatin/etoposide arm. Quality-of-life measures indicated a significant worsening of symptomatology in the cisplatin/etoposide arm for hair loss, nausea and vomiting, and appetite loss. This randomized study provides further evidence that single-agent gemcitabine is an active and effective therapy for patients with non-resectable. locally advanced or metastatic NSCLC and good performance status, and that it is better tolerated than the combination cisplatin/ etoposide.

Cytokeratin 8 and 18 fragments measured in serum and their relation to survival in patients with non-small cell lung cancer.

BACKGROUND: In this study we investigated if the newly developed monoclonal antibodies against Cytokeratin 8 and 18 fragments (Cyk 8/18) have prognostic information in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Serum from 69 patients with NSCLC was investigated using a sandwich ELISA, Cyk 8/18, provided by IDL Biotech, Sollentuna Sweden. RESULTS: Cyk 8/18 levels varied between 0.34-14.2 ng/mL, compared with a cut-off value of 1.0 ng/mL for healthy individuals (95% specificity). Using that cut-off value, 80% of NSCLC patients had elevated levels. A statistically significant diminished survival was found for Cyk 8/18 values of 8.0 ng/mL or higher (p = 0.0001). When survival data and Cyk 8/18 levels were analysed according to continuous Cox regression analysis, increased levels of Cyk 8/18 were significantly related to decreased survival (p = 0.016). CONCLUSIONS: The Cyk 8/18 monoclonal antibody had in this study prognostic information regarding survival in patients with NSCLC.

Aspects on reducing gastrointestinal adverse effects associated with radiotherapy.

Patients receiving cancer therapy are afflicted with a diversity of side effects. Radiotherapy for cancer affecting the head and neck, oesophagus and pelvis is associated with a marked toxicity, specifically encountered as mucosal toxicity. Pain and diarrhoea as well as nausea and vomiting are the most common symptoms, with subsequent problems such as malnutrition and decreased quality of life. These side effects need to be reduced if we are to optimize radiotherapy and to cure patients. Because there is no straightforward way of obviating these side effects, every effort to prevent aggravation and to induce healing of mucosal changes is of prime importance. Numerous agents including antimicrobials, local and systemic analgesics, anti-inflammatory drugs, anti-diarrhoeal drugs, and mucosal protectors alone or in combination with dietetic care have been used and/or are under evaluation in order to palliate the symptoms and increase the quality of life for the patients subjected to radiotherapy. In this article we summarize some aspects within the field that were discussed at the Annual Meeting of the Swedish Society for Oncology in Gavle, 1997.