Perioperative chemotherapy versus neoadjuvant chemoradiation for patients with adenocarcinoma of the distal esophagus in Austria: a retrospective analysis.

BACKGROUND: The aim of this study was to compare the outcome of patients with adenocarcinoma of the distal esophagus (AEG type I) treated with neoadjuvant chemoradiation or perioperative chemotherapy. METHODS: Eligible patients from four Austrian centers were selected to conduct a retrospective analysis. All patients treated between January 2007 and October 2017 with chemotherapy according to EOX-protocol (Epirubicin, Oxaliplatin, Xeloda) or chemoradiation according to CROSS-protocol (carboplatin/paclitaxel + RTX 41.4 Gy), before esophagectomy were included. Primary outcomes disease-free survival (DFS) and overall survival (OS) as well as secondary outcomes downstaging of T- or N-stage and achievement of pathological complete response pCR (ypT0N0M0) were analyzed. Data of 119 patients were included. RESULTS: Complete data was available in 104 patients, 53 patients in the chemoradiation group and 51 patients in the chemotherapy group. The mean number of lymph nodes removed was significantly higher in the EOX group (EOX 29 ± 15.5 vs. CROSS 22 ± 8.8; p < 0.05). Median follow-up in the CROSS group was 17 months (CI 95% 8.8-25.2) and in the EOX group 37 months (CI 95% 26.5-47.5). In the chemotherapy group, the OS rate after half a year, - 1, and 3 years was 92%, 75%, and 51%. After chemoradiation, overall survival after half a year was 85 %, after 1 year 66%, and after 3 years 17%. In the EOX group DFS after ½, - 1, and 3 years was 90%, 73%, and 45%, in the chemoradiation group after half a year 81%, after 1 year 55% and after 3 years 15%. Pathological complete response (pCR) was achieved in 23% of patients after CROSS and in 10% after EOX (p < 0.000). CONCLUSIONS: There seem to be clear advantages for chemoradiation, concerning the major response of the primary tumor, whereas a tendency in favor for chemotherapy is seen in regards to systemic tumor control. Furthermore, the type of neoadjuvant treatment has a significant influence on the number of lymph nodes resected.

Benefit of Adjuvant Radiotherapy for Local Control, Distant Metastasis, and Survival Outcomes in Patients with Localized Soft Tissue Sarcoma: Comparative Effectiveness Analysis of an Observational Cohort Study.

BACKGROUND: This study aimed to quantify the benefit of adjuvant radiotherapy (AXRT) for local control, distant metastasis, and long-term survival outcomes in patients with localized soft tissue sarcoma (STS). METHODS: This single-center retrospective observational study enrolled 433 STS patients who underwent surgery with curative intent. An inverse probability of treatment-weighted (IPTW) analysis was implemented to account rigorously for imbalances in prognostic variables between the adjuvant treatment groups. RESULTS: During a median follow-up period of 5.5 years, the study observed 38 local recurrences (9%), 73 occurrences of distant metastasis (17%), 63 STS-related deaths (15%), and 57 deaths from other causes (13%). As expected, patients receiving AXRT (n = 258, 60%) were more likely to have high-grade G3 tumors (p < 0.0001) than patients not receiving AXRT. A crude analysis showed that AXRT was not associated with improved recurrence-free survival [hazard ratio (HR) 1.00; 95% confidence interval (CI) 0.72-1.38; p = 0.98]. However, after IPTW, AXRT was associated with a 38% relative reduction in the risk of recurrence or death (HR 0.62; 95% CI 0.39-1.00; p = 0.05). This benefit was driven by a strong reduction in the risk of local recurrence (HR 0.42; 95% CI 0.19-0.91; p = 0.03), whereas the relative risk of distant metastasis (HR 0.69; 95% CI 0.39-1.25; p = 0.22) and overall survival (HR 0.76; 95% CI 0.44-1.30; p = 0.32) were only nonsignificantly in favor of AXRT. An exploratory analysis showed an overall survival benefit of AXRT for patients with high-grade G3 tumors (HR 0.51; 95% CI 0.33-0.78; p = 0.002). However, this finding may have been attributable to residual confounding. CONCLUSION: In this observational cohort, AXRT was associated with a 58% reduction in the relative risk of local recurrence. No consistent association between AXRT and lower risks of distant metastasis or death was observed.

Radiation-induced morphea-a rare but severe late effect of adjuvant breast irradiation : Case report and review of the literature.

BACKGROUND: Radiation-induced morphea (RIM) is a circumscribed localized scleroderma that occurs most often in the breast. After an asymptomatic period of one month to several years, the symptoms (circumscribed inflammation, edema, sclerosis) often arise suddenly and cannot be clinically distinguished from a local recurrence in the form of inflammatory carcinoma. CASE: We present a case of a 74-year-old woman who developed this rare and serious local side-effect in connective tissue following neoadjuvant CDK 4/6 inhibitor abemaciclib (Verzenio®) and aromatase inhibitor anastrozole (Arimidex®) therapy and subsequent radiation therapy of the breast. CONCLUSIONS: Little is known about risk factors and pathogenesis of RIM. Here we describe the first case of RIM following immunotherapy. The diagnosis is based on clinical appearance and histopathological examination. Treatment should be initiated in the inflammatory stage in order to prevent or delay irreversible fibrosis and atrophy of the breast.

ÖGRO survey on radiotherapy capacity in Austria : Status quo and estimation of future demands.

BACKGROUND: A comprehensive evaluation of the current national and regional radiotherapy capacity in Austria with an estimation of demands for 2020 and 2030 was performed by the Austrian Society for Radiation Oncology, Radiobiology and Medical Radiophysics (ÖGRO). MATERIALS AND METHODS: All Austrian centers provided data on the number of megavoltage (MV) units, treatment series, fractions, percentage of retreatments and complex treatment techniques as well as the daily operating hours for the year 2014. In addition, waiting times until the beginning of radiotherapy were prospectively recorded over the first quarter of 2015. National and international epidemiological prediction data were used to estimate future demands. RESULTS: For a population of 8.51 million, 43 MV units were at disposal. In 14 radiooncological centers, a total of 19,940 series with a mean number of 464 patients per MV unit/year and a mean fraction number of 20 (range 16-24) per case were recorded. The average re-irradiation ratio was 14%. The survey on waiting times until start of treatment showed provision shortages in 40% of centers with a mean waiting time of 13.6 days (range 0.5-29.3 days) and a mean maximum waiting time of 98.2 days. Of all centers, 21% had no or only a limited ability to deliver complex treatment techniques. Predictions for 2020 and 2030 indicate an increased need in the overall number of MV units to a total of 63 and 71, respectively. CONCLUSION: This ÖGRO survey revealed major regional differences in radiooncological capacity. Considering epidemiological developments, an aggravation of the situation can be expected shortly. This analysis serves as a basis for improved public regional health care planning.

The elevated preoperative derived neutrophil-to-lymphocyte ratio predicts poor clinical outcome in breast cancer patients.

Existing preclinical and clinical data suggest that the presence of a systemic inflammatory response plays a critical role in the progression of several solid tumors. The derived neutrophil-to-lymphocyte ratio (dNLR) represents an easily determinable marker of systemic inflammation and has been proposed as a potential prognostic marker. The present study was performed to validate and further clarify the prognostic relevance of an elevated pre-treatment dNLR in a large cohort of European breast cancer patients. Data from 762 consecutive female breast cancer patients treated from 1999 to 2004 were evaluated. Disease-free survival (DFS) and overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the prognostic relevance, univariate and multivariate Cox regression models were performed for each endpoint. Applying receiver operating characteristics (ROC) analysis, the optimal cutoff level for the dNLR was 3. In univariate analysis, a dNLR ≥3 was associated with poor DFS (hazard ratio (HR) 1.87, 95 % confidence interval (CI) 1.28-2.73, p = 0.001) and OS (HR 1.67, 95 % CI 1.07-2.63, p = 0.025). Multivariate analysis revealed a significant association between the elevated dNLR and poor DFS (hazard ratio (HR) 1.70, 95 % CI 1.09-2.65, p = 0.018) but did not show a significant association between the dNLR and OS (HR 1.54, 95 % CI 0.91-2.59, p = 0.106). The present study shows that the pre-treatment dNLR is an independent prognostic factor that could be useful for future individual risk assessment in breast cancer patients.

The association of an elevated plasma fibrinogen level with cancer-specific and overall survival in prostate cancer patients.

PURPOSE: Fibrinogen plays an important role in the pathophysiology of tumour cell invasion and metastases. In recent studies, an elevated plasma fibrinogen level has been associated with poor prognosis in different types of cancer. The present study was performed to analyse the prognostic impact of an elevated fibrinogen level in prostate cancer patients. METHODS: We evaluated data from 268 prostate cancer patients who underwent 3D conformal radiotherapy between 1999 and 2006 at a single tertiary academic center. Cancer-specific survival (CSS), overall survival (OS), and clinical disease-free survival (DFS) were assessed using the Kaplan-Meier method. Univariable and multivariable Cox regression models were performed for each endpoint. RESULTS: Applying receiver operating characteristics (ROC) curve analysis, the optimal cut-off level for the plasma fibrinogen level was 530 mg dl(-1), respectively. Univariable (HR 3.638, 95 % CI 1.15-11.47, p = 0.027) and multivariable analyses (HR 3.964, 95 % CI 1.06-14.87, p = 0.041) revealed a significant correlation between increased plasma fibrinogen and CSS. Univariable analysis also showed a significant association between the elevated plasma fibrinogen level and decreased OS (HR 3.242, 95 % CI 1.53-6.89, p = 0.002), that remained significant in multivariable analysis (HR 3.215, 95 % CI 1.44-7.19, p = 0.004). No significant associations were found for clinical DFS. CONCLUSION: Although our data show a significant association between an elevated plasma fibrinogen level and poor prostate cancer prognosis, they have to be interpreted cautiously. Limitations of the present study are caused by its retrospective design, the limited accuracy obtained using ROC curve analysis, and potential confounding factors like cardiovascular disease and inflammatory diseases that have not been accounted for.

Impact of VEGF gene polymorphisms and haplotypes on radiation-induced late toxicity in prostate cancer patients.

BACKGROUND AND PURPOSE: Vascular endothelial growth factor (VEGF) is an important determinant of microvascular permeability and angiogenesis and has been shown to be up-regulated during the late phase of radiation injury. The present prospective study was performed to evaluate the role of VEGF gene polymorphisms and haplotypes in the development of radiation-induced late side effects in prostate cancer patients. PATIENTS AND METHODS: The association of VEGF gene polymorphisms and haplotypes with high-grade late rectal or urinary toxicity (defined as late toxicity EORTC/RTOG ≥ 2) was analyzed using 493 prostate cancer patients from the Austrian PROCAGENE study treated with definitive radiotherapy. Seven candidate polymorphisms in the VEGF gene were selected and determined by 5'-nuclease (TaqMan) assays. RESULTS: Within a median follow-up time of 48 months, 42 patients (8.6%) developed high-grade late rectal and 47 patients (9.6%) urinary toxicity, respectively. In a Kaplan-Meier analysis, carriers of the VEGF -7C > T polymorphism were at increased risk of high-grade late rectal toxicity (p = 0.003) and in a multivariate analysis including clinical and dosimetric parameters as potential confounders the VEGF -7C > T polymorphism remained a significant predictor (HR = 2.8, 95% CI 1.349-5.813; p = 0.006). Furthermore, the ATTGT haplotype formed by five polymorphisms upstream of the coding sequence demonstrated a significant association with late rectal toxicity grade ≥ 2 (p = 0.001). No significant associations were found for the remaining polymorphisms and haplotypes. CONCLUSION: We conclude that genetic variants in the VEGF gene may influence the risk of high-grade late rectal toxicity after definitive radiotherapy for prostate cancer.

Preoperative oxaliplatin, capecitabine, and external beam radiotherapy in patients with newly diagnosed, primary operable, cT3NxM0, low rectal cancer: a phase II study.

PURPOSE: In patients with locally advanced rectal cancer (LARC), preoperative chemoradiation is known to improve local control, and down-staging of the tumor serves as a surrogate for survival. Intensification of the systemic therapy may lead to higher downstaging rates and, thus, enhance survival. This phase II study investigated the efficacy and safety of preoperative capecitabine and oxaliplatin in combination with radiotherapy. PATIENTS AND METHODS: Patients with LARC of the mid and lower rectum, T3NxM0 staged by MRI received radiotherapy (total dose 45 Gy) in combination with oral capecitabine (825 mg/m² twice a day on radiotherapy days; weeks 1-4) and oxaliplatin 50 mg/m² intravenously (days 1, 8, 15, and 22). Efficacy was evaluated as rate of tumor down-categorization at the T level. RESULTS: A total of 59 patients were enrolled (19 women, 40 men; median age of 61 years) and all were evaluable for efficacy and toxicity. Down-categorization at the T level was observed in 53% with pathological complete response in 6 patients (10%). Actual total radiotherapy, oxaliplatin and capecitabine doses received were 97%, 90%, and 93% of the protocol-specified preplanned doses, respectively. Grade 3/4 toxicity was observed in 15 patients (25%). The most frequent was diarrhea (12%). CONCLUSIONS: Preoperative chemoradiation with capecitabine and oxaliplatin is feasible in patients with MRI-proven cT3 LARC. The only clinically relevant toxicity was diarrhea. Overall, efficacy of the multimodality treatment was good, but not markedly exceeding that of 5-FU- or capecitabine-based chemoradiation approaches.

Treatment results of radiation therapy for muscle-invasive bladder cancer.

PURPOSE: To assess local control and survival rates in patients with muscle-invasive bladder cancer treated with external-beam radiotherapy and to investigate prognostic factors. PATIENTS AND METHODS: Between 1997 and 2007, 75 patients (male, n = 58; female, n = 17, median age, 74.2 years) with localized transitional cell carcinoma of the bladder (T2, n = 34; T3, n = 32; T4, n = 9) not suitable for radical surgery due to advanced age, comorbidity or inoperability underwent external-beam radiotherapy without simultaneous chemotherapy at the University Clinic of Therapeutic Radiology and Oncology, Medical University of Graz, Austria. A conformal four-field technique was used in all patients to treat the tumor and regional lymph nodes with single daily fractions of 1.8-2 Gy to a total dose of 50-50.4 Gy, followed by a cone-down to encompass the empty bladder which was boosted to 70-70.4 Gy. All patients had undergone transurethral tumor resection prior to radiotherapy which was macroscopically incomplete in 62 patients. RESULTS: Complete response was achieved in 65% of patients. Actuarial 3-year local control and metastases-free survival rates were 52.5% and 63.7%, 3-year local recurrence-free survival rate in complete responders was 71%. In univariate analysis, hydronephrosis, lymph vessel invasion, and macroscopic residual tumor were significantly predictive of disease progression. Hydronephrosis and lymph vessel invasion were also associated with a higher risk of local recurrence. The actuarial 3-year progression-free and overall survival rates were 40.1% and 56.9%, respectively. CONCLUSION: Radiotherapy is an effective treatment option in terms of local control and survival even in elderly patients with locally advanced bladder cancer not suitable for cystectomy.

Wide tangential fields including the internal mammary lymph nodes in patients with left-sided breast cancer. Influence of respiratory-controlled radiotherapy (4D-CT) on cardiac exposure.

PURPOSE: To evaluate the impact of wide-tangent fields including the internal mammary chain during deep inspiration breath-hold (DIBH) radiotherapy in patients with left-sided breast cancer on cardiac exposure. PATIENTS AND METHODS: Eleven patients with left-sided breast cancer were irradiated postoperatively and underwent CT scans during free breathing and DIBH. For scientific interest only, treatment plans were calculated consisting of wide tangents including the ipsilateral mammary lymph nodes using both, the free breathing and respiratory-controlled CT scan. The resulting dose-volume histograms were compared for irradiated volumes and doses to organs at risk. RESULTS: The mean patient age was 51 years (range: 37-65 years). Radiotherapy using wide tangents with DIBH as compared to free breathing led to a significantly lower cardiac exposure. Mean irradiated heart volumes (> or = 20 Gy) were 14 cm(3) (range: 0-51.3 cm(3)) versus 35 cm(3) (range: 2.1-78.7 cm(3); p = 0.01). For eight patients, DIBH reduced irradiated relative lung volume, while in three patients, the lung volume slightly increased. CONCLUSION: Radiation exposure of organs at risk can significantly be reduced for breast cancer patients using the DIBH technique. If radiotherapy of the internal mammary lymph nodes is considered necessary, DIBH may be the preferable technique.

Quality of life and sexual functioning after cervical cancer treatment: a long-term follow-up study.

OBJECTIVE: The purpose of the study was to investigate the long-term treatment side effects on the quality of life (QoL) and sexual functioning of cervical cancer survivors undergoing different treatment regimens. METHODS: QoL and sexual functioning were measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, the Cervix Cancer Module, and the Sexual Activity Questionnaire. RESULTS: One hundred twenty-one cervical cancer survivors (63 Surgery, 38 Surgery/CT, and 20 Surgery/RT) participated. Patients in the Surgery/RT Group reported significantly worse QoL outcomes (lower scores on physical, role, cognitive, and social functioning) compared with patients in the Surgery Group or patients in the Surgery/CT Group. The level of symptoms such as nausea/vomiting, pain, appetite loss, frequent urination (p=0.019), leaking of urine (p=0.015), and the feeling of a tight vagina (p=0.018) was significantly higher in irradiated patients. Concerning sexual functioning, patients in the Surgery/RT Group reported a significantly lower sexual activity rate compared with women in the Surgery Group or women in the Surgery/CT group (p<0.05). However, there were no statistically significant differences concerning sexual pleasure and sexual discomfort among the three treatment groups (p>0.05). CONCLUSIONS: Cervical cancer survivors treated with adjuvant radiotherapy are more likely at risk for impaired QoL. Survivors treated with surgery or adjuvant chemotherapy return to a similar level of QoL as women without a history of cancer. Although the sexual activity rate is lower in irradiated patients their sexual pleasure is similar to patients after surgery and chemotherapy.

Age as a Predictor of Treatment Outcome in Metastatic Testicular Germ Cell Tumors.

BACKGROUND/AIM: To quantify the prognostic impact of age on relapse and mortality in patients with metastatic testicular germ cell tumors (TGCT). PATIENTS AND METHODS: Electronical medical records of 1,225 TGCT patients who were treated at a single academic center between 1994 and 2015 were reviewed. RESULTS: Higher age did not predict for worse progression-free survival (PFS) or for higher progression risk. The corresponding 5-year PFS estimates were 85% in patients younger than 40 years and 83% in the elderly population. Although not statistically significant, higher age was numerically associated with worse overall survival (OS) (univariate HR per five years increase in age=1.18, 95%CI=0.99-1.41). This was explained in regression analysis where age predicted for significantly higher risk of treatment-related death (p=0.022). CONCLUSION: Elderly patients with metastatic TGCT can achieve high cure rates similar to younger patients if they tolerate risk-adapted chemotherapy.

Single nucleotide polymorphisms and haplotypes in the gene for vascular endothelial growth factor and risk of prostate cancer.

Vascular endothelial growth factor (VEGF) plays a key role in the regulation of angiogenesis and has been related to cancer development and progression. To evaluate the role of VEGF single nucleotide polymorphisms (SNPs) and haplotypes in prostate cancer, we performed a case-control study including 702 prostate cancer patients and 702 male age-matched healthy control subjects. Seven VEGF candidate polymorphisms were determined by 5'-nuclease (TaqMan) assays. Furthermore, VEGF plasma levels and genotypes were analysed in a group of 64 healthy men. Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms upstream of the coding sequence (promoter and 5'-untranslated region) and two polymorphisms downstream of the coding sequence. None of the single polymorphisms or haplotypes was significantly associated with the presence of prostate cancer. In a multivariate regression analysis including age, VEGF genotypes and haplotypes as covariates and VEGF plasma level as dependent variable, none of the VEGF polymorphism or haplotypes was a significant predictor of VEGF plasma levels. The present data suggest that polymorphisms or haplotypes in the VEGF gene do not modify the risk of prostate cancer.

Risk stratification for febrile neutropenia in patients with testicular germ cell tumors.

The aim of this study was to detect risk factors for febrile neutropenia (FN) in patients with testicular germ cell tumors (TGCT). In this retrospective cohort study at the Medical University of Graz, we included 413 consecutive TGCT patients who received adjuvant or curative treatment with cisplatin-based chemotherapy. FN occurred in 70 (16.9%) of 413 patients. In univariable logistic regression, higher age (odds ratio (OR) per 5 years = 1.17, 95% CI: 1.02-1.35, P = 0.022), reduced performance status (PS) (OR = 2.73, 1.47-5.06, P = 0.001), seminomatous histology (OR = 2.19, 1.26-3.78, P = 0.005), poor IGCCCG risk class (OR = 4.20, 1.71-10.33, P = 0.002), and prior radiotherapy (pRTX) (OR = 8.98, 2.09-38.61, P = 0.003) were associated with a higher risk of FN. In multivariable analysis adjusting for age and risk classification, only poor PS (OR = 2.06, 1.05-4.03, P = 0.035), seminomatous histology (OR = 2.08, 1.01-4.26, P = 0.047), and pRTX (OR = 7.31, 1.61-33.17, P = 0.010) prevailed. In the subgroup of seminoma patients (n = 104), only pRTX predicted for FN risk (OR = 5.60, 1.24-25.34, P = 0.025). Five of eight seminoma patients with pRTX developed FN (63%), as compared to 22 FN cases (23%) in the 96 seminoma patients without pRTX (P = 0.027). The eight seminoma patients who received pRTX had significantly lower pre-chemo white blood counts (4.7 vs. 6.5 G/L), neutrophil counts (3.2 vs. 4.3 G/L), and platelet counts (185 vs. 272 G/L) than patients without pRTX (all P < 0.0001). TGCT patients with a reduced performance status or who had been previously treated with radiotherapy have an increased risk for neutropenic fever during chemotherapy.

Interleukin-10 [ATA] promoter haplotype and prostate cancer risk: a population-based study.

Interleukin-10 (IL-10) is a multifunctional cytokine acting as inhibitor of inflammatory and immune responses as well as tumour induced angiogenesis. A common [ATA] haplotype formed by polymorphisms at positions -1082, -819 and -592in the promoter of the IL-10 gene is a strong determinant for IL-10 expression. The presence of this haplotype can be determined by analysis of the -592C>A polymorphism. To analyse the role of the IL-10 [ATA] haplotype in prostate cancer we performed a case-control study including 561 prostate cancer patients and 561 male, age-matched, control subjects without malignant disease. The IL-10 -592C>A polymorphism was determined by a 5'-nuclease assay (TaqMan). IL-10 -592 CC, CA and AA genotype frequencies were not significantly different between patients (53.6%, 40.0%, 6.4%) and controls (54.3%, 39.6%, 6.1%; p=0.96). IL-10 genotypes were furthermore not associated with tumour characteristics such as histological grade, T stage, PSA levels at diagnosis, or age at diagnosis. Therefore we conclude that the IL-10 -592C>A promoter polymorphism, tagging the IL-10 low-producer [ATA] haplotype, is not associated with risk for prostate cancer.

Analysis of the prognostic impact of tumor embolization before definitive radiotherapy for cervical carcinoma.

PURPOSE: To assess whether embolization compromises the radiocurability of primary cervical cancer. METHODS AND MATERIALS: Two hundred fifty-four patients with primary cervical cancer (International Federation of Gynecology and Obstetrics [FIGO] stages IB: 47; II: 91; IIIB: 102; IV: 14) were treated with external beam irradiation and Ir-192 high-dose-rate brachytherapy over a period of 15 years. Of these, 24 patients (9.4%) (FIGO stages IB: 1; II: 8; IIIB: 12; IV: 3) had had bilateral embolization of the internal iliac arteries before referral. The median age of the entire cohort was 66 years (range, 34-85 years). Tumor size was >5 cm and paraortic nodes were enlarged (> or =1 cm) on pretreatment CAT scan in 39.4% and 9.1% of patients, respectively. All patients with hemoglobin levels (hb-l) < or =11 g/dL (28.3%) received packed red cell transfusions (PRCT) before and/or during radiotherapy in an attempt to maintain levels >11 g/dL throughout treatment. Cross-table tests were used to compare the distribution of FIGO stage, tumor size, lymph node status, and pretreatment and treatment hb-l of embolized and nonembolized patients. The impact of embolization, along with the above-listed tumor characteristics, on disease-specific survival (DSS), pelvic control (PC), and distant metastases-free survival (MFS) was determined by univariate and multivariate analyses. RESULTS: Embolized patients presented at a statistically significant younger median age (55 vs. 67 years; p = 0.003), with larger tumors (66.7% vs. 36.5%; p = 0.007), and lower pretreatment hb-l (75% vs. 23.5%; p < 0.001) than nonembolized patients. There was no significant difference in stage distribution or lymph node status, and although embolized patients responded better to PRCT (50% vs. 29.6%), this difference was not statistically significant. Univariate analysis showed a trend toward decreased DSS (p = 0.09) and PC (p = 0.07) for embolized patients but no effect on MFS, whereas all other variables tested were significantly correlated with DSS, PC, and MFS (all p < 0.001). In the multivariate model, tumor embolization, FIGO stage, and pretreatment hb-l ceased to impact significantly on outcome. Tumor size remained the most powerful independent predictor for all endpoints tested, followed by treatment hb-l. Paraortic node status was significantly correlated with DSS and MFS. CONCLUSION: Although a trend toward poorer DSS and PC was observed in embolized patients, no impact on radiocurability could be demonstrated in multivariate analysis after controlling for the major tumor characteristics and treatment hb-l.

An elevated preoperative plasma fibrinogen level is associated with poor disease-specific and overall survival in breast cancer patients.

INTRODUCTION: Plasma fibrinogen plays an important role in the pathophysiology of tumor cell invasion and metastases. High plasma fibrinogen levels have been associated with poor prognosis in different types of cancer. In the present study, we evaluated the prognostic significance of the preoperative plasma fibrinogen level in a large cohort of breast cancer patients. MATERIALS AND METHODS: Data from 520 consecutive breast cancer patients, treated between 1999 and 2004, were evaluated. Disease-specific survival (DSS), overall survival (OS), and distant metastasis-free survival (DMFS) were assessed using Kaplan-Meier curves. To evaluate the independent prognostic significance of fibrinogen, multivariable Cox regression models were applied. The influence of fibrinogen on the predictive accuracy was further determined by the Harrell's c-index. RESULTS: Univariable analysis revealed a significant association between an elevated plasma fibrinogen level and DSS (hazard ratio (HR) 1.70, 95% CI 1.07-2.76, p = 0.026) that remained significant in multivariable analysis (HR 1.71, 95% CI 1.02-2.85; p = 0.042). An increased fibrinogen level was also significantly associated with decreased OS in univariable (HR 1.71, 95% CI 1.11-2.64, p = 0.015) and multivariable analysis (HR 1.62, 95% CI 1.01-2.61; p = 0.048). In patients with ER/PR+, HER2- tumors, plasma fibrinogen was associated with DSS in univariable (HR 2.65, 95% CI 1.15-6.14, p = 0.023) and multivariable analysis (HR 3.63, 95% CI 1.37-9.64, p = 0.010). Furthermore, in those patients, the estimated c-index of the multivariable model for DSS was 0.755 without fibrinogen and 0.785 when fibrinogen was added. CONCLUSIONS: An elevated preoperative plasma fibrinogen level may represent an independent prognostic marker for survival in breast cancer patients.

The elevated C-reactive protein level is associated with poor prognosis in prostate cancer patients treated with radiotherapy.

BACKGROUND: C-reactive protein (CRP) is a sensitive marker of inflammation that has been linked with prognosis in various solid tumours. In the present study, we analysed the prognostic relevance of elevated plasma CRP levels in prostate cancer patients treated with radiotherapy. METHODS: A total of 261 prostate cancer patients treated with 3D-conformal radiotherapy were evaluated retrospectively. Cancer specific survival (CSS), overall survival (OS) and clinical disease-free survival (DFS) were assessed using Kaplan-Meier analysis. To evaluate the independent prognostic significance of CRP plasma levels, multivariate Cox regression models were applied. RESULTS: The median follow-time was 80months. Applying receiver operating characteristics (ROC) analysis, the optimal cut-off level for the plasma CRP was 8.6mgl(-1). An elevated CRP level was associated with decreased CSS in univariate (hazard ratio (HR) 3.36, 95% confidence interval (CI) 1.42-7.91; p=0.006) and multivariate analysis (HR 4.31, 95% CI 1.22-15.1; p=0.023). Furthermore, a significant association with OS was detected in univariate (HR 2.69, 95% CI 1.57-4.59; p<0.001) and multivariate analyses (HR 3.24, 95% CI 1.84-5.71, p<0.001). Multivariate analysis also showed a significant association between plasma CRP and clinical DFS (HR 2.07, 95% CI 1.02-4.17; p=0.043). CONCLUSIONS: In the present study, an elevated plasma CRP (⩾8.6mgl(-1)) has been identified as a prognostic factor for poor CSS, OS and DFS in prostate cancer patients undergoing radiotherapy. The association between elevated CRP levels and poor prognosis was independent of other measures of prognosis such as tumour stage, Gleason grading and prostate specific antigen (PSA) level at diagnosis. If confirmed by additional studies, our findings may contribute to future individual risk assessment in prostate cancer patients.

Evaluation of the effect of routine packed red blood cell transfusion in anemic cervix cancer patients treated with radical radiotherapy.

PURPOSE: It is well established that anemia predicts diminished radiocurability in cervix cancer. However, the therapeutic benefit of measures to correct the anemia remains controversial. The objective of this study was to determine the impact of routine transfusion in patients with hemoglobin level (hb-l) < or =11 g/dl. METHODS AND MATERIALS: Since 1985, it has been departmental policy to attempt to correct hb-l < or =11 g/dl before and/or during radiotherapy by red blood cell transfusion (RBCT) in patients undergoing radical radiotherapy for primary cervix cancer. To assess the benefit of RBCT, the charts of 204 patients (FIGO: IB-IV) treated until 1997 were reviewed. Parameters analyzed for their impact on disease-specific survival (DSS), pelvic control (PC), and metastases-free survival (MFS) included pretreatment hb-l, treatment hb-l, stage, tumor size, and lymph node status. To determine any differences in outcome according to type of anemia, a separate analysis was performed, grouping patients by cause of anemia (tumor vs. other medical illness related). RESULTS: Each of the parameters tested was significantly correlated with the end points studied in univariate analysis. Patients whose hb-l were corrected (18.5%) had an outcome that did not differ significantly from that of nontransfused patients, whereas DSS, PC, and MFS (all: p < 0.001) were significantly decreased in nonresponders to RBCT. Subgroup analysis showed no impact of hb-l in patients with other medical illness-related anemia (n = 12). In multivariate analysis treatment, but not pretreatment, hb-l remained predictive for DSS, PC, and MFS. Persistent anemia was associated with a significantly increased risk of death (relative risk: 2.1) and pelvic failure (relative risk: 2.4) compared with nontransfused patients. If only patients with tumor anemia were considered, the respective risks increased (2.7; 3.6). None of the patients with other causes of anemia recurred, whether or not their hb-l was maintained. Assessment of the therapeutic gain in patients who responded to RBCT showed improved PC (p = 0.02) and a trend toward increased DSS (p = 0.06), but no effect on MFS after adjustment for tumor size and lymph node status. CONCLUSION: Treatment hb-l, in addition to tumor size and lymph node status, independently predicted outcome. Although our final multivariate analysis showed a therapeutic benefit for patients whose hb-l was corrected, the response to RBCT was disappointing. Results of our subgroup analysis suggest that the cause of anemia in patients with cervical cancer warrants in-depth investigation.