Adjuvant (chemo)radiotherapy for patients with head and neck cancer: can comorbidity risk scores predict outcome?

PURPOSE: This study compares the objective American Society of Anesthesiologists (ASA) and Adult Comorbidity Evaluation-27 (ACE-27) scores with the subjective Eastern Cooperative Oncology Group performance status (ECOG PS) for patient outcome prediction. METHODS: We retrospectively analyzed head and neck squamous cell carcinoma patients treated with adjuvant (chemo)radiotherapy at the LMU Munich from June 2008 to June 2015. The study focused on associations between patient outcomes; treatment failures; known risk factors (including human papillomavirus [HPV] status and tumor stage); and the comorbidity indices ECOG-PS, ASA score, and ACE-27. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis and identifying independent risk factors. RESULTS: A total of 302 patients were analyzed, 175 received concurrent chemotherapy. Median follow-up was 61.8 months, and median age at diagnosis was 61 years. The 3­ and 5­year overall survival (OS) and disease-free survival (DFS) rates were 70.5%/60.2% and 64.7%/57.6%, respectively. Both ACE-27 and ASA showed significant correlations with OS in univariate and multivariate analyses, while ECOG-PS was significant only in univariate analysis. ASA and ACE-27 scores were also significantly correlated with local and locoregional recurrence, but only HPV status and tumor stage were significant in multivariate models. CONCLUSION: ACE-27 and ASA score effectively categorize patients' risks in adjuvant radiotherapy for head and neck cancer, proving more predictive of overall survival than ECOG-PS. These results underscore the importance of objective comorbidity assessment and suggest further prospective studies.

Intrafractional motion detection for spine SBRT via X-ray imaging using ExacTrac Dynamic.

Purpose: Due to its close vicinity to critical structures, especially the spinal cord, standards for safety for spine stereotactic body radiotherapy (SBRT) should be high. This study was conducted, to evaluate intrafractional motion during spine SBRT for patients without individualized immobilization (e.g., vacuum cushions) using high accuracy patient monitoring via orthogonal X-ray imaging. Methods: Intrafractional X-ray data were collected from 29 patients receiving 79 fractions of spine SBRT. No individualized immobilization devices were used during the treatment. Intrafractional motion was monitored using the ExacTrac Dynamic (ETD) System (Brainlab AG, Munich, Germany). Deviations were detected in six degrees of freedom (6 DOF). Tolerances for repositioning were 0.7 mm for translational and 0.5° for rotational deviations. Patients were repositioned when the tolerance levels were exceeded. Results: Out of the 925 pairs of stereoscopic X-ray images examined, 138 (15 %) showed at least one deviation exceeding the predefined tolerance values. In all 6 DOF together, a total of 191 deviations out of tolerance were recorded. The frequency of deviations exceeding the tolerance levels varied among patients but occurred in all but one patient. Deviations out of tolerance could be seen in all 6 DOF. Maximum translational deviations were 2.6 mm, 2.3 mm and 2.8 mm in the lateral, longitudinal and vertical direction. Maximum rotational deviations were 1.8°, 2.6° and 1.6° for pitch, roll and yaw, respectively. Translational deviations were more frequent than rotational ones, and frequency and magnitude of deviations showed an inverse correlation. Conclusion: Intrafractional motion detection and patient repositioning during spine SBRT using X-ray imaging via the ETD System can lead to improved safety during the application of high BED in critical locations. When using intrafractional imaging with low thresholds for re-positioning individualized immobilization devices (e.g. vacuum cushions) may be omitted.

Intrafractional monitoring of patients using four different immobilization mask systems for cranial radiotherapy.

Background and purpose: Patients receiving cranial radiotherapy are immobilized with a thermoplastic mask to restrict patient motion. Depending on the target volume margins and treatment dose, different mask systems are used. Intrafractional movements can be monitored using stereoscopic X-ray imaging. The aim of the present work was to compare the magnitudes of intrafractional deviation for different mask systems. Material and methods: Four different head mask systems (open face mask, open mask, stereotactic mask, double mask) used in the treatment of 40 patients were investigated. In total 487 treatment fractions and 3708 X-ray images were collected. Deviations were calculated by comparison of the acquired X-ray images with digitally reconstructed radiographs. The results of intrafractional X-ray deviations for translational and rotational axes were compared between the different mask systems. Results: Deviations were below 0.6 mm for translations and below 0.6° for rotations for all mask systems. Along the lateral and longitudinal directions the stereotactic mask was superior, while along the vertical direction the double mask showed the lowest deviations. For low rotational deviations the double mask is the best amongst all other mask systems. Conclusion: As expected, the lowest movement was shown using cranial stereotactic mask systems. The results have shown deviations lower than 0.6 mm and 0.6° using any of the four thermoplastic mask systems.

ExacTrac Dynamic workflow evaluation: Combined surface optical/thermal imaging and X-ray positioning.

In modern radiotherapy (RT), especially for stereotactic radiotherapy or stereotactic radiosurgery treatments, image guidance is essential. Recently, the ExacTrac Dynamic (EXTD) system, a new combined surface-guided RT and image-guided RT (IGRT) system for patient positioning, monitoring, and tumor targeting, was introduced in clinical practice. The purpose of this study was to provide more information about the geometric accuracy of EXTD and its workflow in a clinical environment. The surface optical/thermal- and the stereoscopic X-ray imaging positioning systems of EXTD was evaluated and compared to cone-beam computed tomography (CBCT). Additionally, the congruence with the radiation isocenter was tested. A Winston Lutz test was executed several times over 1 year, and repeated end-to-end positioning tests were performed. The magnitude of the displacements between all systems, CBCT, stereoscopic X-ray, optical-surface imaging, and MV portal imaging was within the submillimeter range, suggesting that the image guidance provided by EXTD is accurate at any couch angle. Additionally, results from the evaluation of 14 patients with intracranial tumors treated with open-face masks are reported, and limited differences with a maximum of 0.02 mm between optical/thermal- and stereoscopic X-ray imaging were found. As the optical/thermal positioning system showed a comparable accuracy to other IGRT systems, and due to its constant monitoring capability, it can be an efficient tool for detecting intra-fractional motion and for real-time tracking of the surface position during RT.

Primary radiation therapy in stage I/II indolent orbital lymphoma - a comprehensive retrospective recurrence and toxicity analysis.

PURPOSE OR OBJECTIVE: To provide a comprehensive recurrence and toxicity analysis of patients treated with radiotherapy alone for stage I/II (Ann-Arbor classification) indolent orbital lymphoma. MATERIAL AND METHODS: We retrospectively reviewed the medical charts of 46 patients (and 51 orbits) treated at our centre with radiotherapy between 1995 and 2012 for biopsy-proven stage I/IIE primary orbital lymphomas. We evaluated treatment response and performed a comprehensive toxicity analysis with correlation to delivered radiation dose. RESULTS: At diagnosis, the median age was 63.5 years (range: 20-92). At initial diagnosis 43 and 3 patients had unilateral, synchronous bilateral involvement while there were 2 cases of contralateral metachronous failure. The predominant histological subtype was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in 42 (91.3%), follicular in 1 (2.2%), lymphoplasmacytic lymphoma in 1 (2.2%) and other indolent histology in 2 (4.3%) patients. Most lymphomas were located in the conjunctiva (18/35.3%) or eyelids (18/35.3%). Thirty-eight (82.6%) patients presented with stage I while 8/46 (17.4%) with stage II disease. The median radiation dose was 39.6 Gy (range: 21.6-48.6 Gy) delivered in 1.8-2 Gy single fractions. At a median follow-up of 83 months (range: 7-258 months), the complete remission rate was 98%. A local relapse was observed in 2/51 (3.9%) orbits and 4/46 (8.7%) patients had systemic relapse. The 5- and 10-year PFS rates were 79.2% (95% CI: 73.0%-85.4%) and 67.6% (95% CI: 59.4%-75.8%); 5- and 10-year OS was 83.6% (95% CI: 77.9%-89.3%) and 76.5% (95% CI: 69.4%-83.6%), respectively. In total, 66 acute toxicity events (all-grade) were observed: 5/51 (9.8%) ≥G2 acute conjunctivitis, 2/51 (3.9%) cases of G2 acute keratitis, 1/51 (2%) cases of ≥G2 ophthalmagia and 12/51 (23.5%) cases of ≥G2 xerophthalmia. Furthermore, 45 chronic adverse events were observed in 34/51 (66.7%) irradiated orbits with 30 late adverse events attributed to cataract. CONCLUSION: Our analysis confirms the role of radiotherapy alone at lower doses in the treatment of indolent orbital lymphomas. Further research is required to assess the efficacy of ultra-low-dose radiotherapy and anti-CD20 monoclonal antibodies to further mitigate long-term sequelae.

Radiation necrosis after a combination of external beam radiotherapy and iodine-125 brachytherapy in gliomas.

PURPOSE: Frequency and risk profile of radiation necrosis (RN) in patients with glioma undergoing either upfront stereotactic brachytherapy (SBT) and additional salvage external beam radiotherapy (EBRT) after tumor recurrence or vice versa remains unknown. METHODS: Patients with glioma treated with low-activity temporary iodine-125 SBT at the University of Munich between 1999 and 2016 who had either additional upfront or salvage EBRT were included. Biologically effective doses (BED) were calculated. RN was diagnosed using stereotactic biopsy and/or metabolic imaging. The rate of RN was estimated with the Kaplan Meier method. Risk factors were obtained from logistic regression models. RESULTS: Eighty-six patients (49 male, 37 female, median age 47 years) were included. 38 patients suffered from low-grade and 48 from high-grade glioma. Median follow-up was 15 months after second treatment. Fifty-eight patients received upfront EBRT (median total dose: 60 Gy), and 28 upfront SBT (median reference dose: 54 Gy, median dose rate: 10.0 cGy/h). Median time interval between treatments was 19 months. RN was diagnosed in 8/75 patients. The 1- and 2-year risk of RN was 5.1% and 11.7%, respectively. Tumor volume and irradiation time of SBT, number of implanted seeds, and salvage EBRT were risk factors for RN. Neither of the BED values nor the time interval between both treatments gained prognostic influence. CONCLUSION: The combination of upfront EBRT and salvage SBT or vice versa is feasible for glioma patients. The risk of RN is mainly determined by the treatment volume but not by the interval between therapies.

Heart sparing radiotherapy in breast cancer: the importance of baseline cardiac risks.

BACKGROUND: Patients with left-sided breast cancer have an increased risk of cardiovascular disease (CVD) after radiotherapy (RT). While the awareness of cardiac toxicity has increased enormously over the last decade, the role of individual baseline cardiac risks has not yet been systematically investigated. Aim of the present study was to evaluate the impact of baseline CVD risks on radiation-induced cardiac toxicity. METHODS: Two hundred ten patients with left-sided breast cancer treated in the prospective Save-Heart Study using a deep inspiration breath-hold (DIBH) technique were analysed regarding baseline risk factors for CVD. Three frequently used prediction tools (Procam, Framingham and Reynolds score) were applied to evaluate the individual CVD risk profiles. Moreover, 10-year CVD excess absolute risks (EAR) were estimated using the individual mean heart dose (MHD) of treatment plans in free breathing (FB) and DIBH. RESULTS: The individual baseline CVD risk factors had a strong impact on the 10-year cumulative CVD risk. The mean baseline risks of the non-diabetic cohort (n = 200) ranged from 3.11 to 3.58%, depending on the risk estimation tool. A large number of the non-diabetic patients had a very low 10-year CVD baseline risk of ≤1%; nevertheless, 8-9% of patients reached ≥10% baseline 10-year CVD risk. In contrast, diabetic patients (n = 10) had significantly higher baseline CVD risks (range: 11.76-24.23%). The mean 10-year cumulative risk (Framingham score) following RT was 3.73% using the DIBH-technique (MHD:1.42Gy) and 3.94% in FB (MHD:2.33Gy), after adding a 10-year-EAR of + 0.34%(DIBH) and + 0.55%(FB) to the baseline risks, respectively. Smoking status was one of the most important and modifiable baseline risk factors. After DIBH-RT, the 182 non-smoking patients had a mean 10-year cumulative risk of 3.55% (3.20% baseline risk, 0.35% EAR) as compared to 6.07% (5.60% baseline risk, 0.47% EAR) for the 28 smokers. CONCLUSION: In the present study, all CVD prediction tools showed comparable results and could easily be integrated into daily clinical practice. A systematic evaluation and screening helps to identify high-risk patients who may benefit from primary prevention. This could result in an even higher benefit than from heart-sparing irradiation techniques alone.

Blood Parameters Demonstrating a Significant Survival Impact in Patients With Locally Advanced NSCLC Undergoing Definitive Chemoradiotherapy.

AIM: We investigated blood parameters in patients with inoperable stage III non-small cell lung cancer (NSCLC) to predict individual outcomes after definitive chemoradiotherapy (CRT). PATIENTS AND METHODS: Blood parameters of consecutive patients undergoing definitive CRT between 2010 and 2016 for inoperable stage III NSCLC before multimodal treatment and at first follow-up were measured and analyzed. RESULTS: Blood parameters from 99 patients were evaluated. Histologically, about 50% of patients had an adenocarcinoma. All patients received platinum-based sequential or concurrent CRT. The median total dose to the primary tumor was 60 (range=48-70) Gy. On multivariate analysis after adjustment for all co-founders, median overall survival for pre-treatment cutoffs were: lactate dehydrogenase (LDH) >250 U/l was 17 vs. 27 months [hazard ratio (HR)=2.05, 95% confidence intervaI (CI)=1.15-3.66; p=0.015], thrombocytosis >400×106/l: 11 vs. 23 months (HR=2.75, 95% CI=1.1-6.88; p=0.03), hypoalbuminemia <3.5 g/dl: 12 vs. 24 months (HR=2.42, 95% CI=1.21-4.84; p=0.013) and post-treatment neutrophilia >7×106/l: 12 vs. 27 months (HR=2.5, 95% CI=1.21-5.17; p=0.013). CONCLUSION: Pre-treatment elevated LDH, thrombocytosis, hypoalbuminemia and post-treatment neutrophilia were associated with significantly worse overall survival in patients with inoperable stage III NSCLC treated with CRT. Patients with both pre-therapeutic elevated LDH and hypoalbuminemia demonstrated a dismal prognosis despite completion of multimodal treatment.

Impact of surface-guided positioning on the use of portal imaging and initial set-up duration in breast cancer patients.

OBJECTIVE: The impact of optical surface guidance on the use of portal imaging and the initial set-up duration in patients receiving postoperative radiotherapy of the breast or chest wall was investigated. MATERIAL AND METHODS: A retrospective analysis was performed including breast cancer patients who received postoperative radiotherapy between January 2016 and December 2016. One group of patients received treatment before the optical surface scanner was installed (no-OSS) and the other group was positioned using the additional information derived by the optical surface scanner (OSS). The duration of the initial set-up was recorded for each patient and a comparison of both groups was performed. Accordingly, the differences between planned and actually acquired portal images during the course of radiotherapy were compared between both groups. RESULTS: A total of 180 breast cancer patients were included (90 no-OSS, 90 OSS) in this analysis. Of these, 30 patients with left-sided breast cancer received radiotherapy in deep inspiration breath hold (DIBH). The mean set-up time was 10 min and 18 s and no significant difference between the two groups of patients was found (p = 0.931). The mean set-up time in patients treated without DIBH was 9 min and 45 s compared to 13 min with DIBH (p < 0.001), as portal imaging was performed in DIBH. No significant difference was found in the number of acquired to the planned number of portal images during the entire radiotherapy treatment for both groups (p = 0.287). CONCLUSION: Optical surface imaging is a valuable addition for primary patient set-up. The findings confirm that the addition of surface-based imaging did not prolong the clinical workflow and had no significant impact on the number of portal verification images carried out during the course of radiotherapy.

Mastectomy or Breast-Conserving Therapy for Early Breast Cancer in Real-Life Clinical Practice: Outcome Comparison of 7565 Cases.

Although the organ preservation strategy by breast-conserving surgery (BCS) followed by radiation therapy (BCT) has revolutionized the treatment approach of early stage breast cancer (BC), the choice between treatment options in this setting can still vary according to patient preferences. The aim of the present study was to compare the oncological outcome of mastectomy versus breast-conserving therapy in patients treated in a modern clinical setting outside of clinical trials. 7565 women diagnosed with early invasive BC (pT1/2pN0/1) between 1998 and 2014 were included in this study (median follow-up: 95.2 months). In order to reduce selection bias and confounding, a subgroup analysis of a matched 1:1 case-control cohort consisting of 1802 patients was performed (median follow-up 109.4 months). After adjusting for age, tumor characteristics and therapies, multivariable analysis for local recurrence-free survival identified BCT as an independent predictor for improved local control (hazard ratio [HR]:1.517; 95%confidence interval:1.092⁻2.108, p = 0.013) as compared to mastectomy alone in the matched cohort. Ten-year cumulative incidence (CI) of lymph node recurrences was 2.0% following BCT, compared to 5.8% in patients receiving mastectomy (p < 0.001). Similarly, 10-year distant-metastasis-free survival (89.4% vs. 85.5%, p = 0.013) was impaired in patients undergoing mastectomy alone. This translated into improved survival in patients treated with BCT (10-year overall survival (OS) estimates 85.3% vs. 79.3%, p < 0.001), which was also significant on multivariable analysis (p = 0.011). In conclusion, the present study showed that patients treated with BCS followed by radiotherapy had an improved outcome compared to radical mastectomy alone. Specifically, local control, distant control, and overall survival were significantly better using the conservative approach. Thus, as a result of the present study, physicians should encourage patients to receive BCS with radiotherapy rather than mastectomy, whenever it is medically feasible and appropriate.

Pattern of care of adjuvant radiotherapy in male breast cancer patients in clinical practice: an observational study.

BACKGROUND AND PURPOSE: Due to the rarity of male breast cancer (male BC), no consensus has been reached regarding the most appropriate curative treatment strategy. The objective of the present observational study was to identify patient and tumor characteristics and assess the role of radiotherapy (RT) in clinical practice. METHODS: Between 1998 and 2014, data of male BC patients treated at two breast centers were consecutively collected and retrospectively analyzed. Patients were stratified based on the addition of adjuvant RT. Data on overall survival (OS) and local recurrence-free survival (LRFS) were estimated with the Kaplan-Meier method and compared by the log-rank test. RESULTS: A consecutive cohort of 58 male BC patients was evaluated. Median follow-up was 56 months. Twenty-one patients (36.2%) received adjuvant RT. Overall, patients undergoing postoperative RT were characterized by more high-risk features. Patients receiving postoperative RT had significantly more frequently a high UICC stage (50 vs. 9.7% UICC III, p = 0.018) and positive lymph nodes as compared to patients undergoing surgery alone (65 vs. 34.4% pN+, p = 0.046). Accordingly, there was a higher proportion of patients receiving axillary lymph node dissection in the RT group (71.4 vs. 35.6%). Mastectomy was performed in 31/37 (86.1%) in the surgery group as compared to 14/21 (66.7%) in patients receiving postoperative RT. In addition, RT patients were more likely to receive endocrine therapy (78.9 vs. 39.3%, p = 0.016). Outcome was not significantly different between the groups (5-year LRFS: 89.8 vs. 80.0%, p = 0.471 and 5­year OS 88.4 vs. 88.9%, p = 0.819). CONCLUSION: The present observational study evaluated the pattern of care in male BC patients treated in clinical practice. Due to its rarity, randomized clinical trials are unlikely and male BC remains an entity with a poor evidence base. Nevertheless, RT remains a crucial component of the multidisciplinary treatment strategy in male BC.

Does deep inspiration breath-hold prolong life? Individual risk estimates of ischaemic heart disease after breast cancer radiotherapy.

PURPOSE: Aim of the current comparative modelling study was to estimate the individual radiation-induced risk for death of ischaemic heart disease (IHD) under free breathing (FB) and deep inspiration breath-hold (DIBH) in a real-world population. MATERIALS AND METHODS: Eighty-nine patients with left-sided early breast cancer were enrolled in the prospective SAVE-HEART study. For each patient three-dimensional conformal treatment plans were created in FB and DIBH and corresponding radiation-induced risks of IHD mortality were estimated based on expected survival, individual IHD risk factors and the relative radiation-induced risk. RESULTS: With the use of DIBH, mean heart doses were reduced by 35% (interquartile range: 23-46%) as compared to FB. Mean expected years of life lost (YLL) due to radiation-induced IHD mortality were 0.11 years in FB, and 0.07 years in DIBH. YLL were remarkably independent of age at treatment in patients with a favourable tumour prognosis. DIBH led to more pronounced reductions in YLL in patients with high baseline risk (0.08 years for upper vs 0.02 years for lower quartile), with favourable tumour prognosis (0.05 years for patients without vs 0.02 years for those with lymph-node involvement), and in patients with high mean heart doses in FB (0.09 years for doses >3 Gy vs 0.02 years for doses <1.5 Gy). CONCLUSION: Ideally, the DIBH technique should be offered to all patients with left-sided breast cancer. However, highest benefits are expected for patients with a favourable tumour prognosis, high mean heart dose or high baseline IHD risk, independent of their age.

Dose variability in different lymph node levels during locoregional breast cancer irradiation: the impact of deep-inspiration breath hold.

PURPOSE: Aim of the present analysis was to evaluate the movement and dose variability of the different lymph node levels of node-positive breast cancer patients during adjuvant radiotherapy (RT) with regional nodal irradiation (RNI) in deep-inspiration breath hold (DIBH). METHODS: Thirty-five consecutive node-positive breast cancer patients treated from October 2016 to February 2018 receiving postoperative RT of the breast or chest wall including RNI of the supra-/infraclavicular lymph node levels (corresponding to levels IV, III, Rotter LN (interpectoral), and some parts of level II) were analyzed. To evaluate the lymph node level movement, a center of volume (COV) was obtained for each lymph node level for free-breathing (FB) and DIBH plans. Geometric shifts and dose differences between FB and DIBH were analyzed. RESULTS: A significant movement of the COV in anterior (y) and cranial (z) dimensions was observed for lymph node levels I-II and Rotter lymph nodes (p < 0.001) due to DIBH. Only minor changes in the lateral dimension (x axis) were observed, without reaching significance for levels III, IV, and internal mammary. There was a significant difference in the mean dose of level I (DIBH vs. FB: 38.2 Gy/41.3 Gy, p < 0.001) and level II (DIBH vs. FB: 45.9 Gy/47.2 Gy, p < 0.001), while there was no significant difference in level III (p = 0.298), level IV (p = 0.476), or internal mammary nodes (p = 0.471). CONCLUSION: A significant movement of the axillary lymph node levels was observed during DIBH in anterior and cranial directions for node-positive breast cancer patients in comparison to FB. The movement leads to a significant dose reduction in level I and level II.

Recent Developments in Radiation Oncology: An Overview of Individualised Treatment Strategies in Breast Cancer.

Radiation therapy (RT) for breast cancer has dramatically changed over the past years, leading to individualized risk-adapted treatment strategies. Historically, the choice of RT regimen was limited to conventional fractionation protocols using standard tangential fields. Nowadays, technological and technical improvements in modern RT have added a variety of other RT modalities, different fractionation schedules, and individualised treatment volumes to the portfolio of breast RT. This review aims to give a short overview on the main topics which have recently found their way into clinical practice: hypofractionated treatment protocols, accelerated partial breast irradiation (APBI) for low-risk patients, deep inspiration breath hold (DIBH) for maximal heart protection, extent of regional nodal irradiation for high-risk patients, and the implementation of new radiation techniques such as intensity modulated RT (IMRT) and volumetric modulated RT (VMAT).

Role of postoperative radiotherapy in reducing ipsilateral recurrence in DCIS: an observational study of 1048 cases.

BACKGROUND: The objective of the present study was to evaluate the effectiveness of postoperative radiotherapy after breast conserving surgery (BCS) in DCIS in a large patient population treated in clinical practice. METHODS: Data were provided by the population-based Munich Cancer Registry. Between 1998 and 2014, 1048 female patients with diagnosis of DCIS and treated at two Breast Care Centres were included in this observational study. The effectiveness of postoperative radiotherapy and variables predicting the use of radiotherapy were retrospectively analysed. RESULTS: After adjusting for age, tumour characteristics and therapies, Cox regression analysis for local recurrence-free survival identified RT as an independent predictor for improved local control (HR: 0.579; 95%CI: 0.384-0.872, p = 0.008). Ten-year cumulative incidence of in-breast recurrences was 20.0% following BCS, compared to 13.6% in patients receiving postoperative radiotherapy (p = 0.012). As an estimate for disease-specific survival, 10-year relative survival was 105.4% for patients receiving postoperative radiotherapy and 101.6% without radiotherapy. On multivariate analysis, postoperative radiotherapy was not associated with improved overall survival (HR 0.526; 95%CI: 0.263-1.052, p = 0.069). Over time, a significant increase of RT was registered: while 1998 only 42.9% of patients received postoperative radiotherapy, the proportion rose to 91.2% in 2014. Women aged < 50 years (OR: 2.559, 95%CI: 1.416-4.625, p < 0.001) or with negative hormone receptor status (OR: 2.625, 95%CI: 1.458-4.728, p = 0.001) or receiving endocrine therapy (OR: 1.762, 95%CI: 1.060-2.927, p = 0.029) were more likely to receive postoperative radiotherapy after BCS. CONCLUSIONS: In conclusion, this study provides insights regarding the adoption and treatment pattern of postoperative RT following BCS for DCIS in a large cohort reflecting "real-life" clinical practice in this setting. Postoperative RT was found to be associated with a reduced risk of ipsilateral recurrence and no survival benefit compared to observation alone.

The clinical significance of fibrinogen plasma levels in patients with diffuse large B cell lymphoma.

BACKGROUND: Fibrinogen plays a crucial role in the pathophysiology of tumour cell growth, invasion and metastasis. The aim of this study was to evaluate the prognostic significance of pretreatment plasma fibrinogen levels in patients with diffuse large B cell lymphoma (DLBCL) METHODS: Data from 372 patients with DLBCL, diagnosed and treated between 2004 and 2013 at two Austrian centres, were evaluated retrospectively. The prognostic influences of plasma fibrinogen levels and other factors, including age, tumour stage and the National Comprehensive Cancer Network-International Prognostic Index, on 5-year overall survival (OS) and 5-year disease-free survival (DFS) were studied using Kaplan-Meier curves as well as univariate and multivariate Cox regression models. RESULTS: Kaplan-Meier analysis revealed that a high fibrinogen plasma level is associated with decreased 5-year OS and 5-year DFS in patients with DLBCL (p<0.001, log-rank test). Furthermore, in multivariate analysis, elevated serum fibrinogen was found to be an independent marker of poor clinical outcome: 5-year OS (HR=1.69, 95% CI 1.06 to 2.72, p=0.029) and 5-year DFS (HR=1.68, 95% CI 1.08 to 2.61, p=0.021). CONCLUSIONS: In the current study, we demonstrate that high plasma fibrinogen levels at diagnosis predict poor outcome in patients with DLBCL. TRIAL REGISTRATION NUMBER: 25-434 ex 12713 and 415-EP/73/127-2012.

Preoperative serum-gamma-glutamyltransferase (GGT) does not represent an independent prognostic factor in a European cohort of patients with non-metastatic renal cell carcinoma.

AIMS: Increasing evidence suggests that the serum-gamma-glutamyltransferase (GGT) might correlate with tumour development and growth rates in various human cancer types. Thus, we decided to investigate the potential prognostic impact of the preoperatively assessed serum-GGT in a European cohort of patients with non-metastatic renal cell carcinoma (RCC). METHODS: Clinicopathological data from 700 consecutive patients with non-metastatic RCC, operated between 2000 and 2010 at a single tertiary academic centre, were evaluated retrospectively. Preoperative serum-GGT was assessed 1 day before surgery. Patients were categorised using a serum-GGT cut-off value of 40 U/L according to a calculation by receiver operating curve analysis. Patients' cancer-specific survival (CSS), metastasis-free survival (MFS), as well as overall survival (OS) were assessed using the Kaplan-Meier method and Cox proportional models. RESULTS: In univariate analysis, an elevated preoperative serum-GGT level (<40 U/L vs ≥40 U/L) was statistically significantly associated with a shorter MFS (HR=1.517, 95% CI 1.047 to 2.197, p=0.027). In multivariate analyses, pathological T-Stage (pT-1 vs pT-2-4, HR=2.065, 95% CI 1.665 to 2.560), tumour grade (G-1+G-2 vs G-3+G-4, HR=1.671, 95% CI 1.261 to 2.213), as well as the presence of histological tumour necrosis (No vs Yes, HR=2.031, 95% CI 1.355 to 3.046) were independent predictors of MFS in patients with RCC, whereas the preoperative serum-GGT failed to reach independent predictor status (<40 U/L vs ≥40 U/L, HR=1.156, 95% CI 0.791 to 1.690). No prognostic role for GGT in OS or CSS could be identified. CONCLUSIONS: In the cohort studied, patients with an elevated (≥40 U/L) preoperative serum-GGT had a subsequently shorter MFS only in univariate analysis. In contrast to previous studies, our data failed to demonstrate preoperatively assessed serum-GGT as an independent prognostic factor in patients with non-metastatic RCC.

Combination of tumour markers CEA and CA19-9 improves the prognostic prediction in patients with pancreatic cancer.

AIMS: Tumour markers including carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA19-9) are frequently determined at the time of diagnosis in patients with pancreatic cancer. Several studies indicate a prognostic relevance of these markers in pancreatic cancer, but space for improvement with regard to the predictive accuracy and ability is given. In this work, the main focus is on mathematical combinations of these two tumour markers in order to validate an improvement of prognostic test results in terms of sensitivity and specificity. METHODS: This retrospective study includes 393 patients with pancreatic cancer, who were treated between the years 2005 and 2012 at the Division of Oncology, Medical University of Graz, Austria. The goal of this study was to explore whether an appropriate combination of two tumour markers leads to a statistically significant improvement of the prognostic prediction. RESULTS: Receiver operating characteristic curves comparison analyses with the classification variable cancer-specific survival showed that the mathematical product of two tumour markers (TM(product)= (CEA×CA19-9); area under the curve (AUC)=0.727; 95% CI 0.680 to 0.770) is significantly better than CEA alone (AUC=0.644; 95% CI 0.594 to 0.691; p=0.003) but not significant compared with CA19-9 (AUC=0.710; 95% CI 0.662 to 0.754; p=0.1215). A linear combination of CEA and CA19-9 (TM(linear)=(85×CEA+CA19-9); AUC=0.748; 95% CI 0.702 to 0.790) is significantly better than CEA (p<0.0001) as well as CA19-9 alone (p=0.0304). CONCLUSIONS: Mathematical combinations of pretherapeutic tumour markers CEA and CA19-9 are feasible and can significantly improve the prognostic prediction in patients with pancreatic cancer.

The significance of pretreatment anemia in the era of R-IPI and NCCN-IPI prognostic risk assessment tools: a dual-center study in diffuse large B-cell lymphoma patients.

BACKGROUND: Anemia is frequently identified at the time of diagnosis in patients with diffuse large B-cell lymphoma (DLBCL); however, studies addressing the prognostic significance of this important clinical parameter are lacking. METHODS: In this dual-center study of patients with DLBCL (n = 556) treated with rituximab-containing regimens, we evaluated the prognostic relevance of anemia at diagnosis in a training set (n = 211) and validated our findings in a second independent patient cohort (n = 345). Using Kaplan-Meier curves as well as univariate and multivariate Cox regression models, we analyzed the impact of anemia on 5-year overall survival (OS) and 5-year disease-free survival (DFS) alongside established prognostic indicators including age, tumor stage, the revised International Prognostic Index (R-IPI), and the recently published NCCN-IPI. The influence of anemia on the predictive accuracy of IPI, R-IPI, and NCCN-IPI prognosis scores was subsequently determined using the Harrell's concordance index. RESULTS: Anemia was an independent predictor of impaired OS and DFS at 5 years in both DLBCL patient cohorts (P < 0.001, log-rank test). In multivariate analysis, hemoglobin level was also a strong and independent prognostic indicator in patients stratified according to R-IPI or NCCN-IPI score. In survival analysis, the estimated concordance index, using IPI, R-IPI, and NCCN-IPI stratification measures (0.69, 0.64, and 0.70, respectively), improved to 0.70, 0.68, and 0.73, respectively, when anemia was also considered. CONCLUSION: In this study, we have demonstrated that anemia at the time of diagnosis is an independent predictor of impaired clinical outcome in DLBCL. Furthermore, consideration of hemoglobin levels may improve the accuracy of recently established prognostic tools in lymphoma. Our data encourage further evaluation of the prognostic utility of this readily accessible biological parameter in prospective clinical trials.

Evaluation of uric acid as a prognostic blood-based marker in a large cohort of pancreatic cancer patients.

BACKGROUND: Recently, chemical blood parameters gain more attraction as potential prognostic parameters in pancreatic cancer (PC). In the present study we investigated the prognostic relevance of the uric acid (UA) level in blood plasma at the time of diagnosis for overall survival (OS) in a large cohort of patients with PC. PATIENTS AND METHODS: Data from 466 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival (OS) was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of the UA level, univariate and multivariate Cox regression models were calculated. RESULTS: None of the clinicopathological parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI) or surgical resection) except gender was associated with UA level. In univariate analysis we observed the elevated UA level (<5.1 versus ≥5.1 mg/dl, p = 0.017) as poor prognostic factor for OS. In the multivariate analysis that included age, gender, tumour grade, tumour stage, surgical resection, CA19-9 level, the KI and UA level we confirmed the UA level as independent prognostic factor for OS (HR = 1.373%; CI = 1.077-1.751; p = 0.011). CONCLUSION: In conclusion, we identified the UA level at time of diagnosis as an independent prognostic factor in PC patients. Our results indicate that the UA level might represent a novel and useful marker for patient stratification in PC management.