Incidence of Morphea following Adjuvant Irradiation of the Breast in 2,268 Patients.

BACKGROUND: Morphea of the breast is an autoimmune reaction of the subcutaneous connective tissue which can be triggered by exposure to ionizing radiation. The literature suggests incidence rates of 1:500 to 1:3,000 which, however, do not seem to match the very small number of cases reported. OBJECTIVES: The aim of the present study was to determine the incidence of morphea following irradiation of the breast in order to generate more evidence about the frequency of this serious and mutilating complication. METHOD: Retrospective analysis of patient data who underwent adjuvant radiotherapy in the period 2009-2018 following breast-conserving surgery and who made use of the recommended radiooncology follow-up examinations in 2018. Analysis was done by descriptive statistics. RESULTS: Of a total of 5,129 patients who had undergone radiotherapy over a 10-year period, follow-up data were available in 2,268 patients. In 2,236 patients (98.6%) the breast had been irradiated using conventional fractionation schemes with a total dose of 50-50.4 Gy; 32 (1.4%) were given a total dose of 40.05 Gy in 15 fractions. During the observation period, 6 patients were diagnosed with morphea (4 unilateral and 2 bilateral) by punch biopsies resulting in a cumulative incidence proportion of 0.26% (95% CI: 0.24-0.28), translating into 1 case for every 378 irradiated patients. CONCLUSIONS: In the case studies reported to date, morphea is described as a very rare complication. In contrast, our data suggest a cumulative incidence of 1:378, which is higher than other authors have estimated. This leads us to suspect that in a large number of patients, morphea is incorrectly diagnosed as an infection (in the early stages) and radiation-induced fibrosis (in later stages).

Clinical parameters predictive for sphincter-preserving surgery and prognostic outcome in patients with locally advanced low rectal cancer.

BACKGROUND: Although controversial, there are data suggesting that clinical parameters can predict the probability of sphincter preserving procedures in rectal cancer. The purpose of this study was to investigate the association between clinical parameters and the sphincter-preserving surgery rate in patients who had undergone neoadjuvant combination therapy for advanced low rectal cancer. METHODS: In this single center study, the charts of 540 patients with locally advanced rectal cancer who had been treated with induction chemotherapy-and/or neoadjuvant concomitant radiochemotherapy (nRCT) over an 11-year period were reviewed in order to identify patients with rectal cancer ≤6 cm from the anal verge, who had received the prescribed nRCT only. Univariate and multivariate analyses were used to identify pretreatment patient- and tumor associated parameters correlating with sphincter preservation. Survival rates were calculated using Kaplan-Meier analyses. RESULTS: Two hundred eighty of the 540 patients met the selection criteria. Of the 280 patients included in the study, 158 (56.4%) underwent sphincter-preserving surgery. One hundred sixty-four of 280 patients (58.6%) had a downsizing of the primary tumor (ypT < cT) and 39 (23.8%) of these showed a complete histopathological response (ypT0 ypN0). In univariate analysis, age prior to treatment, Karnofsky performance status, clinical T-size, relative lymphocyte value, CRP value, and interval between nRCT and surgery, were significantly associated with sphincter-preserving surgery. In multivariate analysis, age (hazard ratio (HR) = 1.05, CI95%: 1.02-1.09, p = 0.003), relative lymphocyte value (HR = 0.94, CI95%: 0.89-0.99, p = 0.029), and interval between nRCT and surgery (HR = 2.39, CI95%: 1.17-4.88, p = 0.016) remained as independent predictive parameters. CONCLUSIONS: These clinical parameters can be considered in the prognostication of sphincter-preserving surgery in case of low rectal adenocarcinoma. More future research is required in this area.

Endocrine therapy with or without whole breast irradiation in low-risk breast cancer patients after breast-conserving surgery: 10-year results of the Austrian Breast and Colorectal Cancer Study Group 8A trial.

PURPOSE: To investigate long-term results of patients with hormonal receptor-positive breast cancer treated with breast-conserving surgery (BCS) and consecutive endocrine therapy (ET) with or without whole breast irradiation (WBI). METHODS AND MATERIALS: Within the 8 A trial of the Austrian Breast and Colorectal Cancer Study Group, a total of 869 patients received ET after BCS which was randomly followed by WBI (n = 439, group 1) or observation (n = 430, group 2). WBI was applied up to a mean total dosage of 50 Gy (+/- 10 Gy boost) in conventional fractionation. RESULTS: After a median follow-up of 9.89 years, 10 in-breast recurrences (IBRs) were observed in group 1 and 31 in group 2, resulting in a 10-year local recurrence-free survival (LRFS) of 97.5% and 92.4%, respectively (p = 0.004). This translated into significantly higher rates for disease-free survival (DFS): 94.5% group 1 vs 88.4% group 2, p = 0.0156. For distant metastases-free survival (DMFS) and overall survival (OS), respective 10-year rates amounted 96.7% and 86.6% for group 1 versus 96.4% and 87.6%, for group 2 (ns). WBI (hazard ratio [HR]: 0.27, p < 0.01) and tumour grading (HR: 3.76, p = 0.03) were found as significant predictors for IBR in multiple cox regression analysis. CONCLUSIONS: After a median follow-up of 10 years, WBI resulted in a better local control and DFS compared with ET alone. The omission of WBI and tumour grading, respectively, were the only negative predictors for LRFS.

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.

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.

Testing the feasibility of augmented digital skin imaging to objectively compare the efficacy of topical treatments for radiodermatitis.

INTRODUCTION: Radiation-induced dermatitis (RID) is routinely graded by visual inspection. Inter-observer variability makes this approach inadequate for an objective assessment of the efficacy of different topical treatments. In this study we report on the first clinical application of a new image-analysis tool developed to measure the relevant effects quantitatively and to compare the effects of two different topical preparations used to treat RID. MATERIALS AND METHODS: After completion of radiotherapy, RID was retrospectively assessed in 100 white female breast cancer patients who had received adjuvant breast irradiation. Of these patients, 34 were treated with R1&R2, a Lactokine-fluid derived from milk proteins, and 66 were treated with Bepanthen. In addition RID was graded independently by two experienced radiation oncologists in accordance with the Common Terminology Criteria for Adverse Events (CTCAE). For quantitative evaluation, the irradiated breast and the non-irradiated contralateral breast were photographed in a standardized manner including a color reference card. For analysis, all images were converted into the color space L*a*b* and mean values were calculated for each of the color parameters. RESULTS: The CTCAE-based grading revealed statistically significant inter-observer variability in the scoring of RID Grades 1, 2 and 3 (p<0.001). A difference between the two topical products could not be observed with visual inspection. By using augmented image analysis methods a statistically significant increase in a*-values (mean 4.15; 95%CI: 5.97-2.33, p<0.001) in patients treated with R1&R2 indicated more intense reddening. Digital subtraction was used to eliminate differences in individual baseline skin tone to generate a new, low-scatter parameter (ΔSEV). CONCLUSIONS: Visual CTCAE-based evaluation of RID was not suitable for assessing the efficacy of the skin treatment products. In contrast, the novel image analysis enabled a quantitative evaluation independent of skin type and baseline skin tone in our cohort suggesting that augmented image analysis may be a suitable tool for this type of investigation. Prospective studies are needed to validate our findings.

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.

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.

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.

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.

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.

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.

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.

Preoperative treatment with capecitabine, cetuximab and radiotherapy for primary locally advanced rectal cancer--a phase II clinical trial.

BACKGROUND/AIM: To investigate the feasibility and safety of preoperative capecitabine, cetuximab and radiation in patients with MRI-defined locally advanced rectal cancer (LARC, cT3/T4). PATIENTS AND METHODS: 31 patients with LARC were treated with cetuximab and capecitabine concomitantly with 45 Gy radiotherapy and resected by total mesorectal excision. Histopathological response and association with KRAS status was evaluated. RESULTS: R0-resection was possible in 27 of 31 (86%) patients. No complete pathological remission was observed. Radiochemotherapy with capecitabine and cetuximab was safe to administer and diarrhea was the main toxicity. KRAS-status did not correlate to down-staging or pathological response concerning T- or N-stage. CONCLUSION: Neoadjuvant therapy with capecitabine and cetuximab in combination with radiotherapy did not lead to complete pathological remission. Treatment tolerability was excellent and toxicity remained low. KRAS status did not influence treatment outcomes. Capecitabine in combination with radiotherapy remains a standard therapy for locally advanced rectal cancer.

Local tumour control and eye preservation after gamma-knife radiosurgery of choroidal melanomas.

BACKGROUND/AIMS: To report on local tumour control and eye preservation after gamma knife radiosurgery (GK-RS) to treat choroidal melanomas. METHODS: A total of 189 patients with choroidal melanoma were treated with GK-RS, with treatment doses between 25 and 80 Grays. The main outcome measures of our retrospective analysis were local tumour control, time to recurrence, eye retention rate and the reason for and time to secondary enucleation. Patient-associated, tumour-associated and treatment-associated parameters were evaluated as potential risk factors. RESULTS: Local tumour control was achieved in 94.4% of patients. The estimated tumour control rates were 97.6% at 1 year, 94.2% at 5 years and 92.4% at 10 years after treatment. Recurrence was observed between 3.1 months and 60.7 months post-treatment (median: 13.5 months). Advanced tumour stage (Tumour, Node, Metastasis (TNM) 3-4) was the most important risk factor for recurrence (Fine-Gray model; subhazard ratio, SHR: 3.3; p=0.079). The treatment dose was not related to tumour recurrence. The eye preservation rate was 81.6% at 5 years after treatment, remaining stable thereafter. Twenty-five eyes (14.1%) had to be enucleated at between 17 days and 68.0 months (median: 13.9 months) after GK-RS, and advanced tumour stage (Cox model; p=0.005), treatment dose (p=0.048), pretreatment visual acuity (p=0.016), and retinal detachment (p=0.027) were risk factors for requiring enucleation. CONCLUSIONS: GK-RS achieved a high tumour control rate, comparable to linear accelerator-based radiotherapy. Advanced TNM stage was a predictive risk factor for tumour recurrence and for secondary enucleation after GK-RS. Lower treatment doses were unrelated to tumour recurrence, although they were associated with an improved eye retention rate.

Induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy with cetuximab for locally advanced squamous cell carcinoma of the head and neck.

PURPOSE: To determine the efficacy and feasibility of induction chemotherapy (ICT) with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy and cetuximab (C) in patients with locally advanced head and neck cancer. PATIENTS AND METHODS: Forty-nine previously untreated patients with local advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) received three courses of ICT consisting of docetaxel 75mg/m(2) day 1, cisplatin 75mg/m(2) day 1 and infusional 5-fluorouracil 750mg/m(2)/day on days 1-5 followed by radiotherapy plus C at 250mg/m(2)/week (after an initial loading dose of 400mg/m(2)). RESULTS: After completion of ICT 44 of 49 patients received radiotherapy plus C. Three months after therapy completion tumour response was observed in 33 patients and after two years, 25 patients were in complete remission (CR). The most common grade 4 toxicity during the whole treatment period was dermatitis (30%), followed by mucositis (27%) and neutropenia (17%) without fever. One toxic related death was observed during ICT. Two-year progression-free survival (PFS) rate was 59% and two-year overall survival (OS) rate was 63%, respectively. CONCLUSION: Concurrent radiotherapy plus C after three courses of ICT was feasible and was associated with promising CR, PFS and OS rates. Further optimisation of dose and sequence is warranted.

Quantification of contralateral breast dose and risk estimate of radiation-induced contralateral breast cancer among young women using tangential fields and different modes of breathing.

PURPOSE: Whole breast irradiation with deep-inspiration breath-hold (DIBH) technique among left-sided breast cancer patients significantly reduces cardiac irradiation; however, a potential disadvantage is increased incidental irradiation of the contralateral breast. METHODS AND MATERIALS: Contralateral breast dose (CBD) was calculated by comparing 400 treatment plans of 200 left-sided breast cancer patients whose tangential fields had been planned on gated and nongated CT data sets. Various anatomic and field parameters were analyzed for their impact on CBD. For a subgroup of patients (aged ≤45 years) second cancer risk in the contralateral breast (CB) was modeled by applying the linear quadratic model, compound models, and compound models considering dose-volume information (DVH). RESULTS: The mean CBD was significantly higher in DIBH with 0.69 Gy compared with 0.65 Gy in normal breathing (P=.01). The greatest impact on CBD was due to a shift of the inner field margin toward the CB in DIBH (mean 0.4 cm; range, 0-2), followed by field size in magnitude. Calculation with different risk models for CBC revealed values of excess relative risk/Gy ranging from 0.48-0.65 vs 0.46-0.61 for DIBH vs normal breathing, respectively. CONCLUSION: Contralateral breast dose, although within a low dose range, was mildly but significantly increased in 200 treatment plans generated under gated conditions, predominately due to a shift in the medial field margin. Risk modeling for CBC among women aged ≤45 years also pointed to a higher risk when comparing DIBH with normal breathing. This risk, however, was substantially lower in the model considering DVH information. We think that clinical decisions should not be affected by this small increase in CBD with DIBH because DIBH is effective in reducing the dose to the heart in all patients.

Karnofsky performance status and lactate dehydrogenase predict the benefit of palliative whole-brain irradiation in patients with advanced intra- and extracranial metastases from malignant melanoma.

PURPOSE: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. METHODS AND MATERIALS: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. RESULTS: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. CONCLUSIONS: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.