The Pre-Treatment Platelet-to-Lymphocyte Ratio as a Prognostic Factor for Loco-Regional Control in Locally Advanced Rectal Cancer.

Chronic inflammatory reactions have been proven to represent relevant mechanisms for the development and progression of cancer in numerous tumor entities. There is evidence that the platelet-to-lymphocyte ratio (PLR) is associated with the prognostic outcome. In rectal cancer, the prognostic role of this parameter has not yet been conclusively clarified. The aim of this study was to further clarify the prognostic significance of the pre-treatment PLR in patients with locally advanced rectal cancer (LARC). In the present study, 603 patients with LARC, who were treated with neoadjuvant chemoradiotherapy (nCRT) and subsequent surgical resection between 2004 and 2019, were retrospectively evaluated. The influence of clinico-pathological and laboratory factors on locoregional control (LC), metastasis-free survival (MFS) and overall survival (OS) was investigated. In univariate analyses, high PLR was significantly associated with worse LC (p = 0.017) and OS (p = 0.008). In multivariate analyses, the PLR remained an independent parameter for the LC (HR = 1.005, 95% CI: 1.000-1.009, p = 0.050). Pre-treatment lactate dehydrogenase (LDH) (HR: 1.005 95% CI:1.002-1.008; p = 0.001) and carcinoembryonic antigen (CEA) (HR: 1.006, 95% CI:1.003-1.009; p < 0.001) were independent predictors for MFS; additionally, age (HR: 1.052, 95% CI:1.023-1.081; p < 0.001), LDH (HR: 1.003, 95% CI:1.000-1.007; p = 0.029) and CEA (HR: 1.006, 95% CI:1.003-1.009; p < 0.001) independently predicted OS. Pre-treatment PLR before nCRT is an independent prognostic factor for LC in LARC, which could be used to further individualize tumor treatment.

Patterns of Disease Progression and Outcome of Patients With Testicular Seminoma Who Relapse After Adjuvant or Curative Radiation Therapy.

PURPOSE: Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy. METHODS AND MATERIALS: Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse. RESULTS: With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients' symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression. CONCLUSIONS: Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy.

The mathematics of erythema: Development of machine learning models for artificial intelligence assisted measurement and severity scoring of radiation induced dermatitis.

Although significant advancements in computer-aided diagnostics using artificial intelligence (AI) have been made, to date, no viable method for radiation-induced skin reaction (RISR) analysis and classification is available. The objective of this single-center study was to develop machine learning and deep learning approaches using deep convolutional neural networks (CNNs) for automatic classification of RISRs according to the Common Terminology Criteria for Adverse Events (CTCAE) grading system. ScarletredⓇ Vision, a novel and state-of-the-art digital skin imaging method capable of remote monitoring and objective assessment of acute RISRs was used to convert 2D digital skin images using the CIELAB color space and conduct SEV* measurements. A set of different machine learning and deep convolutional neural network-based algorithms has been explored for the automatic classification of RISRs. A total of 2263 distinct images from 209 patients were analyzed for training and testing the machine learning and CNN algorithms. For a 2-class problem of healthy skin (grade 0) versus erythema (grade ≥ 1), all machine learning models produced an accuracy of above 70%, and the sensitivity and specificity of erythema recognition were 67-72% and 72-83%, respectively. The CNN produced a test accuracy of 74%, sensitivity of 66%, and specificity of 83% for predicting healthy and erythema cases. For the severity grade prediction of a 3-class problem (grade 0 versus 1 versus 2), the overall test accuracy was 60-67%, and the sensitivities were 56-82%, 35-59%, and 65-72%, respectively. For estimating the severity grade of each class, the CNN obtained an accuracy of 73%, 66%, and 82%, respectively. Ensemble learning combines several individual predictions to obtain a better generalization performance. Furthermore, we exploited ensemble learning by deploying a CNN model as a meta-learner. The ensemble CNN based on bagging and majority voting shows an accuracy, sensitivity and specificity of 87%, 90%, and 82% for a 2-class problem, respectively. For a 3-class problem, the ensemble CNN shows an overall accuracy of 66%, while for each grade (0, 1, and 2) accuracies were 76%, 69%, and 87%, sensitivities were 70%, 57%, and 71%, and specificities were 78%, 75%, and 95%, respectively. This study is the first to focus on erythema in radiation-dermatitis and produces benchmark results using machine learning models. The outcome of this study validates that the proposed system can act as a pre-screening and decision support tool for oncologists or patients to provide fast, reliable, and efficient assessment of erythema grading.

Can Pre-Treatment Inflammatory Parameters Predict the Probability of Sphincter-Preserving Surgery in Patients with Locally Advanced Low-Lying Rectal Cancer?

There is evidence suggesting that pre-treatment clinical parameters can predict the probability of sphincter-preserving surgery in rectal cancer; however, to date, data on the predictive role of inflammatory parameters on the sphincter-preservation rate are not available. The aim of the present cohort study was to investigate the association between inflammation-based parameters and the sphincter-preserving surgery rate in patients with low-lying locally advanced rectal cancer (LARC). A total of 848 patients with LARC undergoing radiotherapy from 2004 to 2019 were retrospectively reviewed in order to identify patients with rectal cancer localized ≤6 cm from the anal verge, treated with neo-adjuvant radiochemotherapy (nRCT) and subsequent surgery. Univariable and multivariable analyses were used to investigate the role of pre-treatment inflammatory parameters, including the C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for the prediction of sphincter preservation. A total of 363 patients met the inclusion criteria; among them, 210 patients (57.9%) underwent sphincter-preserving surgery, and in 153 patients (42.1%), an abdominoperineal rectum resection was performed. Univariable analysis showed a significant association of the pre-treatment CRP value (OR = 2.548, 95% CI: 1.584-4.097, p < 0.001) with sphincter preservation, whereas the pre-treatment NLR (OR = 1.098, 95% CI: 0.976-1.235, p = 0.120) and PLR (OR = 1.002, 95% CI: 1.000-1.005, p = 0.062) were not significantly associated with the type of surgery. In multivariable analysis, the pre-treatment CRP value (OR = 2.544; 95% CI: 1.314-4.926; p = 0.006) was identified as an independent predictive factor for sphincter-preserving surgery. The findings of the present study suggest that the pre-treatment CRP value represents an independent parameter predicting the probability of sphincter-preserving surgery in patients with low-lying LARC.

The AST/ALT (De Ritis) Ratio Predicts Survival in Patients with Oral and Oropharyngeal Cancer.

Aminotransaminases, including aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), are strongly involved in cancer cell metabolism and have been associated with prognosis in different types of cancer. The purpose of the present study was to evaluate the prognostic significance of the pre-treatment AST/ALT ratio in a large European cohort of patients with oral and oropharyngeal squamous cell cancer (OOSCC). Data from 515 patients treated for OOSCC at a tertiary academic center from 2000-2017 were retrospectively analyzed. Levels of AST and ALT were measured prior to the start of treatment. Uni- and multivariate Cox regression analyses were applied to evaluate the prognostic value of the AST/ALT ratio for cancer-specific survival (CSS) and overall survival (OS), survival rates were calculated. Univariate analyses showed a significant association of the AST/ALT ratio with CSS (hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.38-2.12; p < 0.001) and OS (HR 1.69, 95% CI 1.41-2.02; p < 0.001). In multivariate analysis, the AST/ALT ratio remained an independent prognostic factor for CSS and OS (HR 1.45, 95% CI 1.12-1.88, p = 0.005 and HR 1.42, 95% CI 1.14-1.77, p = 0.002). Applying receiver operating characteristics (ROC) curve analysis, the optimal cut-off level for the AST/ALT ratio was 1.44, respectively. In multivariate analysis, an AST/ALT ratio > 1.44 was an independent prognostic factor for poor CSS and OS (HR 1.64, 95% CI 1.10-2.43, p = 0.014 and HR 1.55, 95% CI 1.12-2.15; p = 0.008). We conclude that the AST/ALT ratio is a prognostic marker for survival in OOSCC patients and could contribute to a better risk stratification and improved oncological therapy decisions.

The decreased mean platelet volume is associated with poor prognosis in patients with oropharyngeal cancer treated with radiotherapy.

BACKGROUND: There is considerable evidence that platelets contribute to cancer growth and metastatic dissemination. In recent studies, altered mean platelet volume (MPV) has been associated with prognosis in different types of cancer. However, the prognostic role of the MPV in head and neck squamous cell cancer (HNSCC) is currently discussed controversially. The present study was performed to analyze and further elucidate the prognostic significance of the MPV in HNSCC. METHODS: A total of 319 oropharyngeal squamous cell cancer (OPSCC) patients treated with radiotherapy at a tertiary academic center were enrolled in the present study. Kaplan-Meier method as well as uni- and multivariate Cox proportional hazards were used to evaluate the impact of MPV on cancer-specific survival (CSS), locoregional control (LC) and recurrence-free survival (RFS). RESULTS: The median MPV was 10.30 fL (mean 10.26 ± 1.17fL). Univariate analyses showed a significant association of the MPV with CSS (HR 0.85, 95% CI 0.74-0.98, p = 0.025), LC (HR 0.86, 95% CI 0.74-0.99, p = 0.034) and RFS (HR 0.87, 95% CI 0.76-0.996; p = 0.043). In multivariate analysis, the MPV remained an independent prognostic factor for CSS (HR 0.77, 95% CI 0.63-0.93, p = 0.008), LC (HR 0.80, 95% CI 0.65-0.98, p = 0.030), and RFS (HR 0.83, 95% CI 0.685-0.999, p = 0.049). CONCLUSIONS: Our findings indicate that the MPV is a prognostic marker in OPSCC patients and may contribute to future individual risk assessment.

The Elevated Pre-Treatment C-Reactive Protein Predicts Poor Prognosis in Patients with Locally Advanced Rectal Cancer Treated with Neo-Adjuvant Radiochemotherapy.

The aim of the present study was to investigate the association of the pre-treatment C-reactive protein (CRP) plasma level with survival outcomes in a cohort of 423 consecutive patients with locally advanced rectal cancer treated with neo-adjuvant radiochemotherapy followed by surgical resection. To evaluate the prognostic value of the CRP level for clinical endpoints recurrence-free survival (RFS), local-regional control (LC), metastases-free survival (MFS), and overall survival (OS), uni- and multivariate Cox regression analyses were applied, and survival rates were calculated using Kaplan-Meier analysis. The median follow-up time was 73 months. In univariate analyses, the pre-treatment CRP level was a significant predictor of RFS (hazard ratio (HR) 1.015, 95% CI 1.006-1.023; p < 0.001), LC (HR 1.015, 95% CI 1.004-1.027; p = 0.009), MFS (HR 1.014, 95% CI 1.004-1.023; p = 0.004), and OS (HR 1.016, 95% CI 1.007-1.024; p < 0.001). Additionally, univariate analysis identified the MRI circumferential resection margin (mrCRM) and pre-treatment carcinoembryonic antigen (CEA) as significant predictor of RFS (HR 2.082, 95% CI 1.106-3.919; p = 0.023 and HR 1.005, 95% CI 1.002-1.008; p < 0.001). Univariate analysis also revealed a significant association of the mrCRM (HR 2.089, 95% CI 1.052-4.147; p = 0.035) and CEA (HR 1.006, 95% CI 1.003-1.008; p < 0.001) with MFS. Age and CEA were prognostic factors for OS (HR 1.039, 95% CI 1.013-1.066; p = 0.003 and HR 1.005, 95% CI 1.002-1.008; p < 0.001). In multivariate analysis that included parameters with a p-level < 0.20 in univariate analysis, the pre-treatment CRP remained a significant prognostic factor for RFS (HR 1.013, 95%CI 1.001-1.025; p = 0.036), LC (HR 1.014, 95% CI 1.001-1.027; p = 0.031), and MFS (HR 1.013, 95% CI 1.000-1.027; p = 0.046). The results support the hypothesis that an elevated pre-treatment CRP level is a predictor of poor outcome. If confirmed by additional studies, this easily measurable biomarker could contribute to the identification of patients who might be candidates for more aggressive local or systemic treatment approaches or the administration of anti-inflammatory drugs.

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).

Commissioning, dosimetric characterization and machine performance assessment of the LIAC HWL mobile accelerator for Intraoperative Radiotherapy.

BACKGROUND: The LIAC HWL (Sordina IORT Technologies, Vicenza, Italy) is a recently designed mobile linear accelerator for intraoperative electron radiotherapy (IOeRT), producing high dose rate electron beams at four different energy levels. It features a software tool for the visualization of 2D dose distributions, which is based on Monte Carlo simulations. The aims of this work were to (i) assess the dosimetric characteristics of the accelerator, (ii) experimentally verify calculated data exported from the software and (iii) report on commissioning as well as performance of the system during the first year of operation. METHODS: The electron energies of the LIAC HWL used in this study are 6, 8, 10 and 12 MeV. Diameters of the cylindrically shaped applicators range from 3 to 10cm. We studied two applicator sets with different length ratios of proximal and terminal applicator sections. Reference dosimetry, linearity as well as short- and long-term stability were measured with a PTW Advanced Markus chamber, relative depth dose and profiles were measured using an unshielded diode. Percentage-depth-dose (PDD) and transversal dose profile (TDP) data were exported from the simulation software LIACSim and compared with our measurements. RESULTS: The device reaches dose rates up to 40Gy/min (for 12 MeV). Surface doses for the 10cm applicators are higher than 90%, X-ray background is below 0.6% for all energies. Simulations and measurements of PDD agreed well, with a maximum difference in the depth of the 50% isodose of 0.7mm for the flat-ended applicators and 1mm for the beveled applicators. The simulations slightly underestimate the dose in the lateral parts of the field (difference < 1.8% for flat-ended applicators). The two different applicator sets were dosimetrically equivalent. Long-term stability measurements for the first year of operation ranged from -2.1% to 1.6% (mean: -0.1%). CONCLUSIONS: The system is dosimetrically well suited for IOeRT and performed stably and reliably. The software tool for visualization of dose distributions can be used to support treatment planning, following thorough validation.

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.

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.

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.

128 SHADES OF RED: Objective Remote Assessment of Radiation Dermatitis by Augmented Digital Skin Imaging.

The purpose of our investigation was to develop a novel and state of the art digital skin imaging method capable for remote monitoring and objective assessment of Radiation Induced Dermatitis (RID). Therefore, radiation therapy related side effects were assessed by medical experts according to Common Terminology Criteria for Adverse Events (CTCAE) grade of severity in 20 female breast cancer patients in a clinical trial over the treatment time frame of 25-28 radiation cycles, 50.0-50.4 Gy each. Furthermore the intensity of developed skin erythema was documented by using conventional spectrophotometry plus digital skin imaging. Thereby we could derive the Standardized Erythema Value (SEV), a novel objective parameter, which in contrast to single parametric L* and a* delivers a long dynamic measurement range for analyzing RID from bright to very dark skin tones. Methodical superiority of the SEV could be proven over spectrophotometer measurements in terms of a higher sensitivity and by enabling signal intensity mapping in analyzed skin images. Our thereupon-derived patent enables novel objective dermatologic eHealth applications in a broad range of medical and industrial use by opening likewise the window for augmented dermatology. The first of its kind system is now already further developed in form of the medical device product Scarletred®Vision. It is available on the market for primary usage in clinical trials and in medical routine.

KPS/LDH index: a simple tool for identifying patients with metastatic melanoma who are unlikely to benefit from palliative whole brain radiotherapy.

PURPOSE: Low Karnofsky performance status (KPS) and elevated lactate dehydrogenases (LDHs) as a surrogate marker for tumor load and cell turnover may depict patients with a very short life expectancy. To validate this finding and compare it to other indices, namely, the recursive partitioning analysis (RPA) and diagnosis-specific graded prognostic assessment (DS-GPA), a multicenter analysis was undertaken. METHODS: A retrospective analysis of 234 metastatic melanoma patients uniformly treated with palliative whole brain radiotherapy (WBRT) was done. Univariate and multivariate analyses were used to determine the impact of patient-, tumor-, and treatment-related parameters on overall survival (OS). RESULTS: KPS and LDH emerged as independent factors predicting OS. By combining KPS and LDH values (KPS/LDH index), groups of patients with statistically significant differences in median OS (days; 95 % CI) after onset of WBRT were identified: group 1 (KPS ≥ 70/normal LDH) 234 (96-372), group 2 (KPS ≥ 70/elevated LDH) 112 (69-155), group 3 (KPS <70/normal LDH) 43 (12-74), and group 4 (KPS <70/elevated LDH) 29 (17-41). Between all four groups, statistically significant differences were observed. The RPA and DS-GPA indices failed to distinguish significantly between good and moderate prognosis and were inferior in predicting a very unfavorable prognosis. CONCLUSIONS: The parameters KPS and LDH independently impacted on OS. The combination of both (KPS/LDH index) identified patients with a very short life expectancy, who might be better served by recommending best supportive care instead of WBRT. The KPS/LDH index is simple and effective in terms of time and cost as compared to other prognostic indices.

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.