Dosimetric advantages for cardiac substructures in radiotherapy of esophageal cancer in deep-inspiration breath hold.

BACKGROUND: Radiotherapy is one of the main treatment options for patients with esophageal cancer; however, it has been linked with an increased risk of cardiac toxicities. In the current study, we evaluated the effect of planning the radiation in deep-inspiration breath hold (DIBH) on the dose sparing of cardiac substructures and lung. MATERIALS AND METHODS: In this study, we analyzed 30 radiation therapy plans from 15 patients diagnosed with esophageal cancer planned for neoadjuvant radiotherapy. Radiation plans were generated for 41.4 Gy and delivered in 1.8 Gy per fraction for free-breathing (FB) and DIBH techniques. We then conducted a comparative dosimetric analysis, evaluating target volume coverage, the impact on cardiac substructures, and lung doses across the two planning techniques for each patient. RESULTS: There was no significant disparity in target volume dose coverage between DIBH and FB plans. However, the Dmean, D2%, and V30% of the heart experienced substantial reductions in DIBH relative to FB, with values of 6.21 versus 7.02 Gy (p = 0.011), 35.28 versus 35.84 Gy (p = 0.047), and 5% versus 5.8% (p = 0.048), respectively. The Dmean of the left ventricle was notably lower in DIBH compared to FB (4.27 vs. 5.12 Gy, p = 0.0018), accompanied by significant improvements in V10. Additionally, the Dmean and D2% of the left coronary artery, as well as the D2% of the right coronary artery, were significantly lower in DIBH. The dosimetric impact of DIBH on cardiac substructures proved more advantageous for middle esophageal (ME) than distal esophageal (DE) tumors. CONCLUSION: Radiotherapy in DIBH could provide a method to reduce the radiation dose to the left ventricle and coronaries, which could reduce the cardiac toxicity of the modality.

Combination of nivolumab with standard induction chemotherapy in children and adults with EBV-positive nasopharyngeal carcinoma : Protocol of a prospective multicenter phase 2 trial.

BACKGROUND: Treatment of Epstein-Barr virus(EBV)-positive nasopharyngeal carcinoma (NPC) with cisplatin/5-fluorouracil (5-FU) induction chemotherapy, followed by radiochemotherapy and subsequent interferon­ß, has yielded high survival rates in children, adolescents, and young adults. A previous study has shown that reduction of radiation dose from 59.4 to 54.0 Gy appears to be safe in patients with complete response (CR) to induction chemotherapy. As immune checkpoint-inhibitors have shown activity in NPC, we hypothesize that the addition of nivolumab to standard induction chemotherapy would increase the rate of complete tumor responses, thus allowing for a reduced radiation dose in a greater proportion of patients. METHODS: This is a prospective multicenter phase 2 clinical trial including pediatric and adult patients with their first diagnosis of EBV-positive NPC, scheduled to receive nivolumab in addition to standard induction chemotherapy. In cases of non-response to induction therapy (stable or progressive disease), and in patients with initial distant metastasis, treatment with nivolumab will be continued during radiochemotherapy. Primary endpoint is tumor response on magnetic resonance imaging (MRI) and positron emission tomography (PET) after three cycles of induction chemotherapy. Secondary endpoints are event-free (EFS) and overall survival (OS), safety, and correlation of tumor response with programmed cell death ligand 1 (PD-L1) expression. DISCUSSION: As cure rates in localized EBV-positive NPC today are high with standard multimodal treatment, the focus increasingly shifts toward prevention of late effects, the burden of which is exceptionally high, mainly due to intense radiotherapy. Furthermore, survival in patients with metastatic disease and resistant to conventional chemotherapy remains poor. Primary objective of this study is to investigate whether the addition of nivolumab to standard induction chemotherapy in children and adults with EBV-positive NPC is able to increase the rate of complete responses, thus enabling a reduction in radiation dose in more patients, but also offer patients with high risk of treatment failure the chance to benefit from the addition of nivolumab. TRIAL REGISTRATION: EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) No. 2021-006477-32.

Clinical validation of a semi-automated segmentation algorithm for target volume definition on planning CT and CBCT in stereotactic body radiotherapy (SBRT) for peripheral lung lesions.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is an ablative method for lung malignancies. Here, the definition of the gross target volume (GTV) is subject to interobserver variation. In this study, we aimed to evaluate the interobserver variability during SBRT and its dosimetric impact, as well as to introduce a semi-automated delineation tool for both planning computer tomography (P-CT) and cone beam CT (CBCT) to help to standardise GTV delineation and adaptive volume-change registration. METHODS: The interobserver variation of GTV manual contours from five physicians was analysed in 15 patients after lung SBRT on free breathing (FB) P-CT (n = 15) and CBCT (n = 90) before and after each fraction. The dosimetric impact from interobserver variations of GTV based on the original treatment plan was analysed. Next, the accuracy of an in-house easy-to-use semi-automated-segmentation algorithm for pulmonary lesions was compared with gold standard contours in FB P-CT and CBCT, as well as 4D P-CT of additional 10 patients. RESULTS: The interobserver variability in manual contours resulted in violations of dose coverage of the planning target volume (PTV), which, in turn, resulted in compromised tumour control probability in contours from four physicians. The validation of the semi-automated delineation algorithm using thorax phantom led to a highly reliable accuracy in defining GTVs. Comparing the unsupervised auto-contours with the gold standard delineation revealed high equal high concordance for FB P-CT, 4D P-CT and CBCT, with a DSC of 0.83, 0.76 and 0.8, respectively. The supervised use of the semi-automated delineation tool improved its accuracy, with DSCs of 0.86, 0.86 and 0.8 for FB P-CT, 4D P-CT and CBCT, respectively. The use of the algorithm was associated with a significantly shorter working time. The semi-automated delineation tool can accurately register volume changes in CBCTs. CONCLUSION: The segmentation algorithm provides a reliable, standardised and time-saving alternative for manual delineation in lung SBRT in P-CT and CBCT.

Body Composition as a Predictor of the Survival in Anal Cancer.

Background and aim: Sarcopenia and body composition parameters such as visceral and subcutaneous adipose tissue and visceral-to-subcutaneous adipose tissue ratio have been shown to be relevant biomarkers for prognosis in patients with different types of cancer. However, these findings have not been well studied in anal cancer to date. Therefore, the aim of this study was to evaluate the prognostic value of different body composition parameters in patients undergoing radiation therapy for the treatment of anal cancer with curative intent. Material and Methods: After approval by the institutional ethical committee, we retrospectively identified 81 patients in our local registry, who received radical intensity-modulated radiotherapy for the management of anal squamous cell cancer (ASCC). Clinical information, including body mass index (BMI), survival, and toxicities outcome, were retrieved from the local hospital registry. Based on the pre-therapeutic computer tomography (CT), we measured the total psoas muscle area, visceral adipose tissue area (VAT), subcutaneous adipose tissue area (SAT), and visceral-to-subcutaneous adipose tissue area ratio (VSR). In addition to the classical prognostic factors as T-stage, N-stage, gender, and treatment duration, we analyzed the impact of body composition on the prognosis in univariate and multivariate analyses. Results: Sarcopenia was not associated with increased mortality in anal cancer patients, whereas increased BMI (≥27 kg/m2) and VSR (≥0.45) were significantly associated with worsened overall survival and cancer-specific survival in both univariate and multivariate analyses. VSR-not BMI-was statistically higher in males. Sarcopenia and VSR ≥ 0.45 were associated with advanced T-stages. None of the body composition parameters resulted in a significant increase in treatment-related toxicities. Conclusion: BMI and visceral adiposity are independent prognostic factors for the survival of patients with anal cancer. Measurements to treat adiposity at the time of diagnosis may be needed to improve the survival outcomes for the affected patients.

Two Decades of Brain Tumour Imaging with O-(2-[18F]fluoroethyl)-L-tyrosine PET: The Forschungszentrum Jülich Experience.

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians' rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

Effective Radiosensitization of Bladder Cancer Cells by Pharmacological Inhibition of DNA-PK and ATR.

This study aims at analyzing the impact of the pharmacological inhibition of DNA damage response (DDR) targets (DNA-PK and ATR) on radiosensitization of bladder cancer cell lines of different molecular/histological subtypes. Applying DNA-PK (AZD7648) and ATR (Ceralasertib) inhibitors on SCaBER, J82 and VMCUB-1 bladder cancer cell lines, we revealed sensitization upon ionizing radiation (IR), i.e., the IC50 for each drug shifted to a lower drug concentration with increased IR doses. In line with this, drug exposure retarded DNA repair after IR-induced DNA damage visualized by a neutral comet assay. Western blot analyses confirmed specific inhibition of targeted DDR pathways in the analyzed bladder cancer cell lines, i.e., drugs blocked DNA-PK phosphorylation at Ser2056 and the ATR downstream mediator CHK1 at Ser317. Interestingly, clonogenic survival assays indicated a cell-line-dependent synergism of combined DDR inhibition upon IR. Calculating combined index (CI) values, with and without IR, according to the Chou-Talalay method, confirmed drug- and IR-dose-specific synergistic CI values. Thus, we provide functional evidence that DNA-PK and ATR inhibitors specifically target corresponding DDR pathways retarding the DNA repair process at nano-molar concentrations. This, in turn, leads to a strong radiosensitizing effect and impairs the survival of bladder cancer cells.

Intensity-Modulated Radiotherapy Associated With Improved Survival Outcome in Anal Cancer.

Purpose: To describe the survival and toxicity outcome from a single-centre experience in patients with squamous cell cancer of the anal canal (SCC-AC), related to the impact of technological advances in diagnostics and radiation techniques. Material and Methods: A retrospective cohort study was performed after the approval of the institutional ethical committee (EK 478-21). We identified 142 patients in our registry, who received radical treatment for SCC-AC between 2000 and 2020. Fifty-five patients had FDG PET/CT for initial staging and target volume delineation, 87.33% received concomitant chemoradiotherapy (CRT), 64 patients were treated with 3-dimensional conformal radiotherapy (3DRT) between 2000-2009, and 78 patients with intensity-modulated radiotherapy (IMRT) between 2009-2020. Endpoints for the analysis included locoregional relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). Acute and late toxicities were also reported. Results: At a median follow-up of 31.2 months, the median overall survival was 135 months, 5-year LRFS was 73.1%, 5-year DFS was 65.3%, and 5-year CSS was 75.3%. The use of IMRT was associated with shorter treatment duration. In the univariate analysis, IMRT was associated with significantly improved DFS and CSS for the whole cohort and significantly improved DFS, OS, and CSS for patients who received CRT. In the multivariate analysis, IMRT was associated with the improvement of all survival paraments. The use of FDG PET/CT did not translate into an improvement in the survival outcomes in both univariate and multivariate analyses. Grade-3 and more dermatological toxicities occurred less frequently, but hematological toxicities were more frequent in the IMRT-group. Late side effects and colostomies were less frequently reported in the IMRT group. Conclusion: The use of IMRT in the management of SCC-AC was associated with improvement of the oncological outcomes with improved toxicity profiles in this long-term single-centre experience.

Multimodal Treatment of Nasopharyngeal Carcinoma in Children, Adolescents and Young Adults-Extended Follow-Up of the NPC-2003-GPOH Study Cohort and Patients of the Interim Cohort.

Nasopharyngeal carcinoma (NPC) in children and young adults has been treated within two consecutive prospective trials in Germany, the NPC-91 and the NPC-2003 study of the German Society of Pediatric Oncology and Hematology (GPOH). In these studies, multimodal treatment with induction chemotherapy, followed by radio (chemo)therapy and interferon-beta maintenance, yielded promising survival rates even after adapting total radiation doses to tumor response. The outcome of 45 patients in the NPC-2003 study was reassessed after a median follow-up of 85 months. In addition, we analyzed 21 further patients after closure of the NPC-2003 study, recruited between 2011 and 2017, and treated as per the NPC-2003 study protocol. The EFS and OS of 66 patients with locoregionally advanced NPC were 93.6% and 96.7%, respectively, after a median follow-up of 73 months. Seven patients with CR after induction therapy received a reduced radiation dose of 54 Gy; none relapsed. In young patients with advanced locoregional NPC, excellent long-term survival rates can be achieved by multimodal treatment, including interferon-beta. Radiation doses may be reduced in patients with complete remission after induction chemotherapy and may limit radiogenic late effects.

Quality of life more than 10 years after radiotherapy for localized prostate cancer-impact of time after treatment and prescription dose.

PURPOSE: Analysis of quality of life changes after radiotherapy with focus on the impact of time after treatment and prescription dose. METHODS: Consecutive patients were treated with doses from 70.2/1.8 Gy (n = 206) to 72/1.8-2.0 Gy (n = 176) in a single centre and surveyed using the Expanded Prostate Cancer Index Composite questionnaire. RESULTS: Urinary and bowel bother scores decreased 1 / 3 / 6 points and 7 / 7 / 9 points on average 1 / 5 / 10 years after RT in comparison to baseline scores. The rate of urinary (need of pads in 8% vs. 15% before vs. 10 years after RT; p = 0.01) and bowel (uncontrolled leakage of stool in 5% vs. 12% before vs. 10 years after RT; p < 0.01) incontinence, as well as rectal bleeding (4% vs. 8% before vs. 10 years after RT; p = 0.05) increased. Sexual function scores decreased (erections sufficient for intercourse in 36% vs. 12% before vs. 10 years after RT; p < 0.01). A higher dose had a statistically significant impact on urinary bother and stool incontinence, but also tended to decrease urinary continence. Age and comorbidities did not have an influence on score changes, but on baseline urinary function/bother and baseline sexual function. CONCLUSION: Apart from an increasing rate of erectile dysfunction, urinary and bowel incontinence rates increased with increasing follow-up period. A higher dose was found to be associated with increased urinary problems and larger stool incontinence rates. Age and comorbidities were found to be relevant for baseline scores, but not for score changes.

Prediction of survival outcomes following postoperative radiotherapy after radical prostatectomy for prostate cancer.

Background: To evaluate predictive factors for survival outcomes after post-prostatectomy radiotherapy.Material and methods: In the years 2003-2008, 324 patients have received postoperative radiotherapy a median time of 14 months after radical prostatectomy. All patients have been treated up to 66.0-66.6 Gy in 1.8-2.0 Gy fractions. Predictive factors were analyzed at two stages, using a multivariable Cox regression analysis: (1) based on factors known before radiotherapy and (2) based on prostate-specific antigen response after radiotherapy.Results: Median follow-up after radiotherapy was 121 months. Prostate-specific antigen before radiotherapy, pN1 and Gleason score remained predictive factors for disease-free (hazard ratio, HR of 6.0, 2.3 and 2.5) and overall survival (HR of 2.8, 2.0 and 1.6) in multivariable analysis. Prostate-specific antigen levels increased despite radiotherapy in 27% of patients in the first six months. Failed response following salvage radiotherapy and prostate-specific antigen doubling time at the time of biochemical recurrence were predictive factors for disease-free (HR of 2.8 and 7.3; p < .01) and overall survival (HR of 2.2 and 2.6; p < .01).Conclusion: To reach the best survival outcomes following prostatectomy, salvage radiotherapy should be initiated early with low prostate-specific antigen levels, especially in patients with higher Gleason scores. Patients not responding to radiotherapy and/or patients with a short prostate-specific antigen doubling time after radiotherapy are candidates for early additional treatments.

Quality of Life Changes >10 Years After Postoperative Radiation Therapy After Radical Prostatectomy for Prostate Cancer.

PURPOSE: To analyze long-term quality-of-life (QoL) changes related to postoperative radiation therapy (RT) after radical prostatectomy. METHODS AND MATERIALS: Patients who received postoperative 3-dimensional conformal RT in the years 2003 to 2008 with 1.8 to 2.0 Gy fractions up to 66.0 to 66.6 Gy (n = 181) were surveyed using the Expanded Prostate Cancer Index Composite questionnaire before the beginning of RT (A); on the last day (B); and 2 months (C), 1 to 3 years (D), 6 to 9 years (E), and 10 to 13 years (F) after RT. RESULTS: Mean urinary bother, urinary incontinence bother, and bowel bother score changes (in relation to baseline at time A) of 13, 14, and 7 and 14, 15, and 7 were found at times E and F, respectively (P < .01 for all comparisons). Sexual function scores decreased 6 and 8 points on average (P < .01). Patient age at the time of RT had a considerable impact on urinary bother and urinary incontinence bother, with increasing differences over time when comparing patients aged <68 versus ≥68 years: 0 versus 7 and 0 versus 7 points at time D and 8 versus 23 and 6 versus 35 points at time F, respectively. Patients who did not respond to RT with a decreasing prostate-specific antigen level had greater urinary and urinary incontinence bother and bowel bother score changes >10 years after treatment (25 vs 12; P = .04, 36 vs 10; P = .03, and 20 vs 5; P = .07, respectively). A higher rectal dose was associated with greater acute and long-term bowel bother score decrease. No correlation was found between the dose to the bladder and QoL changes. CONCLUSIONS: In contrast to early evaluations in the first years, significantly decreasing QoL in the urinary, bowel, and sexual domains was found >5 years after RT. Aging is likely to be a major factor. Younger patients who responded to the treatment had the most favorable long-term QoL results. As 3-dimensional conformal RT was used in this study, intensity modulated concepts could result in improved outcomes.

Dosimetric and volumetric effects in clinical target volume and organs at risk during postprostatectomy radiotherapy.

PURPOSE: To assess the reproducibility of the dose-volume distribution of the initial simulation CT, generated using volumetric modulated arc therapy (VMAT) planning, during the radiotherapy of the prostatic bed based on weekly cone beam CTs (CBCT). METHODS: Twenty-three patients, after radical prostatectomy were treated with adjuvant or salvage radiotherapy between July and December 2016 and considered for this evaluation. Weekly CBCT scans (n = 138) were imported into the treatment planning system, and the clinical tumor volume (CTV), the rectum and the bladder were contoured. The initially calculated dose distribution and the dose-volume histograms generated from weekly CBCTs were compared. The prostatic fossa dose coverage was assessed by the proportion of the CTV fully encompassed by the 95% and 98% isodose lines. Rectal and bladder volumes receiving 50, 60 and 65 Gy during the treatment were compared to the initial plan, with statistical significance determined using the one-sample t­test. RESULTS: Marked variations in the total organ volume of the rectum and the bladder were observed. The correlation between rectum volume and V50 was not significant (p = 0.487), while the bladder volume and V50 demonstrated a significant correlation. There was no correlation between urinary bladder volume and CTV. The change in rectal volume correlated significantly with CTV. The dose coverage (D98% and D95%) to the prostatic bed could be achieved for all patients due to the ventral shift in the volume differences of the rectum. CONCLUSION: Weekly CBCTs can be considered as adequate verification tools to assess the interfractional variability of the CTV and organs at risk. The proven volume changes in the urinary bladder and the rectum do not compromise the final delivered dose in the CTV.

Quality of life up to 10 years after external beam radiotherapy and/or brachytherapy for prostate cancer.

PURPOSE: The aim of this study was to evaluate quality-of-life changes up to 10 years following three different radiotherapy concepts. METHODS AND MATERIALS: In the years 2000-2003, 295 patients were treated with external beam radiotherapy (EBRT; n = 135; 70.2 Gy in 1.8 Gy fractions), low-dose-rate brachytherapy (LDR-BT with I-125; n = 94; 145 Gy), and high-dose-rate brachytherapy (HDR-BT with Ir-192; n = 66; 18 Gy in two fractions using 4-6 needles) as a boost to EBRT (50.4 Gy in 1.8 Gy fractions). Quality of life was assessed using the Expanded Prostate Cancer Index Composite at median time of 2, 6, and 10 years after treatment. RESULTS: The urinary function score 2 years after EBRT (mean 93 points) was significantly higher in comparison to HDR-BT + EBRT (80 points, higher doses to the urethra relevant) and LDR-BT (88 points). After 10 years, only HDR-BT + EBRT (75 points) remained worse (LDR-BT 92 points; EBRT 91 points). Urinary incontinence score decreased from 83 to 76 points in the HDR-BT + EBRT group. No significant differences or changes resulted in the bowel domain. The mean sexual function score (i.e., sexuality score) was significantly higher after LDR-BT versus HDR-BT + EBRT and EBRT (30 vs. 19 and 24 points after 2 years and 25 vs. 13 and 15 points after 10 years, respectively)-a lower patient age and a lower percentage with hormonal treatment need to be considered. CONCLUSION: Apart from decreasing sexual function for all patients, decreasing urinary scores were found in the HDR-BT + EBRT group predominantly as a result of increasing incontinence. This study demonstrates the need for optimum BT treatment planning.

Intensity-modulated radiotherapy of prostate cancer with simultaneous integrated boost after molecular imaging with 18F-choline-PET/CT : Clinical results and quality of life.

PURPOSE: To analyze clinical results and quality of life of patients with localized prostate cancer after irradiation of the prostate with an 18F-choline-PET/CT-based simultaneous integrated boost (SIB) in comparison to a control group without SIB. METHODS: A total of 134 patients underwent intensity-modulated radiotherapy from 2007-2010. All patients received a total dose of 76 Gy with 2 Gy fractions to the prostate; 67 patients received an additional SIB of 80 Gy. The median follow-up was 65 months. Quality of life was evaluated with the EPIC (Expanded Prostate Cancer Index Composite) questionnaire. RESULTS: Baseline characteristics were similar in both groups (prostate-specific antigen 11 ng/ml vs. 8 ng/ml, p = 0.20, Gleason score <6 in 36% vs. 46%, p = 0.22, with vs. without SIB). No prostate cancer-related death was observed. No significant difference of quality of life scores was found. The largest difference after 5-6 years in comparison to baseline was reported for sexual bother (mean 15 vs. 17 points with vs. without SIB). Mean urinary scores did not decrease. Bowel bother scores changes were larger in the SIB group (mean 5 vs. 2 points, dependent on SIB volume), with increased bowel problems (15 vs. 2% big/moderate problem with bowel movements, p = 0.03). However, a trend towards higher efficacy with SIB resulted (biochemical recurrence-free survival of 92% vs. 85%, p = 0.17). CONCLUSIONS: The first long-term analysis of patients treated with SIB based on molecular imaging with 18-F-choline-PET/CT showed an excellent biochemical recurrence-free survival, but a larger percentage of bowel problems in comparison to the control group.

Stereotactic body radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma-a multicenter analysis of the German working group "Stereotactic Radiotherapy".

BACKGROUND: Renal cell carcinoma (RCC) is traditionally considered to be radioresistant. Radiotherapy response rates are believed to improve with hypofractionated, high dose stereotactic body radiotherapy (SBRT). However, limited data exist regarding the role of SBRT in the treatment of pulmonary metastases. METHODS: The working group "Stereotactic Radiotherapy" of the German Society of Radiation Oncology analyzed its multi-institutional database of more than 700 patients who received SBRT for pulmonary metastases. Treatment was performed at 10 centers between 2001 and 2016. Patients with metastatic RCC were included in the study. Tumor characteristics, treatment details, and follow-up data including survival, local control (LC), distant metastases, and toxicity were evaluated. RESULTS: A total of 46 RCC patients treated with SBRT for 67 lung metastases were identified, who received a median total biologically effective dose (BEDiso) at planning target volume (PTV) isocenter of 117.0 Gy (range, 48.0-189.0 Gy). A median fractional dose of 20.8 Gy at isocenter (range, 6.0-37.9 Gy) was administered in a median number of 3 fractions (1-8 fractions). After a median follow-up time of 28.3 months for all patients, 1- and 3-year LC rates were 98.1% and 91.9%, with corresponding 1- and 3-year overall survival (OS) of 84.3% and 43.8%, respectively. Pulmonary metastases treated with BEDiso ≥130 Gy showed a trend for superior LC (P=0.054). OS was significantly improved in both uni- and multivariate analysis for patients with higher Karnofsky performance scale, lower maximum pulmonary metastasis diameter and lack of post-SBRT systemic therapy due to progression (P=0.014; P=0.049; P=0.006). Only mild acute and late toxicity was reported. CONCLUSIONS: SBRT for pulmonary metastases from RCC was associated with low treatment-associated toxicity, promising survival, and excellent LC, especially in those patients receiving a BEDiso ≥130 Gy.

Quality of Life After Radiation Therapy for Prostate Cancer With a Hydrogel Spacer: 5-Year Results.

PURPOSE: To evaluate quality of life changes up to 5 years after prostate cancer radiation therapy (RT) with a hydrogel spacer. METHODS AND MATERIALS: In the years 2010 to 2011, 114 patients received external beam radiation therapy to the prostate; 54 patients were selected for a hydrogel injection before the beginning of RT. Treatment was performed applying fractions of 2 Gy up to a total dose of 76 Gy (n=96) or 78 Gy (n=18, all with hydrogel). Patients were surveyed before RT; at the last day of RT; and a median time of 2 months, 17 months, and 63 months after RT using a validated questionnaire (Expanded Prostate Cancer Index Composite). A mean score change of >5 points was defined as clinically relevant. RESULTS: For patients treated with a hydrogel spacer, mean bowel function and bother score changes of >5 points in comparison with baseline levels were found only at the end of RT (10-15 points; P<.01). No spacer patient reported moderate or big problems with his bowel habits overall. Mean bother score changes of 21 points at the end of RT, 8 points at 2 months, 7 points at 17 months, and 6 points at 63 months after RT were found for patients treated without a spacer. A bowel bother score change >10 points was found in 6% versus 32% (P<.01) at 17 months and in 5% versus 14% (P=.2) at 63 months with versus without a spacer. CONCLUSIONS: The first 5-year quality of life results in a group of prostate cancer patients treated with a hydrogel spacer demonstrate excellent treatment tolerability, in particular regarding bowel problems. Further studies with dose-escalated or re-irradiation concepts can be encouraged.

Long-term prognostic significance of rising PSA levels following radiotherapy for localized prostate cancer - focus on overall survival.

BACKGROUND: The aim of this study was to evaluate the long-term prognostic significance of rising PSA levels, particularly focussing on overall survival. METHODS: Two hundred ninety-five patients with localized prostate cancer were either treated with low-dose-rate (LDR) brachytherapy with I-125 seeds as monotherapy (n = 94; 145Gy), high-dose-rate (HDR) brachytherapy with Ir-192 as a boost to external beam RT (n = 66; 50.4Gy in 1.8Gy fractions EBRT + 18Gy in 9Gy fractions HDR) or EBRT alone (70.2Gy in 1.8Gy fractions; n = 135). "PSA bounce" was defined as an increase of at least 0.2 ng/ml followed by spontaneous return to pre-bounce level or lower, biochemical failure was defined according to the Phoenix definition. RESULTS: Median follow-up after the end of radiotherapy was 108 months. A PSA bounce showed to be a significant factor for biochemical control (BC) and overall survival (OS) after ten years (BC10 of 83% with bounce vs. 34% without, p < 0.01; OS10 of 82% with bounce vs. 59% without bounce, p < 0.01). The occurrence of a bounce, a high nadir and the therapy modality (LDR-BT vs. EBRT and HDR-BT + EBRT vs. EBRT) proved to be independent factors for PSA recurrence in multivariate Cox regression analysis. A bounce was detected significantly earlier than a PSA recurrence (median 20 months vs. 32 months after RT; p < 0.01; median PSA doubling time 5.5 vs. 5.0 months, not significant). PSA doubling time was prognostically significant in case of PSA recurrence (OS10 of 72% vs. 36% with PSA doubling time ˃ 5 months vs. ≤ 5 months; p < 0.01). CONCLUSIONS: Rising PSA levels within the first two years can usually be classified as a benign PSA bounce, with favourable recurrence-free and overall survival rates. PSA doubling time is an important predictor for overall survival following the diagnosis of a recurrence.

Influence of Institutional Experience and Technological Advances on Outcome of Stereotactic Body Radiation Therapy for Oligometastatic Lung Disease.

PURPOSE: Many technological and methodical advances have made stereotactic body radiotherapy (SBRT) more accurate and more efficient during the last years. This study aims to investigate whether experience in SBRT and technological innovations also translated into improved local control (LC) and overall survival (OS). METHODS AND MATERIALS: A database of 700 patients treated with SBRT for lung metastases in 20 German centers between 1997 and 2014 was used for analysis. It was the aim of this study to investigate the impact of fluorodeoxyglucose positron-emission tomography (FDG-PET) staging, biopsy confirmation, image guidance, immobilization, and dose calculation algorithm, as well as the influence of SBRT experience, on LC and OS. RESULTS: Median follow-up time was 14.3 months (range, 0-131.9 months), with 2-year LC and OS of 81.2% (95% confidence interval [CI] 75.8%-85.7%) and 54.4% (95% CI 50.2%-59.0%), respectively. In multivariate analysis, all treatment technologies except FDG-PET staging did not significantly influence outcome. Patients who received pre-SBRT FDG-PET staging showed superior 1- and 2-year OS of 82.7% (95% CI 77.4%-88.6%) and 64.8% (95% CI 57.5%-73.3%), compared with patients without FDG-PET staging resulting in 1- and 2-year OS rates of 72.8% (95% CI 67.4%-78.8%) and 52.6% (95% CI 46.0%-60.4%), respectively (P=.012). Experience with SBRT was identified as the main prognostic factor for LC: institutions with higher SBRT experience (patients treated with SBRT within the last 2 years of the inclusion period) showed superior LC compared with less-experienced centers (P≤.001). Experience with SBRT within the last 2 years was independent from known prognostic factors for LC. CONCLUSION: Investigated technological and methodical advancements other than FDG-PET staging before SBRT did not significantly improve outcome in SBRT for pulmonary metastases. In contrast, LC was superior with increasing SBRT experience of the individual center.

Hydrogel injection reduces rectal toxicity after radiotherapy for localized prostate cancer.

PURPOSE: Injection of a hydrogel spacer before prostate cancer radiotherapy (RT) is known to reduce the dose to the rectal wall. Clinical results from the patient's perspective are needed to better assess a possible benefit. METHODS: A group of 167 consecutive patients who received prostate RT during the years 2010 to 2013 with 2­Gy fractions up to 76 Gy (without hydrogel, n = 66) or 76-80 Gy (with hydrogel, n = 101) were included. The numbers of interventions resulting from bowel problems during the first 2 years after RT were compared. Patients were surveyed prospectively before RT, at the last day of RT, and at a median of 2 and 17 months after RT using a validated questionnaire (Expanded Prostate Cancer Index Composite). RESULTS: Baseline patient characteristics were well balanced. Treatment for bowel symptoms (0 vs. 11 %; p < 0.01) and endoscopic examinations (3 vs. 19 %; p < 0.01) were performed less frequently with a spacer. Mean bowel function scores did not change for patients with a spacer in contrast to patients without a spacer (mean decrease of 5 points) >1 year after RT in comparison to baseline, with 0 vs. 12 % reporting a new moderate/big problem with passing stools (p < 0.01). Statistically significant differences were found for the items "loose stools", "bloody stools", "painful bowel movements" and "frequency of bowel movements". CONCLUSION: Spacer injection is associated with a significant benefit for patients after prostate cancer RT.

Metabolic tumour volume of anal carcinoma on (18)FDG PET/CT before combined radiochemotherapy is the only independant determinant of recurrence free survival.

AIM: to determine whether [(18)F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography and X-ray computed tomography (PET/CT) findings and metabolic parameters before combined chemo- and radiotherapy (CRT) have a prognostic value in patients with anal carcinoma. MATERIALS AND METHODS: 45 patients with anal cancer who underwent pre-treatment FDG-PET/CT were included. Metabolic parameters, recurrence and anal carcinoma specific survival were analyzed. RESULTS: SUV max and metabolic volume of the primary tumour were significantly higher in patients with lymph node or distant metastases than in those with locally confined disease (p=0.020 and p=0.015, respectively). The extent of disease (local tumour only, lymph node or distant metastases) was highly predictive of both for recurrence free and disease specific survival (p=0.010 and p<0.001, respectively). Recurrence free (p=0.010) and anal carcinoma specific survival (p=0.006) differed significantly between patients with a metabolic volume ≤45ml and >45ml. Multivariate analysis revealed that a metabolic volume >45ml was the only significant independent determinant (p=0.19) for recurrence free survival whereas for anal carcinoma specific survival the extent of disease was identified as the only significant independent determinant (p=0.002). CONCLUSIONS: the extent of disease on FDG PET/CT before combined radio-chemotherapy is strongly predictive of prognosis in anal cancer. Furthermore, patients with a large metabolic volume of the primary tumour (>45ml) are at significantly higher risk of recurrence.