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Replicative stress promotes genomic instability and tumorigenesis but also presents an effective therapeutic endpoint, rationalizing detailed analysis of pathways that control DNA replication. We show here that the transcription factor E2f4 recruits the DNA helicase Recql to facilitate progression of DNA replication forks upon drug- or oncogene-induced replicative stress. In unperturbed cells, the Trim33 ubiquitin ligase targets E2f4 for degradation, limiting its genomic binding and interactions with Recql. Replicative stress blunts Trim33-dependent ubiquitination of E2f4, which stimulates transient Recql recruitment to chromatin and facilitates recovery of DNA synthesis. In contrast, deletion of Trim33 induces chronic genome-wide recruitment of Recql and strongly accelerates DNA replication under stress, compromising checkpoint signaling and DNA repair. Depletion of Trim33 in Myc-overexpressing cells leads to accumulation of replication-associated DNA damage and delays Myc-driven tumorigenesis. We propose that the Trim33-E2f4-Recql axis controls progression of DNA replication forks along transcriptionally active chromatin to maintain genome integrity. Here the authors show that under replicative stress the E2f4 transcription factor recruits the Recql DNA helicase to facilitate DNA replication. The Trim33 ubiquitin ligase targets E2f4 to limit its interactions with Recql and chromatin. [ABSTRACT FROM AUTHOR]

Purpose: To describe the case of successful radiotherapeutic treatment of a woman suffering from Brooke–Spiegler syndrome who had multiple disfiguring cylindromas on the entire scalp and further tumors on the trunk. Methods: After decades of treatment with conventional therapies including surgery and topically applied salicylic acid, the 73-year-old woman agreed to undergo radiotherapeutic treatment. She received 60 Gy to the scalp and 36 Gy to painful nodules in the lumbar spine region. Results: Over a follow-up period of 14 and 11 years, respectively, the scalp nodules almost completely regressed, while the lumbar nodules became painless and considerably smaller. Apart from alopecia, no late adverse effects of treatment remain. Conclusion: This case should remind us of the potential role that radiotherapy could play in treating Brooke–Spiegler syndrome. The required dose for treatment of such extensive disease is still a matter of debate due to the scarcity of radiotherapeutic experience. This case demonstrates that for scalp tumors, 30 × 2 Gy can result in long-term tumor control, while other dose prescriptions may be adequate for tumors in other locations. [ABSTRACT FROM AUTHOR]

In locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is regarded as standard treatment. We assessed acute toxicities in patients receiving conventional 3D-conformal radiotherapy (3D-RT) and correlated them with dosimetric parameters after re-planning with volumetric modulated arc therapy (VMAT). Patients were randomized within the multicenter CAO/ARO/AIO-12 trial and received 50.4 Gy in 28 fractions and simultaneous chemotherapy with fluorouracil and oxaliplatin. Organs at risk (OAR) were contoured in a standardized approach. Acute toxicities and dose volume histogram parameters of 3D-RT plans were compared to retrospectively calculated VMAT plans. From 08/2015 to 01/2018, 35 patients with LARC were treated at one study center. Thirty-four patients were analyzed of whom 1 (3%) was UICC stage II and 33 (97%) patients were UICC stage III. Grade 3 acute toxicities occurred in 5 patients (15%). Patients with acute grade 1 cystitis (n = 9) had significantly higher Dmean values for bladder (29.4 Gy vs. 25.2 Gy, p < 0.01) compared to patients without bladder toxicities. Acute diarrhea was associated with small bowel volume (grade 2: 870.1 ccm vs. grade 0–1: 647.3 ccm; p < 0.01) and with the irradiated volumes V5 to V50. Using VMAT planning, we could reduce mean doses and irradiated volumes for all OAR: Dmean bladder (21.9 Gy vs. 26.3 Gy, p < 0.01), small bowel volumes V5–V45 (p < 0.01), Dmean anal sphincter (34.6 Gy vs. 35.6 Gy, p < 0.01) and Dmean femoral heads (right 11.4 Gy vs. 25.9 Gy, left 12.5 Gy vs. 26.6 Gy, p < 0.01). Acute small bowel and bladder toxicities were dose and volume dependent. Dose and volume sparing for all OAR could be achieved through VMAT planning and might result in less acute toxicities. [ABSTRACT FROM AUTHOR]

Purpose: The DEGRO Expert Commission on Prostate Cancer has revised the indication for radiation therapy of the primary prostate tumor in patients with synchronous distant metastases with low metastatic burden. Methods: The current literature in the PubMed database was reviewed regarding randomized evidence on radiotherapy of the primary prostate tumor with synchronous low metastatic burden. Results: In total, two randomized trials were identified. The larger study, the STAMPEDE trial, demonstrated an absolute survival benefit of 8% after 3 years for patients with low metastatic burden treated with standard of care (SOC) and additional radiotherapy (RT) (EQD2 ≤ 72 Gy) of the primary tumor. Differences in the smaller Horrad trial were not statistically significant, although risk reduction in the subgroup (< 5 bone metastases) was equal to STAMPEDE. The STOPCAP meta-analysis of both trials demonstrated the benefit of local radiotherapy for up to 4 bone lesions and an additional subanalysis of STAMPEDE also substantiated this finding in cases with M1a-only metastases. Conclusion: Therefore, due to the survival benefit after 3 years, current practice is changing. New palliative SOC is radiotherapy of the primary tumor in synchronously metastasized prostate cancer with low metastatic burden (defined as ≤ 4 bone metastases, with or without distant nodes) or in case of distant nodes only detected by conventional imaging. [ABSTRACT FROM AUTHOR]

Purpose: Dose-escalated external beam radiation therapy (EBRT) and EBRT + high-dose-rate brachytherapy (HDR-BT) boost are guideline-recommended treatment options for localized prostate cancer. The purpose of this study was to compare long-term outcome and toxicity of dose-escalated EBRT versus EBRT + HDR-BT boost. Methods: From 2002 to 2019, 744 consecutive patients received either EBRT or EBRT + HDR-BT boost, of whom 516 patients were propensity score matched. Median follow-up was 95.3 months. Cone beam CT image-guided EBRT consisted of 33 fractions of intensity-modulated radiation therapy with simultaneous integrated boost up to 76.23 Gy (DMean). Combined treatment was delivered as 46 Gy (DMean) EBRT, followed by two fractions HDR-BT boost with 9 Gy (D90%). Propensity score matching was applied before analysis of the primary endpoint, estimated 10-year biochemical relapse-free survival (bRFS), and the secondary endpoints metastasis-free survival (MFS) and overall survival (OS). Prognostic parameters were analyzed by Cox proportional hazard modelling. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation used the Common Toxicity Criteria for Adverse Events (v5.0). Results: The estimated 10-year bRFS was 82.0% vs. 76.4% (p = 0.075) for EBRT alone versus combined treatment, respectively. The estimated 10-year MFS was 82.9% vs. 87.0% (p = 0.195) and the 10-year OS was 65.7% vs. 68.9% (p = 0.303), respectively. Cumulative 5‑year late GU ≥ grade 2 toxicities were seen in 23.6% vs. 19.2% (p = 0.086) and 5‑year late GI ≥ grade 2 toxicities in 11.1% vs. 5.0% of the patients (p = 0.002); cumulative 5‑year late grade 3 GU toxicity occurred in 4.2% vs. 3.6% (p = 0.401) and GI toxicity in 1.0% vs. 0.3% (p = 0.249), respectively. Conclusion: Both treatment groups showed excellent long-term outcomes with low rates of severe toxicity. [ABSTRACT FROM AUTHOR]

Purpose: Various randomized phase III clinical trials have compared moderately hypofractionated to normofractionated radiotherapy (RT). These modalities showed similar effectiveness without major differences in toxicity. This project was conducted by the Prostate Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO) and the Working Party on Radiation Oncology of the German Cancer Society. We aimed to investigate expert opinions on the use of moderately hypofractionated RT as a definitive treatment for localized prostate cancer in German-speaking countries.Methods: A 25-item, web-based questionnaire on moderate-hypofractionation RT was prepared by an internal committee. The experts of the DEGRO were asked to complete the questionnaire.Results: Fourteen active members of DEGRO completed the questionnaire. The questions described indications for selecting patients eligible to receive moderate hypofractionation based on clinical and pathological factors such as age, urinary symptoms, and risk-group. The questions also collected information on the technical aspects of selection criteria, including the definition of a clinical target volume, the use of imaging, protocols for bladder and rectal filling, the choice of a fractionation schedule, and the use of image guidance. Moreover, the questionnaire collected information on post-treatment surveillance after applying moderately hypofractionated RT.Conclusion: Although opinions varied on the use of moderate-hypofractionation RT, the current survey reflected broad agreement on the notion that moderately hypofractionated RT could be considered a standard treatment for localized prostate cancer in German-speaking countries. [ABSTRACT FROM AUTHOR]

Objective: The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. Materials and methods: A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. Results: Metastasis-directed radiotherapy results in high local control (often > 90% within a follow-up of 1–2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. Conclusion: ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations. [ABSTRACT FROM AUTHOR]

Purpose: Integrating moderate hypofractionation to the macroscopic tumor with elective nodal irradiation while sparing the organs at risk (OAR) in chemoradiotherapy of locally advanced non-small-cell lung cancer.Methods: From 2010-2018, treatment, patient and tumor characteristics of 138 patients from two radiation therapy centers were assessed. Chemoradiotherapy by intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) to the primary tumor and macroscopic lymph node metastases was used.Results: A total of 124 (90%) patients received concurrent chemotherapy. 106 (76%) patients had UICC (Union for International Cancer Control) stage ≥IIIB and 21 (15%) patients had an oligometastatic disease (UICC stage IV). Median SIB and elective total dose was 61.6 and 50.4 Gy in 28 fractions, respectively. Furthermore, 64 patients (46%) had an additional sequential boost to the primary tumor after the SIB-IMRT main series: median 6.6 Gy in median 3 fractions. The median cumulative mean lung dose was 15.6 Gy (range 6.2-29.5 Gy). Median follow-up and radiological follow-up for all patients was 18.0 months (range 0.6-86.9) and 16.0 months (range 0.2-86.9), respectively. Actuarial local control rates at 1, 2 and 3 years were 80.4, 68.4 and 57.8%. Median overall survival and progression-free survival was 30.0 months (95% confidence interval [CI] 23.5-36.4) and 12.1 months (95% CI 8.2-16.0), respectively. Treatment-related toxicity was moderate. Radiation-induced pneumonitis grade 2 and grade 3 occurred in 13 (9.8%) and 3 (2.3%) patients.Conclusions: Chemoradiotherapy using SIB-IMRT showed promising local tumor control rates and acceptable toxicity in patients with locally advanced and in part oligometastatic lung cancer. The SIB concept, resulting in a relatively low mean lung dose, was associated with low numbers of clinically relevant pneumonitis. The overall survival appears promising in the presence of a majority of patients with UICC stage ≥IIIB disease. [ABSTRACT FROM AUTHOR]

Due to its low fractionation sensitivity, also known as "alpha/beta ratio," in relation to its surrounding organs at risk, prostate cancer is predestined for hypofractionated radiation schedules assuming an increased therapeutic ratio compared to normofractionated regimens. While moderate hypofractionation (2.2–4 Gy) has been proven to be non-inferior to normal fractionation in several large randomized trials for localized prostate cancer, level I evidence for ultrahypofractionation (>4 Gy) was lacking until recently. An accumulating body of non-randomized evidence has recently been strengthened by the publication of two randomized studies comparing ultrahypofractionation with a normofractionated schedule, i.e., the Scandinavian HYPO-RT trial by Widmark et al. and the first toxicity results of the PACE‑B trial. In this review, we aim to give a brief overview of the current evidence of ultrahypofractionation, make an overall assessment of the level of evidence, and provide recommendations and requirements that should be followed before introducing ultrahypofractionation into routine clinical use. [ABSTRACT FROM AUTHOR]

Purpose: Evaluation of long-term outcome and toxicity of moderately hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost treatment planning and cone beam CT-based image guidance for localized prostate cancer.Methods: Between 2005 and 2015, 346 consecutive patients with localized prostate cancer received primary radiotherapy using cone beam CT-based image-guided intensity-modulated radiotherapy (IG-IMRT) and volumetric modulated arc therapy (IG-VMAT) with a simultaneous integrated boost (SIB). Total doses of 73.9 Gy (n = 44) and 76.2 Gy (n = 302) to the high-dose PTV were delivered in 32 and 33 fractions, respectively. The low-dose PTV received a dose (D95) of 60.06 Gy in single doses of 1.82 Gy. The pelvic lymph nodes were treated in 91 high-risk patients to 45.5 Gy (D95).Results: Median follow-up was 61.8 months. The 5‑year biochemical relapse-free survival (bRFS) was 85.4% for all patients and 93.3, 87.4, and 79.4% for low-, intermediate-, and high-risk disease, respectively. The 5‑year prostate cancer-specific survival (PSS) was 94.8% for all patients and 98.7, 98.9, 89.3% for low-, intermediate-, and high-risk disease, respectively. The 5‑year and 10-year overall survival rates were 83.8 and 66.3% and the 5‑year and 10-year freedom from distant metastasis rates were 92.2 and 88.0%, respectively. Cumulative 5‑year late GU toxicity and late GI toxicity grade ≥2 was observed in 26.3 and 12.1% of the patients, respectively. Cumulative 5‑year late grade 3 GU/GI toxicity occurred in 4.0/1.2%.Conclusion: Moderately hypofractionated radiotherapy using SIB treatment planning and cone beam CT image guidance resulted in high biochemical control and survival with low rates of late toxicity. [ABSTRACT FROM AUTHOR]

In the partnership between the medical departments of Würzburg University, Germany, and Nagasaki University, Japan, palliative care is a relevant topic. The aim of the study was to perform a comparative analysis of the hospital-based palliative care teams in Würzburg (PCT-W) and Nagasaki (PCT-N). Survey of staff composition and retrospective analysis of PCT patient charts in both PCTs were conducted. Patients self-assessed their symptoms in PCT-W and in Radiation Oncology Würzburg (RO-W). The (negative) quality indicator 'percentage of deceased hospitalised patients with PCT contact for less than 3 days before death' (Earle in Int J Qual Health Care 17(6):505–509, 2005) was analysed. Both PCTs follow a multidisciplinary team approach. PCT-N saw 410 cancer patients versus 853 patients for PCT-W (22.8% non-cancer patients). The Eastern Cooperative Oncology Group Performance Status at first contact with PCT-N was 3 or 4 in 39.3% of patients versus 79.0% for PCT-W. PCT-N was engaged in co-management longer than PCT-W (mean 20.7 days, range 1–102 versus mean 4.9 days, range 1–48). The most frequent patient-reported psychological symptom was anxiety (family anxiety: 98.3% PCT-W and 88.7% RO-W, anxiety 97.9% PCT-W and 85.9% RO-W), followed by depression (98.2% PCT-W and 80.3% RO-W). In 14 of the 148 deceased patients, PCT-N contact was initiated less than 3 days before death (9.4%) versus 121 of the 729 deceased PCT-W patients (16.6%). Psychological needs are highly relevant in both Germany and Japan, with more than 85% anxiety and depression in patients in the Japanese IPOS validation study (Sakurai in Jpn J Clin Oncol 49(3):257–262, 2019). This should be taken into account when implementing PCTs. [ABSTRACT FROM AUTHOR]

Aim: To provide an overview on the available treatments to prevent and reduce gynecomastia and/or breast pain caused by antiandrogen therapy for prostate cancer.Methods: The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published and assessed the validity of the information on efficacy and treatment-related toxicity.Results: Eight randomized controlled trials and one meta-analysis were identified. Two randomized trials demonstrated that prophylactic radiation therapy (RT) using 1 × 10 Gy or 2 × 6 Gy significantly reduced the rate of gynecomastia but not breast pain, as compared to observation. A randomized dose-finding trial identified the daily dose of 20 mg tamoxifen (TMX) as the most effective prophylactic dose and another randomized trial described that daily TMX use was superior to weekly use. Another randomized trial showed that prophylactic daily TMX is more effective than TMX given at the onset of gynecomastia. Two other randomized trials described that TMX was clearly superior to anastrozole in reducing the risk for gynecomastia and/or breast pain. One comparative randomized trial between prophylactic RT using 1 × 12 Gy and TMX concluded that prophylactic TMX is more effective compared to prophylactic RT and furthermore that TMX appears to be more effective to treat gynecomastia and/or breast pain when symptoms are already present. A meta-analysis confirmed that both prophylactic RT and TMX can reduce the risk of gynecomastia and/or breast pain with TMX being more effective; however, the rate of side effects after TMX including dizziness and hot flushes might be higher than after RT and must be taken into account. Less is known regarding the comparative effectiveness of different radiation fractionation schedules and more modern RT techniques.Conclusions: Prophylactic RT as well as daily TMX can significantly reduce the incidence of gynecomastia and/or breast pain. TMX appears to be an effective alternative to RT also as a therapeutic treatment in the presence of gynecomastia but its side effects and off-label use must be considered. [ABSTRACT FROM AUTHOR]

Objective: This article aims to provide an overview of the role of combined radiation and androgen deprivation (ADT) therapy in patients with intermediate-risk prostate cancer.Materials and Methods: The current German, European, and NCCN (National Comprehensive Cancer Network) guidelines as well as relevant literature in the PubMed database which provide information on sub-classification within the intermediate-risk group and the use of ADT in terms of oncological outcome were reviewed.Results: Different recommendations for risk-group assessment of patients with localized prostate cancer are available. Subdivision of intermediate risk into a favorable and an unfavorable group seems to be justified to allow for a more individualized therapy in a quite heterogenous group of patients. So far, multiple randomized trials have shown a benefit when radiation therapy (RT) is combined with ADT. The use of dose-escalated RT without ADT also appears to be an adequate therapy associated with a very low rate of cancer-specific deaths. Therefore, taking into account the increased rate of toxicity associated with ADT, dose-escalated RT alone might be justified, especially in favorable intermediate-risk patients.Conclusion: Dose-escalated RT alone appears to be an appropriate treatment in favorable intermediate-risk patients. Addition of short course ADT (4-6 months) might improve outcomes in unfavorable intermediate-risk patients. [ABSTRACT FROM AUTHOR]

Purpose: Primary radiation therapy is a curative treatment option for prostate cancer. The aim of this study was to evaluate the detection of the dominant intraprostatic lesion (DIL) with magnetic resonance imaging (MRI) for radiotherapy treatment planning, the comparison with transrectal ultrasound (TRUS)-guided biopsies and the examination of the dose distribution in relation to the DIL location.Materials and Methods: In all, 54 patients with treatment planning MRI for primary radiotherapy of prostate cancer from 03/2015 to 03/2017 at the Universitätsklinikum Würzburg were identified. The localization of the DIL was based on MRI with T2- and diffusion-weighted imaging. After registration of the MR image sets within Pinnacle3 (Philips Radiation Oncology Systems, Fitchburg, WI, USA), the dose distribution was analyzed. The location of the DIL was compared to the pathology reports in a side-based manner.Results: The DIL mean dose (Dmean) was 77.51 ± 0.77 Gy and in 50/51 cases within the tolerance range or exceeded the prescribed dose. There was a significant difference in Dmean between ventral (n = 21) and dorsal (n = 30) DIL (77.87 ± 0.67 vs. 77.26 ± 0.77 Gy; p = 0.005). MRI-guided localization showed an accuracy and sensitivity of up to 78.8% and 82.1% for inclusion of secondary lesions, respectively.Conclusion: Up to 82.1% of histologically verified intraprostatic lesions were identified in the context of MRI-guided radiotherapy treatment planning. As expected, dorsal DIL tend to be minimally underdosed in comparison to ventral DIL. Adequate dose coverage was achieved in over 98% of patients. [ABSTRACT FROM AUTHOR]

Aim: Overview on the use of androgen deprivation therapy (ADT) added to salvage radiation therapy (SRT) for prostate cancer patients with biochemical recurrence after prostatectomy.Methods: The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published between January 2009 and May 2017, and assessed the validity of the information on outcome parameters including overall survival (OS) and treatment-related toxicity.Results: Two randomized controlled trials and nine relevant retrospective analyses were identified. The RTOG 9601 trial showed an OS improvement for the combination of 2 years of bicalutamide and SRT compared to SRT alone after a median follow-up of 13 years. This improvement appeared to be restricted to those patients with a prostate specific antigen (PSA) level before SRT of ≥0.7 ng/mL. The GETUG AFU-16 trial showed that after a median follow-up of 5 years, the addition of 6 months of goserelin to SRT improved progression-free survival (PFS; based on biochemical recurrence) as compared to SRT alone. ADT in both trials was not associated with increased major late toxicities. Results of retrospective series were inconsistent with a suggestion that the addition of ADT improved biochemical PFS especially in patients with high-risk factors such as Gleason Score ≥8 and in the group with initially negative surgical margins.Conclusions: ADT combined with SRT appears to improve OS in patients with a PSA level before SRT of ≥0.7 ng/mL. In patients without persistent PSA after prostatectomy and PSA levels of <0.7 ng/mL, ADT should not routinely be used, but may be considered in patients with additional risk factors such as Gleason Score ≥8 and negative surgical margins. [ABSTRACT FROM AUTHOR]

Copyright of Wiener Klinisches Magazin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: To evaluate the prognostic value of O-(2-[(18)F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) uptake intensity in World Health Organisation (WHO) tumor grade II-IV gliomas.Methods: We studied 28 patients with WHO tumor grade II-IV gliomas who were referred to our department for radiation therapy. We acquired a FET-PET in all patients, as well as magnetic resonance imaging (MRI) of the brain consisting of at least T2-weighted imaging, flair and pre- and post-contrast T1-weighted imaging. SUVmax was measured and the tumor-to-brain uptake ratio (TBR) of all lesions was calculated based on the SUVmax (TBRmax) or SUVmean (TBRmean) of the contralateral healthy tissue. For this study, volumes were calculated using MRI alone, MRI + the volume with a SUVmax on FET-PET ≥ 2.2 as well as MRI + the volume with an uptake of at least 40 % of the SUVmax.Results: Tumor volumes were a median (range) of 88.6 (2.6-467.4) ml (MRI alone), 84.2 (2.8-474.4) ml (MRI + SUVmax on FET-PET ≥ 2.2) and 101.5 (4.0-512.1) ml (MRI + FET-PET uptake ≥ 40 % SUVmax), respectively. TBR-SUVmean was 2.36 (1.46-4.08); TBR-SUVmax was 1.71 (0.97-2.85). During a follow-up of 18.7 (2.5-36.1) months after FET-PET, 12 patients died of malignant glioma. Patients with a SUVmax ≥ 2.6 had a significantly worse tumor-related mortality (p = 0.005) and progression-free survival (p = 0.038) than those with a lower SUVmax. Multivariate analysis showed that WHO tumor grade (p = 0.001) and SUVmax ≥ 2.6 (p < 0.001) were independent predictors for tumor-related mortality, but not tumor volume or TBRmax or TBRmean. SUVmax ≥ 2.6 (p = 0.007) and being treated for a recurrence rather than for a primary tumor manifestation (p = 0.014) were predictors for progression-free survival, but not TBRmax or TBRmean.Conclusion: In this heterogeneous patient population, higher tracer uptake in FET-PET appears to be associated with a worse tumor-related mortality and a shorter duration of the disease-free interval. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the prognostic value of O-(2-[F]fluoroethyl)- l-tyrosine positron emission tomography (FET-PET) uptake intensity in World Health Organisation (WHO) tumor grade II-IV gliomas. Methods: We studied 28 patients with WHO tumor grade II-IV gliomas who were referred to our department for radiation therapy. We acquired a FET-PET in all patients, as well as magnetic resonance imaging (MRI) of the brain consisting of at least T2-weighted imaging, flair and pre- and post-contrast T1-weighted imaging. SUVmax was measured and the tumor-to-brain uptake ratio (TBR) of all lesions was calculated based on the SUVmax (TBRmax) or SUVmean (TBRmean) of the contralateral healthy tissue. For this study, volumes were calculated using MRI alone, MRI + the volume with a SUVmax on FET-PET ≥ 2.2 as well as MRI + the volume with an uptake of at least 40 % of the SUVmax. Results: Tumor volumes were a median (range) of 88.6 (2.6-467.4) ml (MRI alone), 84.2 (2.8-474.4) ml (MRI + SUVmax on FET-PET ≥ 2.2) and 101.5 (4.0-512.1) ml (MRI + FET-PET uptake ≥ 40 % SUVmax), respectively. TBR-SUVmean was 2.36 (1.46-4.08); TBR-SUVmax was 1.71 (0.97-2.85). During a follow-up of 18.7 (2.5-36.1) months after FET-PET, 12 patients died of malignant glioma. Patients with a SUVmax ≥ 2.6 had a significantly worse tumor-related mortality ( p = 0.005) and progression-free survival ( p = 0.038) than those with a lower SUVmax. Multivariate analysis showed that WHO tumor grade ( p = 0.001) and SUVmax ≥ 2.6 ( p < 0.001) were independent predictors for tumor-related mortality, but not tumor volume or TBRmax or TBRmean. SUVmax ≥ 2.6 ( p = 0.007) and being treated for a recurrence rather than for a primary tumor manifestation ( p = 0.014) were predictors for progression-free survival, but not TBRmax or TBRmean. Conclusion: In this heterogeneous patient population, higher tracer uptake in FET-PET appears to be associated with a worse tumor-related mortality and a shorter duration of the disease-free interval. [ABSTRACT FROM AUTHOR]

Purpose: Advance directives (AD) are becoming increasingly widespread. We examine the prevalence of AD and the factors associated with AD in tumor patients during radiotherapy. Methods: A standardized questionnaire was handed out to all tumor patients on 9 random days with an interval of at least 12 weeks. The data were analyzed in a bivariate and multivariate way. Results: Of 1,208 questionnaires, 658 were completed and returned (54.5%). Of respondents, 23.6% had already signed an AD, 53.3% thought they were likely to sign an AD, 9.0% did not want to sign an AD, and 4.9% were not familiar with advance directives. Patients who have signed an AD and those who are likely to sign one think that ADs facilitate the physician's decision-making process (97.7% cf. 94.5%) and that they ease the burden on relatives (98.5% cf. 98.8%). Regardless of an AD having been signed, every second respondent was of the opinion that AD facilitates consultations rather than serving as a directive (55.1% cf. 57.3%). Patients likely to sign an AD are significantly younger compared to those unlikely to do so and have suffered from their tumor disease for a shorter period of time. Conclusions: Of advance directives is widely accepted among the tumor patients surveyed. Advanced directives are not exclusively seen as instruments for surrogate decision making, but also as mediums to improve communication. Training of physicians and additional offers for patients could increase the actual number of ADs and perhaps improve physicians and relatives understanding of patients needs and wishes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether the tumour uptake of radionuclide in peptide receptor radionuclide therapy (PRRT) of meningioma can be predicted by a PET scan with Ga-labelled somatostatin analogue. Methods: In this pilot trial, 11 meningioma patients with a PET scan indicating somatostatin receptor expression received PRRT with 7.4 GBq Lu-DOTATOC or Lu-DOTATATE, followed by external beam radiotherapy. A second PET scan was scheduled for 3 months after therapy. During PRRT, multiple whole-body scans and a SPECT/CT scan of the head and neck region were acquired and used to determine the kinetics and dose in the voxel with the highest radionuclide uptake within the tumour. Maximum voxel dose and retention of activity 1 h after administration in PRRT were compared to the maximum standardized uptake values (SUV) in the meningiomas from the PET scans before and after therapy. Results: The median SUV in the meningiomas was 13.7 (range 4.3 to 68.7), and the maximum fractional radionuclide uptake in voxels of size 0.11 cm³ was a median of 23.4 × 10 (range 0.4 × 10 to 68.3 × 10). A strong correlation was observed between SUV and the PRRT radionuclide tumour retention in the voxels with the highest uptake (Spearman's rank test, P < 0.01). Excluding one patient who showed large differences in biokinetics between PET and PRRT and another patient with incomplete data, linear regression analysis indicated significant correlations between SUV and the therapeutic uptake ( r = 0.95) and between SUV and the maximum voxel dose from PRRT ( r = 0.76). Observed absolute deviations from the values expected from regression were a median of 5.6 × 10 (maximum 9.3 × 10) for the voxel fractional radionuclide uptake and 0.40 Gy per GBq (maximum 0.85 Gy per GBq) Lu for the voxel dose from PRRT. Conclusion: PET with Ga-labelled somatostatin analogues allows the pretherapeutic assessment of tumour radionuclide uptake in PRRT of meningioma and an estimate of the achievable dose. [ABSTRACT FROM AUTHOR]

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Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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Purpose: To evaluate the delineation of either the rectal volume (RV) or the rectal wall (RW) in intensity-modulated radiotherapy (IMRT) for prostate cancer: influence on dose distribution to the targets and organs at risk (OARs) was investigated. Material and Methods: For ten patients with localized prostate cancer IMRT treatment plans were generated with the RV, wall including the filling, and the RW without the lumen as OAR (plan-RV and plan-RW), respectively. Two different IMRT treatment- planning systems (TPS) were utilized. The influence on target coverage and sparing of OARs was investigated. Results: No influence was seen on target coverage and sparing of the bladder and femoral heads. Doses to the RV were significantly reduced in plan-RV for all evaluated dose levels: maximum 26% and 17%, respectively, in both TPS. The dose distribution to the RW was not significantly different between plan-RV and plan-RW. Conclusion: The different delineation of the OAR rectum significantly affected the inverse IMRT treatment-planning process. The use of the RV as OAR resulted in improved dose distributions to the RV. Therefore, it is suggested using the RV as OAR in IMRT treatment planning of the prostate. [ABSTRACT FROM AUTHOR]

This article presents the results of a study which examined the side effects of adjuvant radiotherapy for locally advanced rectal cancer. It discussed several small bowel complications associated with adjuvant radiotherapy for rectal cancer and the different surgical and radiotherapeutic means in reducing the risk of late small bowel damage.

Purpose: To determine whether a little dose to a large normal lung volume or a high dose to a small lung volume is more critical for induction of clinical pneumonitis. The second question is if dose-volume histogram (DVH) parameters are more reliable, if the lungs are analyzed as separate organs or as a whole organ.Patients and Methods: We analyzed the clinical and DVH data from 49 patients treated for a thoracic malignancy using 3-D conformal treatment plans. 18 patients had developed a clinical pneumonitis (CTC II or III). The majority of patients (n = 48) received radiochemotherapy for non-small-cell lung cancer (NSCLC) with a combination of paclitaxel and carboplatin. Patients were generally treated 5 fx/week, single dose 2 Gy, using a two-series approach (shrinking field) up to a total dose of 60-70 Gy. For every individual patient, the overall dose distribution was recalculated in the Helax-TMS by means of adding dose plans according to the total dose applied in each series. The lungs were defined both as separate organs and as a whole organ. Low-dose volume (< or = 10 Gy, Vlow), moderate-dose volume (> 10-40 Gy, Vmod) and high-dose volume (> 40 Gy, Vhigh), as well as V10-V40 and mean lung dose (MLD) were defined from the cumulative DVH. Dose-effect relationships were fitted with a logistic regression model.Results: Manifestation of clinical pneumonitis was within 3 months from termination of irradiation in all cases. For the ipsilateral lung, the incidence of pneumonitis was closely correlated to Vhigh. The pneumonitis rate increased from 13% up to 60%. By contrast, with increasing Vlow the pneumonitis rate dropped to < 10%. A similar but less pronounced effect was seen for the total lung. The lung volumes Vlow, Vmod and Vhigh of the ipsilateral, contralateral and whole lung were significantly correlated to the corresponding MLD. The incidence of pneumonitis increased with increasing MLD for the ipsilateral lung with a D50 of 32 Gy and a gamma 50 of 0.98. For the whole lung, the observed increase was less steep. MLD showed a close correlation to NTCP calculated by the Kutcher model. However, NTCP calculation overestimated the pneumonitis risk for the ipsilateral lung and underestimated the risk for the whole lung due to the steeper gradient. The logistic regression curve for the DVH parameters V10-V40 showed an increase of steepness toward higher doses. From the logistic regression curves, a DVH template indicating critical borders of V10-V40 was generated for the ipsilateral as well as for the total lung.Conclusion: Our data indicate that it is reasonable to disperse the dose outside the target volume over large areas in order to reduce the volumes of lung receiving > 40 Gy. Reducing the high-dose volume reduces the pneumonitis rate more than a corresponding reduction in the low-dose regions of the DVH. Landmarks for DVH optimization as defined in this analysis may serve as a basis for DVH contrains in IMRT planning. Separate organ analysis produced more reliable results and should be preferred to whole-organ analysis, if techniques mainly involving one side of the lung are applied. Further validation of these constraints is necessary prior to general recommendation. [ABSTRACT FROM AUTHOR]

Aim: Review of the evolution of combined treatment strategies in nasopharyngeal carcinoma.Results: Radiotherapy is accepted standard for treatment of nasopharyngeal cancer. Nevertheless, there is no uniform opinion with regard to doses, fractionation, technique or use of systemic chemotherapy. It is hardly possible to compare the results of recent and historical trials because of different staging systems and because nasopharyngeal cancer occurring in the Oceano-Asian region are biologically different to those in Western countries. Conclusions drawn from former, mostly retrospective analyses are not applicable to newer standards regarding the developments in diagnostics and therapy. Presently simultaneous chemoradiotherapy is standard for lymph node positive nasopharyngeal cancer.Conclusions: It will be necessary to treat patients with different histologic subtypes with an uniform treatment schedule to define the place of combined modality treatment. This will probably be the only way to develop treatment concepts for distinct stages and biological entities. [ABSTRACT FROM AUTHOR]

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