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Current risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity. Genomic classifiers (GC) enable improved risk stratification after surgery, but less data exist for patients treated with definitive radiation therapy (RT) or RT in oligo-/metastatic disease stages. To guide future perspectives of GCs for RT, we conducted (1) a systematic review on the evidence of GCs for patients treated with RT and (2) a survey of experts using the Delphi method, addressing the role of GCs in personalized treatments to identify relevant fields of future clinical and translational research. We performed a systematic review and screened ongoing clinical trials on ClinicalTrials.gov. Based on these results, a multidisciplinary international team of experts received an adapted Delphi method survey. Thirty-one and 30 experts answered round 1 and round 2, respectively. Questions with ≥75% agreement were considered relevant and included in the qualitative synthesis. Evidence for GCs as predictive biomarkers is mainly available to the postoperative RT setting. Validation of GCs as prognostic markers in the definitive RT setting is emerging. Experts used GCs in patients with PCa with extensive metastases (30%), in postoperative settings (27%), and in newly diagnosed PCa (23%). Forty-seven percent of experts do not currently use GCs in clinical practice. Expert consensus demonstrates that GCs are promising tools to improve risk-stratification in primary and oligo-/metastatic patients in addition to existing classifications. Experts were convinced that GCs might guide treatment decisions in terms of RT-field definition and intensification/deintensification in various disease stages. This work confirms the value of GCs and the promising evidence of GC utility in the setting of RT. Additional studies of GCs as prognostic biomarkers are anticipated and form the basis for future studies addressing predictive capabilities of GCs to optimize RT and systemic therapy. The expert consensus points out future directions for GC research in the management of PCa. ispartof: Int J Radiat Oncol Biol Phys vol:116 issue:3 pages:503-520 ispartof: location:United States status: published

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.

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.

Die primare perkutane Strahlentherapie mit oder ohne begleitende Hormontherapie bildet eine der Behandlungsoptionen beim Prostatakarzinom der intermediaren Risikogruppe. Es soll eine kurze Ubersicht der derzeit noch unterschiedlichen Behandlungsansatze im Rahmen der definitiven perkutanen Strahlentherapie gegeben werden. Es erfolgte eine Sichtung der aktuellen Leitlinien und eine Literaturrecherche via PubMed-Datenbank. Es existieren verschiedene Empfehlungen zur Einteilung in Risikogruppen beim lokalisierten Prostatakarzinom. Um der Heterogenitat der intermediaren Risikogruppe Rechnung zu tragen, scheint die Untergruppierung in ein gunstiges und ungunstiges Stadium, einen sinnvollen Ansatz zur Individualisierung der Therapie darzustellen. Randomisierte Studien konnten auch bei Patienten der intermediaren Risikogruppe eine Verbesserung der Therapieergebnisse bei Kombination von Strahlentherapie und Hormontherapie nachweisen. Zeitgleich erhoht der Einsatz der Hormontherapie die Rate an Nebenwirkungen und sollte daher individuell gepruft werden. Die Anwendung der alleinigen dosiseskalierten Strahlentherapie scheint insbesondere bei gunstigerem intermediaren Risikoprofil eine gleichwertige therapeutische Option darzustellen. Bei gunstigerem Risikoprofil scheint eine alleinige dosiseskalierte Strahlentherapie und bei ungunstigem intermediaren Risikoprofil die Kombination mit kurzzeitiger (4–6 Monate) Hormontherapie eine sinnvolle Therapiestrategie zu sein. Weitere Evidenz zu dieser Fragestellung werden die noch ausstehenden Ergebnisse der RTOG-0815-Studie bieten.

Ein Paradigmenwechsel beim Prostatakarzinom mit nur wenigen Metastasen hat eingesetzt und eine Metastasierung bedeutet nicht mehr zwingend eine klassische palliative Situation. Darstellung der aktuellen diagnostischen Moglichkeiten des Prostatakarzinoms im Rahmen der metastasengerichteten interdisziplinaren Therapie und des therapeutischen Vorgehens. Es erfolgte eine Sichtung der aktuellen Literatur inklusive Metaanalysen sowie der Leitlinien und Expertenempfehlungen. Essenziell zur genauen Lokalisation und Detektion und konsekutiv der Therapie von (Oligo‑)Metastasen ist eine moglichst sensitive und prazise diagnostische Bildgebung. Hierzu zahlen neben der etablierten bildgebenden Basisdiagnostik zunehmend auch schnittbildbasierte, funktionale Verfahren wie die multiparametrische Magnetresonanztomographie (mMRT) sowie das PSMA-PET-CT (PSMA: prostataspezifisches Membranantigen). Hinsichtlich der Therapie kann die Bestrahlung von bis zu 3 Metastasen bei Oligometastasierung die androgendeprivationsfreie Zeit und das progressionsfreie Uberleben verlangern sowie die Lebensqualitat erhohen. Ossare und lymphogene Metastasen konnen mit einer hohen Einzeldosis, aber wenigen Fraktionen als hypofraktionierte stereotaktische Bestrahlung therapiert und eine lokale Kontrolle von mehr als 90 %, ein klinisch progressionsfreies Uberleben bis zu 71 % bei sehr niedrigen Toxizitatsraten erreicht werden. Die metastasengerichtete, interdisziplinare Therapie bei oligometastasiertem Prostatakarzinom fuhrt zu einer weiteren Personalisierung sowie zunehmenden Risikoadaption der Behandlungskonzepte und weicht die bisherigen harten Grenzen mit Unterteilung in „palliativ“ und „kurativ“ auf. Hierzu werden vermehrt auch hypofraktionierte Bestrahlungsschemata sowie die stereotaktische Bestrahlung eingesetzt.

Die Salvage-Strahlentherapie (SRT) ist Standard bei Patienten mit biochemischem Progress nach Prostatektomie im primaren Stadium pN0. Randomisierte Studien haben nun den Nutzen einer zusatzlichen Androgendeprivationstherapie (ADT) untersucht. Eine evidenzbasierte, systematische Ubersicht uber die Kombination einer ADT mit einer SRT bei rezidiviertem Prostatakarzinom soll erstellt werden. Die verfugbare Literatur wurde ausgewertet und daraus Behandlungsempfehlungen unter Berucksichtigung von Risikoprofilen abgeleitet. Es liegen die Ergebnisse von zwei randomisierten und mehreren retrospektiven Analysen vor. Die RTOG-9601-Studie zeigte eine Verbesserung des Gesamtuberlebens und des tumorspezifischen Uberlebens durch die Kombination von 24 Monaten Bicalutamid 150 mg/Tag und SRT im Vergleich zur alleinigen SRT. Dieser Vorteil war jedoch nur bei Patienten mit PSA-Werten ≥0,7 ng/ml vor SRT, einem Gleason-Score 7 oder positivem Schnittrand nachweisbar. Die GETUG-AFU-16-Studie zeigte lediglich eine Verbesserung des progressionsfreien Uberlebens (PFS) durch die zusatzliche Gabe von 6 Monaten Goserelin zur SRT. In beiden Studien wurde keine Zunahme schwerer Spatfolgen durch die ADT beobachtet. Retrospektive Studien deuten darauf hin, dass eine zusatzliche ADT das PFS bei Hochrisikopatienten verbessert. Bei Patienten mit PSA-Werten ≥0,7 ng/ml vor SRT verbessert eine ADT zur SRT das Gesamtuberleben. Beim PSA-Wert

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.

Korrespondenz zu 10.1200/JCO.21.01980

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.

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.

AIM This article gives an overview on the current status of hypofractionated radiotherapy in the treatment of prostate cancer with a special focus on the applicability in routine use. METHODS Based on a recently published systematic review the German Society of Radiation Oncology (DEGRO) expert panel added additional information that has become available since then and assessed the validity of the information on outcome parameters especially with respect to long-term toxicity and long-term disease control. RESULTS Several large-scale trials on moderate hypofractionation with single doses from 2.4-3.4 Gy have recently finished recruiting or have published first results suggestive of equivalent outcomes although there might be a trend for increased short-term and possibly even long-term toxicity. Large phase 3 trials on extreme hypofractionation with single doses above 4.0 Gy are lacking and only very few prospective trials have follow-up periods covering more than just 2-3 years. CONCLUSION Until the results on long-term follow-up of several well-designed phase 3 trials become available, moderate hypofractionation should not be used in routine practice without special precautions and without adherence to the highest quality standards and evidence-based dose fractionation regimens. Extreme hypofractionation should be restricted to prospective clinical trials.

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

In patients with prostate cancer (PC) and biochemical relapse after radical prostatectomy, salvage radiotherapy (SRT) could improve PC-specific survival (PCSS) but the timing for initiation is still under discussion. We have demonstrated a low rate of biochemical relapses in a patient series with very low pre-SRT PSA levels after a median follow-up of 42 months. Here, we present an update of that study. Overall, 151 patients were analyzed. A biochemical relapse after SRT was diagnosed when the PSA exceeded the post-SRT nadir by 0.2 ng/ml with subsequent increase. Parameters with significant impact on biochemical progression-free survival (BPFS), PCSS, and overall survival (OS) in univariate analysis were included in a multiple Cox regression analysis. After a median follow-up of 82 months, 18 patients (12 %) had died with 10 (6.6 %) deaths being PC-related. A biochemical progression was diagnosed in 83 patients (55 %). Univariate analysis revealed a significant impact of pre-SRT PSA level, Gleason score, and PSA doubling time (PSADT) on BPFS and for initial tumor stage and Gleason score on OS. Multivariate analysis confirmed the impact of pre-SRT PSA level, Gleason score, and PSADT on BPFS and tumor stage on OS. In this update, the rate of biochemical relapses increased compared with our previous data. Compared to similar studies, we found a remarkably low rate of PC-related deaths. Our data support early initiation of SRT. However, this treatment strategy, triggered by very low PSA levels, could carry the risk of overtreatment in at least a subset of patients.

Aim This article gives an overview on the current status of hypofractionated radiotherapy in the treatment of prostate cancer with a special focus on the applicability in routine use. Methods Based on a recently published systematic review the German Society of Radiation Oncology (DEGRO) expert panel added additional information that has become available since then and assessed the validity of the information on outcome parameters especially with respect to long-term toxicity and long-term disease control. Results Several large-scale trials on moderate hypofractionation with single doses from 2.4–3.4 Gy have recently finished recruiting or have published first results suggestive of equivalent outcomes although there might be a trend for increased short-term and possibly even long-term toxicity. Large phase 3 trials on extreme hypofractionation with single doses above 4.0 Gy are lacking and only very few prospective trials have follow-up periods covering more than just 2–3 years. Conclusion Until the results on long-term follow-up of several well-designed phase 3 trials become available, moderate hypofractionation should not be used in routine practice without special precautions and without adherence to the highest quality standards and evidence-based dose fractionation regimens. Extreme hypofractionation should be restricted to prospective clinical trials.

To evaluate the influence of a preoperative computed tomogram (CT) on delineation of the planning target volume (PTV) for adjuvant radiation therapy of pT3 pNO prostate cancer.

Die Keratitis superficialis chronica des Hundes ist eine unbehandelt fast immer progredient verlaufende Hornhautentzundung, die zur Erblindung fuhren kann. Eine Standardbehandlung gibt es bisher nicht. Systematische Untersuchungen zur Bestrahlung mit Strontium-(Sr-)90 liegen praktisch nicht vor, die Anwendung wird jedoch immer wieder propagiert. Ziel der Untersuchung war es, Wirksamkeit und Nebenwirkungen dieser Therapie zu dokumentieren.

Following radical prostatectomy, between 15 and 60% of all patients with pT3 prostate cancer experience persistence or increasing levels of prostate-specific antigen (PSA) as a sign of tumor persistence or progression within 5 years. Retrospective studies have shown a rate of 35-55% of positive biopsies from the vesicourethral anastomosis in this situation. Best treatment for these disease conditions is under debate, current strategies include adjuvant radiotherapy (RT), 'wait-and-see' and salvage RT or hormone therapy for increasing PSA.A number of retrospective studies have shown an increased rate of local control and 'freedom from treatment failure' following adjuvant RT with doses in the range of 50-60 Gy. However, no survival benefit could be demonstrated by now. Results of three major phase III studies are pending. In case of persisting or increasing PSA levels following radical prostatectomy, 30-70% of these patients will reach an undetectable PSA level after conformal RT with total doses of 60-70 Gy, which will stay undetectable or at least stable within the next 2-5 years in about 50% and therefore offering a chance of cure. When starting RT, PSA should be as low as possible (2 ng/ml). With higher PSA levels the chance of achieving an undetectable PSA again decreases below 35%. High Gleason scores of 8-10, seminal vesicle involvement and a short PSA doubling time are adverse prognostic factors. Severe late side effects of conformal RT are infrequent (3%). In contrast, hormonal treatment is of palliative nature in the long run, with a median time to development of metastases of 4-7 years, and can be offered to patients with progressive disease after RT.Adjuvant RT following radical prostatectomy for pT3 prostate cancer offers higher local control rates and an increase in 'freedom from treatment failure', but no prolongation of survival has yet been shown. In the situation of increasing PSA levels after radical prostatectomy, salvage RT seems to offer a chance of cure in selected patients, although it is difficult to draw firm conclusions because of generally too short follow-up times.

Summary Background: Anal cancer is an evolving problem in HIV-infected patients. In fear of excessive toxicity in patients with HIV infection, aggress

Hintergrund Trotz einer zunehmenden Zahl an Berichten ist das Merkel-Zell-Karzinom eine seltene Erkrankung. Berichte uber eine primare Strahlentherapie sind selten.

Although not an AIDS-defining malignancy, anal cancer is an evolving problem in HIV-infected patients. Treatment-tolerance to radiotherapy as well as to chemotherapy is supposed to be reduced in patients with HIV-infection. From January 1995 to January 1997, four patients with epidermoid cancer of the anal canal and a long history of HIV-infection but without symptoms of AIDS or repeated severe infections were treated with radiotherapy (n = 1) or radiochemotherapy (n = 3). External beam radiotherapy with 45 Gy to the tumor and pelvic as well as inguinal lymphatic drainage was administered. In tumors larger than T2 N0 lesions an additional boost of 9 Gy was given. Chemotherapy consisted of 5-fluorouracil 1000 mg/m2/24 h, d 1-4 two cycles and Mitomycin C either 1 x 15 mg/m2, d 1 in the first, or 2 x 10 mg/m2, d 1, in the first and fifth week of radiotherapy. Acute reactions were mild to moderate in all patients and all but one treatment could be given as scheduled (1 patient with a delay of 4 days). No excessive acute reactions were seen. Because of the short follow-up, late reactions and local control are not yet evaluable.

Adjuvant radiotherapy following radical surgery in NSCLC has long been a matter of debate. The pros and cons have all been discussed thoroughly and the data existing due to their partial outdated nature in respect of the diagnostic and therapeutic maneuvers used make it difficult to rely on them. Based on the existing level of evidence from randomized studies, the decision to irradiate a NSCLC patient postoperatively does not seem to be prudent, as several meta-analyses in fact have rather shown a detrimental effect than any benefit. As the majority of the randomized trials that are the bases of the meta-analyses are neither of good quality nor include those patients that are nowadays regarded as those for whom adjuvant irradiation should be discussed, other sources of information are of relevance. Subanalyses of randomized phase III trials and recently published SEER data are indicative that there is a benefit from adjuvant irradiation not only in terms of freedom from local failure but of overall survival as well. Notably, this is not at the expense of unacceptably high rates of long-term side effects.

Salvage radiotherapy in patients with persisting prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer offers an approach to reduce local recurrence rates and to improve the rate of biochemical freedom from relapse. 30–70% of these patients experience a decrease in their PSA to an undetectable range; in about 40–50% of these patients, PSA remains stable after 5 years. Therefore, radiation therapy offers these patients an ultimate chance of cure. The pre-irradiation PSA value is of particular importance. The PSA level should not exceed 2 ng/ml because otherwise the rate of distant metastases increases significantly. Serious side effects are apparently low, thus confirming the suitability of this therapeutic approach.

4756 Background: Locally confined prostate cancer can be treated by various treatment options (radical prostatectomy [RP] or radiotherapy [RT]) with comparable results but different possible side e...