Successful implementation of online educational lectures of the German Society for Radiation Oncology (DEGRO).

PURPOSE: Modern digital teaching formats have become increasingly important in recent years, in part due to the COVID-19 pandemic. In January 2021, an online-based webinar series was established by the German Society for Radiation Oncology (DEGRO) and the young DEGRO (yDEGRO) working group. In the monthly 120-minute courses, selected lecturers teach curricular content as preparation for the board certification exam for radiation oncology. METHODS: The evaluation of the 24 courses between 01.2021 and 12.2022 was performed using a standardized questionnaire with 21 items (recording epidemiological characteristics of the participants, didactic quality, content quality). A Likert scale (1-4) was used in combination with binary and open-ended questions. RESULTS: A combined total of 4200 individuals (1952 in 2021 and 2248 in 2022) registered for the courses, and out of those, 934 participants (455 in 2021 and 479 in 2022) later provided evaluations for the respective courses (36% residents, 35% specialists, 21% medical technicians for radiology [MTR], 8% medical physics experts [MPE]). After 2 years, 74% of the DEGRO Academy curriculum topics were covered by the monthly webinars. The overall rating by participants was positive (mean 2021: 1.33 and 2022: 1.25) and exceeded the curriculum offered at each site for 70% of participants. Case-based learning was identified as a particularly well-rated method. CONCLUSION: The DEGRO webinar expands the digital teaching opportunities in radiation oncology. The consistently high number of participants confirms the need for high-quality teaching and underlines the advantages of e­learning methods. Optimization opportunities were identified through reevaluation of feedback from course participants. In its design as a teaching format for a multiprofessional audience, the webinar series could be used as a practice model of online teaching for other disciplines.

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.

Individual radiosensitivity reflected by γ-H2AX and 53BP1 foci predicts outcome in PSMA-targeted radioligand therapy.

PURPOSE: γ-H2AX and 53BP1 are fundamental for cellular DNA damage response (DDR) after radiation exposure and are linked to cell repair, arrest, or apoptosis. We aimed to evaluate whether DDR-markers in peripheral blood lymphocytes (PBLs) may have predictive potential for outcome in metastatic castration-resistant prostate cancer (mCRPC) patients receiving [177Lu]Lu-prostate-specific membrane antigen (PSMA) radioligand therapy (RLT). METHODS: We prospectively enrolled 20 men with advanced mCRPC scheduled for PSMA-targeted RLT. Prior to the first cycle of [177Lu]Lu-PSMA RLT, all patients underwent [18F]F-PSMA-1007 positron emission tomography (PET)/computed tomography (CT) for assessment of tumor PSMA expression (assessing maximum standardized uptake value (SUVmax) of all tumor lesions). Blood samples were collected prior to, + 1 h after, and + 24 h after administration of [177Lu]Lu-PSMA, and DDR-markers γ-H2AX and 53BP1 were determined in PBLs through immunocytofluorescence. We then tested the predictive performance of DDR-markers relative to clinical and PET-based parameters for progressive disease (PSA-PD) after 2 cycles. In addition, the predictive value for progression-free survival (PSA-PFS, provided as median and 95% confidence interval [CI]) was explored. RESULTS: Low baseline 53BP1 and γ-H2AX foci (P = 0.17) tended to predict early PSA-PD, whereas low SUVmax was significantly associated with higher risk for PSA-PD (P = 0.04). In Kaplan-Meier analysis, there was a trend towards prolonged PSA-PFS in patients with higher baseline 53BP1 of 6 months (mo; 95%CI, 4-9 mo) compared to 3 mo in patients with low 53BP1 (95% CI, 2-3 mo; P = 0.12). Comparable results were recorded for higher γ-H2AX expression (6 mo [95% CI, 3-9 mo] relative to 3 mo [95% CI, 2-4 mo] in patients with low γ-H2AX; P = 0.12). SUVmax, however, did not demonstrate predictive value (P = 0.29). Consistently, in univariate Cox-regression analysis, baseline 53BP1 foci demonstrated borderline significance for predicting PSA-PFS under [177Lu]Lu-PSMA RLT (P = 0.05). CONCLUSION: In this prospective study investigating mCRPC patients undergoing [177Lu]Lu-PSMA RLT, low baseline DDR-markers in PBLs tended to predict poor outcome. Although the study group was small and results need further confirmation, these preliminary findings lay the foundation for exploring additive radiosensitizing or treatment intensification in future studies with high-risk individuals scheduled for RLT.

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

Neoadjuvant versus definitive radiochemotherapy of locoregionally advanced oesophageal cancer-who benefits?

PURPOSE: For years, there have been discussions on whether neoadjuvant radiochemotherapy followed by surgery (nRCT-S) is superior to definitive radiochemotherapy (dRCT) as the standard of care for locoregionally advanced oesophageal cancer (OC). This retrospective study aimed to evaluate our patient cohort regarding differences in survival and recurrence between nRCT­S and dRCT. METHODS: Data from 68 patients with dRCT and 33 patients with nRCT­S treated from 2010 to 2018 were analysed. Comorbidities were recorded using the Charlson Comorbidity Index (CCI). Recurrence patterns were recorded as in-field or out-field. Kaplan-Meier analyses were used to compare survival data (overall survival [OS], progression-free survival [PFS], and locoregional control [LRC]). RESULTS: Patients with nRCT­S showed significantly lower CCI values than those with dRCT (p = 0.001). The median follow-up was 47 months. The median OS times were 31 months for nRCT­S and 12 months for dRCT (p = 0.009), the median PFS times were 11 and 9 months, respectively (p = 0.057), and the median LRC times were not reached and 23 months, respectively (p = 0.037). The only further factor with a significant impact on OS was the CCI (p = 0.016). In subgroup analyses for comorbidities regarding differences in OS, the superiority of the nRCT­S remained almost significant for CCI values 2-6 (p = 0.061). CONCLUSION: Our study showed significantly longer OS and LRC for patients with nRCT­S than for those with dRCT. Due to different comorbidities in the groups, it can be deduced from the subgroup analysis that patients with few comorbidities seem to especially profit from nRCT­S.

Shift of radiotherapy use during the first wave of the COVID-19 pandemic? An analysis of German inpatient data.

OBJECTIVE: To assess the change in inpatient radiotherapy related to COVID-19 lockdown measures during the first wave of the pandemic in 2020. METHODS: We included cases hospitalized between January 1 and August 31, 2018-2020, with a primary ICD-10 diagnosis of C00-C13, C32 (head and neck cancer, HNC) and C53 (cervical cancer, CC). Data collection was conducted within the Medical Informatics Initiative. Outcomes were fractions and admissions. Controlling for decreasing hospital admissions during holidays, calendar weeks of 2018/2019 were aligned to Easter 2020. A lockdown period (LP; 16/03/2020-02/08/2020) and a return-to-normal period (RNP; 04/05/2020-02/08/2020) were defined. The study sample comprised a control (admission 2018/19) and study cohort (admission 2020). We computed weekly incidence and IR ratios from generalized linear mixed models. RESULTS: We included 9365 (CC: 2040, HNC: 7325) inpatient hospital admissions from 14 German university hospitals. For CC, fractions decreased by 19.97% in 2020 compared to 2018/19 in the LP. In the RNP the reduction was 28.57% (p < 0.001 for both periods). LP fractions for HNC increased by 10.38% (RNP: 9.27%; p < 0.001 for both periods). Admissions for CC decreased in both periods (LP: 10.2%, RNP: 22.14%), whereas for HNC, admissions increased (LP: 2.25%, RNP: 1.96%) in 2020. Within LP, for CC, radiotherapy admissions without brachytherapy were reduced by 23.92%, whereas surgery-related admissions increased by 20.48%. For HNC, admissions with radiotherapy increased by 13.84%, while surgery-related admissions decreased by 11.28% in the same period. CONCLUSION: Related to the COVID-19 lockdown in an inpatient setting, radiotherapy for HNC treatment became a more frequently applied modality, while admissions of CC cases decreased.

Volumetric 68Ga-DOTA-TATE PET/CT for assessment of whole-body tumor burden as a quantitative imaging biomarker in patients with metastatic gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: A quantitative imaging biomarker is desirable to provide a comprehensive measure of whole-body tumor burden in patients with metastatic neuroendocrine tumors, and to standardize the evaluation of treatment-related changes. Therefore, we evaluated volumetric parameters for quantification of whole-body tumor burden from somatostatin receptor (SSR)-targeted PET/CT. METHODS: Thirty-two patients with metastastic grade1/grade 2 gastroenteropancreatic neuroendocrine tumors who underwent a 68Ga-DOTA-TATE PET/CT for staging of disease before initiation of peptide receptor radionuclide therapy were included in this retrospective cohort analysis. Volumetric parameters of tumor lesions, SSR-derived tumor volume (SSR-TV) and total lesion SSR (TL-SSR), were calculated for each patient using a computerized volumetric technique with a 40% SUVmax cut-off, and compared with serum chromogranin A (CgA) levels. Progression-free survival (PFS) was determined in relation to volumetric parameters. In a subgroup of 18 patients, the feasibility of volumetric parameters for treatment monitoring was evaluated. RESULTS: Mean SSR-TV was 178±214 cm3 (range, 9-797 cm3), whereas mean TL-SSR was 4096±5191 cm3 (range, 61-19,203 cm3). Baseline CgA levels were associated with whole-body tumor burden (SSR-TV, r=0.57, P=0.0008; and TL-SSR, r=0.43, P=0.01, respectively). PFS was shorter in patients with high SSR-TV and high TL-SSR (HR 5.16, 95% CI, 1.61-29.67), P=0.009), and SSR-TV (P=0.0067) and TL-SSR (P=0.0215) emerged as the sole predictors of progression in regression analysis. Changes in CgA did not correctly identify treatment response (P=0.25). CONCLUSIONS: SSR-derived volumetric parameters provide a quantitative imaging biomarker for whole-body tumor burden, and may hold potential as a clear-cut measure for assessment of treatment response.

Evaluation of treatment-associated eye toxicity after irradiation in childhood and adolescence-results from the Registry of the Evaluation of Side Effects after Radiotherapy in Childhood and Adolescence (RiSK).

PURPOSE: The aim of the study is to evaluate treatment-related acute and late eye toxicity associated with radiation therapy in childhood and adolescence as correlated with RT (radiotherapy) doses. METHODS: From 2001 to 2016, a total of 1725 children and adolescents undergoing radiation therapy were prospectively documented in the Registry of the Evaluation of Side Effects after Radiotherapy in Childhood and Adolescence (RiSK). The RTOG/EORTC criteria were used to classify ocular acute and late effects. Uni- and multivariate analyses were carried out to evaluate the impact of patient age, pre-existing impairments, and radiation dose on ocular toxicity. RESULTS: Of all documented patients, 593 received dose to the eye and formed the basis of this analysis. In 435 patients, information on acute reaction was available and graded 1, 2, 3, and 4 in 49, 17, 0, and 2 patients, respectively. Information on late toxicity was available in 268 patients and graded 1, 2, 3, and 4 in 15, 11, 11, and 5 patients, respectively. The acute toxicity rate was significantly higher in children who received a maximum dose > 50 Gy to the eye (p < 0.001) and who had a pre-existing eye impairment (p < 0.001 in multivariate analysis). The development of late toxicity was significantly higher for patients experiencing acute toxicity and having received a radiation dose > 50 Gy. CONCLUSION: Acute and late toxicity both correlate with high radiation dose to the eye (> 50 Gy) and acute toxicity additionally with pre-existing eye impairments.

Nasopharyngeal carcinoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Nasopharyngeal carcinoma (NPC) is a rare pediatric tumor. Collaborative studies performed over the last decades showed improved results compared to historical data, but standardized guidelines for diagnosis and management of pediatric NPC are still unavailable. This study presents a European consensus guideline for the diagnosis and treatment of pediatric NPC developed by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT). Main recommendations include induction chemotherapy with cisplatin and 5-flurouracil, concomitant chemoradiotherapy in advanced disease, and to consider maintenance treatment with interferon beta (IFN-ß) for selected high-risk patients. Dose adjustments of radiotherapy based on response to induction chemotherapy may decrease the rates of long-term treatment-related complications that affect most of the survivors.

Impact of sarcopenia in advanced and metastatic soft tissue sarcoma.

INTRODUCTION: Advanced or metastatic soft tissue sarcoma (a/mSTS) is associated with a dismal prognosis. Patient counseling on treatment aggressiveness is pivotal to avoid over- or undertreatment. Recently, evaluation of body composition markers like the skeletal muscle index (SMI) became focus of interest in a variety of cancers. This study focuses on the prognostic impact of SMI in a/mSTS, retrospectively. METHODS: 181 a/mSTS patients were identified, 89 were eligible due to prespecified criteria for SMI assessment. Baseline CT-Scans were analyzed using an institutional software solution. Sarcopenia defining cut-off values for the SMI were established by optimal fitting method. Primary end point was overall survival (OS) and secondary endpoints were progression free survival (PFS), disease control rate (DCR), overall response rate (ORR). Descriptive statistics as well as Kaplan Meier- and Cox regression analyses were administered. RESULTS: 28/89 a/mSTS patients showed sarcopenia. Sarcopenic patients were significantly older, generally tended to receive less multimodal therapies (62 vs. 57 years, P = 0.025; respectively median 2.5 vs. 4, P = 0.132) and showed a significantly lower median OS (4 months [95%CI 1.9-6.0] vs. 16 months [95%CI 8.8-23.2], Log-rank P = 0.002). Sarcopenia was identified as independent prognostic parameter of impaired OS (HR 2.40 [95%-CI 1.4-4.0], P < 0.001). Moreover, DCR of first palliative medical treatment was superior in non-sarcopenic patients (49.2% vs. 25%, P = 0.032). CONCLUSION: This study identifies sarcopenia as a prognostic parameter in a/mSTS. Further on, the data suggest that sarcopenia shows a trend of being associated with first line therapy response. SMI is a promising prognostic parameter, which needs further validation.

[Stereotactic body radiation therapy: radiobiological characteristics, physical-technical prerequisites, clinical applications]. / Extrakranielle Stereotaxie: strahlenbiologische Besonderheiten, physikalisch-technische Voraussetzungen, klinische Einsatzmöglichkeiten.

Radiotherapy of small targets with very high single doses administered in 1 to approximately 12 fractions-carried out under image guidance and with the intention of "tumour ablation"-is called stereotactic body radiation therapy (SBRT) for extracranial tumours or metastases. Radiobiologically, besides damaging the DNA of the tumour cells, the tumour vessels are also occluded and immunological effects are triggered. The safe performance of SBRT requires a very high physical-technical effort in order to ensure sufficient protection of healthy organs. Clinically, SBRT offers a wide range of applications in curative therapy (e.g. non-small-cell lung cancer stage I). Furthermore, it is a conservative, effective and well-tolerated option for the treatment of individual metastases and an optimal combination partner in the therapy of oligometastatic tumours.

Are women more afraid than men? Fear of recurrence in couples with cancer - predictors and sex-role-specific differences.

PURPOSE: Although fear of cancer recurrence (FoR) is one of the major concerns in cancer patients and their partners with approximately 49% reporting moderate to high FoR, few studies investigated predictors and sex-role-specific differences. The aim of the current study was to investigate FoR in couples with different types of cancer and to gain a deeper understanding of sex and role-specific differences and predictors of FoR in patients and partners. DESIGN: Cross-sectional study in Germany. Sample: N = 188 couples with prostate (PC; n=52), laryngeal (LC; n=21) or breast cancer (BC; n=115) participated. All PC and LC patients were males, all BC patients were females. METHODS: Fear of recurrence, depression, and relationship satisfaction were measured with validated questionnaires (Fear of Progression Questionnaire, Patient Health Questionnaire, Hospital Anxiety and Depression Scale, Quality of Marriage Index) in couples with PC, LC, or BC. FINDINGS: Results indicated sex-role-specific differences. For women, FoR was higher for patients (M = 35.76) than for caregivers (M = 27.11). For males, spouses of women with BC (M = 30.1) showed higher FoR than male PC or LC patients (M = 24.9). Moreover, in couples there was a correlation between the FoR of one and the other (PC: r = .51, BC: r = .31, LC: r = .41). Depression was as a significant predictor, with a positive relationship to FoR. Moreover, in men with PC and LC besides depression, age emerged as significant predictor with a negative relationship to FoR. The Actor-Partner-Interdependence-Model showed for couples with PC or LC significant actor effects, both for patients and partners. Moreover, a significant partner effect emerged for patients' depression on partners' FoR. For couples with BC only significant actor effects occurred. CONCLUSIONS: FoR remains a major concern for both cancer patients and their partners. Implications for Psychosocial Providers or Policy: FoR should be considered both in cancer patients and their spouses. In addition, sex and role effects should be taken into account in treatment of FoR.

A novel open-source software-based high-precision workflow for target definition in cardiac radioablation.

INTRODUCTION: Noninvasive ablative radiotherapy of cardiac arrhythmias (stereotactic ablative body radiation) has shown promising initial results. Precise targeting of the arrhythmogenic substrate is paramount to limit adverse effects to healthy myocardium, organs at risk, and cardiac implantable electronic devices. Using electroanatomic maps for treatment planning is technically challenging. METHODS AND RESULTS: Using the free open-source 3D Slicer software platform we established a workflow for high-precision target definition based on electroanatomic maps. An import plug-in for 3D Slicer has been designed that reads electroanatomic maps generated with three mapping systems in widespread clinical use. Using our proposed workflow in a real-world patient case we were able to align the map to the computed tomography (CT) with a mean distance of 3.1 mm. Thus, points defined on the map were translated into CT space with high accuracy and a radiotherapy treatment volume was defined in CT space based on these map-derived points. CONCLUSION: We describe a novel high-precision target definition method for stereotactic ablation of cardiac arrhythmias. Multimodal integration of the electroanatomic map with the planning CT allows for highly accurate localization of previously identified electrophysiological features in CT space. It remains to be shown whether this novel planning workflow leads to superior ablation outcomes when compared with other approaches.

Moderately HRT vs. CRT for localized prostate cancer using image-guided VMAT with SIB: evaluation of acute and late toxicities.

PURPOSE: This retrospective study aims at investigating the effects of moderately hypofractionated radiation therapy (HRT) on acute and late toxicities as well as on early biochemical control and therapeutic efficiency compared to conventional radiation therapy (CRT) in prostate cancer. PATIENTS AND METHODS: We analyzed 55 HRT patients irradiated with the total dose of 60 Gy in 20 fractions delivered over 4 weeks. These patients were compared to a control group of 55 patients who received CRT with a total of <78 Gy in 37-39 fractions delivered over circa 8 weeks. External beam radiation therapy (EBRT) was conducted using daily image-guided (cone beam CT) volumetric modulated arc therapy (VMAT) and a simultaneously integrated boost (SIB) for both groups to protect the rectum. Acute toxicities were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v5, whereas chronic toxicities were assessed in accordance with LENT-SOMA. Patient traits were compared by implementing t­tests and Wilcoxon-Whitney tests for continuous variables, whereas discrete characteristics were evaluated by applying two-tailed Fisher's exact tests. In addition, we calculated average treatment effects (ATE). Thereby, propensity score matching (PSM) based on nearest-neighbor matching considering age, comorbidities, and risk stratification as covariates was applied. The statistical analysis was conducted using Stata 14.2 (StataCorp LLC, TX, USA). RESULTS: As confirmed by the descriptive tests, the ATE revealed that the intensity and occurrence of urinary frequency (p = 0.034) and proctitis (p = 0.027) significantly decreased for the HRT group, whereas all other acute toxicities did not differ significantly between the HRT and CRT groups. For late toxicities, neither statistical tests nor ATE estimation showed significant differences. Also, no significant difference was found regarding the decrease in prostate specific antigen (PSA) after a median follow-up of 13 months (range 2-28 months), which indicates biochemical freedom from progression. CONCLUSION: HRT offers several medical and economic advantages and should therefore be considered as a useful alternative to CRT.

Efficacy of repeated PSMA PET-directed radiotherapy for oligorecurrent prostate cancer after initial curative therapy.

PURPOSE: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligorecurrent disease and treated with a first and a second PSMA (prostate-specific membrane antigen ligand) PET(positron-emission tomography)-directed radiotherapy (RT). PATIENTS AND METHODS: Thirty-two patients with oligorecurrent relapse after curative therapy received a first PSMA PET-directed RT of all metastases. After biochemical progression, all patients received a second PSMA PET-directed RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS) and androgen deprivation therapy-free survival (ADT-FS). The intervals of BPFS were analyzed separately as follows: the interval from the last day of PSMA PET-directed RT to the first biochemical progression was defined as bPFS_1 and the interval from second PSMA PET-directed RT to further biochemical progression was defined as bPFS_2. RESULTS: The median follow-up duration was 39.5 months (18-60). One out of 32 (3.1%) patients died after 47 months of progressive metastatic prostate cancer (mPCa). All patients showed biochemical responses after the first PSMA PET-directed RT and the median prostate-specific antigen (PSA) level before RT was 1.70 ng/mL (0.2-3.8), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range <0.07-3.8; p = 0.004). The median PSA level at biochemical progression after the first PSMA PET-directed RT was 2.9 ng/mL (range 0.12-12.80; p = 0.24). Furthermore, the PSA level after the second PSMA PET-directed RT at the last follow-up (0.52 ng/mL, range <0.07-154.0) was not significantly different (p = 0.36) from the median PSA level (1.70 ng/mL, range 0.2-3.8) before the first PSMA PET-directed RT. The median bPFS_1 was 16.0 months after the first PSMA PET-directed RT (95% CI 11.9-19.2) and the median bPFS_2 was significantly shorter at 8.0 months (95% CI 6.3-17.7) after the second PSMA PET-directed RT (p = 0.03; 95% CI 1.9-8.3). Multivariate analysis revealed no significant parameter for bPFS_1, whereas extrapelvic disease was the only significant parameter (p = 0.02, OR 2.3; 95% CI 0.81-4.19) in multivariate analysis for bPFS_2. The median ADT-FS was 31.0 months (95% CI 20.1-41.8) and multivariate analysis showed that patients with bone metastases, compared to patients with only lymph node metastases at first PSMA PET-directed RT, had a significantly higher chance (p = 0.007, OR 4.51; 95% CI 1.8-13.47) of needing ADT at the last follow-up visit. CONCLUSION: If patients are followed up closely, including PSMA PET scans, a second PSMA PET-directed RT represents a viable treatment option for well-informed and well-selected patients.

Prognostic risk classification for biochemical relapse-free survival in patients with oligorecurrent prostate cancer after [68Ga]PSMA-PET-guided metastasis-directed therapy.

PURPOSE: Since the success of prostate-specific membrane antigen-positron emission tomography (PSMA-PET) imaging for patients with oligorecurrent prostate cancer (ORPC), it is increasingly used for radiotherapy as metastasis-directed therapy (MDT). Therefore, we developed a prognostic risk classification for biochemical relapse-free survival (bRFS) for patients after PSMA-PET-guided MDT after radical prostatectomy. METHODS: We analyzed 292 patients with local recurrence (LR) and/or pelvic lymph node (LN) lesions and/or up to five distant LN, bone (BM), or visceral metastases (VM) detected with [68Ga]PSMA-PET imaging. Median follow-up was 16 months (range 0-57). The primary endpoint was bRFS after MDT. Cox regression analysis for risk factors was incorporated into a recursive partitioning analysis (RPA) with classification and regression tree method. RESULTS: PSA at recurrence ≥ 0.8 ng/mL, BM, and VM was significantly associated with biochemical relapse. RPA showed five groups with tenfold cross-validation of 0.294 (SE 0.032). After building risk classes I to IV (p < 0.0001), mean bRFS was 36.3 months (95% CI 32.4-40.1) in class I (PSA < 0.8 ng/mL, no BM) and 25.8 months (95% CI 22.5-29.1) in class II (PSA ≥ 0.8 ng/mL, no BM, no VM). LR and/or pelvic LNs caused relapse in classes I and II. Mean bRFS was 16.0 months (95% CI 12.4-19.6) in class III (PSA irrelevant, present BM) and 5.7 months (95% CI 2.7-8.7) in class IV (PSA ≥ 0.8 ng/mL, no BM, present VM). CONCLUSION: We developed and internally validated a risk classification for bRFS after PSMA-PET-guided MDT. Patients with PSA < 0.8 ng/mL and local relapse only (LR and/or pelvic LNs) had the most promising bRFS. PSA ≥ 0.8 ng/mL and local relapse only (LR and/or pelvic LNs) indicated intermediate risk for failure. Patients with BM were at higher risk regardless of the PSA. However, those patients still show satisfactory bRFS. In patients with VM, bRFS is heavily decreased. MDT in such cases should be discussed individually.

Efficacy of PSMA ligand PET-based radiotherapy for recurrent prostate cancer after radical prostatectomy and salvage radiotherapy.

BACKGROUND: A substantial number of patients will develop further biochemical progression after radical prostatectomy (RP) and salvage radiotherapy (sRT). Recently published data using prostate-specific membrane antigen ligand positron emission tomography (PSMA - PET) for re-staging suggest that those recurrences are often located outside the prostate fossa and most of the patients have a limited number of metastases, making them amenable to metastasis-directed treatment (MDT). METHODS: We analyzed 78 patients with biochemical progression after RP and sRT from a retrospective European multicenter database and assessed the biochemical recurrence-free survival (bRFS; PSA < nadir + 0.2 ng/ml or no PSA decline) as well as the androgen deprivation therapy- free survival (ADT-FS) using Kaplan-Meier curves. Log-rank test and multivariate analysis was performed to determine influencing factors. RESULTS: A total of 185 PSMA - PET positive metastases were detected and all lesions were treated with radiotherapy (RT). Concurrent ADT was prescribed in 16.7% (13/78) of patients. The median PSA level before RT was 1.90 ng/mL (range, 0.1-22.1) and decreased statistically significantly to a median PSA nadir level of 0.26 ng/mL (range, 0.0-12.25; p < 0.001). The median PSA level of 0.88 ng/mL (range, 0.0-25.8) at the last follow-up was also statistically significantly lower (p = 0.008) than the median PSA level of 1.9 ng/mL (range, 0.1-22.1) before RT. The median bRFS was 17.0 months (95% CI, 14.2-19.8). After 12 months, 55.3% of patients were free of biochemical progression. Multivariate analyses showed that concurrent ADT was the most important independent factor for bRFS (p = 0.01). The median ADT-FS was not reached and exploratory statistical analyses estimated a median ADT-FS of 34.0 months (95% CI, 16.3-51.7). Multivariate analyses revealed no significant parameters for ADT-FS. CONCLUSIONS: RT as MDT based on PSMA - PET of all metastases of recurrent prostate cancer after RP and sRT represents a viable treatment option for well-informed and well-selected patients.

Body image in men with prostate or laryngeal cancer and their female partners.

Objectives: The study examines body image of male cancer patients and their female partners as well as factors influencing body image. Methods: N = 73 heterosexual couples in which the male partner was diagnosed with prostate (PC; n = 52) or laryngeal cancer (LC; n = 21) completed questionnaires on body image acceptance (Self Image Scale), relationship satisfaction (Quality of Marriage Questionnaire), and cancer-related distress (Questionnaire on Stress in Cancer Patients). The body image was assessed from two perspectives: self-acceptance (which measures a person's satisfaction or acceptance of the body) and partner-acceptance (which assesses a person's perception of the partners' appraisals of the body). Results: No differences occurred in body image acceptance between men with PC or LC. Patients with PC rated the perceived partner-acceptance lower than did their female partners. In couples with LC, women rated the self-acceptance of their partners higher than did the patients themselves. Multiple regression analysis revealed that for survivors of PC, cancer-related distress, relationship satisfaction and partner-acceptance emerged as significant predictors of self-acceptance. The only significant predictor of partner-acceptance was men's self-acceptance. Conclusions: The dissatisfaction with physical appearance is found in PK and LK patients and seems to persist for a long time. Impairment of patients' body image should be identified and addressed to prevent the negative effects on psychosocial stress for patients and relationship satisfaction.

Comparison of 68 Ga-PSMA ligand PET/CT versus conventional cross-sectional imaging for target volume delineation for metastasis-directed radiotherapy for metachronous lymph node metastases from prostate cancer.

PURPOSE: To assess the differences in the target volume (TV) delineation of metachronous lymph node metastases between 68 Ga-PSMA ligand PET/CT and conventional imaging in a comparative retrospective contouring study. PATIENTS AND METHODS: Twenty-five patients with biochemical prostate cancer recurrence after primary prostatectomy underwent 68 Ga-PSMA ligand PET/CT in addition to conventional imaging techniques such as CT and/or MR imaging for restaging. All patients were diagnosed with at least one lymph node metastasis. TVs were manually delineated in two different ways: (a) based on conventional imaging (CT/MRI) and (b) based on conventional imaging (CT/MRI) plus 68 Ga-PSMA ligand PET/CT. The size of TVs, overlap rates, and subjective assessment of the difficulty of TV delineation reported by the radiation oncologist (easy/moderate/difficult) were compared. RESULTS: With the additional information from PSMA ligand PET, 47 lymph node metastases were identified and included in the gross tumor volume (GTV). The median clinical target volume (CTV) of non-PET-based TV delineation was statistically larger than the CTV based on PET imaging (134.8 ml [range 6.9-565.2] versus 44.9 ml [range 4.9-481.3; p = 0.001]). The CTV based on CT/MRI enclosed only 81.3% (39/48) of PET-positive lymph nodes. The CT/MRI-based CTV did not enclose all PET-positive lymph nodes in 24% (6/25) of patients. In 12% (3/25) of patients, all PET-positive lymph nodes were outside of the CT/MRI-based CTV. The median overlap rates (TVPET/TVCT/MRIâ€¯× 100) were 45.7% (range 0-96.9) for the GTV and 71.7% (range 9.8-98.2) for the CTV. The assessment of difficulty of contouring revealed that contouring with the additional imaging information of the PET was categorized as easy/moderate in 92% (23/25) and as difficult in 8% (2/25) of the cases, whereas contouring based on CT/MRI without PET was categorized as difficult in 56% (14/25) and as easy/moderate in 44% of the cases (11/25; p = 0.003). CONCLUSION: 68 Ga-PSMA ligand PET/CT is superior to conventional cross-sectional imaging for the delineation of lymph node metastases from prostate cancer. PET-based TV delineation allows for smaller target volumes and should be considered the standard for irradiation of metachronous lymph node metastases in recurrent prostate cancer. Conventional imaging is not sufficiently sensitive for radio-oncological treatment concepts in oligometastatic prostate cancer.

Patterns of relapse as determined by 68Ga-PSMA ligand PET/CT after radical prostatectomy : Importance for tailoring and individualizing treatment.

PURPOSE: To evaluate the patterns of relapse and impact on the intended treatment when using 68Ga-prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) imaging for restaging of disease in patients with biochemical relapse after radical prostatectomy (RP) before salvage radiotherapy (sRT). METHODS: In all, 39 patients with biochemical recurrence after RP who had no primary indication for adjuvant RT due to the absence of biologically unfavorable disease (e.g., extracapsular extension, seminal vesicle invasion, positive margins, or lymph node involvement) underwent a 68Ga-PSMA ligand PET/CT for planning of sRT. RESULTS: PET/CT was positive in 84.6% (33/39) of patients. A total of 61 lesions were observed in these patients (on average 1.8 lesions per patient); 30.3% (10/33) of patients had locally recurrent disease in the prostatic bed. The clinical TNM stage (TNM: tumour-lymph nodes-metastasis-classification) was altered in 69.7% (23/33) of patients following PET, resulting in individualized treatment concepts. A prostate-specific antigen (PSA) >1.0 ng/mL was significantly associated with an increased risk of extrapelvic metastatic disease (p = 0.048). The PSA level at the time of PSMA ligand PET/CT correlated with the peak standardized uptake value (SUVpeak; p = 0.002). According to current clinical guidelines, the remaining 15.4% (6/39) of patients without evidence of disease on PET received sRT with a dose of 66.0 Gy. CONCLUSION: Our results suggest that in patients with biochemical recurrence who did not receive early sRT, a 68Ga-PSMA ligand PET/CT for restaging of disease allows for tailoring and individualizing treatment. Particularly in patients with PSA levels above 1.0 ng/mL, a 68Ga-PSMA ligand PET/CT should be performed for therapy planning, since patients often have metastases not confined to the pelvis.