Dose prescription for stereotactic body radiotherapy: general and organ-specific consensus statement from the DEGRO/DGMP Working Group Stereotactic Radiotherapy and Radiosurgery.

PURPOSE AND OBJECTIVE: To develop expert consensus statements on multiparametric dose prescriptions for stereotactic body radiotherapy (SBRT) aligning with ICRU report 91. These statements serve as a foundational step towards harmonizing current SBRT practices and refining dose prescription and documentation requirements for clinical trial designs. MATERIALS AND METHODS: Based on the results of a literature review by the working group, a two-tier Delphi consensus process was conducted among 24 physicians and physics experts from three European countries. The degree of consensus was predefined for overarching (OA) and organ-specific (OS) statements (≥ 80%, 60-79%, < 60% for high, intermediate, and poor consensus, respectively). Post-first round statements were refined in a live discussion for the second round of the Delphi process. RESULTS: Experts consented on a total of 14 OA and 17 OS statements regarding SBRT of primary and secondary lung, liver, pancreatic, adrenal, and kidney tumors regarding dose prescription, target coverage, and organ at risk dose limitations. Degree of consent was ≥ 80% in 79% and 41% of OA and OS statements, respectively, with higher consensus for lung compared to the upper abdomen. In round 2, the degree of consent was ≥ 80 to 100% for OA and 88% in OS statements. No consensus was reached for dose escalation to liver metastases after chemotherapy (47%) or single-fraction SBRT for kidney primaries (13%). In round 2, no statement had 60-79% consensus. CONCLUSION: In 29 of 31 statements a high consensus was achieved after a two-tier Delphi process and one statement (kidney) was clearly refused. The Delphi process was able to achieve a high degree of consensus for SBRT dose prescription. In summary, clear recommendations for both OA and OS could be defined. This contributes significantly to harmonization of SBRT practice and facilitates dose prescription and reporting in clinical trials investigating SBRT.

Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis.

PURPOSE: Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT. METHODS: A propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test. RESULTS: Median follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2α/ß=1.5 Gy) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis. CONCLUSIONS: Overall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity.

Development of PSMA-PET-guided CT-based radiomic signature to predict biochemical recurrence after salvage radiotherapy.

PURPOSE: To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). MATERIAL AND METHODS: Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. RESULTS: Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. CONCLUSION: This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.

The maximum standardized uptake value in patients with recurrent or persistent prostate cancer after radical prostatectomy and PSMA-PET-guided salvage radiotherapy-a multicenter retrospective analysis.

PURPOSE: This study aims to evaluate the association of the maximum standardized uptake value (SUVmax) in positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET) prior to salvage radiotherapy (sRT) on biochemical recurrence free survival (BRFS) in a large multicenter cohort. METHODS: Patients who underwent 68 Ga-PSMA11-PET prior to sRT were enrolled in four high-volume centers in this retrospective multicenter study. Only patients with PET-positive local recurrence (LR) and/or nodal recurrence (NR) within the pelvis were included. Patients were treated with intensity-modulated-sRT to the prostatic fossa and elective lymphatics in case of nodal disease. Dose escalation was delivered to PET-positive LR and NR. Androgen deprivation therapy was administered at the discretion of the treating physician. LR and NR were manually delineated and SUVmax was extracted for LR and NR. Cox-regression was performed to analyze the impact of clinical parameters and the SUVmax-derived values on BRFS. RESULTS: Two hundred thirty-five patients with a median follow-up (FU) of 24 months were included in the final cohort. Two-year and 4-year BRFS for all patients were 68% and 56%. The presence of LR was associated with favorable BRFS (p = 0.016). Presence of NR was associated with unfavorable BRFS (p = 0.007). While there was a trend for SUVmax values ≥ median (p = 0.071), SUVmax values ≥ 75% quartile in LR were significantly associated with unfavorable BRFS (p = 0.022, HR: 2.1, 95%CI 1.1-4.6). SUVmax value in NR was not significantly associated with BRFS. SUVmax in LR stayed significant in multivariate analysis (p = 0.030). Sensitivity analysis with patients for who had a FU of > 12 months (n = 197) confirmed these results. CONCLUSION: The non-invasive biomarker SUVmax can prognosticate outcome in patients undergoing sRT and recurrence confined to the prostatic fossa in PSMA-PET. Its addition might contribute to improve risk stratification of patients with recurrent PCa and to guide personalized treatment decisions in terms of treatment intensification or de-intensification. This article is part of the Topical Collection on Oncology-Genitourinary.

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.

Retroperitoneal soft tissue sarcoma: low-dose neoadjuvant radiation therapy followed by surgery with or without intraoperative radiotherapy and adjuvant radiation therapy.

BACKGROUND: We describe the clinical history, outcome, and toxicity of five patients with high-grade retroperitoneal soft tissue sarcoma (RSTS) who were treated with neoadjuvant low-dose radiotherapy (RT) followed by resection with or without intraoperative radiotherapy (IORT), followed by adjuvant RT. We aim to provide additional evidence for the various treatment options that exist for this rare tumor entity. METHODS: Most patients presented with mild abdominal symptoms. Diagnosis was confirmed by biopsy. Additional imaging was done by sonography, magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/computed tomography (CT). All patients were treated with neoadjuvant RT of 19.8 Gy in 1.8-Gy fractions followed by resection and postoperative RT up to 45 Gy with a median interval between resection and start of postoperative RT of 5 weeks. Two patients received additional IORT. Median follow-up was 61 months. RESULTS: One patient developed a local recurrence that was diagnosed 30 months after the start of the first therapy. He was treated with a salvage resection and had no evidence of disease at the last follow-up. Another patient developed a right-sided RSTS on the contralateral side from the primary radiation field with pelvic bone infiltration 56 months after the start of RT. He was treated again by RT and resection and was without evidence of disease at last follow-up. Radiotherapy was well tolerated without major toxicity. CONCLUSION: The treatment of RSTS by low-dose neoadjuvant RT, resection with IORT and adjuvant RT seems to be a feasible and effective treatment approach. Further studies comparing neoadjuvant with adjuvant RT are necessary to find the best treatment option.

Repeated SBRT for in- and out-of-field recurrences in the liver.

PURPOSE: To evaluate the feasibility and toxicity profile of repeated stereotactic body radiotherapy (SBRT) for recurrent primary or secondary liver tumors. METHODS: Consecutive patients with primary (hepatocellular carcinoma [HCC] or cholangiocarcinoma [CCC]) or secondary liver cancer (LM), with intrahepatic recurrence or progression after SBRT, underwent re-SBRT in 3 to 12 fractions with a median time of 15 (range 2-66) months between treatments. RESULTS: In all, 24 patients which were previously treated with SBRT (30 lesions) were retreated with SBRT for "in- and out-of-field" recurrences (2nd SBRT: n = 28, 3rd SBRT: n = 2). The median follow-up after re-irradiation was 14 months. The median prescribed dose for the first SBRT was 46.5 (range 33-66 Gy, EQD210 = 70.5) Gy and 48 (range 27-66 Gy, EQD210 = 71) Gy for the re-SBRT. The median mean liver dose (Dmean, liver) was 6 Gy (range 1-25, EQD22 = 7 Gy) for the first SBRT and 10 Gy (range 1-63 Gy, EQD22 = 9 Gy) for the re-SBRT. Of the 30 re-irradiated lesions 6 were re-irradiated in-field resulting in a median EQD22, maximum of 359 (range 120-500) Gy for both treatments, with an α/ß = 2 to account for liver parenchyma. Treatment was well tolerated. Two patients with stent placement before SBRT developed cholangitis 4 and 14 months after re-SBRT. There were no elevations of the serum liver parameters after re-SBRT. One patient developed a grade 3 gastrointestinal bleeding. There was no radiation induced liver disease (RILD) observed. CONCLUSIONS: Repeated liver SBRT is feasible, without excessive liver toxicity, when there is no considerable overlapping with pre-irradiated portions of the stomach or bowel and enough time for the liver to regenerate.

The effect of pasireotide on intestinal anastomotic healing with and without whole-body irradiation in a rat model.

OBJECTIVE: To examine pasireotide's effect on intestinal anastomotic healing under physiological conditions and following preoperative whole-body irradiation. MATERIAL AND METHODS: Forty-five male Wistar rats received an ileoileal end-to-end anastomosis. Group 1 (Co, n = 9) served as control. Group 2 (SOM, n = 10) received pasireotide (60 mg/kg) 6 days preoperatively. Group 3 (R-Co, n = 13) was subjected to 8 Gy whole-body irradiation 4 days preoperatively. Finally, group 4 (R-SOM, n = 13) received pasireotide 6 days preoperatively and whole-body irradiation 4 days preoperatively. On postoperative day 4, anastomotic bursting pressure, histology, IGF-1 staining, and collagen density were examined. RESULTS: Mortality was higher in irradiated animals (30.8% vs. 5.3%, p = 0.021), and anastomotic bursting pressure was significantly lower (median, R-Co = 83 mmHg; R-SOM = 101 mmHg; Co = 149.5 mmHg; SOM = 169 mmHg). Inflammation measured by leukocyte infiltration following irradiation was reduced (p = 0.023), and less collagen was observed, though this was not statistically significant. Bursting pressure did not significantly differ between Co and SOM and between R-Co and R-SOM animals respectively. Semi-quantitative scoring of IGF-1, fibroblast bridging, or collagen density did not reveal significant differences among the groups. CONCLUSION: Whole-body irradiation decreases the quality of intestinal anastomotic wound healing and increases mortality. Pasireotide does not significantly lessen this detrimental effect.

The role of albumin-bilirubin grade and inflammation-based index in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy.

PURPOSE: We evaluated the prognostic accuracy of the albumin-bilirubin (ALBI) grade and the inflammation-based index (IBI) in estimating overall survival (OS) and toxicity in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Forty patients with 47 HCC lesions with a Barcelona Clinic Liver Cancer (BCLC) classification stage B or C were treated with SBRT in 3-12 fractions. The ALBI grade and the IBI were calculated at different time points (baseline, during, at the end of treatment and at follow-up) and compared with the Child-Pugh (CP) score as well as other patient- and treatment-related parameters, concerning OS and toxicity. RESULTS: The median follow-up was 14.3 months for patients alive. The median OS from SBRT was 10 (95% confidence interval 8.3-11.6) months. The local control at 1 year was 79%. A lower IBI during treatment was associated with better OS (p = 0.034) but not CP and ALBI. Higher C­reactive protein levels as well as higher alpha-fetoprotein concentrations correlated with worse survival (p = 0.001). Both higher ALBI (p = 0.02) and CTP (p = 0.001) at baseline correlated with a higher incidence of acute and late toxicities (CTC ≥2). Neither the mean radiation dose to the liver nor the dose to 700 cc of the liver correlated with the occurrence of toxicities. CONCLUSIONS: In this analysis, a higher ALBI grade as well as a higher CP were predictors of higher incidence of toxicity, whereas a lower IBI during treatment correlated with a better OS. These results should be further evaluated in prospective studies.

Comparison of local tumor control in patients with HCC treated with SBRT or TACE: a propensity score analysis.

BACKGROUND: As stereotactic body radiation therapy (SBRT) has shown to be effective and safe in patients with hepatocellular carcinoma (HCC), the aim of our propensity score matched analysis was to evaluate the efficacy of SBRT in comparison to transarterial chemoembolization (TACE) in intermediate and advanced HCC. METHODS: Patients treated with TACE (n = 367) and patients allocated to SBRT (n = 35) were enrolled in this study. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics of TACE and SBRT patients. Local tumor control (LC) 1 year after treatment, overall survival (OS) and 1-year mortality were assessed. RESULTS: Patients treated with SBRT have received more prior HCC treatments compared to TACE patients. The LC 1 year after treatment in the unmatched cohort was 74.4% for TACE patients compared to 84.8% in the SBRT group. Patients treated with TACE showed significantly improved OS (17.0 months vs. 9.0 months, p = 0.016). After propensity score matching, the LC in the TACE (n = 70) and SBRT (n = 35) group was comparable (82.9% vs. 84.8%, p = 0.805) and OS did not differ significantly in both groups. CONCLUSIONS: SBRT after prior HCC therapy in selected patients shows comparable LC at 1 year, OS and 1-year mortality compared to patients treated with TACE.

Biological imaging for individualized therapy in radiation oncology: part II medical and clinical aspects.

Positron emission tomography and multiparametric MRI provide crucial information concerning tumor extent and normal tissue anatomy. Moreover, they are able to visualize biological characteristics of the tumor, which can be considered in the radiation treatment planning and monitoring. In this review we discuss the impact of biological imaging positron emission tomography and multiparametric MRI for radiation oncology, based on the data of the literature and on the experience of our own institution in this field.

Stereotactic body radiotherapy (SBRT) for locally advanced intrahepatic and extrahepatic cholangiocarcinoma.

BACKGROUND: To evaluate the role of ablative radiotherapy doses in the treatment of hilar or intrahepatic cholangiocarcinoma (CCC) using stereotactic body radiotherapy (SBRT). METHODS: Consecutive patients treated from 2007 to 2016 with CCC were evaluated. Local control and toxicities were assessed every 3 months according to the Response Evaluation Criteria In Solid Tumors (RECIST) and the Common Terminology Criteria for Adverse Events v4.0, respectively. Overall survival (OS), local control (LC) and progression free survival were calculated from SBRT. RESULTS: Thirty seven patients with 43 lesions were retrospectively evaluated. The median dose delivered was 45 Gy (range 25-66 Gy) in 3-12 fractions, corresponding to a median equivalent dose in 2 Gy fractions (EQD210) of 56 (range 25-85) Gy. The median follow up was 24 months. The OS at 1 year was 56% with a median OS of 14 (95% CI: 7.8-20.2) months from start of SBRT and 22 (95% CI: 17.5-26.5) months from diagnosis. Eight lesions progressed locally. The local control rate (LC) at 1 year was 78%. The median progression free survival was 9 months (95% CI 2.8-15.2) 21 patients progressed in the liver but out of field and 15 progressed distantly. SBRT was well tolerated. Three patients (9%) developed a Grade III bleeding. Seven patients developed a cholangitis, one due to progression and the other because of a stent dysfunction 2-21(median 8) months from SBRT. CONCLUSION: In patients with locally advanced cholangiocarcinoma, SBRT is a local treatment option with an acceptable toxicity profile which warrants further investigation in prospective trials.

MRI versus 68Ga-PSMA PET/CT for gross tumour volume delineation in radiation treatment planning of primary prostate cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) is widely used in radiation treatment planning of primary prostate cancer (PCA). Focal dose escalation to the dominant intraprostatic lesions (DIPL) may lead to improved PCA control. Prostate-specific membrane antigen (PSMA) is overexpressed in most PCAs. (68)Ga-labelled PSMA inhibitors have demonstrated promising results in detection of PCA with PET/CT. The aim of this study was to compare (68)Ga-PSMA PET/CT with MRI for gross tumour volume (GTV) definition in primary PCA. METHODS: This retrospective study included 22 patients with primary PCA analysed after (68)Ga-PSMA PET/CT and mpMRI. GTVs were delineated on MR images by two radiologists (GTV-MRIrad) and two radiation oncologists separately. Both volumes were merged leading to GTV-MRIint. GTVs based on PET/CT were delineated by two nuclear medicine physicians in consensus (GTV-PET). Laterality (left, right, and left and right prostate lobes) on mpMRI, PET/CT and pathological analysis after biopsy were assessed. RESULTS: Mean GTV-MRIrad, GTV-MRIint and GTV-PET were 5.92, 3.83 and 11.41 cm(3), respectively. GTV-PET was significant larger then GTV-MRIint (p = 0.003). The MRI GTVs GTV-MRIrad and GTV-MRIint showed, respectively, 40 % and 57 % overlap with GTV-PET. GTV-MRIrad and GTV-MRIint included the SUVmax of GTV-PET in 12 and 11 patients (54.6 % and 50 %), respectively. In nine patients (47 %), laterality on mpMRI, PET/CT and histopathology after biopsy was similar. CONCLUSION: Ga-PSMA PET/CT and mpMRI provided concordant results for delineation of the DIPL in 47 % of patients (40 % - 54 % of lesions). GTV-PET was significantly larger than GTV-MRIint. (68)Ga-PSMA PET/CT may have a role in radiation treatment planning for focal radiation to the DIPL. Exact correlation of PET and MRI images with histopathology is needed.

Adjuvant radiotherapy after salvage lymph node dissection because of nodal relapse of prostate cancer versus salvage lymph node dissection only.

BACKGROUND: Nodal pelvic/retroperitoneal recurrent prostate cancer (PCa) after primary therapy can be treated with salvage lymph node dissection (salvage-LND) in order to delay disease progression and offer cure for a subset of patients. Whether adjuvant radiotherapy (ART) in affected regions improves the outcome by elimination of residual tumour burden remains unclear. METHODS: A total of 93 patients with exclusively nodal PCa relapse underwent choline-positron-emission tomography-computed-tomography-directed pelvic/retroperitoneal salvage-LND; 46 patients had surgery only and 47 patients received ART in regions with proven lymph node metastases. In case of subsequent prostate specific antigen (PSA) progression, different imaging modalities were performed to confirm next relapse within or outside the treated region (TR). Mean follow-up was 3.2 years. RESULTS: Lymphatic tumour burden was balanced between the two groups. Additional ART resulted in delayed relapse within TR (5-year relapse-free rate 70.7 %) versus surgery only (5-year relapse-free rate 26.3 %, p < 0.0001). In both treatment arms, time to next relapse outside the TR was almost equal (median 27 months versus 29.6 months, p = 0.359). With respect to the detection of the first new lesion, regardless if present within or outside the TR, 5 years after the treatment 34.3 % of patients in the group with additional ART were free of relapse, versus 15.4 % in the surgery only group (p = 0.0122). ART had no influence on the extent of PSA reduction at latest follow-up compared to treatment with surgery only. CONCLUSION: ART after salvage-LND provides stable local control in TR and results in overall significant improved next-relapse-free survival, compared to patients who received surgery only in case of nodal PCa-relapse.

11C-Choline PET/pathology image coregistration in primary localized prostate cancer.

PURPOSE: The aim of this study was to develop a methodology for the comparison of pathology specimens after prostatectomy (post-S) with PET images obtained before surgery (pre-S). This method was used to evaluate the merit of (11)C-choline PET/CT for delineation of gross tumour volume (GTV) in prostate cancer (PC). METHODS: In 28 PC patients, (11)C-choline PET/CT was performed before surgery. PET/CT data were coregistered with the pathology specimens. GTV on PET images (GTV-PET) was outlined automatically and corrected manually. Tumour volume in the prostate (TVP) was delineated manually on the pathology specimens. Based on the coregistered PET/pathology images, the following parameters were assessed: SUVmax and SUVmean in the tumoral and nontumoral prostate (NP), GTV-PET (millilitres) and TVP (millilitres). RESULTS: PET/pathology image coregistration was satisfactory. Mean SUVmax in the TVP was lower than in the NP: 5.0 and 5.5, respectively (p = 0.093). Considering the entire prostate, SUVmax was located in the TVP in two patients, in the TVP and NP in 12 patients and exclusively in NP in 14 patients. Partial overlap the TVP and GTV-PET was seen in 71% of patients, and complete overlap in 4%. CONCLUSION: PET/pathology image coregistration can be used for evaluation of different imaging modalities. (11)C-Choline PET failed to distinguish tumour from nontumour tissue.

Clinical outcome after total neoadjuvant treatment (CAO/ARO/AIO-12) versus intensified neoadjuvant and adjuvant treatment (CAO/ARO/AIO-04) a comparison between two multicenter randomized phase II/III trials.

BACKGROUND: Total neoadjuvant therapy (TNT) can enhance local tumor regression, but its survival benefits compared to intensified chemoradiotherapy (CRT) followed by adjuvant chemotherapy (CT) remain unclear. METHODS: This is a secondary comparison between 607 patients treated with intensified 5-FU/Oxaliplatin neoadjuvant CRT and adjuvant CT within the experimental arm of the CAO/ARO/AIO-04 phase III trial, and 306 patients treated with TNT within the CAO/ARO/AIO-12 phase II trial. Comparison between clinical-pathological characteristics, surgical quality, and post-surgical complications were analyzed using the Pearson's Chi-squared or Mann-Whitney U test. Oncological outcome was examined with log-rank, Gray's test, and multivariate cox regression. In addition, further subgroup analyses and propensity score matching were performed to optimize the balance of baseline covariates. FINDINGS: Patients treated with CRT followed by consolidation CT had a significantly higher rate of pathological complete remission (pCR) compared to patients treated within the experimental arm of the CAO/ARO/AIO-04 trial (25.3 % vs 17.3 %, P = 0.04). Post-surgical complications were less common in the CAO/ARO/AIO-12 trial. After a median follow-up of 46 months, clinical outcome did not differ significantly in the overall cohort, in any subgroup or after propensity score matching. In multivariate analysis, disease-free survival (DFS) was similar between the experimental arm of the CAO/ARO/AIO-04 trial and treatments arms of the CAO/ARO/AIO-12 trial (vs arm A: HR 0.92 [95 % CI 0.62-1.37], P = 0.69; vs arm B: HR 1.06 [95 % CI 0.72-1.58], P = 0.76). INTERPRETATION: Notwithstanding the limitations of intertrial comparison, TNT did not improve long term oncological outcome in our study compared to the intensified neoadjuvant CRT and adjuvant CT treatment in the CAO/ARO/AIO-04 trial. Improved response rates after TNT offers an attractive option to explore organ preservation in selective patients with locally advanced rectal cancer.