Development and evaluation of two open-source nnU-Net models for automatic segmentation of lung tumors on PET and CT images with and without respiratory motion compensation.

OBJECTIVES: In lung cancer, one of the main limitations for the optimal integration of the biological and anatomical information derived from Positron Emission Tomography (PET) and Computed Tomography (CT) is the time and expertise required for the evaluation of the different respiratory phases. In this study, we present two open-source models able to automatically segment lung tumors on PET and CT, with and without motion compensation. MATERIALS AND METHODS: This study involved time-bin gated (4D) and non-gated (3D) PET/CT images from two prospective lung cancer cohorts (Trials 108237 and 108472) and one retrospective. For model construction, the ground truth (GT) was defined by consensus of two experts, and the nnU-Net with 5-fold cross-validation was applied to 560 4D-images for PET and 100 3D-images for CT. The test sets included 270 4D- images and 19 3D-images for PET and 80 4D-images and 27 3D-images for CT, recruited at 10 different centres. RESULTS: In the performance evaluation with the multicentre test sets, the Dice Similarity Coefficients (DSC) obtained for our PET model were DSC(4D-PET) = 0.74 ± 0.06, improving 19% relative to the DSC between experts and DSC(3D-PET) = 0.82 ± 0.11. The performance for CT was DSC(4D-CT) = 0.61 ± 0.28 and DSC(3D-CT) = 0.63 ± 0.34, improving 4% and 15% relative to DSC between experts. CONCLUSIONS: Performance evaluation demonstrated that the automatic segmentation models have the potential to achieve accuracy comparable to manual segmentation and thus hold promise for clinical application. The resulting models can be freely downloaded and employed to support the integration of 3D- or 4D- PET/CT and to facilitate the evaluation of its impact on lung cancer clinical practice. CLINICAL RELEVANCE STATEMENT: We provide two open-source nnU-Net models for the automatic segmentation of lung tumors on PET/CT to facilitate the optimal integration of biological and anatomical information in clinical practice. The models have superior performance compared to the variability observed in manual segmentations by the different experts for images with and without motion compensation, allowing to take advantage in the clinical practice of the more accurate and robust 4D-quantification. KEY POINTS: Lung tumor segmentation on PET/CT imaging is limited by respiratory motion and manual delineation is time consuming and suffer from inter- and intra-variability. Our segmentation models had superior performance compared to the manual segmentations by different experts. Automating PET image segmentation allows for easier clinical implementation of biological information.

Deep inspiration breath-hold radiation therapy in left-sided breast cancer patients: a single-institution retrospective dosimetric analysis of organs at risk doses.

BACKGROUND: Radiotherapy can induce cardiac injury in left-sided breast cancer cases. Cardiac-sparing irradiation using the deep inspiration breath-hold (DIBH) technique can achieve substantial dose reduction to vulnerable cardiac substructures compared with free breathing (FB). This study evaluated the dosimetric differences between both techniques at a single institution. METHODS: From 2017 to 2019, 130 patients with left-sided breast cancer underwent breast-conserving surgery (BCS; n = 121, 93.1%) or mastectomy (ME; n = 9, 6.9%) along with axillary lymph node staging (n = 105, 80.8%), followed by adjuvant irradiation in DIBH technique; adjuvant systemic therapy was included if applicable. 106 (81.5%) patients received conventional and 24 (18.5%) hypofractionated irradiation. Additionally, 12 patients received regional nodal irradiation. Computed tomography (CT) scans in FB and DIBH position were performed for all patients. Intrafractional 3D position monitoring of the patient surface in deep inspiration and breath gating was performed using Sentinel and Catalyst HD 3D surface scanning systems (C-RAD, Catalyst, C­RAD AB, Uppsala, Sweden). Individual coaching and determination of breathing amplitude during the radiation planning CT was performed. Three-dimensional treatment planning was performed using standard tangential treatment portals (6 or 18 MV). The delineation of cardiac structures and both lungs was done in both the FB and the DIBH scan. RESULTS: All dosimetric parameters for cardiac structures were significantly reduced (p < 0.01 for all). The mean heart dose (Dmean) in the DIBH group was 1.3 Gy (range 0.5-3.6) vs. 2.2 Gy (range 0.9-8.8) in the FB group (p < 0.001). The Dmean for the left ventricle (LV) in DIBH was 1.5 Gy (range 0.6-4.5), as compared to 2.8 Gy (1.1-9.5) with FB (p < 0.001). The parameters for LV (V10 Gy, V15 Gy, V20 Gy, V23 Gy, V25 Gy, V30 Gy) were reduced by about 100% (p < 0.001). The LAD Dmean in the DIBH group was 4.1 Gy (range 1.2-33.3) and 14.3 Gy (range 2.4-37.5) in the FB group (p < 0.001). The median values for LAD such as V15 Gy, V20 Gy, V25 Gy, V30 Gy, and V40 Gy decreased by roughly 100% (p < 0.001). An increasing volume of left lung in the DIBH position resulted in dose sparing of cardiac structures. CONCLUSION: For all ascertained dosimetric parameters, a significant dose reduction could be achieved in DIBH technique.

App-Controlled Treatment Monitoring and Support for Patients With Head and Neck Cancer Undergoing Radiotherapy: Results From a Prospective Randomized Controlled Trial.

BACKGROUND: Head and neck cancers (HNCs) are very common malignancies, and treatment often requires multimodal approaches, including radiotherapy and chemotherapy. Patients with HNC often display a high symptom burden, both due to the disease itself and the adverse effects of the multimodal therapy. Close telemonitoring of symptoms and quality of life during the course of treatment may help to identify those patients requiring early medical support. OBJECTIVE: The App-Controlled Treatment Monitoring and Support for Patients With Head and Neck Cancer (APCOT) trial aimed to investigate the feasibility of integrating electronic patient-reported outcomes (ePROs) in the treatment surveillance pathway of patients with HNC during the course of their radiotherapy. Additionally, the influence of app-based ePRO monitoring on global and disease-specific quality of life and patient satisfaction with treatment was assessed. METHODS: Patients undergoing radiotherapy for histologically proven HNCs at the Department of Radiation Oncology, University Medical Center Freiburg, Germany, were enrolled in this trial and monitored by weekly physician appointments. Patients were randomized between additional ePRO monitoring on each treatment day or standard-of-care monitoring. Feasibility of ePRO monitoring was defined as ≥80% of enrolled patients answering ≥80% of their daily app-based questions. Quality of life and patient satisfaction were assessed by the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30), the head and neck cancer module (H&N35), and the validated Patient Satisfaction Questionnaire Short Form (PSQ-18) at the completion of treatment and compared between trial arms. RESULTS: A total of 100 patients were enrolled in this trial, and 93 patients were evaluable. All patients (100%) in the experimental arm answered ≥80% of the ePRO questions during treatment, reaching the predefined threshold for the feasibility of ePRO monitoring (P<.001 in the binomial test). No clinical or patient-specific factor was found to influence feasibility. Global health and most domains of the general quality of life were comparable between trial arms, but an increased HNC-specific symptom burden was reported by patients undergoing ePRO surveillance. ePRO monitoring resulted in improved patient satisfaction regarding interpersonal manners (P=.01), financial aspects (P=.01), and time spent with a doctor (P=.01). CONCLUSIONS: This trial demonstrated the feasibility of incorporating daily app-based ePRO surveillance for patients with HNC undergoing radiotherapy. Our data, for the first time, demonstrate that telemonitoring in this setting led to increased reporting of HNC-specific symptom burden and significantly improved several domains of patient satisfaction. Further analyses are needed to assess whether our findings hold true outside the context of a clinical trial. TRIAL REGISTRATION: German Clinical Trials Register DRKS00020491; https://drks.de/search/en/trial/DRKS00020491.

The influence of antibiotic administration on the outcomes of head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiation.

PURPOSE: Effects of antibiotic administration on patients' microbiome may negatively influence cancer outcomes, and adverse prognoses after antibiotic application have been demonstrated for cancer patients receiving immune checkpoint inhibitors. While the microbiome may play an important role also in head-and-neck squamous cell carcinoma (HNSCC), the prognostic value of antibiotic treatment here is largely unknown. We therefore analyzed whether antibiotic prescription is associated with impaired oncological outcomes of HNSCC patients undergoing definitive (chemo)radiation. METHODS: A cohort of 220 HNSCC patients undergoing definitive (chemo)radiation between 2010 and 2019 was analyzed. The influence of antibiotic administration on locoregional control, progression-free survival (PFS) and overall survival (OS) was determined using Kaplan-Meier and Cox analyses. RESULTS: A total of 154 patients were treated with antibiotics within 30 days before (chemo)radiation (pretherapeutic) or during (chemo)radiation (peritherapeutic). While antibiotic prescription was not associated with age, ECOG, tumor localization or radiotherapy characteristics, patients treated with antibiotics had significantly higher tumor stages. Peritherapeutic antibiotic administration diminished PFS (HR = 1.397, p < 0.05, log-rank test) and OS (HR = 1.407, p < 0.05), whereas pretherapeutic administration did not. Antibiotic application was an independent prognosticator for OS (HR = 1.703, p < 0.05) and PFS (HR = 1.550, p < 0.05) in the multivariate Cox analysis within the subgroup of patients aged < 75 years. CONCLUSION: Peritherapeutic antibiotic usage was associated with impaired oncological outcomes in HNSCC patients undergoing (chemo)radiation. Further studies including microbiome analyses are required to elucidate underlying mechanisms.

Stereotactic body radiotherapy of adrenal metastases-A dose-finding study.

Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose-volume cut-points associated with decreased local recurrence rates (LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 ≥50 Gy, ≤12 fractions) was analyzed. Details on dose-volume parameters were required (planning target volume: PTV-D98%, PTV-D50%, PTV-D2%; gross tumor volume: GTV-D50%, GTV-mean). Cut-points for LRR were optimized using the R maxstat package. One hundred and ninety-six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n = 101). Cut-point optimization resulted in significant cut-points for PTV-D50% (BED10: 73.2 Gy; P = .003), GTV-D50% (BED10: 74.2 Gy; P = .006), GTV-mean (BED10: 73.0 Gy; P = .007), and PTV-D2% (BED10: 78.0 Gy; P = .02) but not for the PTV-D98% (P = .06). Differences in LRR were clinically relevant (LRR ≥ doubled for cut-points that were not achieved). Further dose-escalation was not associated with further improved LRR. PTV-D50%, GTV-D50%, and GTV-mean cut-points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut-point for the PTV-D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (<2% difference). Associations of cut-points with overall survival (OS) and progression-free survival were not significant but durable freedom from local recurrence was associated with OS in a landmark model (P < .001). To achieve a significant improvement of LRR for adrenal SBRT, a moderate escalation of PTV-D50% BED10 >73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered.

Patient reported outcomes based on EQ-5D-5L questionnaires in head and neck cancer patients: a real-world study.

OBJECTIVE: Health economic comparisons of various therapies are often based on health-related quality of life (HRQOL) using EQ-5D questionnaires within the framework of clinical trials. This real-world study prospectively evaluates the patient reported outcomes (PROs)-based HRQOL of head-and-neck (H&N) cancer patients undergoing modern radiotherapy (RT) to reflect PRO trajectories. METHODS: All H&N cancer patients treated in our clinic between July 2019 and December 2020 who completed the self-reported validated EQ-5D-5L questionnaire (health state index (HI) and Visual Analog Scale (VAS)) at baseline, end of radiotherapy, and at each respective follow up (FU) were included. Descriptive analysis of clinical and sociodemographic data, the frequency and level of each dimension was conducted. To assess the significance of therapy-induced HRQOL changes within and between the group, a distribution-based approach was used. RESULTS: Altogether, 366 participants completed a total of 565 questionnaires. For the whole cohort, HI at baseline was 0.804 (±0.208), 0.830 (±0.162) at RT completion, 0.812 (±0.205) at the first follow-up, and 0.769 (±0.224) at the second follow-up. The respective VAS values were 62.06 (±23,94), 66.73 (±82.20), 63.30 (±22.74), and 65.48 (±23.39). Females showed significantly lower HI values compared to males, but only at baseline (p = 0.034). Significantly lower HI values were also seen in patients with definitive RT as compared to adjuvant RT at baseline (p = 0.023), the second follow-up (p = 0.047), and the third follow-up (p = 0.010). As compared to outpatients, inpatients had significantly lower HI values at RT completion (p = 0.017), the second follow-up (p = 0.007), and the third follow-up (p = 0.031). Subgroup analyses by age (< 65 vs. ≥65) and smoking status (smokers vs. non-smokers) showed no difference at any time point. CONCLUSION: PROs demonstrated detectability of time- and intra-/inter-group therapy-induced HRQOL changes. A further detailed exploration of EQ-5D-5L responsiveness for H&N cancer patients is required.

Incidental irradiation of the regional lymph nodes during deep inspiration breath-hold radiation therapy in left-sided breast cancer patients: a dosimetric analysis.

BACKGROUND: Radiotherapy using the deep inspiration breath-hold (DIBH) technique compared with free breathing (FB) can achieve substantial reduction of heart and lung doses in left-sided breast cancer cases. The anatomical organ movement in deep inspiration also cause unintended exposure of locoregional lymph nodes to the irradiation field. METHODS: From 2017-2020, 148 patients with left-sided breast cancer underwent breast conserving surgery (BCS) or mastectomy (ME) with axillary lymph node staging, followed by adjuvant irradiation in DIBH technique. Neoadjuvant or adjuvant systemic therapy was administered depending on hormone receptor and HER2-status. CT scans in FB and DIBH position with individual coaching and determination of the breathing amplitude during the radiation planning CT were performed for all patients. Intrafractional 3D position monitoring of the patient surface in deep inspiration and gating was performed using Sentinel and Catalyst HD 3D surface scanning systems (C-RAD, Catalyst, C-RAD AB, Uppsala, Sweden). Three-dimensional treatment planning was performed using standard tangential treatment portals (6 or 18 MV). The delineation of ipsilateral locoregional lymph nodes was done on the FB and the DIBH CT-scan according to the RTOG recommendations. RESULTS: The mean doses (Dmean) in axillary lymph node (AL) level I, II and III in DIBH were 32.28 Gy (range 2.87-51.7), 20.1 Gy (range 0.44-53.84) and 3.84 Gy (range 0.25-39.23) vs. 34.93 Gy (range 10.52-50.40), 16.40 Gy (range 0.38-52.40) and 3.06 Gy (range 0.21-40.48) in FB (p < 0.0001). Accordingly, in DIBH the Dmean for AL level I were reduced by 7.59%, whereas for AL level II and III increased by 22.56% and 25.49%, respectively. The Dmean for the supraclavicular lymph nodes (SC) in DIBH was 0.82 Gy (range 0.23-4.11), as compared to 0.84 Gy (range 0.22-10.80) with FB (p = 0.002). This results in a mean dose reduction of 2.38% in DIBH. The Dmean for internal mammary lymph nodes (IM) was 12.77 Gy (range 1.45-39.09) in DIBH vs. 11.17 Gy (range 1.34-44.24) in FB (p = 0.005). This yields a mean dose increase of 14.32% in DIBH. CONCLUSIONS: The DIBH technique may result in changes in the incidental dose exposure of regional lymph node areas.

Stereotactic or conformal radiotherapy for adrenal metastases: Patient characteristics and outcomes in a multicenter analysis.

To report outcome (freedom from local progression [FFLP], overall survival [OS] and toxicity) after stereotactic, palliative or highly conformal fractionated (>12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (≤12 fractions, biologically effective dose [BED10] ≥ 50 Gy), 3DCRT/IMRT (>12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). Three hundred twenty-six patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT and Pall-RT in 260, 27 and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%) and melanoma (6.7%). Unadjusted FFLP was higher after SBRT vs Pall-RT (P = .026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4% and 27.7%). OS was longer after SBRT vs other groups (P < .05) and increased in patients with locally controlled metastases in a landmark analysis (P < .0001). Toxicity was mostly mild; notably, four cases of adrenal insufficiency occurred, two of which were likely caused by immunotherapy or tumor progression. Radiotherapy for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. One-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway.

ERCC2 gene single-nucleotide polymorphism as a prognostic factor for locally advanced head and neck carcinomas after definitive cisplatin-based radiochemotherapy.

Identifying patients with locally advanced head and neck carcinoma on high risk of recurrence after definitive concurrent radiochemotherapy is of key importance for the selection for consolidation therapy and for individualized treatment intensification. In this multicenter study we analyzed recurrence-associated single-nucleotide polymorphisms (SNPs) in DNA repair genes in tumor DNA from 132 patients with locally advanced head and neck carcinoma (LadHnSCC). Patients were treated with definitive radiotherapy and simultaneous cisplatin-based chemotherapy at six partner sites of the German Cancer Consortium (DKTK) Radiation Oncology Group from 2005 to 2011. For validation, a group of 20 patients was available. Score selection method using proportional hazard analysis and leave-one-out cross-validation were performed to identify markers associated with outcome. The SNPs rs1799793 and rs13181 were associated with survival and the same SNPs and in addition rs17655 with freedom from loco-regional relapse (ffLRR) in the trainings datasets from all patients. The homozygote major rs1799793 genotype at the ERCC2 gene was associated with better (Hazard ratio (HR): 0.418 (0.234-0.744), p = 0.003) and the homozygote minor rs13181 genotype at ERCC2 with worse survival (HR: 2.074, 95% CI (1.177-3.658), p = 0.017) in comparison to the other genotypes. At the ffLRR endpoint, rs1799793 and rs13181 had comparable prognostic value. The rs1799793 and rs13181 genotypes passed the leave-one-out cross-validation procedure and associated with survival and ffLRR in patients with LadHnSCC treated with definitive radiochemotherapy. While findings were confirmed in a small validation dataset, further validation is underway within a prospective biomarker study of the DKTK.

Value of PET imaging for radiation therapy.

This comprehensive review written by experts in their field gives an overview on the current status of incorporating positron emission tomography (PET) into radiation treatment planning. Moreover, it highlights ongoing studies for treatment individualisation and per-treatment tumour response monitoring for various primary tumours. Novel tracers and image analysis methods are discussed. The authors believe this contribution to be of crucial value for experts in the field as well as for policy makers deciding on the reimbursement of this powerful imaging modality.

Radiation-induced toxicities and outcomes after radiotherapy are independent of patient age in elderly salivary gland cancer patients: results from a matched-pair analysis of a rare disease.

PURPOSE: This study analyzed survival and toxicity after (chemo)radiotherapy for primary salivary gland cancer patients aged ≥ 65 years and compared these results with younger patients using a matched-pair analysis. METHODS: Twenty-nine elderly patients with primary salivary gland carcinomas treated with (chemo)radiotherapy from 2008 to 2020 at University of Freiburg Medical Center were analyzed for oncological outcomes and therapy-associated toxicities. Local/locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and the influence of clinical parameters on patient outcomes was assessed. A matched-pair analysis was performed after matching with patients < 65 years. RESULTS: Nine patients (31.0%) received definitive (chemo)radiotherapy, and 20 patients (69.0%) were treated in the adjuvant setting. 2-year LRC, PFS and OS ranged at 82.4%, 53.7% and 71.8%, respectively. Smoking (HR 3.980, p = 0.020), reduced performance status (HR 3.735, p = 0.016) and higher comorbidity burden (HR 4.601, p = 0.005) correlated with inferior OS. Using a matched-pair analysis with younger patients, elderly patients exhibited a trend towards reduced OS (HR 3.015, p = 0.065), but not PFS (HR 1.474, p = 0.371) or LRC (HR 1.324, p = 0.633). Acute and chronic grade 3 toxicities occurred in 31.0% and 12.5% of elderly patients, respectively, and the matched-pair analysis revealed no significant differences between age groups regarding treatment-related toxicities. CONCLUSION: Treatment-related toxicities as well as LRC and PFS were comparable for salivary gland cancer patients undergoing radiotherapy. Therefore, concerns for more pronounced toxicities or reduced local/locoregional response rates should not guide treatment decisions in affected elderly patients.

Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (PET-Plan): a multicentre, open-label, randomised, controlled trial.

BACKGROUND: With increasingly precise radiotherapy and advanced medical imaging, the concept of radiotherapy target volume planning might be redefined with the aim of improving outcomes. We aimed to investigate whether target volume reduction is feasible and effective compared with conventional planning in the context of radical chemoradiotherapy for patients with locally advanced non-small-cell lung cancer. METHODS: We did a multicentre, open-label, randomised, controlled trial (PET-Plan; ARO-2009-09) in 24 centres in Austria, Germany, and Switzerland. Previously untreated patients (aged older than 18 years) with inoperable locally advanced non-small-cell lung cancer suitable for chemoradiotherapy and an Eastern Cooperative Oncology Group performance status of less than 3 were included. Undergoing 18F-fluorodeoxyglucose (18F-FDG) PET and CT for treatment planning, patients were randomly assigned (1:1) using a random number generator and block sizes between four and six to target volume delineation informed by 18F-FDG PET and CT plus elective nodal irradiation (conventional target group) or target volumes informed by PET alone (18F-FDG PET-based target group). Randomisation was stratified by centre and Union for International Cancer Control stage. In both groups, dose-escalated radiotherapy (60-74 Gy, 2 Gy per fraction) was planned to the respective target volumes and applied with concurrent platinum-based chemotherapy. The primary endpoint was time to locoregional progression from randomisation with the objective to test non-inferiority of 18F-FDG PET-based planning with a prespecified hazard ratio (HR) margin of 1·25. The per-protocol set was included in the primary analysis. The safety set included all patients receiving any study-specific treatment. Patients and study staff were not masked to treatment assignment. This study is registered with ClinicalTrials.gov, NCT00697333. FINDINGS: From May 13, 2009, to Dec 5, 2016, 205 of 311 recruited patients were randomly assigned to the conventional target group (n=99) or the 18F-FDG PET-based target group (n=106; the intention-to-treat set), and 172 patients were treated per protocol (84 patients in the conventional target group and 88 in the 18F-FDG PET-based target group). At a median follow-up of 29 months (IQR 9-54), the risk of locoregional progression in the 18F-FDG PET-based target group was non-inferior to, and in fact lower than, that in the conventional target group in the per-protocol set (14% [95% CI 5-21] vs 29% [17-38] at 1 year; HR 0·57 [95% CI 0·30-1·06]). The risk of locoregional progression in the 18F-FDG PET-based target group was also non-inferior to that in the conventional target group in the intention-to-treat set (17% [95% CI 9-24] vs 30% [20-39] at 1 year; HR 0·64 [95% CI 0·37-1·10]). The most common acute grade 3 or worse toxicity was oesophagitis or dysphagia (16 [16%] of 99 patients in the conventional target group vs 17 [16%] of 105 patients in the 18F-FDG PET-based target group); the most common late toxicities were lung-related (12 [12%] vs 11 [10%]). 20 deaths potentially related to study treatment were reported (seven vs 13). INTERPRETATION: 18F-FDG PET-based planning could potentially improve local control and does not seem to increase toxicity in patients with chemoradiotherapy-treated locally advanced non-small-cell lung cancer. Imaging-based target volume reduction in this setting is, therefore, feasible, and could potentially be considered standard of care. The procedures established might also support imaging-based target volume reduction concepts for other tumours. FUNDING: German Cancer Aid (Deutsche Krebshilfe).

Intraindividual comparison between 68Ga-PSMA-PET/CT and mpMRI for intraprostatic tumor delineation in patients with primary prostate cancer: a retrospective analysis in 101 patients.

PURPOSE: Accurate delineation of intraprostatic gross tumor volume (GTV) is mandatory for successful fusion biopsy guidance and focal therapy planning of prostate cancer (PCa). Multiparametric magnetic resonance imaging (mpMRI) is the current gold standard for GTV delineation; however, prostate-specific membrane antigen positron emission tomography (PSMA-PET) is emerging as a promising alternative. This study compares GTV delineation between mpMRI and 68Ga-PSMA-PET in a large number of patients using validated contouring approaches. METHODS: One hundred one patients with biopsy-proven primary PCa who underwent mpMRI and 68Ga-PSMA-PET within 3 months before primary treatment were retrospectively enrolled. Clinical parameters (age, PSA, Gleason score in biopsy) were documented. GTV based on MRI and PET images were delineated; volumes measured and laterality determined. Additionally, biopsy data from 77 patients was analyzed. Univariate and multivariate binary logistic regression analyses were performed using concordance in laterality as the endpoint. RESULTS: In total mpMRI and 68Ga-PSMA-PET detected 151 and 159 lesions, respectively. Median GTV-MRI (2.8 ml, 95% CI 2.31-3.38 ml) was significantly (p < 0.0001) smaller than median GTV-PET (4.9 ml, 95% CI 3.9-6.6 ml). 68Ga-PSMA-PET detected significantly more bilateral lesions than mpMRI (71 vs 57, p = 0.03). Analysis of patients with bilateral lesions in biopsy showed a significant higher concordance of laterality in 68Ga-PSMA-PET (p = 0.03). In univariate analysis, PSA level and volume of GTV-MRI had an impact on concordance in laterality (p = 0.02 and p = 0.01), whereas in multivariate analysis, only GTV-MRI volume remained significant (p = 0.04). CONCLUSION: MpMRI and 68Ga-PSMA-PET detect a similar amount of PCa lesions. However, GTV-PET had approximately twice the volume (median 4.9 ml vs 2.8 ml) and detected significantly more bilateral lesions than mpMRI. Thus, 68Ga-PSMA-PET gives highly important complementary information. Since we could not find any strong evidence for parameters to guide when 68Ga-PSMA-PET is dispensable, it should be performed additionally to MRI in patients with intermediate and high-risk PCa according to D'Amico classification to improve GTV delineation.

Molecular Imaging in Photon Radiotherapy.

Nowadays, more than ever before, the treatment of cancer patients requires an interdisciplinary approach more than ever. Radiation therapy (RT) has become an indispensable pillar of cancer treatment early on, offering a local, curative treatment option and symptom control in palliative cases.

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.