A convolutional neural network with self-attention for fully automated metabolic tumor volume delineation of head and neck cancer in [Formula: see text]F]FDG PET/CT.

PURPOSE: PET-derived metabolic tumor volume (MTV) and total lesion glycolysis of the primary tumor are known to be prognostic of clinical outcome in head and neck cancer (HNC). Including evaluation of lymph node metastases can further increase the prognostic value of PET but accurate manual delineation and classification of all lesions is time-consuming and prone to interobserver variability. Our goal, therefore, was development and evaluation of an automated tool for MTV delineation/classification of primary tumor and lymph node metastases in PET/CT investigations of HNC patients. METHODS: Automated lesion delineation was performed with a residual 3D U-Net convolutional neural network (CNN) incorporating a multi-head self-attention block. 698 [Formula: see text]F]FDG PET/CT scans from 3 different sites and 5 public databases were used for network training and testing. An external dataset of 181 [Formula: see text]F]FDG PET/CT scans from 2 additional sites was employed to assess the generalizability of the network. In these data, primary tumor and lymph node (LN) metastases were interactively delineated and labeled by two experienced physicians. Performance of the trained network models was assessed by 5-fold cross-validation in the main dataset and by pooling results from the 5 developed models in the external dataset. The Dice similarity coefficient (DSC) for individual delineation tasks and the primary tumor/metastasis classification accuracy were used as evaluation metrics. Additionally, a survival analysis using univariate Cox regression was performed comparing achieved group separation for manual and automated delineation, respectively. RESULTS: In the cross-validation experiment, delineation of all malignant lesions with the trained U-Net models achieves DSC of 0.885, 0.805, and 0.870 for primary tumor, LN metastases, and the union of both, respectively. In external testing, the DSC reaches 0.850, 0.724, and 0.823 for primary tumor, LN metastases, and the union of both, respectively. The voxel classification accuracy was 98.0% and 97.9% in cross-validation and external data, respectively. Univariate Cox analysis in the cross-validation and the external testing reveals that manually and automatically derived total MTVs are both highly prognostic with respect to overall survival, yielding essentially identical hazard ratios (HR) ([Formula: see text]; [Formula: see text] vs. [Formula: see text]; [Formula: see text] in cross-validation and [Formula: see text]; [Formula: see text] vs. [Formula: see text]; [Formula: see text] in external testing). CONCLUSION: To the best of our knowledge, this work presents the first CNN model for successful MTV delineation and lesion classification in HNC. In the vast majority of patients, the network performs satisfactory delineation and classification of primary tumor and lymph node metastases and only rarely requires more than minimal manual correction. It is thus able to massively facilitate study data evaluation in large patient groups and also does have clear potential for supervised clinical application.

PSMA-PET/CT-guided salvage radiotherapy in recurrent or persistent prostate cancer and PSA < 0.2 ng/ml.

PURPOSE: The purpose of this retrospective, multicenter study was to assess efficacy of PSMA-PET/CT-guided salvage radiotherapy (sRT) in patients with recurrent or persistent PSA after primary surgery and PSA levels < 0.2 ng/ml. METHODS: The study included patients from a pooled cohort (n = 1223) of 11 centers from 6 countries. Patients with PSA levels > 0.2 ng/ml prior to sRT or without sRT to the prostatic fossa were excluded. The primary study endpoint was biochemical recurrence-free survival (BRFS) and BR was defined as PSA nadir after sRT + 0.2 ng/ml. Cox regression analysis was performed to assess the impact of clinical parameters on BRFS. Recurrence patterns after sRT were analyzed. RESULTS: The final cohort consisted of 273 patients; 78/273 (28.6%) and 48/273 (17.6%) patients had local or nodal recurrence on PET/CT. The most frequently applied sRT dose to the prostatic fossa was 66-70 Gy (n = 143/273, 52.4%). SRT to pelvic lymphatics was delivered in 87/273 (31.9%) patients and androgen deprivation therapy was given to 36/273 (13.2%) patients. After a median follow-up time of 31.1 months (IQR: 20-44), 60/273 (22%) patients had biochemical recurrence. The 2- and 3-year BRFS was 90.1% and 79.2%, respectively. The presence of seminal vesicle invasion in surgery (p = 0.019) and local recurrences in PET/CT (p = 0.039) had a significant impact on BR in multivariate analysis. In 16 patients, information on recurrence patterns on PSMA-PET/CT after sRT was available and one had recurrent disease inside the RT field. CONCLUSION: This multicenter analysis suggests that implementation of PSMA-PET/CT imaging for sRT guidance might be of benefit for patients with very low PSA levels after surgery due to promising BRFS rates and a low number of relapses within the sRT field.

UEG and EAES rapid guideline: Systematic review, meta-analysis, GRADE assessment and evidence-informed European recommendations on TaTME for rectal cancer.

BACKGROUND: Evidence and practice recommendations on the use of transanal total mesorectal excision (TaTME) for rectal cancer are conflicting. OBJECTIVE: We aimed to summarize best evidence and develop a rapid guideline using transparent, trustworthy, and standardized methodology. METHODS: We developed a rapid guideline in accordance with GRADE, G-I-N, and AGREE II standards. The steering group consisted of general surgeons, members of the EAES Research Committee/Guidelines Subcommittee with expertise and experience in guideline development, advanced medical statistics and evidence synthesis, biostatisticians, and a guideline methodologist. The guideline panel consisted of four general surgeons practicing colorectal surgery, a radiologist with expertise in rectal cancer, a radiation oncologist, a pathologist, and a patient representative. We conducted a systematic review and the results of evidence synthesis by means of meta-analyses were summarized in evidence tables. Recommendations were authored and published through an online authoring and publication platform (MAGICapp), with the guideline panel making use of an evidence-to-decision framework and a Delphi process to arrive at consensus. RESULTS: This rapid guideline provides a weak recommendation for the use of TaTME over laparoscopic or robotic TME for low rectal cancer when expertise is available. Furthermore, it details evidence gaps to be addressed by future research and discusses policy considerations. The guideline, with recommendations, evidence summaries, and decision aids in user-friendly formats can also be accessed in MAGICapp: https://app.magicapp.org/#/guideline/4494 . CONCLUSIONS: This rapid guideline provides evidence-informed trustworthy recommendations on the use of TaTME for rectal cancer.

PET/CT imaging of prostate cancer in the era of small molecule prostate specific membrane antigen targeted tracers.

Staging and restaging of prostate cancer is crucial for treatment planning and prognosis. Accurate localization is of high relevance for a tailor-made therapy and an early detection of unknown metastatic spread can lead to a survival benefit. Evidence based guidelines that are currently in use were established using data from conventional imaging (such as magnetic resonance imaging (MRI), computed tomography (CT) and bone scintigraphy). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is rapidly evolving with promising results. However, up to now there is little consensus about the usefulness of this method, especially since different guidelines are "biased" depending on the association that shapes them. Firstly, little data exists on the staging of low risk tumors and probably PSMA PET/CT should be avoided in this setup for most patients. On the other hand, it has been recently proven that PSMA PET/CT can replace CT and bone scintigraphy (combined) in staging of advanced prostate cancer. Furthermore, the examination gained general acceptance through its excellent performance in biochemical recurrence, both for castration naïve and castration resistant tumors, and should be implemented where available. It is undisputed that PSMA PET/CT provides a more accurate picture of prostate cancer patients and can lead to both upstaging and downstaging, thus affecting therapeutic management. Though it is not clear yet if the more accurate staging will lead to better therapeutic decisions and improve patient outcomes, PSMA PET/CT appears as the next imaging standard for prostate cancer for the years to come.

Photobiomodulation therapy for the management of radiation-induced dermatitis : A single-institution experience of adjuvant radiotherapy in breast cancer patients after breast conserving surgery.

BACKGROUND: Radiation therapy (RT) comprises a key component in the treatment of breast cancer. Radiation-induced skin toxicity is the major adverse event experienced by patients; however, radiodermatitis (RD) prevention and management remains trivial. It is proven that photobiomodulation (PBM) therapy using light-emitting diode (LED) increases wound healing and depicts an anti-inflammatory effect. This single-institute study evaluates the beneficial role of PBM-LED in preventing/reducing RD during breast cancer RT. PATIENTS AND METHODS: Of 70 consecutively treated patients, 25 patients were treated with PBM-LED twice a week prior to adjuvant 3D conformal RT after breast-conserving surgery. RD was reported using Common Toxicity Criteria for Adverse Events Version 4.0 and pain intensity using a visual analog scale (VAS). For comparison, a control group (n = 45) received RT without PBM-LED. In addition, a "matched" group (n = 25) was generated from the control group based on propensity for potentially confounding variables. RESULTS: In the PBM group, 22 patients (88%) presented grade 1 and 3 (12%) grade 2 RD. In the control group, 25 patients (55.6%) developed grade 1 reactions, 18 patients (40%) grade 2, and 2 (4.4%) patients grade 3 RD. Concerning pain intensity, 15 patients (60%) of the PBM treatment arm reported no pain, 5 patients (20%) VAS 2, and 5 (20%) VAS 3. In the control group, 13 patients (28.9%) reported no pain, 2 (4.4%) VAS 1, 7 (15.6%) VAS 2, 9 patients (20%) reported VAS 3, 12 (26.7%) patients VAS 4, and 2 (4.4%) patients VAS 5. CONCLUSION: PBM-LED therapy applied prior to RT might be effective in decreasing the incidence and sequelae of radiation-induced skin toxicity in breast cancer patients treated with breast-conserving surgery.

Use of Radiotherapy in Advanced Breast Cancer: The Role of a Nurse.

OBJECTIVES: Systemic therapy is the mainstay in advanced breast cancer (ABC), but innovations in radiation oncology have given radiotherapy a crucial role in the treatment of both intracranial and extracranial ABC. Breast cancer specialists include, in addition to medical and clinical oncologists, breast cancer nurses with unique theoretical knowledge and significant clinical experience. This review aims to discuss the function of radiotherapy in ABC and to highlight the role and importance of specialized nursing care for ABC patients receiving radiotherapy. DATA SOURCES: An extensive literature review was conducted on the role of radiotherapy and its implementation in various settings of ABC and the pivotal contribution of nursing practices to the quality of life of these patients, with a particular focus on symptom and side effect management and prevention, education, as well as unmet patient needs. The Advanced Breast Cancer International Consensus Guidelines (ABC-5) were also included. All the above data were combined with the expert and practical considerations of breast cancer specialists within the team. CONCLUSION: The sophisticated application of radiotherapy and the complexity of ABC patient management, concerning symptoms, side effects, and overall well-being necessitate collaborative efforts to optimize patient care. Breast cancer nurses hold a central role in this framework. IMPLICATIONS FOR NURSING PRACTICE: The significance of specialized nursing in contributing to comprehensive patient care for ABC patients treated with radiotherapy outlines the need for extensive training that aims to provide a holistic approach and entails physical, mental, and emotional support and patient and caregiver education.

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation.

PURPOSE: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC. METHODS AND MATERIALS: The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine-Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases. RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P < .05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P = .05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P = .46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P > .05). The median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR, 0.71 [0.53-0.95]; P = .02), increased PFS (HR, 0.66 [0.51-0.87]; P = .003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P = .004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P = .009). CONCLUSIONS: Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC.

Radiomics-based prediction of local control in patients with brain metastases following postoperative stereotactic radiotherapy.

BACKGROUND: Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the risk of local failure (LF) persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk. METHODS: Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of BMs (AURORA) retrospective study (training cohort: 253 patients from 2 centers; external test cohort: 99 patients from 5 centers). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (T2-FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameter set previously determined by internal 5-fold cross-validation and tested on the external test set. RESULTS: The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan-Meier analysis (P < .001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively. CONCLUSIONS: A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow-up routines or intensified therapy.

A Machine Learning Approach for Predicting Biochemical Outcome After PSMA-PET-Guided Salvage Radiotherapy in Recurrent Prostate Cancer After Radical Prostatectomy: Retrospective Study.

BACKGROUND: Salvage radiation therapy (sRT) is often the sole curative option in patients with biochemical recurrence after radical prostatectomy. After sRT, we developed and validated a nomogram to predict freedom from biochemical failure. OBJECTIVE: This study aims to evaluate prostate-specific membrane antigen-positron emission tomography (PSMA-PET)-based sRT efficacy for postprostatectomy prostate-specific antigen (PSA) persistence or recurrence. Objectives include developing a random survival forest (RSF) model for predicting biochemical failure, comparing it with a Cox model, and assessing predictive accuracy over time. Multinational cohort data will validate the model's performance, aiming to improve clinical management of recurrent prostate cancer. METHODS: This multicenter retrospective study collected data from 13 medical facilities across 5 countries: Germany, Cyprus, Australia, Italy, and Switzerland. A total of 1029 patients who underwent sRT following PSMA-PET-based assessment for PSA persistence or recurrence were included. Patients were treated between July 2013 and June 2020, with clinical decisions guided by PSMA-PET results and contemporary standards. The primary end point was freedom from biochemical failure, defined as 2 consecutive PSA rises >0.2 ng/mL after treatment. Data were divided into training (708 patients), testing (271 patients), and external validation (50 patients) sets for machine learning algorithm development and validation. RSF models were used, with 1000 trees per model, optimizing predictive performance using the Harrell concordance index and Brier score. Statistical analysis used R Statistical Software (R Foundation for Statistical Computing), and ethical approval was obtained from participating institutions. RESULTS: Baseline characteristics of 1029 patients undergoing sRT PSMA-PET-based assessment were analyzed. The median age at sRT was 70 (IQR 64-74) years. PSMA-PET scans revealed local recurrences in 43.9% (430/979) and nodal recurrences in 27.2% (266/979) of patients. Treatment included dose-escalated sRT to pelvic lymphatics in 35.6% (349/979) of cases. The external outlier validation set showed distinct features, including higher rates of positive lymph nodes (47/50, 94% vs 266/979, 27.2% in the learning cohort) and lower delivered sRT doses (<66 Gy in 57/979, 5.8% vs 46/50, 92% of patients; P<.001). The RSF model, validated internally and externally, demonstrated robust predictive performance (Harrell C-index range: 0.54-0.91) across training and validation datasets, outperforming a previously published nomogram. CONCLUSIONS: The developed RSF model demonstrates enhanced predictive accuracy, potentially improving patient outcomes and assisting clinicians in making treatment decisions.

Case Report: Post-traumatic splenosis and potential pitfall for PSMA-PET.

Background: 18F-prostate specific membrane antigen (PSMA) PET is fast becoming the gold-standard in prostate cancer, both in staging of intermediate-/high-risk patients and in re-staging patients with biochemical failure. Several pitfalls of 18F-PSMA PET have been reported, and we report, to our best of knowledge, for the first time, a case which could have been falsely diagnosed as peritoneal spread. Case presentation: A 67-year-old patient with high-risk prostate cancer underwent staging with 18F-PSMA-1007 PET/CT (PSMA-PET/CT). PSMA-PET/CT revealed a histologically confirmed prostatic malignancy in the peripheral left zone. Unexpectedly, additional multiple highly PSMA-expressing intraabdominal formations were discovered. Based on apparent anatomic asplenia and a history of traumatic splenic rapture during childhood, a suspicion of post-traumatic splenosis was raised. For further non-invasive evaluation, a C-99 sulphur colloid scintigraphy with SPECT was conducted, confirming the presence of multiple functional ectopic splenic tissues. This is, to our best of knowledge, the first case utilising 18F-PSMA-1007-PET/CT and 99mTc-sulphur colloid SPECT to detect intraabdominal splenosis, highlighting the high potential of nuclear medicine in such trivial cases.

A clinical evaluation of the performance of five commercial artificial intelligence contouring systems for radiotherapy.

Purpose/objectives: Auto-segmentation with artificial intelligence (AI) offers an opportunity to reduce inter- and intra-observer variability in contouring, to improve the quality of contours, as well as to reduce the time taken to conduct this manual task. In this work we benchmark the AI auto-segmentation contours produced by five commercial vendors against a common dataset. Methods and materials: The organ at risk (OAR) contours generated by five commercial AI auto-segmentation solutions (Mirada (Mir), MVision (MV), Radformation (Rad), RayStation (Ray) and TheraPanacea (Ther)) were compared to manually-drawn expert contours from 20 breast, 20 head and neck, 20 lung and 20 prostate patients. Comparisons were made using geometric similarity metrics including volumetric and surface Dice similarity coefficient (vDSC and sDSC), Hausdorff distance (HD) and Added Path Length (APL). To assess the time saved, the time taken to manually draw the expert contours, as well as the time to correct the AI contours, were recorded. Results: There are differences in the number of CT contours offered by each AI auto-segmentation solution at the time of the study (Mir 99; MV 143; Rad 83; Ray 67; Ther 86), with all offering contours of some lymph node levels as well as OARs. Averaged across all structures, the median vDSCs were good for all systems and compared favorably with existing literature: Mir 0.82; MV 0.88; Rad 0.86; Ray 0.87; Ther 0.88. All systems offer substantial time savings, ranging between: breast 14-20 mins; head and neck 74-93 mins; lung 20-26 mins; prostate 35-42 mins. The time saved, averaged across all structures, was similar for all systems: Mir 39.8 mins; MV 43.6 mins; Rad 36.6 min; Ray 43.2 mins; Ther 45.2 mins. Conclusions: All five commercial AI auto-segmentation solutions evaluated in this work offer high quality contours in significantly reduced time compared to manual contouring, and could be used to render the radiotherapy workflow more efficient and standardized.

Development and external validation of an MRI-based neural network for brain metastasis segmentation in the AURORA multicenter study.

BACKGROUND: Stereotactic radiotherapy is a standard treatment option for patients with brain metastases. The planning target volume is based on gross tumor volume (GTV) segmentation. The aim of this work is to develop and validate a neural network for automatic GTV segmentation to accelerate clinical daily routine practice and minimize interobserver variability. METHODS: We analyzed MRIs (T1-weighted sequence ± contrast-enhancement, T2-weighted sequence, and FLAIR sequence) from 348 patients with at least one brain metastasis from different cancer primaries treated in six centers. To generate reference segmentations, all GTVs and the FLAIR hyperintense edematous regions were segmented manually. A 3D-U-Net was trained on a cohort of 260 patients from two centers to segment the GTV and the surrounding FLAIR hyperintense region. During training varying degrees of data augmentation were applied. Model validation was performed using an independent international multicenter test cohort (n = 88) including four centers. RESULTS: Our proposed U-Net reached a mean overall Dice similarity coefficient (DSC) of 0.92 ± 0.08 and a mean individual metastasis-wise DSC of 0.89 ± 0.11 in the external test cohort for GTV segmentation. Data augmentation improved the segmentation performance significantly. Detection of brain metastases was effective with a mean F1-Score of 0.93 ± 0.16. The model performance was stable independent of the center (p = 0.3). There was no correlation between metastasis volume and DSC (Pearson correlation coefficient 0.07). CONCLUSION: Reliable automated segmentation of brain metastases with neural networks is possible and may support radiotherapy planning by providing more objective GTV definitions.

Identifying core MRI sequences for reliable automatic brain metastasis segmentation.

BACKGROUND: Many automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation. METHODS: We analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from seven centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE + T2-FLAIR, T1-CE + T1 + T2-FLAIR, T1-CE + T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 100 patients from five centers. RESULTS: The model based on T1-CE alone achieved the best segmentation performance for BM segmentation with a median Dice similarity coefficient (DSC) of 0.96. Models trained without T1-CE performed worse (T1-only: DSC = 0.70 and T2-FLAIR-only: DSC = 0.73). For edema segmentation, models that included both T1-CE and T2-FLAIR performed best (DSC = 0.93), while the remaining four models without simultaneous inclusion of these both sequences reached a median DSC of 0.81-0.89. CONCLUSIONS: A T1-CE-only protocol suffices for the segmentation of BMs. The combination of T1-CE and T2-FLAIR is important for edema segmentation. Missing either T1-CE or T2-FLAIR decreases performance. These findings may improve imaging routines by omitting unnecessary sequences, thus allowing for faster procedures in daily clinical practice while enabling optimal neural network-based target definitions.

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy.

Importance: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC. Objective: To examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC. Design, Setting, and Participants: The Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022. Interventions: All patients underwent definitive radiotherapy alone or with concomitant systemic treatment. Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate. Results: Among the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P < .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41). Conclusions and Relevance: In this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone.

Development and Validation of a Multi-institutional Nomogram of Outcomes for PSMA-PET-Based Salvage Radiotherapy for Recurrent Prostate Cancer.

Importance: Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer. Objective: To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT. Design, Setting, and Participants: This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022. Exposures: Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible. Main Outcomes and Measures: The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT. Results: In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort. Conclusions and Relevance: This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT.

High-dose-rate brachytherapy for prostate cancer: Rationale, current applications, and clinical outcome.

BACKGROUND: High-dose-rate brachytherapy (HDR BRT) has been enjoying rapid acceptance as a treatment modality offered to selected prostate cancer patients devoid of risk group, employed either in monotherapy setting or combined with external beam radiation therapy (EBRT) and is currently one of the most active clinical research areas. RECENT FINDINGS: This review encompasses all the current evidence to support the use of HDR BRT in various clinical scenario and shines light to the HDR BRT rationale, as an ultimately conformal dose delivery method enabling safe dose escalation to the prostate. CONCLUSION: Valid long-term data, both in regard to the oncologic outcomes and toxicity profile, support the current clinical indication spectrum of HDR BRT. At the same time, this serves as solid, rigid ground for emerging therapeutic applications, allowing the technique to remain in the spotlight alongside stereotactic radiosurgery.

Narrative Review of High-Dose-Rate Interstitial Brachytherapy in Primary or Secondary Liver Tumors.

The optimal management of intrahepatic malignancies involves a multidisciplinary approach. Although surgical resection has been considered the only curative approach, the use of several minimally invasive ablative techniques has dramatically increased the last two decades, mainly due to the fact that they provide similar oncological results with significantly decreased morbidity. Among these modalities, interstitial liver brachytherapy, probably the most flexible liver ablative method, with excellent clinical data on its safety and effectiveness, is frequently not even mentioned as an option in the current peer reviewed literature and guidelines. Brachytherapy is a type of radiotherapy utilizing radionuclides that are directly inserted into the tumor. Compared to external beam radiation therapy, brachytherapy has the potential to deliver an ablative radiation dose over a short period of time, with the advantage of a rapid dose fall-off, that allows for sparing of adjacent healthy tissue. For numerous malignancies such as skin, gynecological, breast, prostate, head and neck, bladder, liver and soft-tissue tumors, brachytherapy as a monotherapy or combined with external beam radiation therapy, has become a standard treatment for many decades. This review article aims to describe the high-dose-rate liver brachytherapy technique, its selection criteria, present its advantages and disadvantages, as well as the available clinical data, in order to help physicians to explore and hopefully introduce liver brachytherapy into their clinical routine.

18F-Fluorodeoxyglucose Positron Emission Tomography of Head and Neck Cancer: Location and HPV Specific Parameters for Potential Treatment Individualization.

Purpose: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is utilized for staging and treatment planning of head and neck squamous cell carcinomas (HNSCC). Some older publications on the prognostic relevance showed inconclusive results, most probably due to small study sizes. This study evaluates the prognostic and potentially predictive value of FDG-PET in a large multi-center analysis. Methods: Original analysis of individual FDG-PET and patient data from 16 international centers (8 institutional datasets, 8 public repositories) with 1104 patients. All patients received curative intent radiotherapy/chemoradiation (CRT) and pre-treatment FDG-PET imaging. Primary tumors were semi-automatically delineated for calculation of SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Cox regression analyses were performed for event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Results: FDG-PET parameters were associated with patient outcome in the whole cohort regarding clinical endpoints (EFS, OS, LRC, FFDM), in uni- and multivariate Cox regression analyses. Several previously published cut-off values were successfully validated. Subgroup analyses identified tumor- and human papillomavirus (HPV) specific parameters. In HPV positive oropharynx cancer (OPC) SUVmax was well suited to identify patients with excellent LRC for organ preservation. Patients with SUVmax of 14 or less were unlikely to develop loco-regional recurrence after definitive CRT. In contrast FDG PET parameters deliver only limited prognostic information in laryngeal cancer. Conclusion: FDG-PET parameters bear considerable prognostic value in HNSCC and potential predictive value in subgroups of patients, especially regarding treatment de-intensification and organ-preservation. The potential predictive value needs further validation in appropriate control groups. Further research on advanced imaging approaches including radiomics or artificial intelligence methods should implement the identified cut-off values as benchmark routine imaging parameters.

Metastasis-Free Survival and Patterns of Distant Metastatic Disease After Prostate-Specific Membrane Antigen Positron Emission Tomography (PSMA-PET)-Guided Salvage Radiation Therapy in Recurrent or Persistent Prostate Cancer After Prostatectomy.

PURPOSE: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) is increasingly used to guide salvage radiation therapy (sRT) in patients with prostate cancer and biochemical recurrence/persistence after prostatectomy. This work examined (1) metastasis-free survival (MFS) after PSMA-PET guided sRT and (2) the metastatic patterns on PSMA-PET images after sRT. METHODS AND MATERIALS: This retrospective, multicenter (9 centers, 5 countries) study included patients referred for PSMA-PET due to recurrent/persistent disease after prostatectomy. Patients with distant metastases (DM) on PSMA-PET before sRT were excluded. Cox regression was performed to assess the effect of clinical parameters on MFS. The distribution of PSMA-PET detected DM after sRT and their respective risk factors were analyzed. RESULTS: All (n = 815) patients received intensity modulated RT to the prostatic fossa. In the case of PET-positive pelvic lymph nodes (PLN-PET) (n = 275, 34%), pelvic lymphatics had been irradiated. Androgen deprivation therapy had been given in 251 (31%) patients. The median follow-up after sRT was 36 months. The 2-/4-year MFS after sRT were 93%/81%. In multivariate analysis, the presence of PLN-PET was a strong predictor for MFS (hazard ratio, 2.39; P < .001). After sRT, DM were detected by PSMA-PET in 128/198 (65%) patients, and 2 metastatic patterns were observed: 43% had DM in sub-diaphragmatic para-aortic LNs (abdominal-lymphatic), 45% in bones, 9% in supra-diaphragmatic LNs, and 6% in visceral organs (distant). Two distinct signatures with risk factors for each pattern were identified. CONCLUSIONS: MFS in our study is lower compared with previous studies, obviously due to the higher detection rate of DM in PSMA-PET after sRT. Thus, it remains unclear whether MFS is a surrogate endpoint for overall survival in PSMA PET-staged patients in the post-sRT setting. PLN-PET may be proposed as a new surrogate parameter predictive of MFS. Analysis of recurrence patterns in PET after sRT revealed risk factor signatures for 2 metastatic patterns (abdominal-lymphatic and distant), which may allow individualized sRT concepts in the future.

Assessment of a commercial EPID dosimetry system to detect radiotherapy treatment errors.

One method for detecting radiotherapy treatment errors is to capture the exit dose using an electronic portal imaging device. In comparison with a baseline integrated image, subsequent fractions can be compared and differences in images suggest a difference in the radiation treatment delivered. The aim of this work was to assess the sensitivity of a commercial software PerFRACTION in detecting such differences, arising from three possible sources: (i) changes in the radiation beam or EPID position; (ii) changes in the patient position; and (iii) changes in the patient anatomy. By systematically introducing errors, PerFRACTION was shown to be very sensitive to changes in the radiation beam. Variation in the beam output could be detected within 0.3%, field size within 0.4 mm, collimator rotation within 0.3° and MLC positioning could be verified to within 0.1 mm. EPID misalignment could be detected within 0.3 mm. PerFRACTION was able to detect the mispositioning of an anthropomorphic phantom by 3 mm with static beams, however there was a relative dependency between the patient geometry and the direction of the shift. VMAT beams were less sensitive to patient misalignments, with a shift of 10 mm only detectable once a strict criterion of 1% dose difference was applied. In another simulated scenario PerFRACTION was also able to detect a weight loss equivalent to a 5 mm change in patient separation in VMAT plans and 10 mm in conformal plans. This work showed that the PerFRACTION software could be relied upon to detect potential radiotherapy treatment errors, arising from a variety of sources.