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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 $$[^{18}$$ [ 18 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 $$[^{18}$$ [ 18 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) ($$\text {HR}_{\text {man}}=1.9$$ HR man = 1.9 ; $$p p < 0.001 vs. $$\text {HR}_{\text {cnn}}=1.8$$ HR cnn = 1.8 ; $$p p < 0.001 in cross-validation and $$\text {HR}_{\text {man}}=1.8$$ HR man = 1.8 ; $$p=0.011$$ p = 0.011 vs. $$\text {HR}_{\text {cnn}}=1.9$$ HR cnn = 1.9 ; $$p=0.004$$ p = 0.004 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.

Radiation therapy remains an essential component of cancer treatment, with nearly 50% of cancer patients receiving radiation therapy at some point during the course of their illness. Of those, the vast majority experience some form of acute radiation dermatitis (ARD) or radiation-induced skin injury. ARD results in significant discomfort, restriction of daily activities, overall decrease in the quality of life and even cessation of the necessary radiation therapy with detrimental survival effects. Unfortunately, research into the causes and possible management strategies for ARD is hindered by the lack of biomarkers for the quantitative assessment of the early changes associated with the condition. This study provides the basis to identify low grade ARD, using Optical Coherence Tomography (OCT) images with the extraction of conventional image intensity and novel features. Twenty-two patients were imaged twice each week until the end of their radiation treatment resulting in 1487 images. The severity of the cases was graded by an expert oncologist. The preliminary results of various machine learning (ML) classifiers have shown that an LDA based approach provided the best performance, separating normal skin from very early ARD, with an accuracy of 85%.

Radiation therapy remains an essential component of cancer treatment, with nearly 50% of cancer patients receiving radiation therapy at some point during the course of their illness. Of those, as many as 90-95% may experience some form of acute radiation dermatitis (ARD) or radiation-induced skin injury. ARD results in significant discomfort, restriction of daily activities, overall decrease in the quality of life and even cessation of the necessary radiation therapy with detrimental survival effects. Unfortunately, research into the causes and possible management strategies for ARD is hindered by the lack of biomarkers for the quantitative assessment of the early changes associated with the condition. This study provides the basis to yield such novel biomarkers using Optical Coherence Tomography (OCT) images with the extraction of conventional image intensity and novel features. Patients were imaged twice each week over the six-week course of their radiation treatment. The severity of the cases was graded by an expert oncologist. Preliminary results, separating normal skin from early ARD, were very promising, yielding an accuracy of 88.3%.

355 Background: We aimed to develop and to validate a multi-institutional nomogram of outcomes for PSMA-PET based salvage radiotherapy (sRT) following radical prostatectomy (RP) for patients with recurrent or persistent prostate cancer (PCa). Methods: Data from patients with a detectable post-RP prostate-specific antigen (PSA) treated with sRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 11 academic institutions from 5 countries. All patients had a PSMA-PET scan prior sRT and patients with distant metastases on PET were excluded from this analysis. The freedom from biochemical failure (FFBF) rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse (BR) was defined as PSA nadir +0.2 ng/ml after sRT. Results: Overall, 1029 patients (training set n=821, external validation set n=208) with a median follow-up of 33 months were included. On PSMA-PET, 427 (42%) and 313 (30%) patients had local and nodal recurrences, respectively. Elective pelvic lymphatics were irradiated in 368 (36%) patients. All patients received sRT to the prostatic fossa receiving a dose of 70 Gy in 103 (10%), 551 (54%) and 375 (36%) patients, respectively. Androgen deprivation therapy (ADT) was given in 325 (32%) patients. On multivariable Cox regression analysis, pre-SRT PSA, ISUP grade, pT stage, surgical margins, ADT use, sRT dose and nodal recurrence on PSMA PET were associated with FFBF. The nomogram concordance index was 0.7 for FFBF in external validation. Conclusions: We present an externally validated contemporary nomogram which can estimate individual patient outcomes after PSMA-PET guided sRT. Positive lymph nodes on PSMA-PET seem to be a new risk factor for BR after sRT.

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.

A growing number of patients with lung cancer are not amenable to surgery due to their age or comorbidities. For this reason, local ablative techniques have gained increasing interest recently in the management of inoperable lung tumors. High-dose-rate percutaneous interstitial brachytherapy, performed under CT-guidance, is a newer form of brachytherapy and is a highly conformal radiotherapy technique. The aim of this study was to describe this method and review the existing literature. Eight articles comprising 234 patients reported toxicity and clinical outcome. The follow-up ranged from 6 to 28 months. Diverse fractionation schemes were reported, with 20 Gy in a single fraction being the most frequently utilized. Toxicity was limited; major pneumothoraces occurred after only 8% of the interventions. Local control rates at one year ranged between 37% and 91%. In conclusion, high-dose-rate percutaneous interstitial brachytherapy is a safe, fast, and efficient treatment option for inoperable lung tumors.

An innovative template, based on thoracic cage surface reconstructions for breast interstitial brachytherapy was developed. Hybrid-inverse-planning-optimisation-based implantations and brachytherapy plans, using three custom anthropomorphic breast phantoms, were utilised for its validation. A user independent, inverse planning and inverse implanting technique is proposed.

Purpose To report the clinical outcomes and treatment-related toxicities after combined high-dose-rate (HDR) brachytherapy (BRT) with external beam radiotherapy (EBRT) for patients with clinically localised high-risk prostate cancer. Material and methods Between 2008 and 2012, three hundred and three consecutive patients with organ-confined high-risk prostate cancer were treated with definitive radiotherapy consisting of HDR-BRT followed by supplemental EBRT. The transrectal 3D-ultrasound-based HDR-BRT boost consisted of two single-fraction implants of 10.5 Gy, prescribed to the 90% of the gland (D90), for a total physical dose of 21.0 Gy delivered to the prostatic gland. EBRT was delivered with conventional fractionation, prescribing 45.0 Gy to the prostatic gland and seminal vesicles. Biochemical failure was defined according to the Phoenix Consensus Criteria, genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated using the Common Toxicity Criteria for Adverse Events (version 3.0). Results The median follow-up was 71.6 months. The 7-year overall survival, biochemical control and metastasis-free-survival rates for the entire cohort were 85.7%, 88.3% and 93.8%, respectively. Androgen deprivation therapy was initiated prior to treatment for 92.7% of patients with a median duration of 12 months. Toxicity was scored per event with late Grade 2, 3 and 4 GU adverse events and was found to be 15.3%, 2.2% and 0.3%, respectively. Late Grade 2 GI toxicity accounted for 0.3% with no instances of Grade 3 or higher late adverse events. Conclusion HDR-BRT with supplemental EBRT results in low biochemical relapse-free survival rates associated with a very low incidence of higher-grade late adverse events.

Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) detects prostate cancer recurrence at low PSA levels. Radiotherapy with dose escalation to the former prostate bed has been associated with improved biochemical recurrence-free survival (BRFS). Thus, we hypothesized that PSMA PET/CT-guided salvage radiotherapy leads to improved BRFS. Methods: A total of 204 consecutive patients were referred for salvage radiotherapy following radical prostatectomy. PSMA PET/CT scans were performed and patients with PSA persistence (109 patients) or evidence of distant metastases (5 patients) were excluded from this analysis. Thus, the following analysis is based on a total of 90 patients who underwent PSMA PET/CT prior to radiotherapy due to biochemical recurrence and received salvage radiotherapy. In case of PET-positive findings, antiandrogen therapy was commenced before initiation of radiotherapy. BRFS (PSA ≤ 0.2 ng/ml) was defined as the study endpoint. Results: PET-positive lesions were detected in 42/90 (47%) patients: 24/42 (27%) fossa recurrence only, 12/42 (13%) pelvic lymph nodes only and 6/42 (7%) fossa and pelvic lymph node recurrence. Median PSA before radiotherapy was 0.44 (0.11 - 6.24). Cumulatively, a total dose of 70.0 Gy (67.2 - 72 Gy) was delivered to local macroscopic tumor, 66 Gy (59.4 - 70.2 Gy) to the prostatic fossa, 60.8 Gy (54 - 66 Gy) to PET-positive lymph nodes and 50.4 Gy (45 - 50.4 Gy) to the lymphatic pathways. After a median follow-up of 23 months, BRFS was 78%. Antiandrogen therapy was ongoing in 4 patients at last follow-up. No significant difference in BRFS between PET-positive (74%) vs. PET-negative patients (82%; p>0.05) was observed at last follow-up. Two patients had late genitourinary toxicity grade 3 and no patient had gastrointestinal toxicity ≥ 3 (NCI-CTCAE v4.03). Conclusion: PSMA PET/CT-guided salvage radiotherapy is an effective and safe local treatment option. No difference in BRFS between PET-positive and PET-negative patients was observed, indicating effective targeting of PET-positive lesions. PSMA PET/CT when readily available should be offered to patients with PSA recurrence for treatment individualization.

Background and purpose To evaluate the oncological outcome of a three-implant high dose rate (HDR) brachytherapy (BRT) protocol as monotherapy for clinically localised prostate cancer. Material and methods Between February 2008 and December 2012, 450 consecutive patients with clinically localised prostate cancer were treated with HDR monotherapy. The cohort comprised of 198 low-, 135 intermediate- and 117 high risk patients being treated with three single-fraction implants of 11.5 Gy delivered to an intraoperative real-time, transrectal ultrasound defined planning treatment volume up to a total physical dose of 34.5 Gy with an interfractional interval of 21 days. Fifty-eight patients (12.8%) received ADT, 32 of whom were high- and 26 intermediate-risk. Biochemical failure was defined according to the Phoenix Consensus Criteria and genitourinary/gastrointestinal toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 3.0. Results The median follow-up time was 56.3 months. The 60-month overall survival, biochemical control and metastasis-free-survival rates were 96.2%, 95.0% and 99.0%, respectively. Toxicity was scored per event with late Grade 2 and 3 genitourinary adverse events of 14.2% and 0.8%, respectively. Late Grade 2 gastrointestinal toxicity amounted 0.4% with no instances of Grade 3 or greater late adverse events to be reported. Conclusions Our results confirm HDR BRT to be a safe and effective monotherapeutic treatment modality for clinically localised prostate cancer.

To review the current status of interstitial high-dose-rate brachytherapy as a salvage modality (sHDR BRT) for locally recurrent prostate cancer after definitive radiotherapy (RT). A literature search was performed in PubMed using “high-dose-rate, brachytherapy, prostate cancer, salvage” as search terms. In all, 51 search results published between 2000 and 2016 were identified. Data tables were generated and summary descriptions created. The main outcome parameters used were biochemical control (BC) and toxicity scores. Eleven publications reported clinical outcome and toxicity with follow-up ranging from 4–191 months. A variety of dose and fractionation schedules were described, including 19.0 Gy in 2 fractions up to 42.0 Gy in 6 fractions. The 5‑year BC ranged from 18–77%. Late grade 3 genitourinary and gastrointestinal toxicity was 0–32% and 0–5.1%, respectively. sHDR BRT appears as safe and effective salvage modality for the reirradiation of locally recurrent prostate cancer after definitive RT.

Purpose To report our results of image-guided interstitial (IRT) high-dose-rate (HDR) brachytherapy (BRT) in the primary treatment of patients with inoperable glioblastoma multiforme (GBM) in the pre-temozolomide period. Material and methods Between 1994 and 2004, 17 patients were treated with HDR BRT for inoperable GBM. Of those, only 11 patients were treated with IRT BRT, and the remaining six patients received combined IRT BRT and external beam radiotherapy (EBRT). Patient's median age was 59.3 years (range, 29-83 years) and median tumor volume was 39.3 cm3 (range, 2-162 cm3). The prescribed HDR dose was median 40 Gy (range, 30-40 Gy), delivered twice daily in 5.0 Gy fractions over four consecutive days. Survival from BRT, toxicity as well as the impact of several prognostic factors was evaluated. Results At a median follow-up of 9.3 months, the median overall survival for the whole population, after BRT alone, and combined BRT with EBRT was 9.3, 7.3, and 10.1 months, respectively. Of the prognostic variables evaluated in univariate analysis, i.e., age, Karnofsky performance score, BRT dose, and tumor volume, only the latter one reached statistical significance. Two patients (11.7%) developed treatment-associated adverse events, with one (5.8%) symptomatic radionecrosis and one (5.8%) severe convulsion episode, respectively. Conclusions For patients with inoperable GBM, IRT HDR BRT alone or in combination with EBRT is a safe and effective irradiation method providing palliation without excessive toxicity.

To report our results of computed tomography-guided interstitial high-dose-rate (HDR) brachytherapy (BRT) in the treatment of patients with recurrent inoperable glioblastoma multiforme (GBM). Between 1995 and 2014, 135 patients were treated with interstitial HDR BRT for inoperable recurrent GBM located within previously irradiated volumes. Patient’s median age was 57.1 years (14–82 years). All patients were pretreated with surgery, postoperative external beam radiation therapy (EBRT) and systemic chemotherapy (ChT). The median recurrent tumor volume was 42 cm3 (2–207 cm3). The prescribed HDR dose was median 40 Gy (30–50 Gy) delivered in twice-daily fractions of 5.0 Gy over consecutive days. No repeat surgery or ChT was administered in conjunction with BRT. Survival from BRT, progression-free survival (PFS), toxicity as well as the impact of several prognostic factors were evaluated. At a median follow-up of 9.2 months, the median overall survival following BRT and the median PFS were 9.2 and 4.6 months, respectively. Of the prognostic variables evaluated in univariate analysis, extent of surgery at initial diagnosis, tumor volume at recurrence, as well as time from EBRT to BRT reached statistical significance, retained also in multivariate analysis. Eight patients (5.9%) developed treatment-associated complications including intracerebral bleeding in 4 patients (2.9%), symptomatic focal radionecrosis in 3 patients (2.2%), and severe convulsion in 1 patient (0.7%). For patients with recurrent GBM, interstitial HDR BRT is an effective re-irradiation method for even larger tumors providing palliation without excessive toxicity.

To evaluate the feasibility and toxicity profile of repeated stereotactic body radiotherapy (SBRT) for recurrent primary or secondary liver tumors. 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. 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/β = 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. 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.

Prostate-specific membrane antigen (PSMA) PET/CT detects prostate cancer recurrence at low levels of prostate-specific antigen (PSA). Radiotherapy with dose escalation to the former prostate bed has been associated with improved biochemical recurrence-free survival (BRFS). Thus, we hypothesized that PSMA PET/CT-guided salvage radiotherapy leads to improved BRFS. Methods: In total, 204 consecutive patients were referred for salvage radiotherapy after radical prostatectomy. PSMA PET/CT scans were performed, and patients with PSA persistence (109 patients) or evidence of distant metastases (5 patients) were excluded from this analysis. Thus, the following analysis is based on a total of 90 patients who underwent PSMA PET/CT before radiotherapy due to biochemical recurrence and received salvage radiotherapy. In cases of PET-positive findings, antiandrogen therapy was commenced before initiation of radiotherapy. BRFS (PSA ≤ 0.2 ng/mL) was defined as the study endpoint. Results: PET-positive lesions were detected in 42 of 90 (47%) patients, 24 of 42 (27%) being fossa recurrence only, 12 of 42 (13%) pelvic lymph node only, and 6 of 42 (7%) both fossa and pelvic lymph node. The median PSA before radiotherapy was 0.44 ng/mL (range, 0.11–6.24 ng/mL). Cumulatively, a total dose of 70.0 Gy (range, 67.2–72 Gy) was delivered to local macroscopic tumor, 66 Gy (range, 59.4–70.2 Gy) to the prostatic fossa, 60.8 Gy (range, 54–66 Gy) to PET-positive lymph nodes, and 50.4 Gy (range, 45–50.4 Gy) to the lymphatic pathways. After a median follow-up of 23 mo, BRFS was 78%. Antiandrogen therapy was ongoing in 4 patients at the last follow-up. No significant difference in BRFS between PET-positive patients (74%) and PET-negative patients (82%; P > 0.05) was observed at the last follow-up. Two patients had late genitourinary toxicity, grade 3, and no patient had gastrointestinal toxicity of grade 3 or higher (National Cancer Institute common terminology criteria for adverse events, version 4.03). Conclusion: PSMA PET/CT-guided salvage radiotherapy is an effective and safe local treatment option. No difference in BRFS between PET-positive and PET-negative patients was observed, indicating effective targeting of PET-positive lesions. PSMA PET/CT when readily available should be offered to patients with PSA recurrence for treatment individualization.

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. 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. 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. 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.

Radiation recall dermatitis (RRD) refers to an acute inflammatory skin reaction appearing on a previously irradiated area following the systemic administration of a reaction-triggering agent. Despite various hypotheses, the pathomechanism of RRD appears complex and is still not fully understood. In addition, no clinical guidelines exist concerning whether drug treatment should be continued upon manifestation of an associated radiation recall phenomenon. We present the case of a patient with docetaxel-induced RRD, which was successfully treated with topical steroids and systemic antihistamines; re-challenge to docetaxel did result in very mild remanifestation of skin reactions.