Interstitial Brachytherapy for Hepatocellular Carcinoma: Analysis of Prognostic Factors for Overall Survival and Progression-Free Survival and Application of a Risk Stratification Model.

INTRODUCTION: Interstitial brachytherapy (iBT) is an effective treatment for hepatocellular carcinoma (HCC). Identification of prognostic factors is pivotal for patient selection and treatment efficacy. This study aimed to assess the impact of low skeletal muscle mass (LSMM) on overall survival (OS) and progression-free survival (PFS) of iBT in patients with HCC. METHODS: For this single-center study, we retrospectively identified 77 patients with HCC who underwent iBT between 2011 and 2018. Follow-up visits were recorded until 2020. The psoas muscle area, psoas muscle index, psoas muscle density (MD), and the skeletal muscle gauge were assessed on the L3 level on pre-treatment cross-sectional CT scans. RESULTS: Median OS was 37 months. 42 patients (54.5%) had LSMM. An AFP level of >400 ng/ml (hazard ratio [HR] 5.705, 95% confidence interval [CI]: 2.228-14.606, p = 0.001), BCLC stage (HR 3.230, 95% CI: 0.972-10.735, p = 0.026), and LSMM (HR 3.365, 95% CI: 1.490-7.596, p = 0.002) showed a relevant association with OS. Weighted hazard ratios were used to form a predictive risk stratification model with three groups: patients with low risk (median OS 62 months), intermediate risk (median OS 31 months), and high risk (median OS 9 months). The model showed a good prediction of 1-year mortality, with an AUC of 0.71. Higher MD was associated with better PFS (HR 0.920, 95% CI: 0.881-0.962, p < 0.001). CONCLUSION: In patients undergoing iBT for HCC, LSMM is associated with worse OS. A risk stratification model based on LSMM, AFP >400 ng/mL, and BCLC stage successfully predicted patient mortality. The model may support and enhance patient selection.

Neoadjuvant radiochemotherapy with cisplatin/5-flourouracil or carboplatin/paclitaxel in patients with resectable cancer of the esophagus and the gastroesophageal junction - comparison of postoperative mortality and complications, toxicity, and pathological tumor response.

PURPOSE: In 2012, the CROSS trial implemented a new neoadjuvant radiochemotherapy protocol for patients with locally advanced, resectable cancer of the esophagus prior to scheduled surgery. There are only limited studies comparing the CROSS protocol with a PF-based (cisplatin/5-fluorouracil) nRCT protocol. METHODS: In this retrospective, monocentric analysis, 134 patients suffering from esophageal cancer were included. Those patients received either PF-based nRCT (PF group) or nRCT according to the CROSS protocol (CROSS group) prior to elective en bloc esophagectomy. Perioperative mortality and morbidity, nRCT-related toxicity, and complete pathological regression were compared between both groups. Logistic regression analysis was performed in order to identify independent factors for pathological complete response (pCR). RESULTS: Thirty-day/hospital mortality showed no significant differences between both groups. Postoperative complications ≥ grade 3 according to Clavien-Dindo classification were experienced in 58.8% (PF group) and 47.6% (CROSS group) (p = 0.2) respectively. nRCT-associated toxicity ≥ grade 3 was 30.8% (PF group) and 37.2% (CROSS group) (p = 0.6). There was no significant difference regarding the pCR rate between both groups (23.5% vs. 30.5%; p = 0.6). In multivariate analysis, SCC (OR 7.7; p < 0.01) and an initial grading of G1/G2 (OR 2.8; p = 0.03) were shown to be independent risk factors for higher rates of pCR. CONCLUSION: We conclude that both nRCT protocols are effective and safe. There were no significant differences regarding toxicity, pathological tumor response, and postoperative morbidity and mortality between both groups. Squamous cell carcinoma (SCC) and favorable preoperative tumor grading (G1 and G2) are independent predictors for higher pCR rate in multivariate analysis.

Local ablation of hepatocellular carcinoma by interstitial brachytherapy: prediction of outcome by diffusion-weighted imaging.

BACKGROUND: Interstitial brachytherapy (iBT) has become a viable treatment option in the therapy of early and intermediate stage hepatocellular carcinoma (HCC). Prognostic imaging tools to predict patient outcome are missing. PURPOSE: To assess the predictive value of baseline diffusion-weighted imaging in HCC before iBT with regard to local tumor control and overall survival (OS). MATERIAL AND METHODS: We retrospectively identified 107 patients who underwent iBT for HCC from 2011 to 2018 from our database. Apparent diffusion coefficient (ADC) values for each treated lesion were analyzed in region of interest measurements. Additionally, explorative combined ratios adjusting total measured lesion area and mean measured lesion area per patient by ADC values were calculated. Measurements underwent a univariate and multivariate Cox regression analysis. The log rank test was then used to verify prognostic cutoff levels for median survival time. RESULTS: A total of 189 lesions in 81 patients were measured. Median survival of patients was 46.0 months. Neither ADC parameter was indicative of local tumor control. Lesion size >5 cm was associated with lower local tumor control (hazard ratio [HR]=4.292, 95% confidence interval [CI]=1.285-14.331; P = 0.018). Average measured lesion area divided by ADCmin (ADCarea mean, min) was identified to independently predict OS (HR=1.994, 95% CI=1.172-3.392; P = 0.011). A cutoff based on the variable's median (0.29 × 10-4 AU) identified patients with poor outcome (OS 36 vs. 61 months) for lower ADCarea mean, min values as verified by the log-rank test (P = 0.040). CONCLUSION: Pre-treatment ADCarea mean, min may serve as an independent predictor of OS in patients with HCC undergoing iBT.

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).

MRI targeted single fraction HDR Brachytherapy for localized Prostate Carcinoma: a feasibility study of focal radiation therapy (ProFocAL).

OBJECTIVES: The aim of the study was to establish the setup and workflow for delivering focal MRI-guided high-dose-rate (HDR) brachytherapy for prostate cancer (PCA) and to assess patient comfort and safety aspects of MRI-guided single-fraction HDR. METHODS: Patients with histologically proven focal low- to intermediate-risk PCA with a single PIRADS 4/5 lesion were treated with percutaneous interstitial HDR brachytherapy in a single fraction with a minimum dose for the gross tumor volume of 20 Gy while sparing the organ at risk (OAR). Using a 3T-MRI, brachytherapy catheters were placed transgluteal in freehand technique. No antibiotic therapy or general analgesics were administered. Patient data, procedure time, patient discomfort, and complications were recorded. Quarterly PSA controls, biannual follow-up imaging, and annual re-biopsy were planned. RESULTS: So far, 9 patients were successfully treated and followed for 6 months. Mean intervention time was 34 min. Using the VAS scale, the pain reported for the intervention ranged from 2 to 3. Short-term follow-up showed no acute genitourinary or gastrointestinal toxicity so far. None of the patients displayed signs of infection. PSA levels in all patients decreased significantly. On follow up no residual PCA was detected treated region so far. PSA levels in all patients decreased significantly. On follow-up, no residual PCA was detected so far. CONCLUSIONS: MR-guided single-fraction focal HDR brachytherapy for localized PCA is feasible as well as safe for the individual patient. Catheters can be placed accurately and maximum therapeutic dose distribution can be restricted to the tumor. Countersigning the minimally invasive character of the procedure, no general anesthesia or antibiosis is necessary. KEY POINTS: • MR-guided focal HDR brachytherapy allows an accurate placement of catheters with maximum therapeutic dose distribution restricted to the tumor. • No major anesthesia or antibiosis is necessary emphasizing the minimal invasive character of the procedure. • Patients with low- and intermediate-risk prostate carcinoma in particular may benefit to halt disease progression whereas treatment-related morbidity is reduced compared with radical therapy.

Biliary duct stenosis after image-guided high-dose-rate interstitial brachytherapy of central and hilar liver tumors : A systematic analysis of 102 cases.

OBJECTIVE: Image-guided high-dose-rate interstitial brachytherapy (iBT) with iridium-192 is an effective treatment option for patients with liver malignancies. Little is known about long-term radiation effects on the bile duct system when central hepatic structures are exposed to iBT. This retrospective analysis investigates the occurrence of posthepatic cholestasis (PHC) and associated complications in patients undergoing iBT. MATERIALS AND METHODS: We identified patients who underwent iBT of hepatic malignancies and had point doses of ≥1 Gy to central bile duct structures. Patients with known bile duct-related diseases or prior bile duct manipulation were excluded. RESULTS: 102 patients were retrospectively included. Twenty-two patients (22%) developed morphologic PHC after a median of 17 (3-54) months; 18 of them were treated using percutaneous transhepatic cholangiopancreatography drainage or endoscopic retrograde cholangiopancreatography. The median point dose was 24.8 (4.4-80) Gy in patients with PHC versus 14.2 (1.8-61.7) Gy in those without PHC (p = 0.028). A dose of 20.8 Gy (biological effective dose, BED3/10 = 165/64.1 Gy) was identified to be the optimal cutoff dose (p = 0.028; 59% sensitivity, 24% specificity). Abscess/cholangitis was more common in patients with PHC compared to those without (4 of 22 vs. 2 of 80; p = 0.029). Median survival did not differ between patients with and without PHC (43 vs. 36 months; p = 0.571). CONCLUSION: iBT of liver malignancies located near the hilum can cause PHC when the central bile ducts are exposed to high point doses. Given the long latency and absence of impact of iBT-induced PHC on median survival, the rate of cholestasis and complications seen in our patients appears to be acceptable.

Local ablation or radioembolization of colorectal cancer metastases: comorbidities or older age do not affect overall survival.

BACKGROUND: Local ablative techniques are emerging in patients with oligometastatic disease from colorectal carcinoma, commonly described as less invasive than surgical methods. This single arm cohort seeks to determine whether such methods are suitable in patients with comorbidities or higher age. METHODS: Two hundred sixty-six patients received radiofrequency ablation (RFA), CT-guided high-dose rate brachytherapy (HDR-BT) or Y90-radioembolization (Y90-RE) during treatment of metastatic colorectal cancer (mCRC). This cohort comprised of patients with heterogenous disease stages from single liver lesions to multiple organ systems involvement commonly following multiple chemotherapy lines. Data was reviewed retrospectively for patient demographics, previous therapies, initial or disease stages at first intervention, comorbidities and mortality. Comorbidity was measured using the Charlson Comorbidity Index (CCI) and age-adjusted Charlson Index (CACI) excluding mCRC as the index disease. Kaplan-Meier survival analysis and Cox regression were used for statistical analysis. RESULTS: Overall median survival of 266 patients was 14 months. Age ≥ 70 years did not influence survival after local therapies. Similarly, CCI or CACI did not affect the patients prognoses in multivariate analyses. Moderate or severe renal insufficiency (n = 12; p = 0.005) was the only single comorbidity identified to negatively affect the outcome after local therapy. CONCLUSION: Interventional procedures for mCRC may be performed safely even in elderly and comorbid patients. In severe renal insufficiency, the use of invasive techniques should be limited to selected cases.

Combined Systemic Chemotherapy and CT-Guided High-Dose-Rate Brachytherapy for Isolated Local Manifestation of Pancreatic Cancer after Surgical Resection.

BACKGROUND: Prospective data on the optimal management of patients with pancreatic ductal adenocarcinoma (PDA) and isolated local manifestation (ILM) after surgery are lacking. Hence, no statements with respect to this entity have been released from most international guidelines including European Society for Medical Oncology, National Comprehensive Cancer Network, and American Society for Clinical Oncology. METHODS: We report for the first time a case-series of 3 patients with PDA and ILM receiving combined systemic chemotherapy and CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT). RESULTS: CT-HDRBT allowed in all patients with pronounced chemotherapy-induced side effects either a pause of cytostatic treatment or de-escalation to a "maintenance" therapy (dose reduction, interval prolongation, scheme modification with withdrawal of most toxic drugs). CONCLUSION: Combining CT-HDRBT to systemic chemotherapy in patients with PDA and ILM is feasible and safe. As for patients with PDA and ILM no standard of care exists, designing an appropriate randomized prospective trial for this highly selected group of patients is challenging.

Adjuvant hysterectomy after radiochemotherapy for locally advanced cervical cancer.

BACKGROUND: External beam radiation therapy (EBRT) with concomitant chemotherapy (cCT) (=RCT) plus intracavitary (±interstitial) brachytherapy (iBT) is standard of care for advanced cervical cancer. The aim of this study was to evaluate morbidity and survival outcome of simple adjuvant hysterectomy (AH) after EBRT/cCT and to compare it with the standard treatment. PATIENTS AND METHODS: Patients with FIGO stage III cervical cancer were treated with EBRT/cCT and then divided in two groups: group 1 was further treated with standard intracavitary/interstitial BT, while group 2 underwent AH. RESULTS: From 881 women with cervical cancer, 248 were eligible for analysis: 161 received iBT and 87 underwent AH. The median follow-up of the study was 53 months. Clinical and pathological characteristics were well balanced in the two groups. After EBRT/cCT, complete clinical response was observed in 121 (48.8%) of 246 patients. Clinical complete response was observed in 81 (50.3%) of 161 patients in group 1. At 6 weeks after EBRT/cCT, 40 (46.0%) of 87 patients in the surgery group had pathological complete response. Intra- and postoperative complications were observed in 10 (11.5%) of 87 cases. The rates of locoregional recurrence and metastasis were similar in both groups. Progression-free (PFS) and disease-specific overall survival (DOS) for these patients were similar between the control and surgery group. Interestingly, PFS and DOS were significantly improved by AH for the patients with residual tumor. CONCLUSION: AH could improve survival in patients with residual disease after RCT and is characterized by a low complication rate.

Hyperfractionated accelerated radiation therapy plus cetuximab plus cisplatin chemotherapy in locally advanced inoperable squamous cell carcinoma of the head and neck : Final 5­year results of a phase II study.

BACKGROUND: Cetuximab (CET) is a potent inhibitor of the epidermal growth factor receptor and has been shown to have activity in squamous cell carcinoma of the head and neck (SCCHN). We conducted a single-arm phase II trial of a combination therapy comprising cisplatin (CIS), CET and hyperfractionated accelerated radiotherapy (HART). PATIENTS AND METHODS: Patients with UICC stage III or IVA/B, M0 SCCHN were enrolled and treated with an initial dose of CET (400 mg/m2) and then with a weekly dosage of 250 mg/m2 during HART. HART was started with a prescribed dosage of 2.0 Gy per day for 3 weeks, followed by 1.4 Gy twice daily to a total dose of 70.6 Gy to the gross tumour volume. CIS (40 mg/m2) was administered weekly (days 1, 8, 15, 22, 29 and 36). The primary objective of the phase II study was to determine the 2­year progression-free survival (PFS). RESULTS: Between November 2007 and November 2010, a total of 74 patients were enrolled in the study, of whom 65 were evaluable (83% were men). Median age was 56 years (range 37-69 years). An Oropharyngeal primary tumour was diagnosed in 49%, T4a,b in 65% and N2/3 in 96% of the patients. Of these patients, 85% were smokers or ex-smokers. Complete remission (CR) was observed in 23 patients (35%). The most common toxicity grade was ≥3, including mucositis (58%) and dysphagia (52%). The 2­ and 5­year overall survival rates were 64 and 41%, the 2­ and 5­year PFS rates were 45 and 32%, and the 2­ and 5­year locoregional control rates were 47 and 33%, respectively. CONCLUSION: The combination of weekly CIS with HART plus CET is a feasible regimen for these unfavourable smoking-induced cancers. However, the parallel US study (RTOG 0522) showed no advantage of the enhanced triple therapy compared to chemoradiotherapy alone.

Radioablation of liver malignancies with interstitial high-dose-rate brachytherapy : Complications and risk factors.

BACKGROUND: To evaluate complications and identify risk factors for adverse events in patients undergoing high-dose-rate interstitial brachytherapy (iBT). MATERIAL AND METHODS: Data from 192 patients treated in 343 CT- or MRI-guided interventions from 2006-2009 at our institution were analyzed. In 41 %, the largest tumor treated was ≥ 5 cm, 6 % of the patients had tumors ≥ 10 cm. Prior to iBT, 60 % of the patients had chemotherapy, 22 % liver resection, 19 % thermoablation or transarterial chemoembolization (TACE). Safety was the primary endpoint; survival data were obtained as the secondary endpoints. During follow-up, MRI or CT imaging was performed and clinical and laboratory parameters were obtained. RESULTS: The rate of major complications was below 5 %. Five major bleedings (1.5 %) occurred. The frequency of severe bleeding was significantly higher in patients with advanced liver cirrhosis. One patient developed signs of a nonclassic radiation-induced liver disease. In 3 patients, symptomatic gastrointestinal (GI) ulcers were detected. A dose exposure to the GI wall above 14 Gy/ml was a reliable threshold to predict ulcer formation. A combination of C-reactive protein ≥ 165 mg/l and/or leukocyte count ≥ 12.7 Gpt/l on the second day after the intervention predicted infection (sensitivity 90.0 %; specificity 92.8 %.) Two patients (0.6 %) died within 30 days. Median overall survival after the first liver treatment was 20.1 months for all patients and the local recurrence-free surviving proportion was 89 % after 12 months. CONCLUSIONS: Image-guided iBT yields a low rate of major complications and is effective.

Locally ablative treatment of breast cancer liver metastases: identification of factors influencing survival (the Mammary Cancer Microtherapy and Interventional Approaches (MAMMA MIA) study).

BACKGROUND: Liver metastases from breast cancer (LMBC) are typically considered to indicate systemic disease spread and patients are most often offered systemic palliative treatment only. However, retrospective studies suggest that some patients may have improved survival with local treatment of their liver metastases compared to systemic therapy alone. In the absence of randomized trials, it is important to identify patient characteristics indicating that benefit from local treatment can be expected. METHODS: 59 patients undergoing radiofrequency ablation (RFA), interstitial brachytherapy (BT), or radioembolization (RE) of LMBC as a salvage treatment were studied. Potential factors influencing survival were analyzed in a multivariate Cox model. For factors identified to have an independent survival impact, Kaplan-Meier analysis and comparison of overall survival (OS) using the log-rank test was performed. RESULTS: Median OS following local interventional treatment was 21.9 months. Considering only factors evaluable at treatment initiation, maximum diameter of liver metastases (≥3.9 cm; HR: 3.1), liver volume (≥ 1376 mL; HR: 2.3), and history of prior chemotherapy (≥ 3 lines of treatment; HR: 2.5-2.6) showed an independent survival impact. When follow-up data were included in the analysis, significant factors were maximum diameter of liver metastases (≥ 3.9 cm; HR: 3.1), control of LMBC during follow-up (HR: 0.29), and objective response as best overall response (HR: 0.21). Neither the presence of any extrahepatic metastases nor presence of bone metastases only had a significant survival impact. Median OS was 38.7 vs. 16.1 months in patients with metastases < vs. ≥ 3.9 cm, 36.6 vs. 10.2 months for patients having objective response vs. stable/progressive disease, and 38.5 vs. 14.2 months for patients having controlled vs. non-controlled disease at follow-up. CONCLUSION: Local control of LMBC confers a survival benefit and local interventional treatment for LMBC should be studied in a randomized trial. Patients with small metastases and limited history of systemic LMBC treatment are most likely to benefit from local approaches. Limited extrahepatic disease should not lead to exclusion from a randomized study and should not be a contraindication for local LMBC treatment as long as no randomized data are available.

Feasibility of MRI targeted single fraction HDR brachytherapy for localized prostate carcinoma: ProFocAL-study.

PURPOSE: A potential method for focal therapy in locally advanced prostate cancer is focal brachytherapy (F-BT). The purpose of this research was to evaluate midterm F-BT oncologic, functional, and toxicological results in men who had therapy for prostate cancer. MATERIALS AND METHODS: Between 2016 and 2020, F-BT was used to treat 37 patients with low- to intermediate-risk prostate cancer. The recommended dosage was 20 Gy. Failure was defined as the existence of any prostate cancer that has persisted in-field after treatment. The F-BT oncologic and functional outcomes served as the main and secondary objectives, respectively. RESULTS: A median 20-month follow-up (range 14-48 months). 37 patients received F-BT and enrolled in the study; no patient experienced a biochemical recurrence in the first 24 months, according to Phoenix criteria. In the control biopsies, only 6 patients showed in-field failure. The median initial IPSS was 6.5, at 6 months was 6.0, and at 24 months was 5.0. When the median ICIQ-SF score was 0 at the baseline, it remained 0 at 6-, 12-, and 24 months. Overall survival and biochemical disease-free survival after 3 years were all at 100% and 86.4%, respectively. There was no notable acute gastro-intestinal (GI) or genitourinary (GU) adverse effects. No intraoperative or perioperative complications occurred. CONCLUSIONS: For selected patients with low- or intermediate-risk localized prostate cancer, F-BT is a safe and effective therapy.

A single-institution retrospective analysis of intraoperative radiation boost during breast-conservation treatment for breast cancer.

BACKGROUND: As part of a breast-conservation strategy for breast cancer, there are presently no data from randomized controlled studies on the use of intraoperative radiation (IORT) as a tumor bed boost. The effectiveness and safety of IORT as a boost therapy at a tertiary cancer center were retrospectively reviewed in this study. METHODS: Patients had breast-conserving surgery from 2012 to 2016 that included staging of the axillary lymph nodes, a single dose of 20 Gy IORT with 50-kV photons, whole-breast irradiation (WBI), and (neo-)adjuvant systemic treatment (if applicable). During the follow-up patients were monitored for the assessment of acute and late toxicities (using the Common Terminology Criteria for Adverse Events version 4.03). Results included ipsilateral (IBTR), contralateral (CBE), and distant metastasis-free (DMFS) breast progression-free survival, as well as overall survival (OS). RESULTS: The 68 patients had a median follow-up of 91.5 months (with a range of 9-125). Most patients (n = 51) had T1 disease and were clinically node negative. Only a small number of individuals had triple negative or high-grade illness. The majority of patients had sentinel node biopsy, and three (4.4%) had to have their tumors removed again since their original margins were positive. Finally, there were no distinct tumor bed margins. Neoadjuvant chemotherapy was administered to ten (14.7%). The median duration from BCS to WBI was 54.5 days, and conventionally fractionated WBI was used to accomplish WBI most frequently (n = 57, 96.6%). IORT was administered in a single 20 Gy dosage. 50 Gy was the median WBI dosage (range 40.05-50.4 Gy). There were no grade 4 adverse events for any patients in. Toxicities following surgery were minimal. There were only one patient with grade 3 toxicity (radiation dermatitis) to observe. Five tumor bed recurrences and two contralateral breast incident each occurred. CONCLUSION: This work adds to the preliminary evidence already in the literature and supports the use of IORT in boost settings. When randomized trials like TARGIT-B are eventually published, these hopeful findings should be prospectively evaluated.

Can alternative liver function scores facilitate the establishment of an indication for radioablative therapy in patients with hepatocellular carcinoma?

BACKGROUND AND PURPOSE: ALBI and IBI are new scores to evaluate the liver function in patients with hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the prognostic abilities of those scores in patients treated with interstitial brachytherapy (iBT). MATERIALS AND METHODS: 190 patients treated with iBT between 01.01.2006 and 01.01.2018 were included in this study. The clinical target dose was 15 Gy. The patients were all in Child-Pugh stadium A or B and across the Barcelona Clinic Liver Cancer (BCLC) Stages 0-C. Retrospectively ALBI and IBI were calculated pre- and post-therapeutic until 6 months after iBT. Hazards ratios were calculated, and p values corrected using the false discovery rate according to Benjamini and Hochberg. RESULTS: The median overall survival was 23.5 months (CI 19-28.5 months), and the median progression-free survival was 7.5 months (CI 6-9 months). Elevated ALBI showed a significantly higher risk to die with a hazard ratio (HR) of 2.010 (ALBI 2 vs. 1) and 4082 (ALBI 3 vs. 1), respectively. The IBI did also show a higher risk with an HR of 1.816 (IBI 1 vs. 0) and 4608 (IBI 2 vs. 0), respectively. Even 3 months after therapy elevated ALBI and IBI showed poor overall survival. Concerning progression-free survival, ALBI and IBI could not provide any relevant additional information. CONCLUSION: ALBI and IBI are useful tools to predict the overall survival in patients treated with iBT and might be helpful to assign the patients to the appropriate therapy.

Prevention of radiation-induced liver toxicity after interstitial HDR brachytherapy by pentoxifylline and ursodeoxycholic acid: patient compliance and outcome in a randomized trial.

AIM: To investigate the impact of pentoxifylline (PTX, 3 × 400 mg per day) and ursodeoxycholic acid (UDCA, 3 × 250 mg per day) administered for 12 weeks on radiation-induced liver toxicity. MATERIALS AND METHODS: Inclusion criteria were liver metastases of extrahepatic malignancies undergoing HDR-BT. 36 patients were prospectively randomized to the medication (N = 18) or control arm (N = 18) and follow-up by hepatobiliary magnetic resonance imaging (MRI) was scheduled 6 and 12 weeks after local ablation by HDR-BT. We determined the threshold doses of fRILI by image fusion of MRI with the dosimetry data. RESULTS: 32 patients completed the study schedule. Per-protocol treatment was limited to 8 patients in the medication group and 16 patients in the control group. 22 adverse events of any grade likely or certainly related to PTX were recorded in 12 patients leading to the discontinuation of the study medication in 7 patients and to a dose reduction of PTX in 2 patients. In the per-protocol population, statistical analysis failed to prove a reduction of fRILI 6 and 12 weeks after HDR-BT. The incidence of adverse effects attributed to PTX (70.6%) was well above the data found in the literature for its approved indication. CONCLUSION: The study endpoint was not met mainly attributed to the low statistical power of the small per-protocol cohort. Independently, PTX cannot be recommended for the reduction of radiation-induced liver toxicity in oncologic patients undergoing HDR-BT of liver metastases. Further studies might focus on a combination of UDCA with other potential drugs to help establish a preventive and tolerable regimen.

Local tumor control of intermediate and advanced stage hepatocellular carcinoma after local ablative treatment with image-guided interstitial high-dose-rate brachytherapy: A subgroup analysis of 286 HCC nodules.

PURPOSE: Image-guided interstitial high-dose-rate brachytherapy (iBT) has been demonstrated to offer high local tumor control rates (LTC) of >90% after local ablation of intermediate and advanced hepatocellular carcinoma (HCC; BCLC B and C). The purpose of this study was to show the efficacy of iBT stratified by subgroups and to identify clinical characteristics associated with superior local tumor control (LTC) based on a highly heterogenous patient population METHODS AND MATERIALS: A cumulative number of 286 HCC nodules in 107 patients were retrospectively analyzed. Clinical and imaging follow-ups were conducted every 3 months after treatment. Analyzed clinical factors were: etiology, presence of liver cirrhosis, radiographic features, lesion size, pretreatment, administered dose, presence of portal hypertension, portal vein thrombosis, and level of alpha-fetoprotein (AFP). RESULTS: LTC rate was 88.8% for a median follow-up of 14.3 months (range 3-81 months; 95% CI: 85-92%). Median minimal enclosing tumor dose (D100) was 16.1 Gy (range 7.1-30.3 Gy; reference dose 15 Gy). Subgroup analysis showed significant fewer local recurrences for alcoholic liver disease (ALD)-related HCCs compared to those related to other causes of liver cirrhosis (nonalcoholic fatty liver disease, virus-related liver cirrhosis and other causes) (p = 0.015). LTC was significantly lower after prior surgical resection (p = 0.046). No significant variance was observed for the applied D100 in each group or for all other clinical factors tested. CONCLUSIONS: IBT achieves high LTC rates across treated subgroups. However, further studies should particularly address the possible impact of underlying etiology on local recurrence with emphasis on a possible higher radiosensitivity of ALD-related HCCs.

Needle track seeding in colorectal carcinoma after local ablation by high-dose-rate brachytherapy: a retrospective study of 1,107 catheter placements.

Purpose: Image-guided brachytherapy with a single-fraction irradiation (high-dose-rate brachytherapy - HDR-BT) is a promising local ablation technique for unresectable liver metastases. The occurrence of needle track seeding after biopsy and microwave ablation (MWA) has been documented primarily in hepatocellular carcinoma (HCC). Comprehensive data on colorectal metastases and treatment with HDR-BT is missing. The aim of this study was to investigate the incidence of extra- and intra-hepatic track seeding after HDR-BT in patients with colorectal metastases of the liver, and the identification of possible risk factors. Material and methods: Patients with at least one treatment of HDR-BT were included. Two readers identified possible track seeding after at least 3 months of follow-up. For verification, we used image fusion of CT/MRI images from 3D irradiation plan and follow-up. Intra- and extra-hepatic seeding were included. As possible risk factors, demographics, tumor grading, and aspects of catheter placement were identified, and generalized linear mixed model for evaluation was applied. Results: On total, 138 patients were included in the study (85 males). We treated 472 liver lesions with 1,107 catheter placements. Sixteen needle track lesions were identified with a catheter-based risk of 1.5% and patient-based risk of 10.9% during a median follow-up of 543 days. Extra-hepatic track seeding (patient-based risk of 1.4%) was found in two patients only. Possible risk factors were tumor grading (p = 0.01) and using MRI-guidance (p = 0.02). There was also a correlation with a high number of interventions per patient (p = 0.009) and number of treated lesions (p = 0.04). Conclusions: Brachytherapy for treatment of colorectal metastases is associated with a similar risk for extra-hepatic track seeding compared to radio-frequency ablation (RFA). Intra-hepatic seeding, which has not been studied extensively before, occurs more often with seeding frequency comparable to biopsy of colorectal metastases. Possible risk factors could be tumor grading and using MRI-guidance.

Sarcopenia does not limit overall survival after interstitial brachytherapy for breast cancer liver metastases.

Purpose: Sarcopenia has been identified as a prognostic marker of clinical outcomes in several diseases. However, the influence of sarcopenia on non-surgical local treatments in breast cancer liver metastases (BCLM) is unknown. Therefore, the purpose of this study was to assess the effect of sarcopenia among patients with BCLM undergoing interstitial brachytherapy (iBT). Aim of the study was to evaluate the influence of baseline computed tomography (CT) psoas body composition parameters, including psoas muscle area (PMA), psoas muscle index (PMI), muscle density, and skeletal muscle gauge (SMG) on clinical variables in patients undergoing image-guided iBT. Material and methods: Computed tomography scans of patients undergoing iBT for BCLM from 2006-2017 were retrospectively analyzed. PMA, PMI, and SMG were measured on pre-treatment CT scans. Parameters were associated with overall survival using logistic regression analysis. Results: Sixty patients were included in the analysis. 27 patients (45%) were considered sarcopenic. Median overall survival was 27 months (SD = 4.0 months). In univariate analysis, neither PMA (HR = 0.956, 95% CI: 0.855-1.068, p = 0.423), average density (HR = 1.028, 95% CI: 0.985-1.072, p = 0.207), PMI (HR = 0.951, 95% CI: 0.701-1.290, p = 0.746), nor SMG (HR = 1.002, 95% CI: 0.998-1.006, p = 0.440) were associated with overall survival. There was no influence of sarcopenia on OS (HR = 0.975, 95% CI: 0.532-1.787, p = 0.934). Conclusions: Sarcopenia does not predict overall survival in patients undergoing iBT for BCLM. Interstitial BT may therefore be a suggested treatment option in sarcopenic patients with BCLM eligible for local ablation.