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.

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.

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.

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.

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.

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.

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.

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.

Radiation exposure to the kidney with interstitial iridium-192 high-dose-rate brachytherapy: Extent and rare morphologic changes of radiation nephropathy.

Purpose: We sought to investigate functional parameters and morphologic changes of the renal parenchyma after treatment with image-guided brachytherapy using single-fraction irradiation (high-dose-rate brachytherapy - HDR-BT) of primary kidney lesions, and primary and secondary lesions of the liver, lymph node, and adrenal gland close to renal structures. Material and methods: Patients ineligible for surgery were included. We prospectively investigated renal function loss within one year via renal scintigraphy and laboratory parameters (KDOQI stage). Radiation exposure to the kidney was measured by volume receiving 5 Gy (V5). We observed morphologic changes on CT or MRI, with follow-up every three months. Results: In total, 35 patients were included (21 males, 14 females). Eight patients were treated for extra-renal malignancies. The mean V5 of the ipsilateral kidney was 70.0 ±42.4 ml equaling to 44.9% parenchymal volume. After renal treatment, V5 renal volume was 77.8 ±42.2 ml (48.7%) compared with 44.0 ±33.0 ml (32.0%) after extra-renal treatment. No significant reduction in KDOQI stage after 12 months of follow-up were found. Three patients developed morphologic changes in the renal parenchyma, with only one showing a decrease in renal function after 12 months. Conclusions: CT-guided HDR-BT is a viable treatment modality for local ablative treatment of renal and adjacent masses, with no significant reduction of the KDOQI stage as a predictor for complications of chronic kidney disease. However, larger cohorts need to be analyzed to identify vulnerable patients, as in rare cases, plain dosimetry seems insufficient to predict renal function loss after HDR-BT.

Functional and mutational analysis after radiation and cetuximab treatment on prostate carcinoma cell line DU145.

BACKGROUND: Epidermal Growth Factor Receptor is often overexpressed in advanced prostate carcinoma. In-vitro-studies in prostate carcinoma cell line DU145 have demonstrated increased sensibility to radiation after cetuximab treatment, but clinical data are not sufficient to date. METHODS: We analyzed effects of radiation and cetuximab in DU145 and A431 using proliferation, colony-forming-unit- and annexin-V-apoptosis-assays. Changes in protein expression of pEGFR and pERK1/2 after radiation and cetuximab treatment were analyzed. Using NGS we also investigated the impact of cetuximab long-term treatment. RESULTS: Cell counts in DU145 were reduced by 44% after 4 Gy (p = 0.006) and 55% after 4 Gy and cetuximab (p < 0.001). The surviving fraction (SF) was 0.69 after 2 Gy, 0.41 after 4 Gy and 0.15 after 6 Gy (each p < 0.001). Cetuximab treatment did not alter significantly growth reduction in 4 Gy radiated DU145 cells, p > 0.05 or SF, p > 0.05, but minor effects on apoptotic cell fraction in DU145 were detected. Using western blot, there were no detectable pEGFR and pERK1/2 protein signals after cetuximab treatment. No RAS mutation or HER2 amplification was detected, however a TP53 gen-mutation c.820G > T was found. CONCLUSIONS: Radiation inhibits cell-proliferation and colony-growth and induces apoptosis in DU145. Despite blocking MAP-Kinase-pathway using cetuximab, no significant radiation-sensitizing-effect was detected. Cetuximab treatment did not induce resistance-mutations. Further research must clarify which combination of anti-EGFR treatment strategies can increase radiation-sensitizing-effects.

Impact of radiotherapy protocol adherence in NSCLC patients treated with concurrent chemoradiation: RTQA results of the PET-Plan trial.

INTRODUCTION: The success of intensification and personalisation of the curative treatment of non-small cell lung cancer (NSCLC) is strongly associated with the precision in radiotherapy. Here, we evaluate the impact of radiotherapy protocol adherence in a prospective multicentre trial. METHODS: In the open-label, randomised, controlled PET-Plan trial, patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume delineation informed by 1F-FDG PET and CT plus elective nodal irradiation (arm A) or target volumes informed by PET alone (arm B) and received iso-toxically dose-escalated concurrent chemoradiation. The prospectively organised quality assurance program (RTQA) included individual case review by predefined criteria. For evaluation, protocol adherence was scored as per protocol (pP), with minor (miD), intermediate (inD) and major (maD) deviations. In order to exclude biases through patients who discontinued treatment, patients who received ≥60 Gy were additionally analysed. RESULTS: Between 05/2009-11/2016, 205 patients were randomized, 204 patients started treatment according to protocol of which 31 (15%) patients had maD. Patients with maD had an inferior overall survival (OS) (HR 2.9, 95% CI 1.8-4.4, p < 0.0001) and a higher risk of loco-regional progression (HR 5.7, 95% CI 2.7-11.1, p < 0.0001). These results were significant also in the subgroup of patients receiving ≥ 60 Gy. Patients with maD concerning normal tissue delineation and/or dose constraints had a worse OS (p = 0.006) although no higher incidence of grade ≥ 3 toxicities. CONCLUSIONS: Non-adherence to the radiotherapy protocol was associated with an inferior OS and loco-regional control. These results underline the importance of RTQA.

Efficacy and Toxicity of Different Chemotherapy Protocols for Concurrent Chemoradiation in Non-Small Cell Lung Cancer-A Secondary Analysis of the PET Plan Trial.

(1) Background: The optimal chemotherapy (CHT) regimen for concurrent chemoradiation (cCRT) is not well defined. In this secondary analysis of the international randomized PET-Plan trial, we evaluate the efficacy of different CHT. (2) Methods: Patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume definition and received isotoxically dose-escalated cCRT using cisplatin 80 mg/m2 (day 1, 22) and vinorelbin 15 mg/m2 (day 1, 8, 22, 29) (P1) or cisplatin 20 mg/m2 (day 1-5, 29-33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P2) or carboplatin AUC1 (day 1-5, 29-33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P3) or other CHT at the treating physician's discretion. (3) Results: Between 05/2009 and 11/2016, 205 patients were randomized and 172 included in the per-protocol analysis. Patients treated in P1 or P2 had a better overall survival (OS) compared to P3 (p = 0.015, p = 0.01, respectively). Patients treated with carboplatin had a worse OS compared to cisplatin (HR 1.78, p = 0.03), but the difference did not remain significant after adjusting for age, ECOG, cardiac function creatinine and completeness of CHT. (4) Conclusions: Carboplatin doublets show no significant difference compared to cisplatin, after adjusting for possibly relevant factors, probably due to existing selection bias.

Interstitial Brachytherapy for Limited (<4 cm) and Large (≥4 cm) Hepatic Metastases from Rare and Less Common Cancers.

BACKGROUND/AIM: Interstitial brachytherapy (iBT) seems to achieve higher local tumor control rates for lesions limited in size. The objective was to evaluate the efficacy and safety of iBT in the treatment of limited and large liver metastases from rare or less common cancers (RLCC). PATIENTS AND METHODS: A total of 194 unresectable liver metastases categorized as limited (<4 cm, n=153, subgroup A) and large lesions (≥4 cm, n=41, subgroup B) were treated. Clinical and image-based follow-up was conducted every 3 months after iBT. RESULTS: Cumulative local recurrence (CLR) rate was 9.8% (19 recurrences; A: n=16; B: n=3). No significant difference in CLR was noted between subgroup A and B (A:10.5%, B:7.3%, p=0.339). Median follow-up was 6.2 months (range=2.2-92.9 months). Complication assessment revealed 5 severe adverse events (grade 3: 4.3%, grade 4 and 5: 0%) with 4 events in A and 1 event in B. CONCLUSION: IBT is a feasible, effective, and safe minimally invasive treatment for small and large liver metastases from RLCC.

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.

Efficacy and safety of percutaneous computed tomography-guided high-dose-rate interstitial brachytherapy in treatment of oligometastatic lymph node metastases of retroperitoneal space.

PURPOSE: To assess efficacy, safety, and outcome of computed tomography (CT)-guided high-dose-rate (HDR) interstitial brachytherapy in patients with oligometastatic lymph node metastases of the retroperitoneal space. MATERIAL AND METHODS: 24 patients with a total of 47 retroperitoneal lymph node metastases from different primary tumors were treated with CT-guided interstitial brachytherapy using an 192Ir source (single fraction irradiation). Every three months after treatment, clinical and imaging follow-up were conducted to evaluate local control and safety. RESULTS: Median follow-up was 9.6 months (range, 2.9-39.0 months). Local tumor control rate was 95.7%. The median diameter of the gross tumor volume was 2.2 cm (range, 1-8.6 cm), treated with a median D100 (minimal enclosing tumor dose) of 14.9 Gy (range, 4.5-20.6 Gy). One severe adverse event (grade three) was recorded.Cumulative median progression-free survival was 4.2 months (range, 1.4-23.7 months), and cumulative median overall survival after interstitial brachytherapy was 15.9 months (range, 3.8-39.0 months). CONCLUSIONS: CT-guided HDR interstitial brachytherapy is a safe and feasible method for local ablation of oligometastatic lymph node metastases of the retroperitoneal space, and might provide a well-tolerated additional therapeutic option in the multidisciplinary management of selected patients.

Comparative analysis between interstitial brachytherapy and stereotactic body irradiation for local ablation in liver malignancies.

PURPOSE: Interstitial high-dose-rate brachytherapy (BT) is an alternative treatment option to stereotactic body radiotherapy (SBRT) for the ablative treatment of liver malignancies. The aim of the present comparative planning study was to reveal the possibilities and limitations of both techniques with regard to dosimetric properties. METHODS AND MATERIALS: Eighty-five consecutive patients with liver malignancy diagnosis were treated with interstitial BT between 12/2008 and 09/2009. The prescription dose of BT varied between 15 and 20 Gy, depending on histology. For dosimetric comparison, virtual SBRT treatment plans were generated using the original BT planning CTs. Additional margins reflecting the respiratory tumor motion were added to the target volumes for SBRT planning. RESULTS: The mean PTVBT was 34.7 cm3 (0.5-410.0 cm3) vs. a mean PTVSBRT of 73.2 cm3 (6.1-593.4 cm3). Regarding the minimum peripheral dose (D99.9), BT achieved the targeted prescription dose of 15 Gy/20 Gy better without violating organ at risk constraints. The dose exposure of the liver was significantly influenced by treatment modality. The liver exposure to 5 Gy was statistically lower with 611 ± 43 cm3 for BT as compared with 694 ± 37 cm3 for SBRT plans (20-Gy group, p = 0.001), corresponding to 41.8% vs. 45.9% liver volume, respectively. CONCLUSIONS: To the best of our knowledge, this is the first report on the comparison of clinically treated liver BT treatments with virtually planned SBRT treatments. The planning study showed a superior outcome of BT regarding dose coverage of the target volume and exposed liver volume. Nevertheless, further studies are needed to determine ideal applicability for each treatment approach.