Noninvasive inter- and intrafractional motion control in ultrahypofractionated radiation therapy of prostate cancer using RayPilot HypoCath™-a substitute for gold fiducial-based IGRT?

PURPOSE: In ultrahypofractionated radiation concepts, managing of intrafractional motion is mandatory because tighter margins are used and random errors resulting from prostate movement are not averaged out over a large number of fractions. Noninvasive live monitoring of prostate movement is a desirable asset for LINAC-based prostate stereotactic body radiation therapy (SBRT). METHODS: We prospectively analyzed a novel live tracking device (RayPilot HypoCath™; Micropos Medical AB, Gothenburg, Sweden) where a transmitter is noninvasively positioned in the prostatic urethra using a Foley catheter in 12 patients undergoing ultrahypofractionated intensity-modulated radiation therapy (IMRT) of the prostate. Gold fiducials (Innovative Technology Völp, Innsbruck, Austria) were implanted to allow comparison of accuracy and positional stability of the HypoCath system and its ability to be used as a standalone IGRT method. Spatial stability of the transponder was assessed by analyzing transmitter movement in relation to gold markers (GM) in superimposed kV image pairs. Inter- and intrafractional prostate movement and the impact of its correction were analyzed. RESULTS: A total of 64 fractions were analyzed. The average resulting deviation vector compared to the GM-based position was 1.2 mm and 0.7 mm for inter- and intrafractional motion, respectively. The mean intrafractional displacement vector of the prostate was 1.9 mm. Table readjustment due to exceeding the threshold of 3 mm was required in 18.8% of fractions. Repositioning reduced the time spent outside the 3­mm margin from 7.9% to 3.8% of beam-on time. However, for individual patients, the time spent outside the 3­mm margin was reduced from to 49% to 19%. CONCLUSION: the HypoCath system allows highly accurate and robust intrafractional motion monitoring. In conjunction with cone beam CT (CBCT) for initial patient setup, it could be used as a standalone image-guided radiation therapy (IGRT) system.

First clinical application of image-guided intraoperative electron radiation therapy with real time intraoperative dose calculation in recurrent rectal cancer: technical procedure.

Intraoperative radiation therapy (IORT) is a radiation technique applying a single fraction with a high dose during surgery. We report the first abdomino-pelvic application of an image-guided intraoperative electron radiation therapy with intraoperative real time dose calculation based on the individual intraoperative patient anatomy. A patient suffering from locoregionally recurrent rectal cancer after treatment with neoadjuvant re-chemoradiation was chosen for this approach. After surgical removal of the recurrence, an adequate IORT applicator was placed as usual. A novel mobile imaging device (ImagingRing, MedPhoton) was positioned around the patient covering the region to be treated with the IORT-applicator in place. It allowed the acquisition of three-dimensional intraoperative cone-beam computed tomography images suitable for dose calculation using an automated scaling (heuristic object and head scatter as well as hardening corrections) of Hounsfield units. After image acquisition confirmed the correct applicator position, the images were transferred to our treatment planning system for intraoperative dose calculation. Treatment could be accomplished using the calculated dose distribution. We herein describe the details of the procedure including necessary adjustments in the typically used IORT equipment and work flow. We further discuss the pros and cons of this new approach generally overcoming a decade long limitation of IORT procedures as well as future perspectives regarding IORT treatments.

Pretreatment 18-FDG-PET/CT parameters can serve as prognostic imaging biomarkers in recurrent NSCLC patients treated with reirradiation-chemoimmunotherapy.

BACKGROUND AND PURPOSE: Our study aimed to assess whether quantitative pretreatment 18F-FDG-PET/CT parameters could predict prognostic clinical outcome of recurrent NSCLC patients who may benefit from ablative reirradiation. MATERIALS AND METHODS: Forty-eight patients with recurrent NSCLC of all UICC stages who underwent ablative thoracic reirradiation were analyzed. Twenty-nine (60%) patients received immunotherapy with or without chemotherapy in addition to reirradiation. Twelve patients (25%) received reirradiation only and seven (15%) received chemotherapy and reirradiation. Pretreatment 18-FDG-PET/CT was mandatory in initial diagnosis and recurrence, based on which volumetric and intensity quantitative parameters were measured before reirradiation and their impact on overall survival, progression-free survival, and locoregional control was assessed. RESULTS: With a median follow-up time of 16.7 months, the median OS was 21.8 months (95%-CI: 16.2-27.3). On multivariate analysis, OS and PFS were significantly influenced by MTV (p < 0.001 for OS; p = 0.006 for PFS), TLG (p < 0.001 for OS; p = 0.001 for PFS) and SUL peak (p = 0.0024 for OS; p = 0.02 for PFS) of the tumor and MTV (p = 0.004 for OS; p < 0.001 for PFS) as well as TLG (p = 0.007 for OS; p = 0.015 for PFS) of the metastatic lymph nodes. SUL peak of the tumor (p = 0.05) and the MTV of the lymph nodes (p = 0.003) were only PET quantitative parameters that significantly impacted LRC. CONCLUSION: Pretreatment tumor and metastastic lymph node MTV, TLG and tumor SUL peak significantly correlated with clinical outcome in recurrent NSCLC patients treated with reirradiation-chemoimmunotherapy.

Chemo-Radio-Immunotherapy for NSCLC III: ESR/ATS Thresholds for DLCO Correlate with Radiation Dosimetry and Pneumonitis Rate.

INTRODUCTION: Durvalumab following chemoradiotherapy (CRT) for non-small cell lung cancer stage III has become the standard of care (SoC) in the past few years. With this regimen, 5-year overall survival (OS) has risen to 43%. Therefore, adequate pulmonary function (PF) after treatment is paramount in long-term survivors. In this respect, carbon monoxide diffusing capacity (DLCO), which represents the alveolar compartment, seems to be a suitable measure for residual lung capacity. The aim of the current analysis was to correlate DLCO with pneumonitis and radiation dose. PATIENTS AND METHODS: One hundred and twelve patients with histologically confirmed NSCLC III treated between 2015/10 and 2022/03 were eligible for this study. Patients received two cycles of platinum-based induction chemotherapy followed by high-dose radiotherapy (RT). As of 2017/09, durvalumab maintenance therapy was administered for one year. The clinical endpoints were based on the thresholds jointly published by the European Respiratory Society (ERS) and the American Thoracic Society (ATS). Pre-treatment DLCO of 60% was correlated to the incidence of pneumonitis, whereas the post-treatment DLCO decline of 10% was related to radiation dose. RESULTS: Patients with a pre-treatment DLCO < 60% had a higher probability of pneumonitis (n = 98; r = 0.175; p-value 0.042), which could be reproduced in the subgroup of patients who did not receive durvalumab (n = 40; r = 0.288; p-value 0.036). In these individuals, the decline in DLCO ≥ 10% depended significantly on the size of the lung volume receiving between 45% and 65% (V65-45%) of the total radiation dose (r = 0.354; p-value = 0.020) and V20 Total Lung (r = 0.466; corrected p-value = 0.042). CONCLUSIONS: The current analysis revealed that DLCO is a predictor for clinically relevant pneumonitis and a monitoring tool for post-treatment lung function as it correlates with radiation dose. This underlines the importance of peri-treatment lung function testing.

How We Treat Localized Rectal Cancer-An Institutional Paradigm for Total Neoadjuvant Therapy.

Total neoadjuvant therapy (TNT)-the neoadjuvant employment of radiotherapy (RT) or chemoradiation (CRT) as well as chemotherapy (CHT) before surgery-may lead to increased pathological complete response (pCR) rates as well as a reduction in the risk of distant metastases in locally advanced rectal cancer. Furthermore, increased response rates may allow organ-sparing strategies in a growing number of patients with low rectal cancer and upfront immunotherapy has shown very promising early results in patients with microsatellite instability (MSI)-high/mismatch-repair-deficient (dMMR) tumors. Despite the lack of a generally accepted treatment standard, we strongly believe that existing data is sufficient to adopt the concept of TNT and immunotherapy in clinical practice. The treatment algorithm presented in the following is based on our interpretation of the current data and should serve as a practical guide for treating physicians-without any claim to general validity.

Durvalumab after Sequential High Dose Chemoradiotherapy versus Standard of Care (SoC) for Stage III NSCLC: A Bi-Centric Trospective Comparison Focusing on Pulmonary Toxicity.

Introduction: The standard of care (SoC) for unresectable stage III non-small-cell lung cancer (NSCLC) is durvalumab maintenance therapy after concurrent chemoradiation in patients with PD-L1 > 1%. However, the concurrent approach is only amenable for about one-third of patients due to co-morbidities. Although sequential regimens are usually not regarded as curative, these schedules applied in a dose-escalated manner may be similarly radical as SoC. As combining high-dose radiation and durvalumab remains a question of debate this retrospective bi-center study aims to evaluate pulmonary toxicity after high-dose chemoradiotherapy beyond 70 Gy compared to SoC. Patients and Methods: Patients with NSCLC stage III received durvalumab after either sequential high-dose chemoradiation or concomitant SoC. Chemotherapy consisted of platinum combined with either pemetrexed, taxotere, vinorelbine, or gemcitabine. The primary endpoint was short-term pulmonary toxicity occurring within six months after the end of radiotherapy (RT). Results: A total of 78 patients were eligible for this analysis. 18F-FDG-PET-CT, cranial MRT, and histological/cytological verification were mandatory in the diagnostic work-up. The high-dose and SoC group included 42/78 (53.8%) and 36/78 (46.2%) patients, respectively, which were matched according to baseline clinical variables. While the interval between the end of RT and the start of durvalumab was equal in both groups (p = 0.841), more courses were administered in the high-dose cohort (p = 0.031). Pulmonary toxicity was similar in both groups (p = 0.599), whereas intrathoracic disease control was better in the high-dose group (local control p = 0.081, regional control p = 0.184). Conclusion: The data of this hypothesis-generating study suggest that sequential high-dose chemoradiation followed by durvalumab might be similar to SoC in terms of pulmonary toxicity and potentially more effective with respect to intra-thoracic disease control. Larger trials with a prospective design are warranted to validate these results.

Radiotherapy for hormone-sensitive prostate cancer with synchronous low burden of distant metastases.

PURPOSE: The DEGRO Expert Commission on Prostate Cancer has revised the indication for radiation therapy of the primary prostate tumor in patients with synchronous distant metastases with low metastatic burden. METHODS: The current literature in the PubMed database was reviewed regarding randomized evidence on radiotherapy of the primary prostate tumor with synchronous low metastatic burden. RESULTS: In total, two randomized trials were identified. The larger study, the STAMPEDE trial, demonstrated an absolute survival benefit of 8% after 3 years for patients with low metastatic burden treated with standard of care (SOC) and additional radiotherapy (RT) (EQD2 ≤ 72 Gy) of the primary tumor. Differences in the smaller Horrad trial were not statistically significant, although risk reduction in the subgroup (< 5 bone metastases) was equal to STAMPEDE. The STOPCAP meta-analysis of both trials demonstrated the benefit of local radiotherapy for up to 4 bone lesions and an additional subanalysis of STAMPEDE also substantiated this finding in cases with M1a-only metastases. CONCLUSION: Therefore, due to the survival benefit after 3 years, current practice is changing. New palliative SOC is radiotherapy of the primary tumor in synchronously metastasized prostate cancer with low metastatic burden (defined as ≤ 4 bone metastases, with or without distant nodes) or in case of distant nodes only detected by conventional imaging.

Carbon Monoxide Diffusing Capacity (DLCO) Correlates with CT Morphology after Chemo-Radio-Immunotherapy for Non-Small Cell Lung Cancer Stage III.

Introduction: Curatively intended chemo-radio-immunotherapy for non-small cell lung cancer (NSCLC) stage III may lead to post-therapeutic pulmonary function (PF) impairment. We hypothesized that the decrease in global PF corresponds to the increase in tissue density in follow-up CTs. Hence, the study aim was to correlate the dynamics in radiographic alterations to carbon monoxide diffusing capacity (DLCO) and FEV1, which may contribute to a better understanding of radiation-induced lung disease. Methods: Eighty-five patients with NSCLC III were included. All of them received two cycles of platinum-based induction chemotherapy followed by high dose radiation. Thereafter, durvalumab was administered for one year in 63/85 patients (74%). Pulmonary function tests (PFTs) were performed three months and six months after completion of radiotherapy (RT) and compared to baseline. At the same time points, patients underwent diagnostic CT (dCT). These dCTs were matched to the planning CT (pCT) using RayStation® Model Based Segmentation and deformable image registration. Differential volumes defined by specific isodoses were generated to correlate them with the PFTs. Results: In general, significant correlations between PFTs and differential volumes were found in the mid-dose range, especially for the volume of the lungs receiving between 65% and 45% of the dose prescribed (V65−45%) and DLCO (p<0.01). This volume range predicted DLCO after RT (p-value 0.03) as well. In multivariate analysis, DLCO (p-value 0.040) and FEV1 (p-value 0.014) predicted pneumonitis. Conclusions: The current analysis revealed a strong relation between the dynamics of DLCO and CT morphology changes in the mid-dose range, which convincingly indicates the importance of routinely used PFTs in the context of a curative treatment approach.

Oligometastasis in breast cancer-current status and treatment options from a radiation oncology perspective.

Evidence from a few small randomized trials and retrospective cohorts mostly including various tumor entities indicates a prolongation of disease free survival (DFS) and overall survival (OS) from local ablative therapies in oligometastatic disease (OMD). However, it is still unclear which patients benefit most from this approach. We give an overview of the several aspects of stereotactic body radiotherapy (SBRT) in extracranial OMD in breast cancer from a radiation oncology perspective. A PubMed search referring to this was conducted. An attempt was made to relate the therapeutic efficacy of SBRT to various prognostic factors. Data from approximately 500 breast cancer patients treated with SBRT for OMD in mostly in small cohort studies have been published, consistently indicating high local tumor control rates and favorable progression-free (PFS) and overall survival (OS). Predictors for a good prognosis after SBRT are favorable biological subtype (hormone receptor positive, HER2 negative), solitary metastasis, bone-only metastasis, and long metastasis-free interval. However, definitive proof that SBRT in OMD breast cancer prolongs DFS or OS is lacking, since, with the exception of one small randomized trial (n = 22 in the SBRT arm), none of the cohort studies had an adequate control group. Further studies are needed to prove the benefit of SBRT in OMD breast cancer and to define adequate selection criteria. Currently, the use of local ablative SBRT should always be discussed in a multidisciplinary tumor board.

Long-Term Results of the TARGIT-A Trial: More Questions than Answers.

Background: During the last decade, partial breast irradiation (PBI) has gained traction as a relevant treatment option for patients with early-stage low-risk breast cancer after breast-conserving surgery. The TARGIT-A prospective randomized trial compared a "risk-adapted" intraoperative radiotherapy (IORT) approach with 50-kv X-rays (INTRABEAM®) as the PBI followed by optional whole-breast irradiation (WBI) and conventional adjuvant WBI in terms of observed 5-year in-breast recurrence rates. Recently, long-term data were published. Since the first publication of the TARGIT-A trial, a broad debate has been emerged regarding several uncertainties and limitations associated with data analysis and interpretation. Our main objective was to summarize the data, with an emphasis on the updated report and the resulting implications. Summary: From our point of view, the previously unresolved questions still remain and more have been added, especially with regard to the study design, a change in the primary outcome measure, the significant number of patients lost to follow-up, and the lack of a subgroup analysis according to risk factors and treatment specifications. Key Message: Taking into account the abovementioned limitations of the recently published long-term results of the TARGIT-A trial, the German Society of Radiation Oncology (DEGRO) Breast Cancer Expert Panel adheres to its recently published recommendations on PBI: "the 50-kV system (INTRABEAM) cannot be recommended for routine adjuvant PBI treatment after breast-conserving surgery."

Hypofractionated Whole Breast Irradiation and Boost-IOERT in Early Stage Breast Cancer (HIOB): First Clinical Results of a Prospective Multicenter Trial (NCT01343459).

Background and purpose: To investigate intraoperative electron radiation therapy (IOERT) as a tumor bed boost during breast conserving surgery (BCS) followed by hypofractionated whole breast irradiation (HWBI) on age-correlated in-breast recurrence (IBR) rates in patients with low- to high-risk invasive breast cancer. Material and methods: BCS and IOERT (11.1 Gy) preceded a HWBI (40.5 Gy) in 15 fractions. Five-year IBR-rates were compared by a sequential ratio test (SQRT) with best evidences in three age groups (35−40 y and 41−50 y: 3.6%, >50 y: 2%) in a prospective single arm design. Null hypothesis (H0) was defined to undershoot these benchmarks for proof of superiority. Results: Of 1445 enrolled patients, 326 met exclusion criteria, leaving 1119 as eligible for analysis. After a median follow-up of 50 months (range 0.7−104), we detected two local recurrences, both in the age group >50 y. With no observed IBR, superiority was demonstrated for the patient groups 41−50 and >50 y, respectively. For the youngest group (35−40 y), no appropriate statistical evaluation was yet possible due to insufficient recruitment. Conclusions: In terms of five-year IBR-rates, Boost-IOERT followed by HWBI has been demonstrated to be superior in patients older than 50 and in the age group 41−50 when compared to best published evidence until 2010.

High Dose Thoracic Re-Irradiation and Chemo-Immunotherapy for Centrally Recurrent NSCLC.

INTRODUCTION: Thoracic re-irradiation for recurrent lung cancer dates back four decades, when the first small series on 29 patients receiving palliative doses was published. With 5-year overall survival rates of 57% in PDL-1 positive patients after primary chemo-radio-immunotherapy, the number of patients who experience loco-regional relapse will increase in the near future. In this context, centrally recurring lung tumors pose a major treatment challenge. Hence, the aim of the current review is to compile the available evidence on curatively intended thoracic re-irradiation for this special clinical situation. METHODS: A systematic literature search according to the PRISMA guidelines was performed. A study was included when the following criteria were met: (1) 66% of the patients had NSCLC, (2) a total dose of 50 Gy in the second course and/or a biologically effective dose of at least 100 Gy in both treatment courses was administered, (3) re-irradiation was administered with modern radiation techniques, (4) 50% or more of the patients had a centrally located relapse, (5) the minimum cohort size was 30 patients. RESULTS: Of the initial 227 studies, 11 were analyzed, 1 of which was prospective. Median overall survival (OS) was 18.1 months (range 9.3-25.1), median progression free survival (PFS) was nine months (range 4.5-16), and median loco-regional control (LRC) was 12.1 months (range 6.5-20). Treatment-related mortality rates ranged from 2% to 14%. The total dose at re-irradiation correlated with both LRC (p-value = 0.012) and OS (p-value = 0.007) with a close relation between these two clinical endpoints (p-value = 0.006). The occurrence of acute toxicity grade 1 to 4 depended on the PTV size at re-irradiation (p-value = 0.033). CONCLUSION: The evidence regarding curative re-irradiation for centrally recurrent NSCLC is primarily based on scarce retrospective data, which are characterized by a high degree of heterogeneity. The OS in this clinically challenging situation is expected to be around 1.5 years after re-treatment. Patients with a good performance score, younger age, small tumors, and a longer interval to recurrence potentially benefit most from re-irradiation. In this context, prospective trials are warranted to achieve substantial advances in the field.

Hsa-miR-3651 could serve as a novel predictor for in-breast recurrence via FRMD3.

BACKGROUND: MicroRNAs are small non-coding RNAs with pivotal regulatory functions in multiple cellular processes. Their significance as molecular predictors for breast cancer was demonstrated in the past 15 years. The aim of this study was to elucidate the role of hsa-miR-3651 for predicting of local control (LC) in early breast cancer. RESULTS: By means of high-throughput technology, hsa-miR-3651 was found to be differentially expressed between patients who experienced local relapse compared to those without (N = 23; p = 0.0035). This result could be validated in an independent cohort of 87 patients using RT-qPCR (p < 0.0005). In a second analysis step with a chip-based microarray containing 70,523 probes of potential target molecules, FERM domain protein 3 (FRMD3) was found to be the most down-regulated protein (N = 21; p = 0.0016). Computational analysis employing different prediction algorithms revealed FRMD3 as a likely downstream target of hsa-miR-3651 with an 8mer binding site between the two molecules. This could be validated in an independent patient set (N = 20, p = 0.134). CONCLUSION: The current study revealed that hsa-miR-3651 is a predictor of LC in early breast cancer via its putative target protein FRMD3. Since microRNAs interfere in multiple pathways, the results of this hypothesis generating study may contribute to the development of tailored therapies for breast cancer in the future.

Moderately hypofractionated radiotherapy as definitive treatment for localized prostate cancer: Pattern of practice in German-speaking countries : A survey of the Prostate Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO) and the Working Party on Radiation Oncology of the German Cancer Society (DKG-ARO).

PURPOSE: Various randomized phase III clinical trials have compared moderately hypofractionated to normofractionated radiotherapy (RT). These modalities showed similar effectiveness without major differences in toxicity. This project was conducted by the Prostate Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO) and the Working Party on Radiation Oncology of the German Cancer Society. We aimed to investigate expert opinions on the use of moderately hypofractionated RT as a definitive treatment for localized prostate cancer in German-speaking countries. METHODS: A 25-item, web-based questionnaire on moderate-hypofractionation RT was prepared by an internal committee. The experts of the DEGRO were asked to complete the questionnaire. RESULTS: Fourteen active members of DEGRO completed the questionnaire. The questions described indications for selecting patients eligible to receive moderate hypofractionation based on clinical and pathological factors such as age, urinary symptoms, and risk-group. The questions also collected information on the technical aspects of selection criteria, including the definition of a clinical target volume, the use of imaging, protocols for bladder and rectal filling, the choice of a fractionation schedule, and the use of image guidance. Moreover, the questionnaire collected information on post-treatment surveillance after applying moderately hypofractionated RT. CONCLUSION: Although opinions varied on the use of moderate-hypofractionation RT, the current survey reflected broad agreement on the notion that moderately hypofractionated RT could be considered a standard treatment for localized prostate cancer in German-speaking countries.

Re-Irradiation for Locally Recurrent Lung Cancer: A Single Center Retrospective Analysis.

The treatment of locally recurrent lung cancer is a major challenge for radiation-oncologists, especially with data on high-dose reirradiation being limited to small retrospective studies. The aim of the present study is to assess overall survival (OS) for patients with locally recurrent lung cancer after high-dose thoracic reirradiation. Thirty-nine patients who were re-irradiated for lung cancer relapse between October 2013 and February 2019 were eligible for the current retrospective analysis. All patients were re-irradiated with curative intent for in-field tumor recurrence. The diagnostic work-up included a mandatory 18F-FDG-PET-CT scan and-if possible-histological verification. The ECOG was ≤2, and the interval between initial and second radiation was at least nine months. Thirty patients (77%) had non-small cell lung cancer (NSCLC), eight (20%) had small cell lung cancer (SCLC), and in one patient (3%) histological confirmation could not be obtained. More than half of the patients (20/39, 51%) received re-treatment with dose differentiated accelerated re-irradiation (DART) at a median interval of 20.5 months (range: 6-145.3 months) after the initial radiation course. A cumulative EQD2 of 131 Gy (range: 77-211 Gy) in a median PTV of 46 mL (range: 4-541 mL) was delivered. Patients with SCLC had a 3 mL larger median re-irradiation volume (48 mL, range: 9-541) compared to NSCLC patients (45 mL, range: 4-239). The median cumulative EQD2 delivered in SCLC patients was 84 Gy (range: 77-193 Gy), while NSCLC patients received a median cumulative EQD2 of 135 Gy (range: 98-211 Gy). The median OS was 18.4 months (range: 0.6-64 months), with tumor volume being the only predictor (p < 0.000; HR 1.007; 95%-CI: 1.003-1.012). In terms of toxicity, 17.9% acute and 2.6% late side effects were observed, with a toxicity grade >3 occurring in only one patient. Thoracic high dose reirradiation plays a significant role in prolonging survival, especially in patients with small tumor volume at recurrence.

IOERT versus external beam electrons for boost radiotherapy in stage I/II breast cancer: 10-year results of a phase III randomized study.

BACKGROUND: Intraoperative radiotherapy with electrons (IOERT) boost could be not inferior to external beam radiotherapy (EBRT) boost in terms of local control and tissue tolerance. The aim of the study is to present the long-term follow-up results on local control, esthetic evaluation, and toxicity of a prospective study on early-stage breast cancer patients treated with breast-conserving surgery with an IOERT boost of 10 Gy (experimental group) versus 5 × 2 Gy EBRT boost (standard arm). Both arms received whole-breast irradiation (WBI) with 50 Gy (2 Gy single dose). METHODS: A single-institution phase III randomized study to compare IOERT versus EBRT boost in early-stage breast cancer was conducted as a non-inferiority trial. Primary endpoints were the evaluation of in-breast true recurrences (IBTR) and out-field local recurrences (LR) as well as toxicity and cosmetic results. Secondary endpoints were overall survival (OS), disease-free survival (DFS), and patient's grade of satisfaction with cosmetic outcomes. RESULTS: Between 1999 and 2004, 245 patients were randomized: 133 for IOERT and 112 for EBRT. The median follow-up was 12 years (range 10-16 years). The cumulative risk of IBTR at 5-10 years was 0.8% and 4.3% after IOERT, compared to 4.2% and 5.3% after EBRT boost (p = 0.709). The cumulative risk of out-field LR at 5-10 years was 4.7% and 7.9% for IOERT versus 5.2% and 10.3% for EBRT (p = 0.762). All of the IOERT arm recurrences were observed at > 100 months' follow-up, whereas the mean time to recurrence in the EBRT group was earlier (55.2 months) (p < 0.05). No late complications associated with IOERT were observed. The overall cosmetic results were scored as good or excellent in physician and patient evaluations for both IOERT and EBRT. There were significantly better scores for IOERT at all time points in physician and patient evaluations with the greatest difference at the end of EBRT (p = 0.006 objective and p = 0.0004 subjective) and most narrow difference at 12 months after the end of EBRT (p = 0.08 objective and p = 0.04 subjective analysis). CONCLUSION: A 10-Gy IOERT boost during breast-conserving surgery provides high local control rates without significant morbidity. Although not significantly superior to external beam boosts, the median time to local recurrences after IOERT is prolonged by more than 4 years.

Radiotherapy in nodal oligorecurrent prostate cancer.

OBJECTIVE: The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. MATERIALS AND METHODS: A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. RESULTS: Metastasis-directed radiotherapy results in high local control (often > 90% within a follow-up of 1-2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. CONCLUSION: ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations.