DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer.

PURPOSE: The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis. MATERIALS AND METHODS: For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation). CONCLUSION AND RECOMMENDATIONS: Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1-4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5-10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8-12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting.

Pharmaceutical management of acute radiation dermatitis in the German speaking radiation oncology community.

BACKGROUND: Radiation dermatitis (RD) remains the most common side effect in radiation therapy (RT) with various pharmaceutical options available for prevention and treatment. We sought to determine pharmaceutical management patterns of radiation dermatitis among radiation oncology professionals. METHODS: We conducted a survey on RD among the German-speaking community of radiation oncologists inquiring for their opinion on preventive and therapeutic pharmaceutical approaches for acute RD. RESULTS: 244 health professionals participated. Dexpanthenol lotion is the agent most widely used both for prevention (53.0%) and treatment (76.9%) of RD, followed by urea (29.8%) for prevention and corticosteroids (46.9%) for treatment. A wide range of substances is used by participants, though the overall experience with them is rather limited. 32.5% of participants do generally not recommend any preventative treatment. 53.4% of participants recommend alternative medicine for RD management. While seldomly used, corticosteroids were considered most effective in RD therapy, followed by dexpanthenol and low-level laser therapy. A majority of participants prefers moist over dry treatment of moist desquamation and 43.8% prescribe antiseptics. CONCLUSIONS: Pharmaceutical management of RD in the German-speaking radiation oncology community remains controversial, inconsistent, and partially not supported by evidence-based medicine. Stronger evidence level and interdisciplinary consensus is required amongst practitioners to improve these care patterns.

Risk assessment, surveillance, and nonpharmaceutical prevention of acute radiation dermatitis: results of a multicentric survey among the German-speaking radiation oncology community.

PURPOSE: Radiation dermatitis (RD) represents one of the most frequent side effects in radiotherapy (RT). Despite technical progress, mild and moderate RD still affects major subsets of patients and identification and management of patients with a high risk of severe RD is essential. We sought to characterize surveillance and nonpharmaceutical preventive management of RD in German-speaking hospitals and private centers. METHODS: We conducted a survey on RD among German-speaking radiation oncologists inquiring for their evaluation of risk factors, assessment methods, and nonpharmaceutical preventive management of RD. RESULTS: A total of 244 health professionals from public and private institutions in Germany, Austria, and Switzerland participated in the survey. RT-dependent factors were deemed most relevant for RD onset followed by lifestyle factors, emphasizing the impact of treatment conceptualization and patient education. While a broad majority of 92.8% assess RD at least once during RT, 59.0% of participants report RD at least partially arbitrarily and 17.4% stated to classify RD severity solely arbitrarily. 83.7% of all participants were unaware of patient-reported outcomes (PROs). Consensus exists on some lifestyle recommendations like avoidance of sun exposure (98.7%), hot baths (95.1%), and mechanical irritation (91.8%) under RT, while deodorant use (63.4% not at all, 22.1% with restrictions) or application of skin lotion (15.1% disapproval) remain controversial and are not recommended by guidelines or evidence-based practices. CONCLUSION: Identification of patients at an increased risk of RD and subsequent implementation of adequate preventive measures remain relevant and challenging aspects of clinical routines. Consensus exists on several risk factors and nonpharmaceutical prevention recommendations, while RT-dependent risk factors, e.g., the fractionation scheme, or hygienic measures like deodorant use remain controversial. Surveillance is widely lacking methodology and objectivity. Intensifying outreach in the radiation oncology community is needed to improve practice patterns.

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.

Adjuvant hypofractionated radiotherapy with simultaneous integrated boost after breast-conserving surgery: results of a prospective trial.

PURPOSE: We report results of a multicenter prospective single-arm phase II trial (ARO-2013-04, NCT01948726) of moderately accelerated hypofractionated radiotherapy with a simultaneous integrated boost (SIB) in patients with breast cancer receiving adjuvant radiotherapy after breast-conserving surgery. METHODS: The eligibility criteria included unifocal breast cancer with an indication for adjuvant radiotherapy to the whole breast and boost radiotherapy to the tumor bed. The whole breast received a dose of 40 Gy and the tumor bed a total dose of 48 Gy in 16 fractions of 2.5 and 3 Gy, respectively. Radiotherapy could be given either as 3D conformal RT (3D-CRT) or as intensity-modulated radiotherapy (IMRT). The study was designed as a prospective single-arm trial to evaluate the acute toxicity of the treatment regimen. The study hypothesis was that the frequency of acute skin reaction grade ≥2 would be 20% or less. RESULTS: From November 2013 through July 2014, 149 patients were recruited from 12 participating centers. Six patients were excluded, leaving 143 patients for analysis. Eighty-four patients (58.7%) were treated with 3D-CRT and 59 (41.3%) with IMRT. Adherence to the treatment protocol was high. The rate of grade ≥2 skin toxicity was 14.7% (95% confidence interval 9.8-21.4%). The most frequent grade 3 toxicity (11%) was hot flashes. CONCLUSION: This study demonstrated low toxicity of and high treatment adherence to hypofractionated adjuvant radiotherapy with SIB in a multicenter prospective trial, although the primary hypothesis was not met.

Post-neoadjuvant treatment with capecitabine and trastuzumab emtansine in breast cancer patients-sequentially, or better simultaneously?

PURPOSE: Following neoadjuvant chemotherapy for breast cancer, postoperative systemic therapy, also called post-neoadjuvant treatment, has been established in defined risk settings. We reviewed the evidence for sequencing of postoperative radiation and chemotherapy, with a focus on a capecitabine and trastuzumab emtansine (T-DM1)-based regimen. METHODS: A systematic literature search using the PubMed/MEDLINE/Web of Science database was performed. We included prospective and retrospective reports published since 2015 and provided clinical data on toxicity and effectiveness. RESULTS: Six studies were included, five of which investigated capecitabine-containing regimens. Of these, four were prospective investigations and one a retrospective matched comparative analysis. One randomized prospective trial was found for T­DM1 and radiotherapy. In the majority of these reports, radiation-associated toxicities were not specifically addressed. CONCLUSION: Regarding oncologic outcome, the influence of sequencing radiation therapy with maintenance capecitabine chemotherapy in the post-neoadjuvant setting is unclear. Synchronous administration of capecitabine is feasible, but reports on possible excess toxicities are partially conflicting. Dose reduction of capecitabine should be considered, especially if normofractionated radiotherapy is used. In terms of tolerance, hypofractionated schedules seem to be superior in terms of toxicity in concurrent settings. T­DM1 can safely be administered concurrently with radiotherapy.

Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward.

Moderate hypofractionation is the standard of care for adjuvant whole-breast radiotherapy after breast-conserving surgery for breast cancer. Recently, 10-year results from the FAST and 5­year results from the FAST-Forward trial evaluating adjuvant whole-breast radiotherapy in 5 fractions over 5 weeks or 1 week have been published. This article summarizes recent data for moderate hypofractionation and results from the FAST and FAST-Forward trial on ultra-hypofractionation. While the FAST trial was not powered for comparison of local recurrence rates, FAST-Forward demonstrated non-inferiority for two ultra-hypofractionated regimens in terms of local control. In both trials, the higher-dose experimental arms resulted in elevated rates of late toxicity. For the lower dose experimental arms of 28.5 Gy over 5 weeks and 26 Gy over 1 week, moderate or marked late effects were similar in the majority of documented items compared to the respective standard arms, but significantly worse in some subdomains. The difference between the standard arm and the 26 Gy of the FAST-Forward trial concerning moderate or marked late effects increased with longer follow-up in disadvantage of the experimental arm for most items. For now, moderate hypofractionation with 40-42.5 Gy over 15-16 fractions remains the standard of care for the majority of patients with breast cancer who undergo whole-breast radiotherapy without regional nodal irradiation after breast-conserving surgery.

Heart-sparing radiotherapy techniques in breast cancer patients: a recommendation of the breast cancer expert panel of the German society of radiation oncology (DEGRO).

PURPOSE: The aim of this review was to analyze the respective efficacy of various heart-sparing radiotherapy techniques. MATERIAL AND METHODS: Heart-sparing can be performed in three different ways in breast cancer radiotherapy: by seeking to keep the heart out of treated volumes (i.e. by prone position or specific breathing techniques such as deep inspiration breath-hold [DIBH] and/or gating), by solely irradiating a small volume around the lumpectomy cavity (partial breast irradiation, PBI), or by using modern radiation techniques like intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) or protons. This overview presents the available data on these three approaches. RESULTS: Studies on prone position are heterogeneous and most trials only refer to patients with large breasts; therefore, no definitive conclusion can be drawn for clinical routine. Nonetheless, there seems to be a trend toward better sparing of the left anterior descending artery in supine position even for these selected patients. The data on the use of DIBH for heart-sparing in breast cancer patients is consistent and the benefit compared to free-breathing is supported by several studies. In comparison with whole breast irradiation (WBI), PBI has an advantage in reducing the heart dose. Of note, DIBH and PBI with multicatheter brachytherapy are similar with regard to the dose reduction to heart structures. WBI by IMRT/VMAT techniques without DIBH is not an effective strategy for heart-sparing in breast cancer patients with "standard" anatomy. A combination of DIBH and IMRT may be used for internal mammary radiotherapy. CONCLUSION: Based on the available findings, the DEGRO breast cancer expert panel recommends the use of DIBH as the best heart-sparing technique. Nonetheless, depending on the treatment volume and localization, other techniques may be employed or combined with DIBH when appropriate.

Radiotherapy after skin-sparing mastectomy with immediate breast reconstruction in intermediate-risk breast cancer : Indication and technical considerations.

BACKGROUND: Skin-sparing (SSME) and nipple-sparing mastectomy (NSME) were developed to improve the cosmetic results for breast cancer (BC) patients, both allowing for immediate breast reconstruction. Recommendations for post-mastectomy radiotherapy (PMRT) are primarily derived from trials where patients were treated by standard mastectomies. Due to their more conservative character, SSME and especially NSME potentially leave more glandular tissue at risk for subclinical disease. METHODS: Rates and sites of locoregional failures following SSME and NSME plus/minus reconstruction were analyzed regarding tumor stage and biological risk factors. In particular, the role of PMRT in "intermediate"-risk and early stage high-risk breast cancer patients was revisited. Implications on targeting and dose delivery of PMRT were critically reviewed. RESULTS: The value of PMRT in stage III BC remains undisputed. For node-negative BC patients, the majority of reports classify clinical and biological features such as tumor size, close surgical margins, premenopausal status, multicentricity, lymphangiosis, triple-negativity, HER2-overexpression, and poor tumor grading as associated with higher rates of locoregional relapse, thus, building an "intermediate" risk group. Surveys revealed that the majority of radiation oncologists use risk-adaptive models also considering the number of coinciding factors for the estimation of recurrence probability following SSME and NSME. Constellations with a 10-year locoregional recurrence risk of >10% are usually triggering the indication for PMRT. There was no common belief that the amount of residual tissue, e.g., tissue thickness over flaps, serves as additional decision aid. Modern treatment planning can ensure optimal dose distribution for PMRT in almost all patients with SSME. There are no reliable data supporting a reduction of the treatment volume from the CTV chest wall, e.g., to the nipple-areola complex, to the dorsal aspect behind the implant volume, the pectoralis muscle, nor the regional interpectoral, axillary, or complete regional lymph nodes only. The omission of a skin bolus in intermediate-risk BC does not compromise oncological safety. CONCLUSIONS: For intermediate-risk as well as early stage high-risk BC patients, the DEGRO Breast Cancer Expert Panel recommends the use of PMRT following SSME and NSME when a 10-year locoregional recurrence risk is likely to be greater than 10%, as estimated by clinical and biological risk factors. Subvolume-only radiation is discouraged outside of trials. The impact of adequate systemic treatment and the value of radiotherapy on optimal locoregional tumor control, with the goal of less than 5% LRR at 10-years follow-up, has to be verified in prospective trials.

Heart toxicity from breast cancer radiotherapy : Current findings, assessment, and prevention.

BACKGROUND: Late cardiac toxicities caused by (particularly left-sided) breast radiotherapy (RT) are now recognized as rare but relevant sequelae, which has prompted research on risk structure identification and definition of threshold doses to heart subvolumes. The aim of the present review was to critically discuss the clinical evidence on late cardiac reactions based on dose-dependent outcome reports for mean heart doses as well as doses to cardiac substructures. METHODS: A literature review was performed to examine clinical evidence on radiation-induced heart toxicities. Mean heart doses and doses to cardiac substructures were focused upon based on dose-dependent outcome reports. Furthermore, an overview of radiation techniques for heart protection is given and non-radiotherapeutic aspects of cardiotoxicity in the multimodal setting of breast cancer treatment are discussed. RESULTS: Based on available findings, the DEGRO breast cancer expert panel recommends the following constraints: mean heart dose <2.5 Gy; DmeanLV (mean dose left ventricle) < 3 Gy; V5LV (volume of LV receiving ≥5 Gy) < 17%; V23LV (volume of LV receiving ≥23 Gy) < 5%; DmeanLAD (mean dose left descending artery) < 10 Gy; V30LAD (volume of LAD receiving ≥30 Gy) < 2%; V40LAD (volume of LAD receiving ≥40 Gy) < 1%. CONCLUSION: In addition to mean heart dose, breast cancer RT treatment planning should also include constraints for cardiac subvolumes such as LV and LAD. The given constraints serve as a clinicians' aid for ensuring adequate heart protection. The individual decision between sufficient protection of cardiac structures versus optimal target volume coverage remains in the physician's hand. The risk of breast cancer-specific mortality and a patient's cardiac risk factors must be individually weighed up against the risk of radiation-induced cardiotoxicity.

Oligometastases in prostate cancer : Metabolic response in follow-up PSMA-PET-CTs after hypofractionated IGRT.

BACKGROUND: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMAPET/CT) is a new and evolving diagnostic method in prostate cancer with special impact on treatment planning in image-guided radiotherapy (IGRT). Initial results of metabolic response in repeated PSMA PET/CTs after hypofractionated IGRT for metastatic lesions are reported here. MATERIALS AND METHODS: Of 280 patients investigated with 68Ga-PSMA PET/CT in the period from 01/2014 through 12/2016 in the authors' department, patients were selected according to the following criteria: oligometastatic disease at initial PSMA PET/CT defined as not more than five metastatic lesions, hypofractionated IGRT to all lesions, no systemic therapy in the last 6 months and during follow-up, and at least one follow-up PSMA PET after radiotherapy. Radiotherapy was administered to all PSMA PET-detected lesions (CTV = PET-GTV + 1 to 2 mm), mostly with 35 Gy in five fractions (one lesion with four fractions of 7 Gy due to dose constraints, two lymph nodes with 50 Gy in 25 fractions to an extended volume plus a boost of 7 Gy × 2 to the PET-positive volume). Metabolic response of irradiated lesions was evaluated on repeated PSMA PET/CTs according to PERCIST criteria. Five patients with a total number of 12 PSMA PETs matched the criteria. Patients received radiotherapy to all PET-positive lesions and had at least one (in one case three) follow-up PSMA PET examinations after radiotherapy with an interval to the first PET of 2-15 months; the median follow-up for all patients was 11 months. RESULTS: The mean prostate-specific antigen (PSA) values at the time of examination were 8.9 ± 8.5 ng/ml (median 3.3 ng/ml, range 0.17-21.8 ng/ml). A total number of 18 metastatic deposits were detected. The PET-positive tumor volume was 5.9 ± 13.3 cm3 (median 1.25 cm3). The mean standardized uptake value (mean SUVmax) of the 18 metastatic lesions decreased from 19.9 ± 23.3 (mean ± SD) prior to RT to 5.4 ± 4.6 at post-radiotherapy PSMA PET/CT. Using PERCIST criteria, 14 lesions (78%) showed a metabolic response in PSMA PET with a reduction of SUV of at least 30%, as well as a significant decrease in lesion size; in seven of these lesions, no uptake of 68Ga-PSMA was detectable. In follow-up PET scans, only two lesions showed metabolic progression with an increase in SUVmax yielding a local progression-free survival of 88% after 1 year. There was a correlation between the time interval after radiotherapy (median 3 months, range 1-9 months) and response (p = 0.04) with better metabolic response after longer follow-up. CONCLUSIONS: Preliminary results of this study show high metabolic response rates of PSMA PET-positive metastatic lesions after hypofractionated radiotherapy in follow-up PSMA PET with promising local control rates. An interval of several months may be required to fully estimate the efficacy of radiotherapy in control PSMA PET.

Neoadjuvant chemotherapy for breast cancer-background for the indication of locoregional treatment.

Neoadjuvant chemotherapy (NACT) has been widely adopted into the multidisciplinary management of breast cancer. The prognostic impact of treatment response has been clearly demonstrated. However, the impact of treatment response on the indication for adjuvant radiotherapy is unclear. This review summarizes important implications of NACT and treatment response on the risk of recurrence and locoregional multidisciplinary management from the standpoint of radiation oncology.

Individualization of post-mastectomy radiotherapy and regional nodal irradiation based on treatment response after neoadjuvant chemotherapy for breast cancer : A systematic review.

PURPOSE: To review the evidence regarding post-mastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NACT) for breast cancer, with a special focus on individualization of adjuvant radiotherapy based on treatment response. METHODS: A systematic literature search using the PubMed/Medline database was performed. We included prospective and retrospective reports with a minimum of 10 patients that had been published since 1st January 2000, and provided clinical outcome data analyzed by treatment response and radiotherapy. RESULTS: Out of 763 articles identified via PubMed/Medline and hand search, 68 full text-articles were assessed for eligibility after screening of title and abstract. 13 studies were included in the systematic review, 9 for PMRT and 5 for RNI. All included studies were retrospective reports. CONCLUSIONS: There is a considerable lack of evidence regarding the role of adjuvant radiotherapy and its individualization based on treatment response after NACT. Results of prospective randomized trials such as NSABP B­51/RTOG 1304 and Alliance A11202 are eagerly awaited.

Predictive and prognostic value of tumor volume and its changes during radical radiotherapy of stage III non-small cell lung cancer : A systematic review.

PURPOSE: Lung cancer remains the leading cause of cancer-related mortality worldwide. Stage III non-small cell lung cancer (NSCLC) includes heterogeneous presentation of the disease including lymph node involvement and large tumour volumes with infiltration of the mediastinum, heart or spine. In the treatment of stage III NSCLC an interdisciplinary approach including radiotherapy is considered standard of care with acceptable toxicity and improved clinical outcome concerning local control. Furthermore, gross tumour volume (GTV) changes during definitive radiotherapy would allow for adaptive replanning which offers normal tissue sparing and dose escalation. METHODS: A literature review was conducted to describe the predictive value of GTV changes during definitive radiotherapy especially focussing on overall survival. The literature search was conducted in a two-step review process using PubMed®/Medline® with the key words "stage III non-small cell lung cancer" and "radiotherapy" and "tumour volume" and "prognostic factors". RESULTS: After final consideration 17, 14 and 9 studies with a total of 2516, 784 and 639 patients on predictive impact of GTV, GTV changes and its impact on overall survival, respectively, for definitive radiotherapy for stage III NSCLC were included in this review. Initial GTV is an important prognostic factor for overall survival in several studies, but the time of evaluation and the value of histology need to be further investigated. GTV changes during RT differ widely, optimal timing for re-evaluation of GTV and their predictive value for prognosis needs to be clarified. The prognostic value of GTV changes is unclear due to varying study qualities, re-evaluation time and conflicting results. CONCLUSION: The main findings were that the clinical impact of GTV changes during definitive radiotherapy is still unclear due to heterogeneous study designs with varying quality. Several potential confounding variables were found and need to be considered for future studies to evaluate GTV changes during definitive radiotherapy with respect to treatment outcome.

Situation of young radiation oncologists, medical physicists and radiation biologists in German-speaking countries : Results from a web-based survey of the Young DEGRO working group.

BACKGROUND AND PURPOSE: The working group "Young DEGRO" (yDEGRO) was established in 2014 by the German Society of Radiation Oncology (DEGRO). We aimed to assess the current situation of young radiation oncologists, medical physicists and radiation biologists. METHODS: An online survey that included 52 questions or statements was designed to evaluate topics related to training, clinical duties and research opportunities. Using the electronic mailing list of the DEGRO and contact persons at university hospitals in Germany as well as at four hospitals in Switzerland and Austria, young professionals employed in the field of radiation oncology were invited to participate in the survey. RESULTS: A total of 260 responses were eligible for analysis. Of the respondents 69 % had a professional background in medicine, 23 % in medical physics and 9 % in radiation biology. Median age was 33 years. There was a strong interest in research among the participants; however a clear separation between research, teaching and routine clinical duties was rarely present for radiation oncologists and medical physicists. Likewise, allocated time for research and teaching during regular working hours was often not available. For radiation biologists, a lack of training in clinical and translational research was stated. CONCLUSION: This survey details the current state of education and research opportunities in young radiation oncologists, medical physicists and radiation biologists. These results will form the basis for the future working program of the yDEGRO.

Value and efficiency of sentinel lymph node diagnostics in patients with penile carcinoma with palpable inguinal lymph nodes as a new multimodal, minimally invasive approach.

PURPOSE: The international guidelines recommend sentinel lymph node biopsy (SLNB) for lymph node staging in penile cancer with non-palpable inguinal lymph nodes (LN) but it is not recommended with palpable inguinal LN. The aim of this study was to evaluate the reliability and morbidity of SLNB in combination with an ultrasound-guided resection of suspect inguinal LNs as a new multimodal, minimally invasive staging approach in these patients. METHODS: We performed SLNB in 26 penile cancer patients with 42 palpable inguinal LNs. Prior to the combined staging procedures the patients underwent an ultrasound examination of the groins as well as planar lymphatic drainage scintigraphy and SPECT/CT scans. During the surgical procedure, the radioactive-labelled sentinel lymph nodes and, in addition, sonographically suspect LNs, were resected under ultrasound guidance. Follow-up screening was done by ultrasound examination of the groins according to the guidelines of the European Association of Urology. RESULTS: Nineteen groins of 42 preoperatively palpable inguinal findings were histologically tumor-positive. SLNB alone showed lymphogenic metastases in 14 groins. Sonography revealed five further metastatic groins, which would not have been detected during SLNB due to a tumor-related blockage of lymphatic drainage or a so-called re-routing of the tracer. During follow-up, none of the 28 groins with tumor-negative LN status showed any LN recurrence in this combined investigation technique. The median follow-up period was 46 (24 to 92) months. Morbidity of this procedure was low at 4.76 % in relation to the number of groins resp. 7.69 % in relation to the number of patients. CONCLUSIONS: The results show that this combined procedure is a reliable multimodal diagnostic approach for treatment of penile cancer patients with palpable inguinal LNs. It is associated with low morbidity rates. SLNB alone would lead to a significantly higher false-negative rate in these patients. The encouraging results of this work can extend the range of indications for nuclear medicine in the form of SLNB using radioactive tracers in this patient group.

10-Year experience regarding the reliability and morbidity of radio guided lymph node biopsy in penile cancer patients and the associated radiation exposure of medical staff in this procedure.

BACKGROUND: The guidelines of the European Association of Urologists (EAU), of the German Society of Nuclear Medicine (DGN), and the European Society for Medical Oncology (ESMO) recommend sentinel lymph node biopsy (SLNB) for lymph node staging in penile cancer with non-palpable inguinal lymph nodes as one diagnostic method. Despite this, the method is neither widely nor regularly applied in Germany - the same applies to many other countries, which may be due to insecurity in dealing with open radioactive tracers. This study aims to assess the reliability and morbidity of this method, as well as the associated radioactive burden for clinical staff. METHODS: Between 2006 and 2016, 34 patients with an invasive penile carcinoma and inconspicuous inguinal lymph node status underwent SLNB in 57 groins after application of a radiotracer (Tc-99 m nanocolloid). We collected the results prospectively. The reliability of the method was assessed by determining the false-negative rate. In addition, we evaluated complication rates and determined the radioactive burden for the clinical staff both pre- and intraoperatively. RESULTS: SLNB was performed in 34 patients with penile cancer with non-palpable inguinal lymph nodes in 57 groins. In two patients inguinal lymph node metastases were detected by means of SLNB. In one patient recurrent inguinal lymph node disease was found after negative SLNB in both groins. Thus, the false negative rate was 3.13 % per patient (1/32 patients) and 3.51 % per groin (2/57 groins). The morbidity rate was 2.94 % per patient (1/34 patients) and 1.75 % per groin (1/57 groins). Radiation exposure for the clinical staff during this procedure was low at a maximum of ca. four µSV per intervention. CONCLUSIONS: SLNB is a reliable method with low morbidity that is associated with a low radiation burden for clinical staff. Due to the enhanced methodological and logistic demands, this intervention should be performed in specialized centres and in an interdisciplinary approach.