Patterns of failure after radical prostatectomy in prostate cancer - implications for radiation therapy planning after 68Ga-PSMA-PET imaging.

BACKGROUND: Salvage radiotherapy (SRT) after radical prostatectomy (RPE) and lymphadenectomy (LAE) is the appropriate radiotherapy option for patients with persistent/ recurrent prostate cancer (PC). 68Ga-PSMA-PET imaging has been shown to accurately detect PC lesions in a primary setting as well as for local recurrence or for lymph node (LN) metastases. OBJECTIVE: In this study we evaluated the patterns of recurrence after RPE in patients with PC, putting a highlight on the differentiation between sites that would have been covered by a standard radiation therapy (RT) field in consensus after the RTOG consensus and others that would have not. METHODS AND MATERIALS: Thirty-one out of 83 patients (37%) with high-risk PC were the subject of our study. Information from 68Ga-PSMA-PET imaging was used to individualize treatment plans to include suspicious lesions as well as possibly boost sites with tracer uptake in LN or the prostate bed. For evaluation, 68Ga-PSMA-PET-positive LN were contoured in a patient dataset with a standard lymph drainage (RTOG consensus on CTV definition of pelvic lymph nodes) radiation field depicting color-coded nodes that would have been infield or outfield of that standard lymph drainage field and thereby visualizing typical patterns of failure of a "blind" radiation therapy after RPE and LAE. RESULTS: Compared to negative conventional imaging (CT/MRI), lesions suspicious for PC were detected in 27/31 cases (87.1%) by 68Ga-PSMA-PET imaging, which resulted in changes to the radiation concept. There were 16/31 patients (51.6%) that received a simultaneous integrated boost (SIB) to a subarea of the prostate bed (in only three cases this dose escalation would have been planned without the additional knowledge of 68Ga-PSMA-PET imaging) and 18/31 (58.1%) to uncommon (namely presacral, paravesical, pararectal, preacetabular and obturatoric) LN sites. Furthermore, 14 patients (45.2%) had a changed TNM staging result by means of 68Ga-PSMA-PET imaging. CONCLUSION: Compared to conventional CT or MRI staging, 68Ga-PSMA-PET imaging detects more PC lesions and, thus, significantly influences radiation planning in recurrent prostate cancer patients enabling individually tailored treatment.

Differentiation of irradiation and cetuximab induced skin reactions in patients with locally advanced head and neck cancer undergoing radioimmunotherapy: the HICARE protocol (head and neck cancer: immunochemo and radiotherapy with erbitux) - a multicenter phase IV trial.

BACKGROUND: In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before. METHODS/DESIGN: The HICARE study is a national, multicenter, prospective phase IV study exploring the different types of skin reactions that occur in patients with LASCCHN undergoing radioimmun(chemo)therapy with the EGFR inhibitor cetuximab. 500 patients with LASCCHN will be enrolled in 40 participating sites in Germany. Primary endpoint is the rate of radiation dermatitis NCI CTCAE grade 3 and 4 (v. 4.02). Radioimmunotherapy will be applied according to SmPC, i.e. cetuximab will be administered as loading dose and then weekly during the radiotherapy. Irradiation will be applied as intensity-modulated radiation therapy (IMRT) or 3D-dimensional radiation therapy. DISCUSSION: The HICARE trial is expected to be one of the largest trials ever conducted in head and neck cancer patients. The goal of the HICARE trial is to differentiate skin reactions caused by radiation from those caused by the monoclonal antibody cetuximab, to evaluate the incidence and severity of these skin reactions and to correlate them with outcome parameters. Besides, the translational research program will help to identify and confirm novel peripheral blood based molecular predictors and surrogates for treatment response and resistance. TRIAL REGISTRATION: Clinical Trial Identifier, NCT01553032 (clinicaltrials.gov)EudraCT number: 2010-019748-38.

Breast cancer and funnel chest. Comparing helical tomotherapy and three-dimensional conformal radiotherapy with regard to the shape of pectus excavatum.

BACKGROUND AND PURPOSE: Preserving lung, heart, and the contralateral breast from toxicity is a technical challenge in women with funnel chest, who require breast irradiation. The purpose of this study was to determine whether helical tomotherapy (HT) offers an advantage compared to three-dimensional (3D) conformal radiotherapy (CRT) for patients with pectus excavatum with regard to its shape. PATIENTS AND METHODS: Ten breast cancer patients with pectus excavatum were graded into a low or high deformation group using different indices, measured and calculated by using the planning CT. A planning comparison was performed, creating plans for CRT and HT. Target uniformity, target conformity, and exposure to the organs at risk (OARs) were compared. RESULTS: The uniformity and conformity of the target dose distribution and the median/average dose of the planning target volume (PTV) was inferior in CRT compared to HT in both deformation groups. By using tomotherapy, the volume of the lungs, the contralateral breast, and the heart, which received high dose exposure, could be significantly reduced. Tomotherapy plans led to a significantly higher low dose exposure to the lungs and contralateral breast. CONCLUSION: This is the first study which evaluates a group of 10 breast cancer patients with funnel chest. Better uniformity and conformity combined with a significant reduction of high dose exposure to the OARs can be reached using tomotherapy. However, tomotherapy plans have a significantly larger volume of low dose to the lungs and contralateral breast. Therefore, the stochastic risk should be considered after low dose exposure in women with low deformation.

Single-fraction image-guided robotic radiosurgery efficiently controls local prostate cancer recurrence after radical prostatectomy.

Purpose: To assess the therapeutic potential of single-fraction robotic stereotactic ablative body radiotherapy (SABR) in patients with locally recurrent prostate cancer (PC) after radical prostatectomy (RP). Materials and methods: We included 35 patients with biochemical failure after RP with single-site local recurrence in the prostate bed diagnosed by PSMA PET/CT. About 20/35 pts had previously received post-surgical adjuvant radiation therapy.High-resolution multiparametric magnetic resonance imaging (mpMRI) for exact visualization of tumor tissue was performed at 1.5 (n = 23; Siemens Magnetom Aera) or 3 Tesla (n = 12; Siemens Magnetom VIDA, Siemens Healthineers, Erlangen, Germany). Using the MRI and PET/CT dataset for planning, SABR was carried out after ultrasound-guided placement of a single gold fiducial marker at the site of tumor recurrence using a CyberKnife M6 unit (Accuray Inc., Sunnyvale, USA). Due to the high diagnostic accuracy of PSMA PET/CT and mpMRI, pre-SABR biopsy of tumor tissue was not deemed necessary. PSMA PET/CT performed in median 88 days before SABR confirmed the absence of distant metastases. MpMRI was performed at a median of 22 days prior to the intervention. SABR was performed in a single fraction with a dose of 20 (5/35), 21 (27/35) or 22 (3/35) Gy. Follow-up serum PSA was measured every 3 months thereafter. Results: Median patient age was 72 years (57-80 years) and median time from RP to SABR was 96.8 months (IQR, 69.3-160.2). Median serum PSA before SABR was 1.38 ng/mL (IQR 0.75-2.72). At 3 months, median PSA had dropped significantly in 27/35 patients to a median of 0.35 ng/mL (IQR 0.25-0.68). At 6 months, 30/35 patients showed biochemical response to SABR, while five patients were progressing: three had systemic disease on PSMA PET/CT, while two patients had rising PSA values without a visible correlate on PET/CT. The median follow-up time was 16 months. Grade 1 genitourinary (GU) toxicity was reported in 3/35 patients (9%) and grade 1 gastrointestinal (GI) toxicity in 2/35 patients (6%), respectively. Conclusion: SABR is an efficient new treatment option in the management of single-site local recurrent PC without the evidence of systemic disease; due to its very low toxicity, it is an alternative to surgical re-treatment or other focal therapies. It can significantly delay the onset of androgen deprivation therapy (ADT) in biochemical failure after radical prostatectomy.

Impact of 68Ga-PSMA-PET imaging on target volume definition and guidelines in radiation oncology - a patterns of failure analysis in patients with primary diagnosis of prostate cancer.

BACKGROUND: 68Ga-PSMA-PET-imaging has proven to be a highly sensitive and specific diagnostic element for patients with prostate cancer (PC). Does the standard clinical target volume (CTV) cover the majority of 68Ga-PSMA-PET detected lymph nodes (LNs) in a primary setting? METHODS: 25 out of 159 patients with primary PC who underwent 68Ga-PSMA-PET-imaging were analyzed in the process of this study. These 25 high-risk patients had a total of 126 LNs with positive 68Ga-PSMA-ligand uptake. A standard CTV according to the 'Radiation Therapy Oncology Group' consensus was delineated and LNs were judged whether they were in- or outside of this target volume. With a Pearson correlation we additionally evaluated whether the Gleason score, the prostate-specific antigen (PSA) value or the risk according to the Roach formula correlate with a higher chance of LNs being outside of the CTV in uncommon LN locations. RESULTS: 81 (64.3%) of 126 LNs were covered by the CTV with a complete coverage of all positive LNs inside the respective radiation volume in 11 of 25 patients (44%). LNs that were not covered by the CTV included (para-aortic,) common-iliac, pre-sacral, obturatoric, para-rectal, para-vesical and pre-acetabular locations. In a statistical analysis neither the Gleason score, nor the PSA value, nor the calculated risk with the Roach formula correlated with LNs being inside or outside of the CTV in this patient group. CONCLUSION: 68Ga-PSMA-PET-imaging proves to be a valuable asset for patients and physicians for primary diagnosis and treatment planning. In our study, trusting the RTOG consensus for CTV delineation would have led to up to 35.7% of all LNs not to be included in the clinical radiation volume, which might have resulted in insufficient radiation dose coverage.

[Radiotherapeutic management of lymphatic fistulas : An effective but disregarded therapy option]. / Strahlentherapeutisches Management von Lymphfisteln : Eine effektive, aber wenig beachtete Therapieoption.

BACKGROUND: Lymphatic fistulas and lymphoceles are known complications after vascular surgery of the groin and after extended surgical interventions in the pelvic region. Unfortunately, conservative standard therapies are not always successful. OBJECTIVES: Evaluation of the therapeutic efficacy and related side effects of percutaneous low-dose irradiation in patients with lymphorrhea and definition of its importance. MATERIAL AND METHODS: Current presentation of previously published case series, reviews and guidelines. RESULTS: The use of low-dose irradiation therapy with single doses of 0.3-0.5 Gy leads to a cessation of the lymphatic flow in a high percentage of patients when standard therapies do not show a sufficient effect. With cessation of lymphorrhea irradiation should be terminated. Acute side effects have not been reported and the risk of tumor induction is almost negligible. CONCLUSION: Low-dose irradiation is an effective and very well-tolerated therapeutic alternative in the treatment of lymphatic fistulas and lymphorrhea when conservative therapies are unsuccessful.