Therapie des frühen und lokal fortgeschrittenen Rektumkarzinoms

Kasuistik: Vor 5 Jahren wurde bei einem männlichen 39-jährigen Patienten ein frühes Rektumkarzinom diagnostiziert, das mittels anteriorer Rektumresektion behandelt wurde. Aufgrund des lokal begrenzten Stadiums ohne Befall lokoregionärer Lymphknoten (pT2 pN0 cM0 R0) wurde keine adjuvante Therapie durchgeführt. Hinweise auf eine genetische Disposition zur Entwicklung eines kolorektalen Karzinoms hatten sich nicht gefunden. Die Kontrolluntersuchungen und die letzte Rektoskopie vor 3 Monaten hatten bislang keinen Hinweis auf ein Rezidiv der Erkrankung ergeben. Jetzt stellt sich der Patient mit Schmerzen bei der Defäkation bei seinem Hausarzt vor. Der rektale Tastbefund ist unauffällig, die Untersuchung wird allerdings vom Patienten als sehr schmerzhaft empfunden. Der Hausarzt überweist den Patienten zu einem niedergelassenen Gastroenterologen. Dieser führt eine Rektoskopie und eine Koloskopie durch, die keinen pathologischen Befund erbringen. In der Endosonographie zeigt sich allerdings eine rechtsseitige extraluminale Raumforderung in Höhe der Anastomose. Unter endosonographischer Kontrolle wird die Raumforderung punktiert. In der zytologischen Aufarbeitung finden sich Zellen eines Adenokarzinoms, passend zu einem Rezidiv des bekannten Rektumkarzinoms. Der Patient wird in ein onkologisches Zentrum zum Staging und zur Klärung des therapeutischen Vorgehens eingewiesen. Im Rahmen der Staginguntersuchungen wird eine [18F]-2-Fluoro-2-desoxy-D-Glucose-Positronenemissionstomographie/Computertomographie (FDG-PET/CT) durchgeführt, bei der sich keine Hinweise auf eine regionale und eine distante Metastasierung ergeben (Abbildung 1). Der Rezidivtumor zeigt hingegen einen deutlich erhöhten FDG-Uptake. Es finden sich keine Hinweise auf eine Infiltration des Beckenbodens bzw. des knöchernen Beckens. Somit liegt ein lokal begrenztes und damit prinzipiell resektables Karzinomrezidiv vor (rcT3 cN0 cM0). Der Empfehlung der interdisziplinären Tumorkonferenz zur präoperativen Radiochemotherapie (RCT) mit nachfolgender abdominoperinealer Resektion stimmt der Patient in Kenntnis der kurativen Intention zu. Aufgrund des extraluminalen Rezidivs und des geringen Alters des Patienten wird eine kombinierte RCT (3D-geplante Strahlentherapie des Beckens mit 5 × 1,8 Gy pro Woche bis 45 Gy Gesamtdosis; Oxaliplatin mit 85 mg/m2/d an den Tagen 1, 15, 29; 5-Fluorouracil 300 mg/m2/d an den Tagen 1-5, 8-12, 15-19, 22-26, 29-33) durchgeführt. Die Therapie wird insgesamt bis auf leichte Pollakisurie gut vertragen. Nennenswerte hämatologische und intestinale Toxizitäten werden nicht beobachtet. Eine in der 4. Therapiewoche durchgeführte FDG-PET/CT-Untersuchung des Beckens zeigt bereits einen rückläufigen Tumor im Sinne eines guten, frühen Ansprechens auf die Therapie. 4 Wochen nach Ende der RCT stellt sich der Patient zum Restaging und zur Planung der Operation erneut vor. In der FDG-PET/CT finden sich weder in der Computertomographie noch in der FDG-PET Hinweise auf einen makroskopischen Tumorrest. Es liegt bildgebend eine komplette Remission vor (Abbildung 3). Aufgrund der vorausgegangenen anterioren Rektumresektion wird eine perineale Rektumamputation (Operation nach Miles) durchgeführt. Der postoperative Verlauf ist weitgehend komplikationslos. Der Patient erhält intraoperativ ein Descendostoma. In der histopathologischen Aufarbeitung findet sich ein Typ T3 pN0 extraluminales Rektumkarzinomrezidiv mit deutlichen regressiven Veränderungen nach neoadjuvanter RCT (vitales Tumorgewebe in 3% des gesamten resezierten Tumors). Der Tumor ist mit ausreichendem Sicherheitssaum operiert. Die bisherigen Verlaufskontrollen über 2 Jahre nach Therapie des Rezidivtumors zeigen keinen Hinweis auf ein erneutes Tumorrezidiv oder Fernmetastase

Dodes (diagnostic nodes) for Guideline Manipulation

Background: Treatment recommendations (guidelines) are commonly represented in text form. Based on parameters (questions) recommendations are defined (answers). Objectives: To improve handling, alternative forms of representation are required. Methods: The concept of Dodes (diagnostic nodes) has been developed. Dodes contain answers and questions. Dodes are based on linked nodes and additionally contain descriptive information and recommendations. Dodes are organized hierarchically into Dode trees. Dode categories must be defined to prevent redundancy. Results: A centralized and neutral Dode database can provide standardization, which is a requirement for the comparison of recommendations. Centralized administration of Dode categories can provide information about diagnostic criteria (Dode categories) underutilized in existing recommendations (Dode trees). Conclusions: Representing clinical recommendations in Dode trees improves their manageability, handling and updateability

Treatment Outcomes for Men with Clinical Stage II Nonseminomatous Germ Cell Tumours Treated with Primary Retroperitoneal Lymph Node Dissection: A Systematic Review

CONTEXT Guidelines recommend primary retroperitoneal lymph node dissection (RPLND) as a treatment option for tumour marker-negative stage II nonseminomatous germ cell tumour (NSGCT). OBJECTIVE To review the literature on oncological outcomes for men with stage II NSGCT treated with RPLND. EVIDENCE ACQUISITION A systematic review of studies describing clinicopathological outcomes following primary RPLND in stage II NSGCT was conducted in the MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. Baseline data, perioperative and postoperative parameters, and oncological outcomes were collected. EVIDENCE SYNTHESIS In total, 12 of 4387 studies were included, from which we collected data for 835 men. Among men with clinical stage II NSGCT, pathological stage II was confirmed in 615 of 790 patients (78%). Most studies administered adjuvant chemotherapy in cases with large lymph nodes, multiple affected lymph nodes, or persistently elevated tumour markers. Recurrence was observed in 12-40% of patients without adjuvant chemotherapy and 0-4% of patients who received adjuvant chemotherapy. CONCLUSIONS The literature describing RPLND in clinical stage II NSGCT is heterogeneous and no meta-analysis was possible, but RPLND can provide accurate staging and may be curative in selected patients. PATIENT SUMMARY We reviewed the literature to summarise results after surgical removal of enlarged lymph nodes in the back of the abdomen in men with testis cancer. This procedure provides accurate information on how far the cancer has spread and may provide a cure in selected patients

Postoperative radiotherapy for meningiomas - a decision-making analysis.

BACKGROUND The management of meningiomas is challenging, and the role of postoperative radiotherapy is not standardized. METHODS Radiation oncology experts in Swiss centres were asked to participate in this decision-making analysis on the use of postoperative radiotherapy (RT) for meningiomas. Experts from ten Swiss centres agreed to participate and provided their treatment algorithms. Their input was converted into decision trees based on the objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies in clinical routine. RESULTS Several criteria used for decision-making in postoperative RT in meningiomas were identified: histological grading, resection status, recurrence, location of the tumour, zugzwang (therapeutic need to treat and/or severity of symptoms), size, and cell division rate. Postoperative RT is recommended by all experts for WHO grade III tumours as well as for incompletely resected WHO grade II tumours. While most centres do not recommend adjuvant irradiation for WHO grade I meningiomas, some offer this treatment in recurrent situations or routinely for symptomatic tumours in critical locations. The recommendations for postoperative RT for recurrent or incompletely resected WHO grade I and II meningiomas were surprisingly heterogeneous. CONCLUSIONS Due to limited evidence on the utility of postoperative RT for meningiomas, treatment strategies vary considerably among clinical experts depending on the clinical setting, even in a small country like Switzerland. Clear majorities were identified for postoperative RT in WHO grade III meningiomas and against RT for hemispheric grade I meningiomas outside critical locations. The limited data and variations in clinical recommendations are in contrast with the high prevalence of meningiomas, especially in elderly individuals

Dose escalation for stereotactic arrhythmia radioablation of recurrent ventricular tachyarrhythmia - a phase II clinical trial

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75-85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation. OBJECTIVE: A single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk. METHODS: Patients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D. DISCUSSION: DEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure

Therapy of clinical stage IIA and IIB seminoma: a systematic review

Purpose The optimal treatment for clinical stage (CS) IIA/IIB seminomas is still controversial. We evaluated current treatment options. Methods A systematic review was performed. Only randomized clinical trials and comparative studies published from January 2010 until February 2021 were included. Search items included: seminoma, CS IIA, CS IIB and therapy. Outcome parameters were relapse rate (RR), relapse-free (RFS), overall and cancer-specific survival (OS, CSS). Additionally, acute and long-term side effects including secondary malignancies (SMs) were analyzed. Results Seven comparative studies (one prospective and six retrospective) were identified with a total of 5049 patients (CS IIA: 2840, CS IIB: 2209). The applied treatment modalities were radiotherapy (RT) (n = 3049; CS IIA: 1888, CSIIB: 1006, unknown: 155) and chemotherapy (CT) or no RT (n = 2000; CS IIA: 797, CS IIB: 1074, unknown: 129). In CS IIA, RRs ranged from 0% to 4.8% for RT and 0% for CT. Concerning CS IIB RRs of 9.5%–21.1% for RT and of 0%–14.2% for CT have been reported. 5-year OS ranged from 90 to 100%. Only two studies reported on treatment-related toxicities. Conclusions RT and CT are the most commonly applied treatments in CS IIA/B seminoma. In CS IIA seminomas, RRs after RT and CT are similar. However, in CS IIB, CT seems to be more effective. Survival rates of CS IIA/B seminomas are excellent. Consequently, long-term toxicities and SMs are important survivorship issues. Alternative treatment approaches, e.g., retroperitoneal lymph node dissection (RPLND) or dose-reduced sequential CT/RT are currently under prospective investigation

The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases

Background: The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO)stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. Methods: From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. Results: In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1–4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n= 213 pts.; 300 lesions) and breast cancer (n= 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1–13) and dose per fraction (median: 18.5 Gy; range 3–37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control

Therapy of clinical stage IIA and IIB seminoma: a systematic review

\ua9 2021, The Author(s). Purpose: The optimal treatment for clinical stage (CS) IIA/IIB seminomas is still controversial. We evaluated current treatment options. Methods: A systematic review was performed. Only randomized clinical trials and comparative studies published from January 2010 until February 2021 were included. Search items included: seminoma, CS IIA, CS IIB and therapy. Outcome parameters were relapse rate (RR), relapse-free (RFS), overall and cancer-specific survival (OS, CSS). Additionally, acute and long-term side effects including secondary malignancies (SMs) were analyzed. Results: Seven comparative studies (one prospective and six retrospective) were identified with a total of 5049 patients (CS IIA: 2840, CS IIB: 2209). The applied treatment modalities were radiotherapy (RT) (n = 3049; CS IIA: 1888, CSIIB: 1006, unknown: 155) and chemotherapy (CT) or no RT (n = 2000; CS IIA: 797, CS IIB: 1074, unknown: 129). In CS IIA, RRs ranged from 0% to 4.8% for RT and 0% for CT. Concerning CS IIB RRs of 9.5%–21.1% for RT and of 0%–14.2% for CT have been reported. 5-year OS ranged from 90 to 100%. Only two studies reported on treatment-related toxicities. Conclusions: RT and CT are the most commonly applied treatments in CS IIA/B seminoma. In CS IIA seminomas, RRs after RT and CT are similar. However, in CS IIB, CT seems to be more effective. Survival rates of CS IIA/B seminomas are excellent. Consequently, long-term toxicities and SMs are important survivorship issues. Alternative treatment approaches, e.g., retroperitoneal lymph node dissection (RPLND) or dose-reduced sequential CT/RT are currently under prospective investigation

Oligorecurrent nodal prostate cancer: radiotherapy quality assurance of the randomized PEACE V-STORM phase II trial.

PURPOSE Aim of this study is to report the results of the radiotherapy quality assurance program of the PEACE V-STORM randomized phase II trial for pelvic nodal oligorecurrent prostate cancer (PCa). MATERIAL AND METHODS A benchmark case (BC) consisting of a postoperative case with 2 nodal recurrences was used for both stereotactic body radiotherapy (SBRT, 30 Gy/3 fx) and whole pelvic radiotherapy (WPRT, 45 Gy/25 fx + SIB boost to 65 Gy). RESULTS BC of 24 centers were analyzed. The overall grading for delineation variation of the 1st BC was rated as 'UV' (Unacceptable Variation) or 'AV' (Acceptable Variation) for 1 and 7 centers for SBRT (33%), and 3 and 8 centers for WPRT (46%), respectively. An inadequate upper limit of the WPRT CTV (n=2), a missing delineation of the prostate bed (n=1), and a missing nodal target volume (n=1 for SBRT and WPRT) constituted the observed 'UV'. With the 2nd BC (n=11), the overall delineation review showed 2 and 8 'AV' for SBRT and WPRT, respectively, with no 'UV'. For the plan review of the 2nd BC, all treatment plans were per protocol for WPRT. SBRT plans showed variability in dose normalization (Median D90% = 30.1 Gy, range 22.9-33.2Gy and 30.6 Gy, range 26.8-34.2Gy for nodes 1 and 2 respectively). CONCLUSIONS Up to 46% of protocol deviations were observed in delineation of WPRT for nodal oligorecurrent PCa, while dosimetric results of SBRT showed the greatest disparities between centers. Repeated BC resulted in an improved adherence to the protocol, translating in an overall acceptable contouring and planning compliance rate among participating centers