PURPOSE:Malignant tumours in the parotid gland can originate either from the gland itself or as a result of metastatic spread of other tumours, such as cutaneous squamous cell carcinomas (CSCC) of the head and neck area. The aim of this study was to analyse and compare the clinical behaviour of primary as well as CSCC metastatic parotid cancers with special emphasis on therapy and oncologic outcome.METHODS:Clinical and histopathological data of 342 patients with parotid gland malignomas surgically treated in a tertiary referral centre between 1987 and 2015 were retrospectively assessed. Oncologic outcomes of all cases with CSCC metastasis of the parotid gland (n = 49) were compared to those of primary parotid gland carcinomas (n = 293).RESULTS:Mean age at diagnosis was 72.3 years for CSCC patients versus 56.8 years in patients with primary parotid carcinoma. A total of 83.7% of CSCC patients were male, compared to 48.8% in the group of primary carcinomas. Forty-five out of 49 CSCC patients underwent total parotidectomy and neck dissection (91.8%). A total of 93.9% out of all CSCC patients received adjuvant radiotherapy. Five-year overall survival (OS) was 32.6% in CSCC patients versus 77.2% in primary parotid carcinoma patients.CONCLUSION:As compared to primary parotid cancers, we could show that patients suffering from CSCC metastases to the parotid gland presented with significantly higher age and worse survival.

Aims Neoadjuvant chemoradiation reduces tumour volume and improves the R0 resection rate, followed by extended survival for patients with advanced oesophageal cancer. The degree of tumour regression has high prognostic relevance. To date, there is still no generally accepted tumour regression grading system. The aim of this study was to compare the prognostic discrimination power of different histological regression grading systems: (i) the fibrosis/tumour ratio within the primary tumour (Mandard classification), (ii) the percentage of residual vital tumour cells (VTC) compared to the original primary tumour (Cologne Regression) and (iii) the ypT category, in patients with cT3 carcinoma of the oesophagus after neoadjuvant chemoradiation. Methods and results This study included 216 patients with oesophageal cancer clinically staged as cT3NxM0 and treated from 2009 to 2012 with standardised chemoradiation followed by oesophagectomy [median age 62 years, 176 (81%) male and 138 (64%) adenocarcinoma patients]. The subgroup frequencies of the three classification systems were ypT category: ypT0 = 18%, ypT1 = 14%, ypT2 = 23%, ypT3 = 44%, ypT4 = 1%; Mandard classification: TRG1 = 18%, TRG2 = 26%, TRG3 = 24%, TRG4 = 30%, TRG5 = 2%; and Cologne Regression Scale: no tumour = 18%, 1-10% VTC = 27%, 10-50% VTC = 26% and >50% VTC = 29%. The Mandard and Cologne Regression classifications showed better prognostic differentiation for the subgroups than the ypT category. The four-tiered Cologne Regression system had a good prognostic relevance. Comparing results of the re-evaluated Cologne Regression classification with the classification by routine pathological report showed very good inter-rater agreement, with kappa value 0.891. Conclusion Compared to the original primary tumour, the tumour regression grading system using the percentage of residual vital tumour has prognostic relevance.

The large mediastinal mass (LMM) at initial staging represents a risk factor in Hodgkin lymphoma (HL) and is measured by X-ray. Depending on location of the LMM, different results can occur regardless of the initial lymphoma volume. To assess this risk factor more accurately, we evaluated the method of volumetry in 77 patients of HD13/14 study of the German Hodgkin Study Group. Furthermore, volume calculations based on three or only one diameter, were performed to simplify volume assessment. Inter-rater reliability was good for all methods. The 3-diameter measurement produced larger volumes than volumetric assessment with an intraclass correlation coefficient (ICC) of 0.93, which could be improved to 0.95 by multiplying volumes with a correction factor of 0.86. The 1-dimensional measurement strongly overestimated the volume with an ICC of 0.7. In conclusion, the simplified volume estimation based on 3 largest diameters provides a reliable concept for the staging of HL patients.

Background The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. Methods The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. Results Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. Conclusion In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Purpose The role of postoperative irradiation to contralateral non-involved neck nodes in lateralized carcinoma of the head and neck is not clear. The contralateral neck failure rate in head and neck carcinoma treated postoperatively with ipsilateral neck irradiation only was evaluated. Methods Patients with carcinoma of the oral cavity, oropharynx, or hypopharynx without midline extension treated between 1990 and 2016 were analyzed. After tumor resection and neck dissection (ND), radiotherapy was given to the primary tumor site and ipsilateral neck. High-risk patients additionally received concurrent chemotherapy. Freedom from contralateral neck recurrence (FCNR), locoregional control rate (LRC), overall survival (OS), and disease-free survival (DFS) were evaluated. Results 197 patients (median age 60.7 years, 66.5% males, 52.8% oropharyngeal carcinomas) were analyzed. Complete resection (R0) was achieved in 85.8% of cases. Ipsilateral ND was performed in all patients and contralateral ND in 144 patients (73.1%). Concurrent chemotherapy was given to 59 patients (30.0%). After a median follow-up of 45.5 months, OS and DFS of all patients were 73.6% and 70.9% at 5 years, respectively. A total of 45 patients (22.8%) suffered from a locoregional recurrence, lymph node metastases of the contralateral neck developed in 12 patients (6.1%) only. There was no significant difference in contralateral nodal failure rate with or without performance of contralateral ND. Conclusion Regional failure of the contralateral neck was low after surgery and ipsilateral neck irradiation in head and neck carcinomas without midline extension, supporting evidence that contralateral neck radiotherapy can safely be omitted in selected cases.

The GHSG HD16 study (NCT00736320) has demonstrated that involved-field radiotherapy (IFRT) after 2 cycles of ABVD chemotherapy could not be safely omitted in low-risk early-stage Hodgkin lymphoma (HL). A PET-driven treatment stratification after chemotherapy was applied for this central question. To shed more light on the mechanisms of IFRT in this setting, we report on the side effects of IFRT as well as timing and localization of relapses of PET-negative patients after treatment with or without consolidating 20 Gy IFRT. Between 2009 and 2015, we recruited 1150 patients with newly diagnosed, early-stage favorable HL aged 18 – 75 years for this randomized phase 3 trial. Patients were randomly assigned to receive standard combined-modality treatment (CMT) with 2 x ABVD and 20 Gy IFRT or PET-guided treatment, where IFRT was restricted to patients with Deauville score (DS) ≥ 3 after 2 x ABVD.The staging images were checked centrally and our reference center has created a specification for protocol-conform IFRT, which was documented on a radiation plan for each patient prior to therapy. For the present analysis, recurrent sites documented at follow-up were correlated with the radiation plan. Infield relapse was present when the recurring sites were at least in part within the area to be irradiated; outfield relapse when there were any recurring sites outside the area to be irradiated (thus, one relapse can be both infield and outfield). A total of 328 and 300 patients, respectively, were PET-negative (DS 0 - 2) in the CMT arm and in the PET-guided arm. Among the 328 patients who were irradiated, 3.4% experienced any acute toxicity of CTCAE grade 3 during IFRT; most frequently dysphagia (1.8%) and mucositis (0.9%).There were no grade 4 toxicities. A total of 24 second malignancies have been observed thus far, with no difference between treatment arms (5-year cumulative incidence 5.6% vs. 4.6%, p=0.54). After median follow-up of 47 months, there were no progressions, 2 early relapses and 13 late relapses in the CMT arm, and 1 progression, 9 early relapses and 19 late relapses after chemotherapy alone. An increased rate of local recurrences was observed in the arm without IFRT: 8.7% of patients without IFRT having an infield relapse vs. 2.1% in the combined modality arm (p=0.0003). In contrast, there was no relevant difference in the rate of outfield recurrences (3.7 % with IFRT vs. 4.7 % without IFRT, p=0.55). In the population of PET-negative patients of the HD16 study it could be shown that the renunciation of consolidating radiotherapy leads to a higher rate of local and early recurrences, indicating that the PFS differences observed in HD16 are in fact attributed to IFRT. The therapy-associated side effects of IFRT were marginal and the incidence of second malignancies was not increased thus far. IFRT should continue to be considered standard after 2 cycles of ABVD to avoid intensive and toxic salvage therapies such as autologous stem cell transplantation.

Die stereotaktische Radiochirurgie mittels CyberKnife® stellt eine neue Therapieoption bei uvealen Melanomen dar.

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.

To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients.

Radiation therapy represents an alternative treatment to radical prostatectomy in the management of clinically localized prostate cancer. Radiation-induced second neoplasms are defined by a latency period of at least 5 years, location within the field of radiation therapy, and a histology which differs from the primary tumor. Based on the data in the literature, there is a consistently increased risk of bladder cancer (HR: 1.67, 95% CI 1.55-1.80), rectal cancer (HR: 1.79, 95% CI 1.34-2.38), and colorectal cancer (HR: 1.79, 95% CI 1.34-23.8) following percutaneous radiation therapy. Following brachytherapy only an increased for the development of bladder cancer (HR: 2.14, 95% CI 1.03-3.94) has been observed. The incidence of second neoplasms increases significantly and continuously with the posttreatment time interval. Although bladder cancers following RT of the prostate are usually more locally advanced and of high grade, no negative impact in terms of overall survival and cancer-specific survival has been observed. Symptoms or findings of microhematuria need to be examined thoroughly after radiation therapy to identify bladder cancer quite early.

Radiotherapy is an established local treatment in patients with various malignancies. Systemic responses following local irradiation have been described as abscopal effects. Modern cancer immunotherapy with immune checkpoint inhibitors has shown impressive response rates and prolongation of survival even in heavily pretreated patients with advanced solid malignancies and lymphomas. Radiotherapy has been shown to modulate immune response, and its application in the context of immune checkpoint inhibition has recently evolved into an active field of research. Prospective studies investigating combination treatment are currently ongoing and will answer questions as to the optimal schedule and radiation dosing. This short review focuses on the immunomodulatory role of radiotherapy and the use of immune checkpoint inhibition with a special focus on Hodgkin lymphoma.

AIM:The aim of this study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in the treatment of patients with adrenal metastases in oligometastatic non-small-cell lung cancer (NSCLC).PATIENTS AND METHODS:Between November 2012 and May 2015, fifteen patients with oligometastatic non-small cell lung cancer and adrenal metastases were treated with the Cyberknife® system. The primary endpoint was local control.RESULTS:The 1-year and 2-year local control rates were 60% and 46.6%, respectively. The differences in local control for patients with metachronous and synchronous metastases reached statistical significance (p=0.00028). Two-year overall survival of 91.2% for patients with metachronous metastases was also more favourable compared to patients with synchronous adrenal metastases with 42.8%.CONCLUSION:Extracranial stereotactic radiotherapy with the Cyberknife® is a safe and non-invasive technique that extends the therapeutic spectrum in the treatment of patients with adrenal metastases in oligometastatic NSCLC.

IntroductionStereotactic body radiation therapy (SBRT) is applied in the oligometastatic setting to treat liver metastases. However, factors influencing tumor control probability (TCP) other than radiation dose have not been thoroughly investigated. Here we set out to investigate such factors with a focus on the influence of histology and chemotherapy prior to SBRT using a large multi-center database from the German Society of Radiation Oncology.Methods452 SBRT treatments in 363 patients were analyzed after collection of patient, tumor and treatment data in a multi-center database. Histology was considered through random effects in semi-parametric and parametric frailty models. Dose prescriptions were parametrized by conversion to the maximum biologically effective dose using alpha/beta of 10Gy (BEDmax).ResultsAfter adjusting for histology, BEDmax was the strongest predictor of TCP. Larger PTV volumes, chemotherapy prior to SBRT and simple motion management techniques predicted significantly lower TCP. The model predicted a BED of 209±67Gy10 necessary for 90% TCP at 2years with no prior chemotherapy, but 286±78Gy10 when chemotherapy had been given. Breast cancer metastases were significantly more responsive to SBRT compared to other histologies with 90% TCP at 2years achievable with BEDmax of 157±80Gy10 or 80±62Gy10 with and without prior chemotherapy, respectively.ConclusionsBesides dose, histology and pretreatment chemotherapy were important factors influencing local TCP in this large cohort of liver metastases. After adjusting for prior chemotherapy, our data add to the emerging evidence that breast cancer metastases do respond better to hypofractionated SBRT compared to other histologies.

Purpose or ObjectiveTo determine the maximum tolerated dose (MTD) of fractionated extracranial stereotactic radiotherapy (ESRT) to lymph nodal recurrences in different clinical settings. Material and MethodsPatients enrolled in a phase I clinical trial entered the analysis.Each enrolled subject was included in a different study arm, according to nodal site and previous treatment.Dose has been prescribed according to ICRU 62.A four no-coplanar beams class solution or a volumetric technique (VMAT) have been applied in all patients.The planning target volume (PTV) has been defined as gross tumour volume (GTV) plus 5-15 mm.According to different arms, patients received an ESRT dose ranging from 20 Gy up to the maximum planned dose of 50 Gy in 5 fractions.Dose-limiting toxicity (DLT) was any grade > 3 acute toxicity or any grade > 2 late toxicity.The MTD was exceeded if 2 of 6 or 4 of 12 patients in a cohort experienced DLT.Results 101 patients (M/F: 47/54; median age 67 years, range 43-87years) with 128 nodal lesions were treated.were treated.Of these, 48 (37.5%) were nodal recurrences in neck or chest, 34 (26.5%) were in abdomen and 46 (35.9%) were in pelvis.The primary tumour was most frequently gynaecologic cancer (44%), followed by genito-urinary cancer (22%), gastro-intestinal (13%), lung (13%) and other (9%).The median ESRT delivered dose was 35 Gy (20-50) in five fractions.With a median follow up of 19 months (4-104), the overall response rate was 88% (CI95: 80-93.6;Complete Response: 68%; Partial Response: 20%), with only 5% of patients developing disease progression.No DLT was recorded in this group of patients.Two-and 4-year local control were 81% and 70.2%, respectively.Two-and 4-year metastases free survival were 43.5% and 30.9%, respectively. ConclusionIn quite varied setting of lymph nodal recurrences an ESRT treatment in five fractions up to a dose of 50 Gy is safe and well tolerated.

Die Strahlentherapie (perkutane Radiotherapie, Low-dose-rate- [LDR-] oder High-dose-rate- [HDR-]Brachytherapie) stellt eine der therapeutischen Alternativen zur radikalen Prostatektomie des organbegrenzten bzw. des lokal fortgeschrittenen Prostatakarzinoms (PCa) dar. Strahlentherapieassoziierte Sekundärmalignome werden definitionsgemäß nach einer Latenzperiode von mindestens 5 Jahren, der Lokalisation innerhalb des Strahlenfeldes sowie einer vom Primärtumor abweichenden Histologie diagnostiziert. Basierend auf den Daten der Literatur zeigt sich gegenüber der Allgemeinbevölkerung bzw. der nicht strahlentherapierten PCa-Patienten reproduzierbar ein erhöhtes sekundäres Karzinomrisiko für die Entwicklung eines Blasenkarzinoms (Hazard Ratio [HR] 1,67; 95 %-Konfidenzintervall [‑KI] 1,55–1,80) sowie eines Rektum- (HR 1,79; 95 %-KI 1,34–2,38) und kolorektalen Karzinoms (HR 1,79; 95 %-KI 1,34–23,8) nach perkutaner Radiotherapie. Nach Brachytherapie ergibt sich nur ein erhöhtes Risiko für die Entwicklung eines Harnblasenkarzinoms (HR 2,14; 95 %-KI 1,03–3,94). Die Inzidenz der Sekundärneoplasien steigt mit zunehmender Dauer der Nachbeobachtung an. Bis dato konnten keine negativen Auswirkungen der Strahlentherapie auf das Gesamtüberleben und das tumorspezifische Überleben nach radikaler Zystektomie nachgewiesen werden, wenngleich die Rate an lokal fortgeschrittenen T3/4-Tumoren nach Radiatio deutlich gegenüber den Kontrollgruppen erhöht ist. Ab dem 5. posttherapeutischen Jahr sollten Symptome oder Zufallsbefunde, die auf ein Blasenkarzinom hindeuten könnten (Mikrohämaturie), einer intensiven Diagnostik zugeführt werden.

OBJECTIVES:Lymph node ratio (LNR) is an established predictor in different entities of carcinoma, including head and neck malignancies. In oropharyngeal squamous cell carcinoma (OPSCC), lymph node involvement differs between human papilloma virus (HPV)-positive and HPV-negative tumours. Herein, we evaluate the impact of HPV association on the concept of LNR.METHODS:88 surgically treated patients were included in this retrospective chart review. HPV-positive and HPV-negative OPSCC were evaluated for prediction of outcome by LNR separately. The endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS).RESULTS:The OS of all patients was 60.1%. In univariate analysis, LNR was a significant predictor of overall survival rate (P=.008) in OPSCC independently of the HPV status, as well as extracapsular spread (ECS). T-classification was only a significant predictor in the univariate analysis in HPV-positive OPSCC carcinoma. However, in the multivariate analysis LNR remained predictor of prognosis in all OPSCC and in HPV-negative OPSCC. In patients with HPV-positive OPSCC, only T-classification reached significance to predict OS.CONCLUSION:Prognosis of primarily operated HPV-positive patients might be more dependent on the extent of primary tumour site, whereas prognosis of HPV-negative patients is based more on cervical metastatic spread, represented by LNR.