Search

Background: Modern radiotherapy plays an important role in therapy of advanced head and neck carcinomas. However, no clinical studies have been published addressing the effectiveness of postoperative radiotherapy in patients with small tumor (pT1, pT2) and concomitant ipsilateral metastasis of a single lymph node (pN1), which would provide a basis for a general treatment recommendation.Methods/design: The present study is a non-blinded, prospective, multi-center randomized controlled trial (RCT). As the primary clinical endpoint, overall-survival in patients receiving postoperative radiation therapy vs. patients without adjuvant therapy following curative intended surgery is compared. The aim of the study is to enroll 560 adult males and females for 1:1 randomization to one of the two treatment arms (irradiation/no irradiation). Since patients with small tumor (T1/T2) but singular lymph node metastasis are rare and the amount of patients consenting to randomization is not predictable in advance, all patients rejecting randomization will be treated as preferred and enrolled in a prospective observational study (comprehensive cohort design) after giving informed consent. This observational part of the trial will be performed with maximum consistency to the treatment and observation protocol of the RCT. Because the impact of patient preference for a certain treatment option is not calculable, parallel design of RCT and observational study may provide a maximum of evidence and efficacy for evaluation of treatment outcome. Secondary clinical endpoints are as follows: incidence and time to tumor relapse (locoregional relapse, lymph node involvement and distant metastatic spread), Quality of life as reported by EORTC (QLQ-C30 with H&N 35 module), and time from operation to orofacial rehabilitation. All tumors represent a homogeneous clinical state and therefore additional investigation of protein expression levels within resection specimen may serve for establishment of surrogate parameters of patient outcome.Conclusion: The inherent challenges of a rare clinical condition (pN1) and two substantially different therapy arms would limit the practicality of a classical randomized study. The concept of a Comprehensive Cohort Design combines the preference of a randomized study, with the option of careful data interpretation within an observational study.Trial Registration: ClinicalTrials.gov: NCT00964977. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases., Patients and Methods: This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death., Results: Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients., Conclusions: In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases., Patients and Methods: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases., Results: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all p<0.05). The calculated concordance-index for the nomogram was 0.73 (concordance indexes of all prognostic factors between 0.54 and 0.6). Based on the nomogram the training cohort was divided into 4 groups and 2-year OS ranged between 24.2% and 76.1% (predicted OS between 30.2% and 78.4%). The nomogram discriminated between risk groups in the two validation cohorts (concordance index 0.68 and 0.67)., Conclusions: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting., Key Message: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting., (Copyright © 2017 Elsevier B.V. All rights reserved.)

To examine the impact of comorbidity on overall survival (OS) in a population-based study of patients with head and neck cancer who were treated between 2009 and 2011. Data of 1094 patients with primary head and neck carcinomas without distant metastasis from the Thuringian cancer registries were evaluated concerning the influence of patient's characteristics and comorbidity on OS. Data on comorbidity prior to head and neck cancer diagnosis was adapted to the Charlson Comorbidity (CCI), age-adjusted CCI (ACCI), head and neck CCI (HNCCI), simplified comorbidity score (SCS), and to the Adult Comorbidity Evaluation-27 (ACE-27). Most patients were male (80%; median age: 60 years; 50% stage IV tumors). Smoking, alcohol abuse, and anemia were registered for 38%, 33%, and 23% of the patients, respectively. Predominant therapy was surgery + radiochemotherapy (30%), surgery (29%), and surgery + radiotherapy (21%). Mean CCI, ACCI, HNCCI, SCS and ACE-27 were 1.0 ± 1.5, 2.6 ± 2.1, 0.6 ± 0.8, 4.4 ± 4.2, and 0.9 ± 0.9, respectively. Median follow-up was 25.7 months. Multivariable analyses showed that higher age, higher UICC stage, no therapy, including surgery or radiotherapy, alcohol abuse, and anemia, higher comorbidity were independent risk factors for worse OS (all P < 0.05). According to the discriminatory power analysis none of the five comorbidity scores was superior to the other scores to prognosticate OS. This population-based study showed that comorbidity is frequent in German patients with head and neck cancer and is an important risk factor for poor OS. Comorbidity should be routinely assessed and taken into account in prospective clinical trials., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background and Purpose: To compare early side effects and patient compliance of accelerated partial breast irradiation (APBI) with multicatheter brachytherapy to external beam whole breast irradiation (WBI) in a low-risk group of patients with breast cancer., Material and Methods: Between April 2004 and July 2009, 1328 patients with UICC stage 0-IIA breast cancer were randomized to receive WBI with 50Gy and a boost of 10Gy or APBI with either 32.0Gy/8 fractions, or 30.1Gy/7 fractions (HDR-brachytherapy), or 50Gy/0.60-0.80Gy per pulse (PDR-brachytherapy). This report focuses on early side-effects and patient compliance observed in 1186 analyzable patients. ClinicalTrials.gov identifier: NCT00402519., Results: Patient compliance was excellent in both arms. Both WBI and APBI were well tolerated with moderate early side-effects. No grade 4 toxicity had been observed. Grade 3 side effects were exclusively seen for early skin toxicity (radiation dermatitis) with 7% vs. 0.2% (p<0.0001), and breast infection with 0% vs. 0.2% (p=n.s.) for patients treated with WBI and APBI. The incidence of grades 1-2 early side effects for WBI and APBI was 86% vs. 21% (p<0.0001) for skin toxicity, 2% vs. 20% (p<0.0001) for mild hematoma, and 2% vs. 5% (p=0.01) for mild breast infection rates, respectively. No differences had been found regarding grades 1-2 early breast pain (26% vs. 29%, p=0.23)., Conclusions: APBI with interstitial multicatheter brachytherapy was tolerated very well and dramatically reduced early skin toxicity in comparison to standard WBI., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The current literature on stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by small patient cohorts with heterogeneous primary tumors, metastases location and dose regimes. Hence, this study established a multi-institutional database of 700 patients treated with SBRT for pulmonary metastases to identify prognostic factors influencing survival and local control., Materials and Methods: All German radiotherapy departments were contacted and invited to participate in this analysis. A total number of 700 patients with medically inoperable lung metastases treated with SBRT in 20 centers between 1997 and 2014 were included in a database. Primary and metastatic tumor characteristics, treatment characteristics and follow-up data including survival, local control, distant metastases, and toxicity were evaluated. Lung metastases were treated with median PTV-encompassing single doses of 12.5Gy (range 3.0-33.0Gy) in a median number of 3 fractions (range 1-13)., Results: After a median follow-up time of 14.3 months, 2-year local control (LC) and overall survival (OS) were 81.2% and 54.4%, respectively. In multivariate analysis, OS was most significantly influenced by pretreatment performance status, maximum metastasis diameter, primary tumor histology, time interval between primary tumor diagnosis and SBRT treatment and number of metastases. For LC, independent prognostic factors were pretreatment performance status, biological effective dose (BED) at PTV isocenter (BEDISO) and single fraction (PTV-encompassing) dose in multivariate analysis. Radiation-induced pneumonitis grade 2 or higher was observed in 6.5% of patients. The only factor significantly influencing toxicity was BEDISO (p=0.006)., Conclusion: SBRT for medically inoperable patients with pulmonary metastases achieved excellent local control and promising overall survival. Important prognostic factors were identified for selecting patients who might benefit most from this therapy approach., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: We compared different image-guidance (IG) strategies for prostate cancer with high-precision IG intensity-modulated radiation therapy (IMRT) using TomoTherapy® (Accuray Inc., Madison, WI, USA) and linear accelerator (LINAC)-IMRT and their impact on planning target volume (PTV) margin reduction. Follow-up data showed reduced bladder toxicity in TomoTherapy patients compared to LINAC-IMRT. The purpose of this study was to quantify whether the treatment delivery technique and decreased margins affect reductions in bladder toxicity., Patients and Methods: Setup corrections from 30 patients treated with helical TomoTherapy and 30 treated with a LINAC were analyzed. These data were used to simulate three IG protocols based on setup error correction and a limited number of imaging sessions. For all patients, gastrointestinal (GI) and genitourinary (GU) toxicity was documented and correlated with the treatment delivery technique., Results: For fiducial marker (FM)-based RT, a margin reduction of up to 3.1, 3.0, and 4.8 mm in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions, respectively, could be achieved with calculation of a setup correction from the first three fractions and IG every second day. Although the bladder volume was treated with mean doses of 35 Gy in the TomoTherapy group vs. 22 Gy in the LINAC group, we observed less GU toxicity after TomoTherapy., Conclusion: Intraprostate FMs allow for small safety margins, help decrease imaging frequency after setup correction, and minimize the dose to bladder and rectum, resulting in lower GU toxicity. In addition, IMRT delivered with TomoTherapy helps to avoid hotspots in the bladder neck, a critical anatomic structure associated with post-RT urinary toxicity.

Purpose: Most radiobiological models for prediction of tumor control probability (TCP) do not account for the fact that many events could remain unobserved because of censoring. We therefore evaluated a set of TCP models that take into account this censoring., Methods and Materials: We applied 2 fundamental Bayesian cure rate models to a sample of 770 pulmonary metastasis treated with stereotactic body radiation therapy at German, Austrian, and Swiss institutions: (1) the model developed by Chen, Ibrahim and Sinha (the CIS99 model); and (2) a mixture model similar to the classic model of Berkson and Gage (the BG model). In the CIS99 model the number of clonogens surviving the radiation treatment follows a Poisson distribution, whereas in the BG model only 1 dominant recurrence-competent tissue mass may remain. The dose delivered to the isocenter, tumor size and location, sex, age, and pretreatment chemotherapy were used as covariates for regression., Results: Mean follow-up time was 15.5 months (range: 0.1-125). Tumor recurrence occurred in 11.6% of the metastases. Delivered dose, female sex, peripheral tumor location and having received no chemotherapy before RT were associated with higher TCP in all models. Parameter estimates of the CIS99 were consistent with the classical Cox proportional hazards model. The dose required to achieve 90% tumor control after 15.5 months was 146 (range: 114-188) Gy10 in the CIS99 and 133 (range: 101-164) Gy10 in the BG model; however, the BG model predicted lower tumor control at long (≳20 months) follow-up times and gave a suboptimal fit to the data compared to the CIS99 model., Conclusions: Biologically motivated cure rate models allow adding the time component into TCP modeling without being restricted to the follow-up period which is the case for the Cox model. In practice, application of such models to the clinical setting could allow for adaption of treatment doses depending on whether local control should be achieved in the short or longer term., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Purpose: To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors., Materials and Methods: A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison., Results: After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort., Conclusions: Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results., Methods: We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519., Findings: Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1.44% (95% CI 0.51-2.38) with APBI and 0.92% (0.12-1.73) with whole-breast irradiation (difference 0.52%, 95% CI -0.72 to 1.75; p=0.42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3.2% with APBI versus 5.7% with whole-breast irradiation (p=0.08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7.6% versus 6.3% (p=0.53). The risk of severe (grade 3) fibrosis at 5 years was 0.2% with whole-breast irradiation and 0% with APBI (p=0.46)., Interpretation: The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival., Funding: German Cancer Aid., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: The objective of this study was to examine patterns of care and survival in a population-based sample of patients with parotid cancer who were treated in Thuringia, a federal state in Germany, between 1996 and 2011., Methods: Data of 295 patients with primary parotid cancer from the Thuringian cancer registry were evaluated for patient's characteristics, tumor stage, incidence, and trends in treatment, cancer-specific survival (CSS), and overall survival (OS)., Results: Stages IV tumors and the amount of tumors in all age cohorts ≥45 years of age increased significantly during the observation period (p = 0.002; age all p < 0.05, respectively). The highest increase in crude incidence was observed for salivary duct carcinomas [relative risk per decade (RR) 5.46; 95% confidence interval (CI) 1.14-26.14] and rare carcinoma subtypes (RR 9.99; 95% CI 1.85-53.94). CSS at 5 years and at 10 years for all patients was 82.4 and 82.4%, respectively. OS at 5 years and at 10 years for all patients was 60.1 and 48.2%, respectively. CSS and OS did not improve over the time. Salivary duct carcinoma showed the lowest 5-year OS (35.6%). Acinic cell carcinoma had the highest OS rate (85.3%). Multivariate Cox models revealed that higher grading (G3/G4) was a more powerful independent predictor of decreased OS than TNM stage., Conclusions: CSS and OS did not improve during the study period. Incidence of parotid cancer increased significantly in elderly patients. It seems that grading is next to patient's age the better predictor of OS than TNM stage.

Background: The new TomoDirect™ modality offers a non-rotational option with discrete beam angles. We have investigated this mode for TBI with the intention to test the feasibility and to establish it as a clinical routine method. Special foci were directed onto treatment planning, dosimetric accuracy and practical aspects., Patients and Methods: TBI plans were calculated with TomoDirect™ for a Rando™ phantom and all patients with an intended fractionated total body irradiation between November 2013 and May 2014 (n = 8). Finally, four of these patients were irradiated with TomoDirect™. Additionally we studied variations in the modulation factor, pitch, field width of Y-jaws and dose grid during optimization. Dose measurements were performed using thermoluminescent rods in the Rando™ phantom, with the Delta4® and with ionization chambers in a solid water phantom., Results: For all eight calculated plans with a prescribed dose of 12 Gy Dmean was 12.09-12.33 Gy (12,25 ± 0.08 Gy), D98 11.2-11.6 Gy (11.45 ± 0.12 Gy) and D2 12.6-13.1 Gy (12.94 ± 0.13 Gy). Dmean of inner lungs was 8.73 ± 0.22 Gy on the left side and 8.69 ± 0.27 Gy on the right side. When single planning parameters are varied with otherwise constant parameters, the modulation factor showed the greatest impact on dose homogeneity and treatment time. The impact of the pitch was marginally, and almost equal homogeneity can be obtained with field width of Y-jaws 5 cm and 2.5 cm. Measurements with thermoluminescent rods (n = 25) in the Rando™ phantom showed a mean dose deviation between measured and calculated dose of 0.66 ± 2.26%. 18 of 25 TLDs had a deviation below 3%, seven of 25 TLDs between 3% and 5%., Conclusion: TBI with TomoDirect™ allows a superior homogeneity compared to conventional methods, where lung blocks are widely accepted. The treatment is performed only in supine position and is robust and comfortable for the patient. TomoDirect™ allows the implementation of organ-specific dose prescriptions. So the discussion about the balance between the need for aggressive treatment and limited toxicity can be renewed with the new potentials of TomoDirect™ - for children as well as for adults - and possibly yield a better clinical outcome in the future.

Introduction: The objective of this study was to examine patterns of care and survival in a population-based sample of patients with head neck cancer (HNC) who were treated in Thuringia, a federal state in Germany, between 1996 and 2011., Methods: Data of 6291 patients with primary HNC from the Thuringian cancer registry were used to evaluate for patient's characteristics, tumor stage, incidence, and trends in treatment and overall survival (OS)., Results: The distribution between stages I-IV did not change significantly during the observation period. Crude incidences of HNC increased significantly between 1996 and 2011 from 13.77 to 20.39 (relative risk [RR]=1.34; 95% confidence interval [CI]=1.25-1.45). This increase was mainly driven by a significant increase of oropharynx cancer (from 3.29 to 5.85; RR=1.67; 95%CI=1.49-1.88) and cancer of the oral cavity (3.41-5.90; RR=1.5; 95%CI=1.33-1.69). The relative frequency of multimodal therapy increased (RR=1.42; 95%CI=1.3-1.55). The use of cetuximab increased (RR=473.32; 95%CI=51.57-4344.51). The 5-year and 10-year OS for the entire cohort was 49.1% and 34.1%, respectively. The multivariable analysis has proven that male gender, age ⩾60years, therapy without surgery, and TNM stage were independent significant negative risk factors for OS (all p<0.0001)., Conclusions: OS did not improve during the study period. Incidence of oral cancer is significantly increasing. Although modern treatment strategies have been included in routine HNC care over the time, outcome has not improved significantly., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Adverse effects and hazards which have their origin from radiation using conventional techniques like 3-D conformal radiotherapy and total radiation doses are well known. However little is known about the sprectum of especially late toxicity after radiation using new technologies like intensity modulated radiotherapy (IMRT) combined with novel target volume and dose concepts. Since IMRT allows for selective protection of the large salivary glands this technique improves the intermediate term quality of life and is the standard of care despite many details need further prospective evaluation. Combining cytotoxic drugs and radiotherapy yield improved survival in well-defined high risk patients. However morbidity and mortality of these protocols are high and deserve special expertise and supportive therapy. EGF-receptor antibodies have gained well defined indications, albeit specific toxicities in combination with irradiation deserve prospective studies and special attention.

Background: Neurocognitive decline observed after radiotherapy (RT) for brain tumors in long time survivors is attributed to radiation exposure of the hippocampus and the subventricular zone (SVZ). The potential of sparing capabilities for both structures by optimized intensity modulated stereotactic radiotherapy (IMSRT) is investigated., Methods: Brain tumors were irradiated by stereotactic 3D conformal RT or IMSRT using m3 collimator optimized for PTV and for sparing of the conventional OARs (lens, retina, optic nerve, chiasm, cochlea, brain stem and the medulla oblongata). Retrospectively both hippocampi and SVZ were added to the list of OAR and their dose volume histograms were compared to those from two newly generated IMSRT plans using 7 or 14 beamlets (IMSRT-7, IMSRT-14) dedicated for optimized additional sparing of these structures. Conventional OAR constraints were kept constant. Impact of plan complexity and planning target volume (PTV) topography on sparing of both hippocampi and SVZ, conformity index (CI), the homogeneity index (HI) and quality of coverage (QoC) were analyzed. Limits of agreement were used to compare sparing of stem cell niches with either IMSRT-7 or IMSRT-14. The influence of treatment technique related to the topography ratio between PTV and OARs, realized in group A-D, was assessed by a mixed model., Results: In 47 patients CI (p ≤  0.003) and HI (p  <  0.001) improved by IMSRT-7, IMSRT-14, QoC remained stable (p  ≥  0.50) indicating no compromise in radiotherapy. 90% of normal brain was exposed to a significantly higher dose using IMSRT. IMSRT-7 plans resulted in significantly lower biologically effective doses at all four neural stem cell structures, while contralateral neural stem cells are better spared compared to ipsilateral. A further increase of the number of beamlets (IMSRT-14) did not improve sparing significantly, so IMSRT-7 and IMSRT-14 can be used interchangeable. Patients with tumors contacting neither the subventricular zone nor the cortex benefit most from IMSRT (p  <  0.001)., Conclusion: The feasibility of neural stem cell niches sparing with sophisticated linac based inverse IMSRT with 7 beamlets in an unselected cohort of intracranial tumors in relation to topographic situation has been demonstrated. Clinical relevance testing neurotoxicity remains to be demonstrated.

Adverse effects and hazards which have their origin from radiation using conventional techniques like 3-D conformal radiotherapy and total radiation doses are well known. However little is known about the sprectum of especially late toxicity after radiation using new technologies like intensity modulated radiotherapy (IMRT) combined with novel target volume and dose concepts. Since IMRT allows for selective protection of the large salivary glands this technique improves the intermediate term quality of life and is the standard of care despite many details need further prospective evaluation. Combining cytotoxic drugs and radiotherapy yield improved survival in well-defined high risk patients. However morbidity and mortality of these protocols are high and deserve special expertise and supportive therapy. EGF-receptor antibodies have gained well defined indications, albeit specific toxicities in combination with irradiation deserve prospective studies and special attention., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for unresectable locally advanced head and neck cancer. This phase I study was designed to investigate the safety and tolerability of a split-dose TPF ICT regimen prior to surgery for locally advanced resectable oral and oropharyngeal cancer., Methods: Patients received TPF split on two dosages on day 1 and 8 per cycle for one or three 3-week cycles prior to surgery and postoperative radiotherapy or radiochemotherapy. Docetaxel was escalated in two dose levels, 40 mg/m2 (DL 0) and 30 mg/m2 (DL -1), plus 40 mg/m2 cisplatin and 2000 mg/m2 fluorouracil per week using a 3 +3 dose escalation algorithm., Results: Eighteen patients were enrolled and were eligible for toxicity and response. A maximum tolerated dose of 30 mg/m2 docetaxel per week was reached. The most common grade 3+ adverse event was neutropenia during ICT in 10 patients. Surgery reached R0 resection in all cases. Nine patients (50%) showed complete pathologic regression., Conclusions: A split-dose regime of TPF prior to surgery is feasible, tolerated and merits additional investigation in a phase II study with a dose of 30 mg/m docetaxel per week., Trial Registration Number: NCT01108042 (ClinicalTrials.gov Identifier).

Conclusion: Neither elective selective neck dissection nor any conservative treatment option in pT2cN0 glottic cancer showed a significant advantage on survival. This should be the basis for future treatment standardization. Obligatory documentation of the R status and cause of death in the cancer registries will improve the data interpretation in the future., Objectives: Optimal adjuvant treatment of pT2cN0 glottic cancer is not well defined. The impact of neck dissection or radio(chemo)therapy for better outcome is unknown., Methods: In a retrospective cancer registry study we analyzed the survival of 73 patients with pT2cN0 glottic cancer in Thuringia, Germany, treated surgically between 1996 and 2005., Results: In all, 35 patients had undergone elective neck dissection, the remaining 38 patients had not. Histopathology revealed occult lymph node metastasis in three patients. Adjuvant radiotherapy was delivered to 17 patients and radiochemotherapy to 4. Overall, 52 patients received an adjuvant treatment. The 5-year recurrence-free survival rate was 60.8% and the 5-year overall survival rate was 56.5%. Multivariate but not univariate analysis revealed age >62 years (p = 0.05) and neck dissection (p = 0.033) as significant negative risk factors for tumor recurrence. Looking at overall survival, the site of primary surgery and radiotherapy were significant univariate risk factors, whereas multivariate analysis did not reveal any independent risk factor. No adjuvant treatment or combinations of adjuvant treatment resulted in better recurrence-free or overall survival (p = 0.253; p = 0.279).

Introduction: A number of national and international societies have published recommendations regarding the required equipment and manpower that is assumed to be necessary to treat a specific number of patients with radiotherapy. None of these recommendations were based on actual time measurements needed for specific radiotherapy procedures. The German Society of Radiation Oncology (DEGRO) was interested in substantiating their recommendations by prospective evaluations of all important core procedures of radiotherapy in the most frequent cancer treated by radiotherapy. The results of the examinations of radiotherapy in head and neck cancer (HNC) patients are presented in this manuscript., Patients and Methods: Four radiation therapy centers (University of Jena, University of Erlangen, University of Düsseldorf and the community hospital of Neuruppin) participated in this prospective study. Working time of the different occupational groups and room occupancies for the core procedures of radiotherapy in HNC were prospectively documented during a 4-month period and subsequently statistically analyzed., Results: The time needed per patient varied considerably between individual patients and between centers for all evaluated procedures. Room occupancy, presence of technicians, and overall medical staff times were 21 min, 26 min, and 42 min, respectively, for planning CT with i.v. contrast medium (n = 79), and 23 min, 44 min, and 51 min respectively, for planning CT without contrast medium (n = 45). Definition of the target volume (n = 91) was the most time consuming procedure for the physicians taking 1 h 45 min on average. Medical physicists spent a mean time of 3 h 8 min on physical treatment planning (n = 97) and 1 h 8 min on authorization of the treatment plan (n = 71). Treatment simulations (n = 185) required an average room occupancy of 23 min, and a mean technicians presence of 47 min. The mean room occupancy (n = 84) was 24 min for the first radiotherapy including portal imaging associated with a mean presence of the technicians of 53 min. For routine radiotherapy sessions (n = 2,012) and routine radiotherapy sessions including portal imaging (n = 407), mean room occupancies were 13 min and 16 min, respectively. The presence of increasing number of technicians was significantly associated with shorter room occupancy. IMRT including portal imaging (n = 213) required an average room occupancy of 24 min and a mean technician time of 48 min., Conclusion: The data presented here allow an estimate of the required machine time and manpower needed for the core procedures of radiotherapy in an average head and neck cancer patient treated with a specific number of fractions. However, one has to be aware that a number of necessary and time consuming activities were not evaluated in the present study.

Background: The positive effect of radiation therapy for patients with advanced oropharyngeal squamous cell carcinoma (OSCC) has been substantially verified. The present work investigated whether a meta-analysis of current data is able to evaluate the effectiveness of postoperative radiotherapy (PORT) in patients with small OSCC (pT1, pT2) and a single ipsilateral lymph node metastasis (pN1)., Methods: The meta-analysis comprises randomized and non-randomized studies. High-risk tumors were excluded and defined by size ≥ pT3/pT4, lymph node involvement ≥ pN2, or presence of additional histological risk factors, e.g., involved positive resection margins, extra nodal spread of the disease, or lymphangiosis carcinomatosa. The primary outcome analyzed mortality between the different treatment arms., Results: Only one prospective randomized clinical trial and six retrospective observational studies were adequate for evaluation. Descriptive analysis revealed a marginally higher mortality in the irradiation group (44% vs. 34%). In contrast, a forest plot presentation of two of seven studies with and without events in the control and therapy arms presented an advantage for the irradiation group with the limitation of large heterogeneity and a lack of statistical significance., Conclusion: Present data are poor and exhibit limited internal and external validity; thus, direct comparison was not possible with the eligible studies. Therefore, a meta-analysis of present data may not serve as the basis for a general treatment recommendation but underlines the need of prospective, randomized, controlled clinical trials.

Purpose: To evaluate the impact of age on treatment-related acute morbidity, on modifications of drug doses and radiotherapy and on disease-free and overall survival in non-elderly and elderly with high-risk cervical cancer treated with concurrent radiochemotherapy following laparoscopic surgery., Methods: One hundred and two patients with high-risk FIGO I - IVA cervical cancer (77 non-elderly [< 60 years] and 25 elderly [≥ 60 years]) were treated by radical hysterectomy with lymphadenectomy (n = 91) and postoperative radiochemotherapy or radical radiochemotherapy alone after laparoscopic lymph node dissection (n = 11) patients received five to six cycles of cis-platin, 40 mg/sqm weekly, given concurrently to pelvic radiotherapy of 45-50.4 Gy in 5-6 weeks. Paraaortic radiotherapy with 45 Gy was performed when laparoscopic staging revealed paraaortic node metastases. Acute morbidity was prospectively scored weekly. Toxicity-related protocol violations (treatment breaks or dose reduction) were related with age, 5-year overall survival (OS) and progression-free survival (PFS) rates., Results: Clinical stages and histologic subtypes were equally distributed. Grade 3/4 leukopenia, anemia, diarrhea and nausea occurred more frequently in the elderly. 16 (22%) non-elderly and 6 (25%) elderly needed a modification of drug dose. 10/77 (13%) non-elderly patients and 11/25 (44%) of the elderly needed an unscheduled treatment break (p = 0.002). OS and PFS were not different between age groups. The 5-year OS rate was 47 ± 6% for non-elderly patients and 45 ± 10% for the elderly. Patients with/without treatment breaks had a 5-year OS rate of 39 ± 11%/48 ± 6%. The 5-year PFS rate is 49 ± 6% for non-elderly patients and 47 ± 11% for the elderly. Patients with/without treatment breaks had a 5-year PFS probability of 50 ± 12%/48 ± 6%. FIGO stage retains its prognostic significance irrespective of age., Conclusions: Concurrent radiochemotherapy caused slightly higher acute toxicity with increasing age. Adjustment of treatment intensity was more frequent in the elderly but did not result in detrimental outcome figures.

Background: Recent developments enable to deliver rotational IMRT with standard C-arm gantry based linear accelerators. This upcoming treatment technique was benchmarked in a multi-center treatment planning study against static gantry IMRT and rotational IMRT based on a ring gantry for a complex parotid gland sparing head-and-neck technique., Methods: Treatment plans were created for 10 patients with head-and-neck tumours (oropharynx, hypopharynx, larynx) using the following treatment planning systems (TPS) for rotational IMRT: Monaco (ELEKTA VMAT solution), Eclipse (Varian RapidArc solution) and HiArt for the helical tomotherapy (Tomotherapy). Planning of static gantry IMRT was performed with KonRad, Pinnacle and Panther DAO based on step&shoot IMRT delivery and Eclipse for sliding window IMRT. The prescribed doses for the high dose PTVs were 65.1Gy or 60.9Gy and for the low dose PTVs 55.8Gy or 52.5Gy dependend on resection status. Plan evaluation was based on target coverage, conformity and homogeneity, DVHs of OARs and the volume of normal tissue receiving more than 5Gy (V5Gy). Additionally, the cumulative monitor units (MUs) and treatment times of the different technologies were compared. All evaluation parameters were averaged over all 10 patients for each technique and planning modality., Results: Depending on IMRT technique and TPS, the mean CI values of all patients ranged from 1.17 to 2.82; and mean HI values varied from 0.05 to 0.10. The mean values of the median doses of the spared parotid were 26.5Gy for RapidArc and 23Gy for VMAT, 14.1Gy for Tomo. For fixed gantry techniques 21Gy was achieved for step&shoot+KonRad, 17.0Gy for step&shoot+Panther DAO, 23.3Gy for step&shoot+Pinnacle and 18.6Gy for sliding window.V5Gy values were lowest for the sliding window IMRT technique (3499 ccm) and largest for RapidArc (5480 ccm). The lowest mean MU value of 408 was achieved by Panther DAO, compared to 1140 for sliding window IMRT., Conclusions: All IMRT delivery technologies with their associated TPS provide plans with satisfying target coverage while at the same time respecting the defined OAR criteria. Sliding window IMRT, RapidArc and Tomo techniques resulted in better target dose homogeneity compared to VMAT and step&shoot IMRT. Rotational IMRT based on C-arm linacs and Tomotherapy seem to be advantageous with respect to OAR sparing and treatment delivery efficiency, at the cost of higher dose delivered to normal tissues. The overall treatment plan quality using Tomo seems to be better than the other TPS technology combinations.

Purpose: To evaluate the role of pre-interventional fused high resolution T2-weighted images with parametrically analysed dynamic contrast enhanced T1-weighted magnetic resonance (MR) images (DCE-MRI) and 1H magnetic resonance spectroscopy (MRS) for a precise biopsy for the detection of prostate cancer and for the delineation of intraprostatic subvolumes for intensity modulated radiation therapy (IMRT)., Inclusion Criteria: Pathological prostate-specific antigen values (PSA) and/or previously negative transrectal ultrasound guided biopsy. Standardised biopsy of the prostate divided into 20 regions. Image fusion of coloured parametric maps derived from DCE-MRI and MRS (single voxel spectroscopy, SVS; chemical shift imaging, CSI) with T2 images for morphological localisation using the MR-workstation, a separate CAD-workstation (CAD: computer aided diagnosis) or a radiation treatment planning system. Correlation of these intraprostatic subvolumes with histology and cytokeratin-positive areas in prostatectomy species., Results: DCE-MRI: Sensitivity 82%, specificity 89%, accuracy 88%, positive predictive value 61%, negative predictive value 96%. SVS: Sensitivity 55%, specificity 62%. CSI: Sensitivity 68%, specificity 67%. False positive findings due to prostatitis, adenomatous hyperplasia, false negative findings due to low signal (PIN (prostatic intraepithelial neoplasia), cut-off level for DCE-MRI: lesions smaller 3 mm and less than 30% cancer cells, for SVS: lesions smaller 8 mm and less than 50% cancer cells), for CSI: lesions smaller 4 mm and less than 40% cancer cells. Our MR data are correlated with published choline PET/CT data (PET/CT: hybrid scanner of positron emission tomography and computed tomography)., Conclusions: DCE-MRI and MRS are helpful for a precise biopsy of the prostate. The European Society for Therapeutic Radiology and Oncology (ESTRO) guidelines 2006 for radiation treatment planning of the prostate have to be revised, if the standardised biopsy will be replaced by a lesion-orientated biopsy. Until now it is unclear, if the parametric maps of DCE-MRI and MRS can be used for radiation treatment planning of the prostate.

In the present study, the impact of respiratory gating on the beam characteristics of a linear accelerator is investigated. The main focus is put on the influence of the duty cycle. Measurements were performed on a linear accelerator type Oncor (Siemens) with photon energies 6 MV and 15 MV, equipped with the Anzai gating system AZ-733V. Depth dose curves and beam profiles were found not to be significantly altered by gating even for duty cycles down to 5% for realistic respiration frequencies (dose variations all <2.5%). However, for very small duty cycles, the absolute dosimetry changes significantly (dose deviations > 10%), leading to clinically relevant underdoses. The crucial parameter for the dosimetry is the number of monitor units per gate. Our results imply that treatment planning for respiratory gating can be performed on the basis of data obtained under ungated operation if and only if the absolute gates sizes during treatment are sufficiently large. The limiting values for the gate sizes have to be determined individually for each accelerator.

Purpose: To quantify the relative peripheral photon doses (PD) to healthy tissues outside the treated region for different IMRT technologies and linac head designs., Material and Methods: Measurements were performed on an Elekta linac for various energies (6 MV, 10 MV, 25 MV) at different depths at a distance of 29 cm off-axis (vertical measurements) and different distances from the field edge at constant depth of 10 cm (horizontal measurements). These measurements were compared with results obtained on a Siemens linac at 6 MV and 15 MV. TLD-700 detectors were used to quantify the PDs relative to the dose in the volume exposed with the primary beam. Intensity modulated (IM)-beams with identical fluence patterns were generated with a segmental multileaf (sMLC) technique and with lead-containing cerrobend compensators (MCP96). PD values of IM beams were compared with open beam values. All measurement results of the two different linacs, the different IM methods and the different energies were normalized to the same mean dose., Results: PD values were distinctly higher near the surface (0.5-20 mm) than at larger depth and showed the same trend for all photon beam energies. In comparison with the open field, the photon dose component of PD for IM beams delivered with a segmental MLC technique were increased by a factor varying from 1.2 to 1.8, depending on photon energy and depth. This ratio was around 2 for compensator based IMRT. Depending on depth and distance from the field edge the PD on the Siemens machine was about 30% to 50% higher than on the Elekta machine for the same nominal photon energy., Conclusion: The treatment head design of a linac has a large impact on PD in IMRT as well as for open beams. PD can be minimized by proper selection of treatment delivery method and photon beam energy.

Differences in tumorbiology and age-associated changes, such as an impaired functional status and the presence of comorbidities, can result in treatment decisions differing from established standards, as standard treatments have often been established through clinical trials mainly including younger patients. Neither therapeutic nihilism due to advanced age nor treatment according to established standards at all costs is the optimal treatment for elderly patients. This article summarizes recently published data regarding the treatment of elderly patients according to main tumor types., (Copyright 2009 S. Karger AG, Basel.)

Objective: The primary goal of this study was to examine the need for psychosocial support in a consecutive sample of cancer patients undergoing radiotherapy (RT). Out of an initial sample of 250 patients, 239 patients could be assessed at the beginning of their RT. Two hundred eight patients were reassessed at the end of RT 4-8 weeks later., Methods: Measures comprised the Hornheide Screening Instrument, the Multidimensional Fatigue Inventory, the Resilience Scale, and the Short Form 12 as a measure of health-related quality of life (QoL). Medical and radiological data were continuously registered., Results: Within the sample, the need for psychosocial support as reflected in the screening instrument was high (>70%). Patients with the need for psychosocial support revealed significantly higher fatigue scores than patients who where not identified as needing psychosocial support. Furthermore, a negative correlation of the need for psychosocial support and QoL as well as resilience could be observed. QoL turned out to be the strongest predictor for the need of psychosocial support., Conclusion: The study confirmed that the need for psychosocial support is an important aspect in the treatment of cancer patients undergoing RT, which appeared to be powerfully predicted by the patients' health-related QoL. Fatigue turned out to be an important illness- and treatment-related factor that affects QoL. Psychological interventions for cancer patients should explicitly focus on decreasing patients' fatigue and increasing their resilience, thus improving their QoL.

Purpose: To assess the incidence of clinical lymph edema after lymphadenectomy and postoperative radiotherapy (RT)., Patients and Methods: From 1994-2002 192 patients with risk factors for recurrence received radiotherapy with FIGO I (58.8%), II (35.4%), III (4.2%) or IV (1.6%). RT consisted of teletherapy (10.4%), brachytherapy of the vaginal vault (20.8%) or a combination of both (68.8%). Additional chemotherapy was given in 69 patients (35.9%). Surgery comprised laparoscopically assisted radical vaginal hysterectomy (LARVH) (35.4%), radical abdominal hysterectomy (RAH) (48.4%), simple hysterectomy (HE) (11.5%) or exenteration (4.7%)., Results: 73 patients had lymph node metastases, 119 had negative lymph nodes. In patients with LARVH 6-74 (median 30) lymph nodes were removed, with RAH 3-70 (median 21 lymph nodes), and after HE or exenteration 5-50 (median 13 lymph nodes). 90 patients had 25 or less lymph nodes removed, 83 patients more than 25 lymph nodes removed. Prognostic factors, such as age, FIGO stages, histologic grading and type of histology were well balanced in these cohorts. 45 (23.4%) of all patients developed clinically relevant lymph edema of the lower limb with a median latency of 11 (1-121) months. When 25 or less lymph nodes were removed 17.8% of patients developed leg edema, when more than 25 lymph nodes were removed 32.5% of patients were diagnosed with lymph edema (p = 0.025). Radiotherapy and chemotherapy had no influence on the incidence of leg edema. Overall survival at 5 (10) years was independent of number of lymph nodes removed., Conclusion: The data suggest increasing rates of leg edema with increasing number of lymph nodes dissected independent of the type of radiotherapy and chemotherapy performed. The lymph node sampling policy should be planned carefully in respect to minimize the risk of leg lymph edema.

Purpose: To quantify the relative peripheral doses (PD) to healthy tissues outside the treated region for different intensity-modulated radiotherapy (IMRT) technologies., Material and Methods: On a linear accelerator (linac) Oncor Impression (Siemens OCS) with two photon energies (6 MV, 15 MV), point dose measurements were performed at different depths in a solid phantom at 29 cm off-axis distance inplane. PD associated with artificial fluence distributions were compared with open beam contributions, where intensity-modulated (IM) beams were generated by segmented multileaf-modulated (sMLM) IMRT, by tin+wax compensators (TWComp), and by lead-containing cerrobend compensators (CComp). The field size of the open field and the maximum area (isocenter distance) exposed with the primary beam for the IMRT fields was 20 x 22 cm2. Measurements were performed with two kinds of thermoluminescence dosimeters to quantify photon and neutron components separately. Furthermore, experiments were done with and without phantom material in the direct beam to separate different scatter dose components., Results: The results for the photon components and the neutron components are reverse. For the open field, the photon components increase with decreasing photon energy. In comparison with the open field, the photon components are further (factor 1.2-1.8 depending on energy and depth) increased when delivering IMRT with sMLM. When using CComp or TWComp, this factor is even higher and reaches a maximum of 2.4. At depths beyond 20 mm, photon component values slightly decrease with increasing photon energy for all types of IMRT techniques. Near the surface (10 mm depth), photon component values are distinctly higher than those at larger depth, and they increase with increasing photon energy. As expected, neutron components could be detected only for 15 MV. For sMLM and compensators, neutron components increased by factors 4 and 1.5 relative to the open field. The experiments with different scatter conditions show that about 50-70% of the photon components and all neutron components NPD are caused by radiation emanating from the linac head., Conclusion: PD in IMRT can be minimized by proper selection of treatment delivery method and photon beam energy. When selecting the IMRT technique in centers where compensator IMRT and MLC IMRT is available, PD burden should be taken into account. The large amount of photon components and neutron components caused by leakage radiation from the treatment head leads to the recommendation that radiation protection aspects for patients undergoing IMRT should be considered in linac design. For further clarification, additional experiments have to be carried out on other types of linacs.