5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial.

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.

Prostate cancer treated with image-guided helical TomoTherapy® and image-guided LINAC-IMRT : Correlation between high-dose bladder volume, margin reduction, and genitourinary toxicity.

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.

Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1).

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).

Effectiveness of postoperative radiotherapy in patients with small oral and oropharyngeal squamous cell carcinoma and concomitant ipsilateral singular cervical lymph node metastasis (pN1) : A meta-analysis.

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.

Evaluation of time, attendance of medical staff, and resources during radiotherapy for head and neck cancer patients: the DEGRO-QUIRO trial.

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.

[Special considerations in chemo- and radiotherapy and supportive care of elderly patients with cancer]. / Besonderheiten der Chemo- und Radiotherapie bei älteren Tumorpatienten und spezielle Aspekte der supportivenTherapie.

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.

Experimental determination of peripheral photon dose components for different IMRT techniques and linear accelerators.

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.

Experimental determination of peripheral doses for different IMRT techniques delivered by a Siemens linear accelerator.

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.

The need for psychosocial support and its determinants in a sample of patients undergoing radiooncological treatment of cancer.

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.

The influence of resilience on fatigue in cancer patients undergoing radiation therapy (RT).

PURPOSE: The primary goal of the study was to determine if resilience influences fatigue in a consecutive sample of cancer patients treated with radiotherapy (RT) at the beginning and at the end of the treatment. METHODS: Out of an initial sample of 250 patients, 239 could be assessed at the beginning of their RT. Two hundred and eight patients were reassessed at the end of RT 4-8 weeks later. Measures comprised the Resilience Scale (RS), the Multidimensional Fatigue Inventory (MFI), and the SF-12 as a measure of health related Quality of Life (QoL). Medical data were continuously registered. RESULTS: As hypothesized, the sample revealed higher scores in the MFI and lower scores in the SF-12 than normative samples. Resilience scores were higher than in the norm population. Fatigue increased during RT. Using multiple regression analyses, fatigue scores at the beginning of treatment were shown to be higher in inpatients and patients undergoing palliative treatment. Initial fatigue was best predicted by the patients' initial resilience scores. Changes of fatigue scores during RT depended on initial scores, decrease in Hb and the patients' experience with RT. Resilience could not be determined as a predictor of changes in fatigue during RT. CONCLUSIONS: The study confirmed that fatigue is an important problem among RT patients. Resilience turned out to powerfully predict the patients' fatigue at least early in RT. This result is in line with other studies, showing resilience to be an important psychological predictor of QoL and coping in cancer patients. On the other hand, resilience seems to have little influence on treatment related fatigue during RT.

[Radiophysical characteristics of different detectors for use in dosimetry]. / Strahlenphysikalische Einflussgrössen bei der Dosimetrie mit verschiedenen Detektortypen.

The present study investigated the radiophysical influences on the measurement of dosimetry basic data, attributable to field size, photon energy and detector type. A natural diamond detector, two ionisation chambers, different Si-diodes and a EBT-Gafchromic film were studied for this purpose. The characteristics of the detectors were investigated with regard to the measurement of output factors, lateral beam profiles and relative depth-dose curves for narrow and wide photon beams of 15 MV Significant differences in output factors were obtained with different detectors. For narrow fields, the natural diamond detector and the diodes PTW-60012 and SCX_WH-PFD measured output factors close to those of the EBT-Gafchromic film. The output facto rfor large fields was overestimated by the unshielded diode PTW 60012 and the PinPoint-chamber PTW-31006 because of their over-response to scattered photons. The relative depth dose distributions for wide beams at large depths agree well for the diamond, the ionisation chambers and the shielded Diode SCX_ WH-PFD and PTW-60008, while the measured dose was overestimated by an unshielded diode PTW-60012. Considering the influence due to the sensitive materials and the construction of the detectors the manufacturers of dosimeters have specified the application ranges for the various types of detectors.

Role of comorbidity on outcome of head and neck cancer: a population-based study in Thuringia, Germany.

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.

Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy.

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.

Bayesian Cure Rate Modeling of Local Tumor Control: Evaluation in Stereotactic Body Radiation Therapy for Pulmonary Metastases.

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.

Stereotactic body radiotherapy (SBRT) for medically inoperable lung metastases-A pooled analysis of the German working group "stereotactic radiotherapy".

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.

GEC-ESTRO multicenter phase 3-trial: Accelerated partial breast irradiation with interstitial multicatheter brachytherapy versus external beam whole breast irradiation: Early toxicity and patient compliance.

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.

Intensity-modulated Total Body Irradiation (TBI) with TomoDirect™.

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.

Incidence, treatment, and outcome of parotid carcinoma, 1996-2011: a population-based study in Thuringia, Germany.

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.

Molecular whole-body cancer staging using positron emission tomography: consequences for therapeutic management and metabolic radiation treatment planning.

A prospective analysis was performed in 124 non-small cell lung cancer patients to determine the role of F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) for molecular (metabolic) staging (n=63), therapy monitoring after induction-chemotherapy (n=34), and conformal radiation treatment planning (n=27). Staging by FDG-PET was significantly more accurate than CT (p<0.001) and changed therapeutic management in 52% of all patients. After induction-chemotherapy, patients with complete metabolic remission histologically did not show vital tumor cells in contrast to patients with metabolic partial remission or progressive disease. Metabolic radiation treatment planning by PET led to smaller planning target volumes (PTVs) for radiation therapy (between 3% and 21% in 25/27 patients), resulting in a reduction of dose exposure to healthy tissue. In two patients, PET-PTV was larger than CT-based PTV, since PET detected lymph node metastases smaller than 1 cm. FDG-PET provides clinically important information; changes therapeutic management, can predict noninvasively effectiveness of chemotherapy, and may lead to better tumor control with less radiation-induced toxicity.

[Intensity modulated radiotherapy (IMRT) with compensators]. / Intensitätsmodulierte Strahlentherapie (IMRT) mit Kompensatoren.

The irradiation with intensity-modulated fields is possible with static as well as dynamic methods. In our university hospital, the intensity-modulated radiotherapy (IMRT) with compensators was prepared and used for the first time for patient irradiation in July 2001. The compensators consist of a mixture of tin granulate and wax, which is filled in a milled negative mould. The treatment planning is performed with Helax-TMS (MDS Nordion). An additional software is used for editing the modulation matrix ("Modifix"). Before irradiation of the first patient, extensive measurements have been carried out in terms of quality assurance of treatment planning and production of compensators. The results of the verification measurements have shown that IMRT with compensators possesses high spatial and dosimetric exactness. The calculated dose distributions are applied correctly. The accuracy of the calculated monitor units is normally better than 3%; in small volumes, further dosimetric inaccuracies between calculated and measured dose distributions are mostly less than 3%. Therefore, the compensators contribute to the achievement of high-level IMRT even when apparatuses without MLC are used. This paper describes the use of the IMRT with compensators, presents the limits of this technology, and discusses the first practical experiences.