External-Beam-Accelerated Partial-Breast Irradiation Reduces Organ-at-Risk Doses Compared to Whole-Breast Irradiation after Breast-Conserving Surgery.

In order to evaluate organ-at-risk (OAR) doses in external-beam-accelerated partial-breast irradiation (APBI) compared to standard whole-breast irradiation (WBI) after breast-conserving surgery. Between 2011 and 2021, 170 patients with early breast cancer received APBI within a prospective institutional single-arm trial. The prescribed dose to the planning treatment volume was 38 Gy in 10 fractions on 10 consecutive working days. OAR doses for the contralateral breast, the ipsilateral, contralateral, and whole lung, the whole heart, left ventricle (LV), and the left anterior descending coronary artery (LAD), and for the spinal cord and the skin were assessed and compared to a control group with real-world data from 116 patients who underwent WBI. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Compared to WBI, APBI led to reduced OAR doses for the contralateral breast (0.4 ± 0.6 vs. 0.8 ± 0.9 Gy, p = 0.000), the ipsilateral (4.3 ± 1.4 vs. 9.2 ± 2.5 Gy, p = 0.000) and whole mean lung dose (2.5 ± 0.8 vs. 4.9 ± 1.5 Gy, p = 0.000), the mean heart dose (1.6 ± 1.6 vs. 1.7 ± 1.4 Gy, p = 0.007), the LV V23 (0.1 ± 0.4 vs. 1.4 ± 2.6%, p < 0.001), the mean LAD dose (2.5 ± 3.4 vs. 4.8 ± 5.5 Gy, p < 0.001), the maximum spinal cord dose (1.5 ± 1.1 vs. 4.5 ± 5.7 Gy, p = 0.016), and the maximum skin dose (39.6 ± 1.8 vs. 49.1 ± 5.8 Gy, p = 0.000). APBI should be recommended to suitable patients to minimize the risk of secondary tumor induction and the incidence of consecutive major cardiac events.

Synthetic CTs for MRI-only brain RT treatment: integration of immobilization systems.

PURPOSE: Auxiliary devices such as immobilization systems should be considered in synthetic CT (sCT)-based treatment planning (TP) for MRI-only brain radiotherapy (RT). A method for auxiliary device definition in the sCT is introduced, and its dosimetric impact on the sCT-based TP is addressed. METHODS: T1-VIBE DIXON was acquired in an RT setup. Ten datasets were retrospectively used for sCT generation. Silicone markers were used to determine the auxiliary devices' relative position. An auxiliary structure template (AST) was created in the TP system and placed manually on the MRI. Various RT mask characteristics were simulated in the sCT and investigated by recalculating the CT-based clinical plan on the sCT. The influence of auxiliary devices was investigated by creating static fields aimed at artificial planning target volumes (PTVs) in the CT and recalculated in the sCT. The dose covering 50% of the PTV (D50) deviation percentage between CT-based/recalculated plan (∆D50[%]) was evaluated. RESULTS: Defining an optimal RT mask yielded a ∆D50[%] of 0.2 ± 1.03% for the PTV and between -1.6 ± 3.4% and 1.1 ± 2.0% for OARs. Evaluating each static field, the largest ∆D50[%] was delivered by AST positioning inaccuracy (max: 3.5 ± 2.4%), followed by the RT table (max: 3.6 ± 1.2%) and the RT mask (max: 3.0 ± 0.8% [anterior], 1.6 ± 0.4% [rest]). No correlation between ∆D50[%] and beam depth was found for the sum of opposing beams, except for (45°â€¯+ 315°). CONCLUSION: This study evaluated the integration of auxiliary devices and their dosimetric influence on sCT-based TP. The AST can be easily integrated into the sCT-based TP. Further, we found that the dosimetric impact was within an acceptable range for an MRI-only workflow.

End-to-end testing for stereotactic radiotherapy including the development of a Multi-Modality phantom.

PURPOSE: A new insert for a commercially available end-to-end test phantom was designed and in-house manufactured by 3D printing. Subsequently, the insert was tested for different stereotactic radiation therapy workflows (SRS, SBRT, FSRT, and Multimet) also in comparison to the original insert. MATERIAL AND METHODS: Workflows contained imaging (MR, CT), treatment planning, positioning, and irradiation. Positioning accuracy was evaluated for non-coplanar x-ray, kV- and MV-CBCT systems, as well as surface guided radiation therapy. Dosimetric accuracy of the irradiation was measured with an ionization chamber at four different linear accelerators including dynamic tumor tracking for SBRT. RESULTS: CT parameters of the insert were within the specification. For MR images, the new insert allowed quantitative analysis of the MR distortion. Positioning accuracy of the phantom with the new insert using the imaging systems of the different linacs was < 1 mm/degree also for MV-CBCT and a non-coplanar imaging system which caused > 3 mm deviation with the original insert. Deviation of point dose values was <3% for SRS, FSRT, and SBRT for both inserts. For the Multimet plans deviations exceeded 10% because the ionization chamber was not positioned in each metastasis, but in the center of phantom and treatment plan. CONCLUSION: The in-house manufactured insert performed well in all steps of four stereotactic treatment end-to-end tests. Advantages over the commercially available alternative were seen for quantitative analysis of deformation correction in MR images, applicability for non-coplanar x-ray imaging, and dynamic tumor tracking.

External Beam Accelerated Partial Breast Irradiation in Early Breast Cancer and the Risk for Radiogenic Pneumonitis.

In order to evaluate the risk for radiation-associated symptomatic pneumonitis in a prospective external beam accelerated partial breast irradiation (APBI) trial, between 2011 and 2021, 170 patients with early stage breast cancer were enclosed in the trial. Patients were eligible for study participation if they had a histologically confirmed breast cancer or an exclusive ductal carcinoma in situ (DCIS), a tumor size ≤3 cm, free safety margins ≥2 mm, no involved axillary lymph nodes, tumor bed clips, and were ≥50 years old. Patients received APBI with 38 Gy with 10 fractions in 10 consecutive working days. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Median follow-up was 56 (1−129) months. Ipsilateral lung MLD, V20, and V30 were 4.3 ± 1.4 Gy, 3.0 ± 2.0%, and 1.0 ± 1.0%, respectively. Radiogenic pneumonitis grade 2 appeared in 1/170 (0.6%) patients two months after radiotherapy. Ipsilateral MLD, V20, and V30 were 6.1 Gy, 7, and 3% in this patient. Additionally, individual radiosensitivity was increased in this specific patient. Compared to WBI, APBI leads to lower lung doses. Using APBI, the risk of symptomatic radiogenic pneumonitis is very low and may be limited, with an ipsilateral V20 < 3% to very exceptional cases associated with innate risk factors with an increased radiation susceptibility.

12â€¯× 6 Gy stereotactic radiotherapy for lung tumors. Is there a difference in response between lung metastases and primary bronchial carcinoma?

PURPOSE: The aim of this study was to evaluate the safety and long-term tumor control after stereotactic radiotherapy (SRT) with 12â€¯× 6 Gy of patients with primary bronchial carcinoma (BC) or with pulmonary metastases (MET) of various solid tumors. Local progression-free survival (LPFS), progression-free survival (PFS), overall survival (OS), and prognostic factors were compared. METHODS: Between May 2012 and January 2020, 168 patients with 206 pulmonary lesions (170 MET and 36 primary BC) were treated with 12â€¯× 6 Gy (BED10 116 Gy). The irradiated pulmonary MET were from the following cancers: 47 (27.6%) head and neck, 37 (21.8%) rectum or colon, 30 (17.6%) bronchial, 13 (7.6%) malignant melanoma, 9 (5.3%) esophageal, 9 (5.3%) sarcoma, and 25 (14.8%) other. RESULTS: The median follow-up was 16.26 months (range: 0.46-89.34) for BC and 19.18 months (0.89-91.11) for MET. Survival rates at 3 years were: OS 43% for BC and 35% for MET; LPFS BC 96% and MET 85%; PFS BC 35% and MET 29%. The most frequently observed grade 3 adverse events (AEs) were pneumonitis (5.9% BC, 4.8% MET), pulmonary fibrosis (2.9% BC, 4% MET), and pulmonary embolism (2.9% BC, 0.8% MET). The favorable prognostic effects on overall survival of patients with MET were female gender (log-rank: p < 0.001), no systemic progression (log-rank; p = 0.048, multivariate COX regression p = 0.039), and malignant melanoma histology (log-rank; p = 0.015, multivariate COX regression p = 0.020). For patients with BC, it was tumor location within the lower lobe (vs. upper lobe, log-rank p = 0.027). LPFS of patients with metastatic disease was beneficially influenced by female gender (log-rank: p = 0.049). CONCLUSION: The treatment concept of 12â€¯× 6 Gy is associated with 96% local progression-free survival for BC and 85% for pulmonary metastases after 3 years. There was no difference in response after SRT of primary lung carcinoma or pulmonary metastases.

Time course of pain response and toxicity after whole-nerve-encompassing LINAC-based stereotactic radiosurgery for trigeminal neuralgia-a prospective observational study.

PURPOSE: To prospectively evaluate the time course of pain response and toxicity after linear accelerator-based whole-nerve-encompassing radiosurgery (LINAC-SRS) using a uniform treatment schedule for dosing and target volume definition in patients with refractory trigeminal neuralgia. METHODS: From December 2012 to December 2016, 21 patients were treated using a standardized protocol. Patients received LINAC-SRS with 70 Gy to the cisternal portion while aiming for the 90% isodose to fully envelope the nerve in one cross-sectional plane. Data on pain, analgesics, and toxicity were gathered prospectively. Four time intervals (1-6, 6-12, 12-18, and 18-24 months) were defined and compared to baseline and each other. RESULTS: The median follow-up from radiotherapy was 16 months. Freedom from pain was achieved at least once in 90.5, 81.0, and 85.7% of patients for everyday pain, rest pain, and pain peaks, respectively. At 1-6 months, pain was significantly reduced in everyday routine (mean VAS, 2.0/10 vs. 5.8/10; P = 0.004), at rest (1.5/10 vs. 4.0/10; P = 0.002), and for pain peaks (2.9/10 vs. 10/10; P < 0.001), as was the number of analgesics (mean 1.5 vs. 2.9; P < 0.001). No significant increase in pain or analgesics was observed for subsequent time intervals. At last follow-up, reduction in pain compared to baseline for everyday routine (2.1/10 vs. 5.8/10; P = 0.010) and for pain peaks (3.3/10 vs. 10/10; P < 0.001) was significant, whereas it was not for rest pain (1.8/10 vs. 3.9/10; P = 0.073). Most toxicities were related to trigeminal nerve impairment, with 42.9% reporting new-onset hypoesthesia at last follow-up. CONCLUSION: This study provides prospective data after whole nerve encompassing LINAC-SRS for trigeminal neuralgia. No significant pain relapse was observed.

Treatment planning for spinal radiosurgery : A competitive multiplatform benchmark challenge.

PURPOSE: To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. METHODS: Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. RESULTS: All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002). CONCLUSIONS: High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.

Stereotactic radiotherapy as primary definitive or postoperative treatment of intracranial meningioma of WHO grade II and III leads to better disease control than stereotactic radiotherapy of recurrent meningioma.

The aim of this study was to evaluate long-term clinical outcome, prognostic factors and quality of life after adjuvant or definitive fractionated stereotactic radiotherapy (SRT) of meningioma WHO grade II and III or at recurrence. 131 patients with 138 meningioma (64 WHO grade II, 16 WHO grade III, 58 without histology) of the skull base, falx and convexity were treated between 01/2002 and 01/2015 at the Erlangen University Hospital by fractionated stereotactic radiotherapy (SRT) as primary treatment (adjuvant or definitive) and at recurrence. 53% (n = 53) lesions of patients with primary tumour received postoperative SRT and 47% (n = 47) as definitive treatment (without surgery). All 38 lesions (100%) of recurrent meningioma underwent surgery followed by SRT. SRT was mostly given in 28, 30 or 25 fractions to a median dose of 54.0 Gy in the reference point. Progression-free-survival at 8 years for patients with meningioma at primary treatment were significantly better with 100% for patients with definitive SRT (p = 0.008) or 85% for patients with adjuvant SRT (p = 0.009) compared to 42% after treatment (surgery + SRT) of recurrence. Progression-free-survival at 8 years for patients with SRT as adjuvant treatment after gross total resection of WHO grade II meningioma were significantly better at 83% (p = 0.016) compared to 46% after adjuvant SRT of recurrence. In 31% of patients after primary treatment and in 38.5% after recurrence treatment an improvement of pain symptoms was achieved. The favourable prognostic factor for better PFS at recurrence treatment was tumor location (skull base or convexity better compared to the falx). Postoperative SRT of WHO grade II meningioma after gross total resection (GTR) can effectively reduce recurrence risk.

Predictors for occlusion of cerebral AVMs following radiation therapy : Radiation dose and prior embolization, but not Spetzler-Martin grade.

BACKGROUND: Intracranial arteriovenous malformations (AVMs) may show a harmful development. AVMs are treated by surgery, embolization, or radiation therapy. OBJECTIVE: This study investigated obliteration rates and side effects in patients with AVMs treated by radiation therapy. METHODS: A total of 40 cases treated between 2005 and 2013 were analyzed. Single-dose stereotactic radiosurgery (SRS) was received by 13 patients and 27 received hypofractionated stereotactic radiation therapy (HSRT). In 20 patients, endovascular embolization had been performed prior to irradiation and 24 patients (60 %) had a history of previous intracranial hemorrhage. RESULTS: Treatment resulted in complete obliteration (CO) in 23/40 cases and partial obliteration in 8/40. CO was achieved in 85 % of patients receiving SRS compared to 44 % of those receiving HSRT. In the HSRT group, a first indication of an influence of AVM volume on obliteration rate was found. Equivalent 2 Gy fraction doses (EQD2) >70 Gy showed an obliteration rate of 50 %. Prior embolization was significantly associated with a higher portion of CO (p = 0.032). Median latency period (24.2 vs. 26 months) until CO was similar in both groups (SRS vs. HSRT). The rate of intracranial hemorrhage in patients with no prior bleeding events was 0 %. CONCLUSION: Excellent obliteration rates were achieved by SRS. Consistent with the literature, this data analysis suggests that the results of HSRT are volume-dependent. Furthermore, regimens with EQD2 doses >70 Gy appear more likely to achieve obliteration than schemes with lower doses. The findings indicate that radiation therapy does not increase the risk of bleeding. Prior embolization may have a good prognostic impact.

Effective local control of vertebral metastases by simultaneous integrated boost radiotherapy: preliminary results.

BACKGROUND: The primary endpoint was to improve local tumour control of patients with metastatic spinal tumours by stereotactic body radiotherapy (SBRT) and dose escalation by simultaneous, integrated boost (PTV-boost). We used a whole vertebral body (PTV-elective) contouring approach. Secondary endpoints were severity of acute and chronic adverse effects and overall survival. METHODS: In all, 33 patients with metastases of the vertebral column were treated at Erlangen University Hospital. SBRT was given in 12 or 10 fractions. The metastatic lesion (PTV-boost) received 3.6 Gy (range 3.0-4.51 Gy) per fraction for a total of 42.0 Gy (24.36-48.0 Gy) and the whole vertebra (PTV-elective) received 2.85 Gy (range 1.8-3.6 Gy) per fraction for a total of 32.39 Gy (range 21.60-38.0 Gy). Patients were followed up every 3 months. RESULTS: Local control rate of all patients was 93% at 12 and 24 months. The overall survival rate was 54% at 12 months, 38% at 24 months and 18% at 36 months. No radiation myelopathy occurred. The most frequently observed adverse events in 3 cases was oesophagitis grade 2. CONCLUSION: SBRT with simultaneous, integrated boost was associated with excellent local control of 93% after 24 months. This result shows the possibility of delivering escalated doses to the target while still keeping the incidence of side effects low. This study forms the basis for a future randomised controlled trial comparing conventional radiotherapy (10 fractions of 3 Gy) with hypofractionated dose intensified SBRT (12 fractions of 3 Gy + integrated boost 12 fractions of 4 Gy) for improvement of local tumour control and pain.

Evaluation of calculation algorithms implemented in different commercial planning systems on an anthropomorphic breast phantom using film dosimetry.

PURPOSE: To evaluate the accuracy of dose calculation algorithms of different planning systems for postoperative tangential radiotherapy in breast cancer. MATERIAL AND METHODS: On a CT dataset of an anthropomorphic phantom, a structure set of the left lung, clinical target volume (CTV), planning target volume, heart, and external contour were delineated. The dataset was processed by six radiation oncology centers participating in this multicenter dosimetry project. Conventional plans with two tangential wedged fields were generated in MasterPlan, Pinnacle, Eclipse, TMS, and PrecisePLAN. Plan calculations were done using the beam data of local linacs. The dose distributions were verified under local conditions with Gafchromic-EBT films. RESULTS: In all planning systems, deviations between calculation and measurement were around +/-3% in the CTV in the measured plane. Only small areas with deviations of +/-5% were detected. Pencil-beam (PB) calculations overestimated the dose inside the lung by up to 23%. Collapsed cone (CC) underestimated the lung dose by up to 6%. CONCLUSION: CC calculates the dose distribution more accurately than PB. Inside regions with electron disequilibrium, however, the dose is slightly underestimated.

Hypofractionated stereotactic radiotherapy for brain metastases--results from three different dose concepts.

PURPOSE: To evaluate efficacy and toxicity of hypofractionated stereotactic radiotherapy (hfSRT) with three different dose concepts for irresectable brain metastases not amenable to radiosurgery (SRS) using non-invasive fixation of the skull. PATIENTS AND METHODS: From 6/2000 to 6/2005, 150 patients with 228 brain metastases were treated at the dedicated stereotactic radiosurgery system Novalis (BrainLAB, Feldkirchen, Germany) in two German treatment centers. Three different dose concepts were applied: 5 x 6-7 Gy (A: 72 brain metastases), 10 x 4 Gy (B: 59 brain metastases) and 7 x 5 Gy (C: 97 brain metastases). Median planning target volume (PTV) was 6.1 cm(3) (range, 0.02-95.97). RESULTS: Rates of complete remission (CR), partial remission (PR), no change (NC) and progressive disease (PD) were 42%, 30%, 21% and 7%, respectively (median follow-up 28 months). Median survival was 16 months. Survival at 6 and 12 months was 83% and 66%, respectively. Side effects were dependent on the PTV and on dose concept (median PTV in case of increasing edema or necrosis: 17 cm3, A: 22%, C: 7%). HfSRT with 10 x 4 Gy (B) was well tolerated without side effects. CONCLUSION: Hypofractionated stereotactic radiotherapy is an effective and safe treatment. In case of brain metastases >15 cm(3) (diameter >3 cm) and concerning toxicity, 10 x 4 Gy seem to be more advantageous than shorter fractionation with higher doses while 5 x 6-7 Gy and 7 x 5 Gy were followed by higher response rates. Further specification of tolerance doses and tolerance according to the different brain regions has to be done.

Survival and quality of life after hypofractionated stereotactic radiotherapy for recurrent malignant glioma.

PURPOSE: To prospectively evaluate efficacy, side effects and quality of life in patients with recurrent malignant glioma after hypofractionated stereotactic radiotherapy. METHODS AND MATERIALS: From 1/2003 to 8/2005, 15 patients with recurrent malignant glioma were prospectively scheduled for hfSRT with 5 x 7 Gy (90%-isodose). Median gross tumor volume and planning target volume were 5.75 (range, 0.77-21.94) and 22.4 (range, 4.22-86.79) cc, respectively. Irradiation was performed with the dedicated stereotactic radiosurgery system Novalistrade mark (BrainLAB, Heimstetten, Germany). RESULTS: Rates of remission, no change and progressive disease were 27%, 33%, and 40%, respectively, after a median follow-up of 9 months. Progression-free survival rates at 6 and 12 months were 75% and 53% respectively. Quality of life, measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire scores could be kept stable in two thirds of the patients for a median time of 9 months, respectively. CONCLUSION: Hypofractionated stereotactic radiotherapy with 5 x 7 Gy of recurrent high grade glioma is an effective treatment that helps to maintain quality of life for an acceptable period, comparable to the results obtained with current chemotherapy schedules. Combined approaches of radiotherapy, chemotherapy and other targeted therapies deserve further inverstigation.

Hypofractionated stereotactic radiotherapy for primary and secondary intrapulmonary tumors: first results of a phase I/II study.

PURPOSE: To evaluate the feasibility, efficacy, and side effects of dose escalation in hypofractionated stereotactic radiotherapy (hfSRT) for intrapulmonary tumors with the Novalis system (BrainLAB AG, Heimstetten, Germany). PATIENTS AND METHODS: From 07/2003 to 01/2005, 21 patients/39 tumors were treated with 5 x 7 Gy (n = 21; total dose 35 Gy) or 5 x 8 Gy (n = 18; total dose 40 Gy). There were three cases of primary lung cancer, the remainder were metastases. Median gross tumor volume (GTV) and planning target volume (PTV) were 2.89 cm(3) (range, 0.15-67.94 cm(3)) and 25.75 cm(3) (range, 7.18-124.04 cm(3)), respectively. RESULTS: Rates of complete remission, partial remission, no change, and progressive disease were 51%, 33%, 3%, and 13%, respectively. No grade 4 toxicity occurred, nearly all patients had grade 1 initially. One grade 3 toxicity, i.e., dyspnea, was documented for a period of 6 months after therapy. Radiosurgery quality assurance guidelines could be met. CONCLUSION: hfSRT of primary and secondary lung tumors using a schedule of five fractions at 7-8 Gy each was well tolerated. Further dose escalation is planned.

Large topographic variability of upper abdominal lymphatics and the consequences for radiation treatment planning.

BACKGROUND AND PURPOSE: Inclusion of regional lymph nodes usually is indicated when treating upper gastrointestinal malignancies. Lymphatics follow the large vessels of this region. Vascular variability with consequences for planning treatment volume (PTV) was studied. MATERIALS AND METHODS: Upper abdominal metric relationship of the vascular origins was analysed in CT scans in 104 patients to estimate its influence on PTV variability. PTV volumes were calculated based on these. Additionally, the PTV size of 3D plans of 34 patients with pancreatic adenocarcinoma (PDAC) was analysed depending on different PTV definitions. RESULTS: Vascular origin varied most for the inferior mesenteric artery (IMA) with substantial PTV size differences. Volumetric variability was analysed for PDAC (IMA versus renal hilum as caudal margin). Additional PTV for IMA was < 100 cc (median) but ranged up to 350 cc in CT (100-199 ml in 14/34 and > 200 ml in 3/34 patients). Data from treatment planning confirmed this observation. CONCLUSIONS: Considerable vascular and lymphatic variability obliges to base PTV on the individual vascular anatomy. For most patients the caudal PTV margin for PDAC can safely be set at the IMA. But PTV should be restricted when the additional volume would lead to a significant increase to avoid haematotoxicity from concomitant gemcitabine which is proportional with PTV size. The risk of kidney toxicity is also subject to PTV expansion in the caudal direction.

Phase II trial of hypofractionated stereotactic radiotherapy for brain metastases: results and toxicity.

PURPOSE: To prospectively evaluate efficacy and side effects of hypofractionated stereotactic radiotherapy (hfSRT) for irresectable brain metastases not amenable to radiosurgery (SRS). METHODS AND MATERIALS: From 1/2003 to 2/2005, 51 patients with 72 brain metastases were included in a prospective phase II-trial and accepted for treatment at the dedicated stereotactic radiosurgery system Novalis (BrainLAB, Heimstetten, Germany). In case of planned or prior whole brain radiotherapy (WBRT), hfSRT was to be performed with 5 x 6 Gy, otherwise with 5 x 7 Gy. This dose was prescribed to the 90% isodose line which should cover 100% of the planning target volume (PTV). RESULTS: Rates of complete remission (CR), partial remission (PR), no change (NC) and progressive disease (PD) were 66.7%, 18.1%, 12.5% and 2.8%, respectively, after a median follow-up of 7 months. Median survival was 11 months. Disease-specific survival and survival related to brain metastases were strongly associated with the size of gross tumor volume (GTV), the planning target volume (PTV), Karnofsky Performance Score (KPS) and number of metastases. Side effects, i.e., increase in T2w-signal area, duration of steroid intake and size of new or progressive necrotic centre of metastasis, were dependent on the volume of normal brain irradiated with more than 4 Gy per fraction (V(4Gy)). Significantly more patients with a V(4Gy)> or =23 cc developed radiological signs of side effects from hfSRT. CONCLUSION: Hypofractionated stereotactic radiotherapy with 5 x 6-7 Gy is an effective and safe treatment for brain metastases not amenable to single high-dose radiosurgery. The normal brain volume receiving >4 Gy per fraction may not exceed 20 cc.

Dose escalation in large anterior skull-base tumors by means of IMRT. First experience with the Novalis system.

PURPOSE: To evaluate the feasibility and tolerance of dose escalation with stereotactic intensity-modulated radiotherapy (sIMRT) for skull-base tumors. PATIENTS AND METHODS: Between 01/2003 and 12/2004, twelve patients were treated. Nine were exclusively treated at the Novalis site with one planning target volume (PTV) field boost, three were administered boost IMRT treatment (two with each one PTV-shrinking field, one with single PTV) after conventional three-dimensional conformal radiotherapy. This resulted in 23 PTVs with a median volume of 93.63 cm3 (range, 88.58-125.88 cm3). Dose calculation was done by the pencil-beam algorithm. Median total doses of 66.6, 77.4, and 63.9 Gy were prescribed for sIMRT alone, sIMRT after 3-D conformal irradiation of the nasopharynx and cervical lymph nodes with 59.4 Gy, and for reirradiation, respectively. RESULTS: 95% isodose PTV coverage was reached in 86.5% (range, 80-93%). Homogeneity (Dmax/Dref) was 1.11, 1.09, and 1.08. Median total doses to 50% of chiasm, right and left optic nerve were 16.21, 16.82 and 10.23 Gy. 11/12 patients are locally controlled with a median follow-up of 11 months (range, 3-23 months), one has died of pulmonary embolism after cerebrospinal dissemination of retinal adenocarcinoma. CONCLUSION: SIMRT enables dose escalation to tumors located close to critical organs. Inverse planning for micro-multileaf collimator stereotactic irradiation is practicable in the daily routine irradiation program. SIMRT needs special verification and still, the following parameters have to be standardized: IMRT dose specification, dose maxima, length of radiation delivery time.

Radiosurgery of small skull-base lesions. No advantage for intensity-modulated stereotactic radiosurgery versus conformal arc technique.

BACKGROUND AND PURPOSE: Intensity-modulated stereotactic radiotherapy (IMSRT) has shown the ability to conform the dose to concavities and to better avoid critical organs for large tumors. Given the availability of an electronically driven micro-multileaf collimator, both intensity-modulated stereotactic radiosurgery (IMSRS) and dynamic conformal arc (DCA) technique (DCA) can be performed at the Novalis Shaped Beam Surgery Center, University of Erlangen-Nuremberg, Germany, since 12/2002. This study evaluates both techniques in small skull-base tumors treated with radiosurgery. MATERIAL AND METHODS: Between 12/2002 and 04/2004, a total of 109 radiosurgical procedures were performed in 77 patients, equally distributed between patients with acoustic neuroma (AN), pituitary adenoma (PA) and meningeoma (M). Six index patients (n = 2 AN, n = 1 PA, n = 3 M) routinely planned for dynamic arc stereotactic radiosurgery were replanned using the IMSRS approach (BrainScan, BrainLAB, Heimstetten, Germany). The RTOG radiosurgery quality assurance guidelines, isodose volumes, doses to organs at risk (OAR), and dose delivery criteria were compared. RESULTS: DCA was superior to IMSRS for homogeneity and coverage. IMSRS could keep the high-dose-irradiated volumes (90% isodose volume) lower than DCA in the PA and AN with very small volumes, but all other lower dose volumes were larger for IMSRS. Dose maxima to OAR were higher for IMSRS. Treatment delivery time for IMSRS would clearly exceed treatment time for DCA by a factor of 2-3. The integral absorbed dose to the brain was much higher in the IMSRS than in the DCA approach (factor 2-3). CONCLUSION: RTOG radiosurgery guidelines were best met by the DCA rather than IMSRS approach for the treatment of small skull-base lesions. The IMSRS approach will increase the time for planning, dose delivery and integral dose to the brain. Thus, IMSRT techniques are recommended for fractionated stereotactic radiotherapy to larger volumes rather than for radiosurgery in small skull-base lesions.

[Fractionated stereotactically guided radiotherapy for pharmacoresistant epilepsy]. / Fraktionierte, stereotaktisch geführte Radiotherapie der pharmakoresistenten Epilepsie.

AIM: This prospective study evaluated the efficiency of fractionated stereotactically guided radiotherapy as a treatment of pharmacoresistant temporal lobe epilepsy. PATIENTS AND METHODS: Inclusion criteria were patients aged between 17 and 65 years with one-sided temporally located focus, without sufficient epilepsy control by antiepileptic drugs or neurosurgery. Between 1997 and 1999, two groups of six patients each were treated with 21 Gy (7 times 3 Gy) and 30 Gy (15 times 2 Gy). Study end points were seizure frequency, intensity, seizure length and neuropsychological parameters. RESULTS: All patients experienced a marked reduction in seizure frequency. The mean reduction of seizures was 37% (range 9-77%, i. e. seizures reduced from a monthly mean number of 11.75 to 7.52) at 18 months following radiation treatment and 46% (23-94%, i. e. 0.2-23 seizures per month) during the whole follow-up time. Seizure length was reduced in five out of eleven patients and intensity of seizures in seven out of eleven patients. CONCLUSION: Radiotherapy was identified as safe and effective for pharmacoresistant epilepsy since a very good reduction of seizure frequency was observed. It is no substitute for regular use of antiepileptic drugs, but means an appropriate alternative for patients with contraindication against neurosurgery or insufficient seizure reduction after neurosurgery.