Prior surgical intervention and tumor size impact clinical outcome after precision radiotherapy for the treatment of optic nerve sheath meningiomas (ONSM)

<p>Abstract</p> <p>Purpose</p> <p>We analyzed our long-term experience with fractionated stereotactic radiotherapy (FSRT) in patients with meningioma of the optic nerve sheath (ONSM).</p> <p>Patients and Methods</p> <p>Between January 1991 and January 2010, 40 patients with ONSM were treated using FSRT. Of these, 19 patients received radiotherapy as primary treatment, and 21 patients were treated after surgical resection. The median target volume was 9.2 ml, median total dose was 54 Gy in median single fractions of 1,8 Gy.</p> <p>Results</p> <p>Local progression-free survival was 100%. Median survival after FSRT was 60 months (range 4-228 months). In all patients overall toleration of FSRT was very good. Acute toxicity was mild. Prior to RT, 29 patients complained about any kind of visual impairment including visual field deficits, diplopia or amaurosis. Prior surgical resection was identified as a negative prognostic factor for visual outcome, whereas patients with larger tumor volumes demonstrated a higher number of patients with improvement of pre-existing visual deficits.</p> <p>Conclusion</p> <p>Long-term outcome after FSRT for ONSM shows improved vision in patients not treated surgically prior to RT; moreover, the best improvement of visual deficits are observed in patients with larger target volumes. The absence of tumor recurrences supports that FSRT is a strong alternative to surgical resection especially in small tumors without extensive compression of normal tissue structures</p

The influence of orthopedic corsets on the incidence of pathological fractures in patients with spinal bone metastases after radiotherapy

Background: Clinical care of unstable spinal bone metastases in many centers often includes patient immobilization by means of an orthopedic corset in order to prevent pathological fractures. The aim of this retrospective analysis was to evaluate the incidence of pathological fractures after radiotherapy (RT) in patients with and without orthopedic corsets and to assess prognostic factors for pathological fractures in patients with spinal bone metastases. Methods: The incidence of pathological fractures in 915 patients with 2.195 osteolytic metastases in the thoracic and lumbar spine was evaluated retrospectively on the basis of computed tomography (CT) scans between January 2000 and January 2012 depending on prescription and wearing of patient-customized orthopedic corsets. Results: In the corset group, 6.8 and 8.0 % in no-corset group showed pathological fractures prior to RT, no significant difference between groups was detected (p = 0.473). After 6 months, patients in the corset group showed pathological fractures in 8.6 % and in no-corset group in 9.3 % (p = 0.709). The univariate and bivariate analyses demonstrated no significant prognostic factor for incidence of pathological fractures in both groups. Conclusions: In this analysis, we could show for the first time in more than 900 patients, that abandoning a general corset supply in patients with spinal metastases does not significantly cause increased rates of pathological fractures. Importantly, the incidence of pathological fracture after RT was small

Treatment of meningioma and glioma with protons and carbon ions

The rapid rise of particle therapy across the world necessitates evidence to justify its ever-increasing utilization. This narrative review summarizes the current status of these technologies on treatment of both meningiomas and gliomas, the most common benign and malignant primary brain tumors, respectively. Proton beam therapy (PBT) for meningiomas displays high rates of long-term local control, low rates of symptomatic deterioration, along with the potential for safe dose-escalation in select (but not necessarily routine) cases. PBT is also associated with low adverse events and maintenance of functional outcomes, which have implications for quality of life and cost-effectiveness measures going forward. Data on carbon ion radiation therapy (CIRT) are limited; existing series describe virtually no high-grade toxicities and high local control. Regarding the few available data on low-grade gliomas, PBT provides opportunities to dose-escalate while affording no increase of severe toxicities, along with maintaining appropriate quality of life. Although dose-escalation for low-grade disease has been less frequently performed than for glioblastoma, PBT and CIRT continue to be utilized for the latter, and also have potential for safer re-irradiation of high-grade gliomas. For both neoplasms, the impact of superior dosimetric profiles with endpoints such as neurocognitive decline and neurologic funcionality, are also discussed to the extent of requiring more data to support the utility of particle therapy. Caveats to these data are also described, such as the largely retrospective nature of the available studies, patient selection, and heterogeneity in patient population as well as treatment (including mixed photon/particle treatment). Nevertheless, multiple prospective trials (which may partially attenuate those concerns) are also discussed. In light of the low quantity and quality of available data, major questions remain regarding economic concerns as well

Ion therapy within the trimodal management of superior sulcus tumors: the INKA trial

Background: The standard trimodal treatment concept in locally advanced and non-metastasized non-small-cell superior sulcus tumors consists of a preoperative chemoradiation followed by surgical resection. High linear energy transfer (LET) radiation as, for example, C12 heavy-ion beam therapy theoretically offers biological advantages compared to high energy x-ray therapy as, for example, higher biological efficiency. Methods/Design: In the present prospective, single-armed, open pilot study performed at the Heidelberg Ion-Beam Therapy Center (HIT) in Heidelberg, the radiation treatment within the standard trimodal concept will be exchanged against C12 heavy-ion beam treatment and apply 39GyE in 13 single fractions in combination with a chemotherapy consisting of cisplatin and vinorelbine (local standard). The primary endpoint is feasibility and safety measured by the incidence of NCI-CTCAE grade 3/4 toxicity and/or discontinuation due to any reason. Secondary endpoint is the degree of regression in the histological specimen. The main inclusion criteria are histologically confirmed non-small-cell superior sulcus tumor, nodal disease stage ≤ N2, Karnofsky performance score ≥70%, patient age between 18 and 75 years as well as written informed consent. The main exclusion criteria include medical contraindications against elements of the trimodal treatment concept, PET confirmed nodal disease stage N3, stage IV disease, prior thoracic irradiation and decompensated diseases of the lung, cardio-vascular system, metabolism, hematopoietic and coagulation system and renal function. Furthermore, patients with implanted active medical devices without certification for ion-beam therapy are not allowed to take part in the study. Trial registration number: DRKS00006323 (www.drks.de)

Long term results after fractionated stereotactic radiotherapy (FSRT) in patients with craniopharyngioma: maximal tumor control with minimal side effects

Purpose: There are already numerous reports about high local control rates in patients with craniopharyngioma but there are only few studies with follow up times of more than 10 years. This study is an analysis of long term control, tumor response and side effects after fractionated stereotactic radiotherapy (FSRT) for patients with craniopharyngioma. Patients and methods: 55 patients who were treated with FSRT for craniopharyngioma were analyzed. Median age was 37 years (range 6–70 years), among them eight children < 18 years. Radiotherapy (RT) was indicated for progressive disease after neurosurgical resection or postoperatively after repeated resection or partial resection. A median dose of 52.2 Gy (50 – 57.6 Gy) was applied with typical dose per fraction of 1.8 Gy five times per week. The regular follow up examinations comprised in addition to contrast enhanced MRI scans thorough physical examinations and clinical evaluation. Results: During median follow up of 128 months (2 – 276 months) local control rate was 95.3% after 5 years, 92.1% after 10 years and 88.1% after 20 years. Overall survival after 10 years was 83.3% and after 20 years 67.8% whereby none of the deaths were directly attributed to craniopharyngioma. Overall treatment was tolerated well with almost no severe acute or chronic side effects. One patient developed complete anosmia, another one’s initially impaired vision deteriorated further. In 83.6% of the cases with radiological follow up a regression of irradiated tumor residues was monitored, in 7 cases complete response was achieved. 44 patients presented themselves initially with endocrinologic dysfunction none of them showed signs of further deterioration during follow up. No secondary malignancies were observed. Conclusion: Long term results for patients with craniopharyngioma after stereotactic radiotherapy are with respect to low treatment related side effects as well as to local control and overall survival excellent

Comparison of intensity modulated radiotherapy (IMRT) with intensity modulated particle therapy (IMPT) using fixed beams or an ion gantry for the treatment of patients with skull base meningiomas

<p>Abstract</p> <p>Background</p> <p>To examine the potential improvement in treatment planning for patients with skull base meningioma using IMRT compared to carbon ion or proton beams with and without a gantry.</p> <p>Methods</p> <p>Five patients originally treated with photon IMRT were selected for the study. Ion beams were chosen using a horizontal beam or an ion gantry. Intensity controlled raster scanning and the intensity modulated particle therapy mode were used for plan optimization. The evaluation included analysis of dose-volume histograms of the target volumes and organs at risk.</p> <p>Results</p> <p>In comparison with carbon and proton beams only with horizontal beams, carbon ion treatment plans could spare the OARs more and concentrated on the target volumes more than proton and photon IMRT treatment plans. Using only a horizontal fixed beam, satisfactory plans could be achieved for skull base tumors.</p> <p>Conclusion</p> <p>The results of the case studies showed that using IMPT has the potential to overcome the lack of a gantry for skull base tumors. Carbon ion plans offered slightly better dose distributions than proton plans, but the differences were not clinically significant with established dose prescription concepts.</p

Neurological outcome after emergency radiotherapy in MSCC of patients with non-small cell lung cancer - a prospective trial

Background: The aim of this trial was to investigate neurological outcome after emergency RT in MSCC of NSCLC patients with acute neurological deficit. Methods This pilot trial was prospective, non-randomized, and monocentre, ten patients were treated from July 2012 until June 2013. After onset of neurological symptoms RT was started within 12 hours. The neurological outcome was assessed at baseline, and six weeks after RT using the ASIA Impairment Scale (AIS). Results: The results showed an improved neurological outcome in one patient (10%), one patient (10%) had a decreased, and five patients (50%) a constant outcome after six weeks. Three patients (30%) died within the first six weeks following RT, additional 4 patients (40%) died within 4 month due to tumor progression. Conclusion: In this group of NSCLC patients we were able to show that emergency RT in MSCC with acute neurological deficit had no considerable benefit in neurological outcome. Therefore, short-course regime or best supportive care due to poor survival should be considered for these patients with additional distant metastases. Patients with favorable prognosis may be candidates for long-course RT. Trial Registration: Clinical trial identifier http://www.clinicaltrials.gov

Lymphadenectomy in women with endometrial cancer: aspiration and reality from a radiation oncologist’s point of view

Background: To investigate the meaning of lymphadenectomy (LNE) in women with endometrial cancer (EC) for clinical outcome and secondly to determine the impact of the method of adjuvant radiotherapy (RT) on survival as well as to define prognostic factors. Methods: 322 patients (pts) underwent adjuvant RT for endometrioid EC at our department from 2004 until 2012 and were included in this retrospective study. Chi-square test, LogRank test and Cox regression were used for statistical analyses. Results: Median age at diagnosis: 66 years. FIGO stages: FIGO I 69.4 %, FIGO II 15.3 %, FIGO III 14.5 %, FIGO IV 0.9 %. Surgical staging: 30.6 % pelvic/paraaortic LNE, 45 % sole pelvic LNE, 8.8 % sampling of suspicious lymph nodes, 15.6 % no LNE. Adjuvant chemotherapy (ChT): 3.2 %. Sole intravaginal brachytherapy (IVB): 60.2 %. IVB + external beam radiotherapy (EBRT): 39.8 %. 5-year local recurrence free survival (LRFS): 90.6 %, distant metastases free survival (DMFS): 89.8 %, overall survival (OS):79.3 %. In multivariate analysis age (p = .007), pT stage (p = .029), lymph node status (p = .003), grading (p = .011) and lymphovascular space invasion (LVSI; p = .008) remained as independent prognostic factors for OS. Resection status (p = .01) and LVSI (p = .014) were independent prognostic factors for LRFS and LVSI (p = .008) was the only independent prognostic factor for DMFS. There was no statistically significant survival benefit from LNE in LRFS (p = .561), DMFS (p = .981) or OS (p = .791). 5-year LRFS in stage I and II: 96.0 and 82.9 % after sole IVB, 90.8 and 81.6 % after combined IVB/EBRT (p = .105; p = .970). 5-year OS rates for stage I and II: 86.5 and 71.3 % after sole IVB, 84.2 % and 69.2 % after combined IVB/EBRT (p = .153; p = .619). Conclusion: Comprehensive surgical staging is rarely performed and may be omitted in women with endometrioid EC in stages I-II. Sole IVB delivers equally good local control as combined IVB/EBRT in pts with FIGO stage I and II disease. LVSI deserves more attention as a prognostic factor and these pts may require a combined local and systemic therapy

High-dose single-fraction IMRT versus fractionated external beam radiotherapy for patients with spinal bone metastases: study protocol for a randomized controlled trial

Background: Stereotactic body radiation therapy (SBRT)using intensity-modulated radiotherapy (IMRT) can be a safe modality for treating spinal bone metastasis with enhanced targeting accuracy and an effective method for achieving good tumor control and a rigorous pain response. Methods/design: This is a single-center, prospective randomized controlled trial to evaluate pain relief after RT and consists of two treatment groups with 30 patients in each group. One group will receive single-fraction intensity-modulated RT with 1×24 Gy, and the other will receive fractionated RT with 10×3 Gy. The target parameters will be measured at baseline and at 3 and 6 months after RT. Discussion: The aim of this study is to evaluate pain relief after RT in patients with spinal bone metastases by means of two different techniques: stereotactic body radiation therapy and fractionated RT. The primary endpoint is pain relief at the 3-month time-point after RT. Secondly, quality of life, fatigue, overall and bone survival, and local control will be assessed. Trial registration ClinicalTrials.gov identifier NCT02358720 (June 2, 2015)

Oncogene addiction and radiation oncology: effect of radiotherapy with photons and carbon ions in ALK-EML4 translocated NSCLC

Background: Patients with Echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) positive lung cancer are sensitive to ALK-kinase inhibitors. TAE684 is a potent second generation ALK inhibitor that overcomes Crizotinib resistance. Radiotherapy is an integral therapeutic component of locally advanced lung cancer. Therefore, we sought to investigate the effects of combined radiotherapy and ALK-inhibition via TAE684 in ALK-positive vs. wild type lung cancer cells. Methods: Human non-small cell lung cancer (NSCLC) cell lines harboring wild-type ALK (A549), EML4-ALK translocation (H3122) and murine Lewis Lung Cancer (LLC) cells were investigated. Cells were irradiated with 1–4 Gy X-Rays (320 keV) and carbon ions (Spread-out Bragg Peak, SOBP (245.4–257.0 MeV/u)) at Heidelberg Ion Therapy center. TAE684 was administered at the dose range 0–100 nM. Clonogenic survival, proliferation and apoptosis via caspase 3/7 expression level were assessed in all three cell lines using time-lapse live microscopy. Results: TAE684 inhibited the proliferation of H3122 cells in a dose-dependent manner with a half maximal inhibitory concentration (IC50) of ~ 8.2 nM. However, A549 and LLC cells were relatively resistant to TAE684 and IC50 was not reached at concentrations tested (up to 100 nM) in proliferation assay. The antiproliferative effect of TAE684 was augmented by radiotherapy in H3122 cells. TAE684 significantly sensitized H3122 cells to particle therapy with carbon ions (sensitizer enhancement ratio ~1.61, p &lt; 0.05). Caspase 3/7 activity was evidently enhanced after combination therapy in H3122 cells. Conclusions: This is the first report demonstrating synergistic effects of combined TAE684 and radiotherapy in EML4-ALK positive lung cancer cells. In addition to conventional photon radiotherapy, ALK-inhibition also enhanced the effects of particle irradiation using carbon ions. Our data indicate beneficial effects of combined ALK-inhibition and radiotherapy in treatment of this distinct subpopulation of NSCLC that warrant further evaluation