A Study of 100 Cases

Introduction. Incidence of meningioma increases with age. Surgery has been the mainstay treatment. Elderly patients, however, are at risk of severe morbidity. Therefore, we conducted this study to analyze long-term outcomes of linac-based fractionated stereotactic radiotherapy (FSRT) for older adults (aged ≥65 years) with meningioma and determine prognostic factors. Materials and Methods. Between October 1998 and March 2009, 100 patients (≥65, median age, 71 years) were treated with FSRT for meningioma. Two patients were lost to follow-up. Eight patients each had grade I and grade II meningiomas, and five patients had grade III meningiomas. The histology was unknown in 77 cases (grade 0). Results. The median follow-up was 37 months, and 3-year, 5-year, and 10-year progression-free survival (PFS) rates were 93.7%, 91.1%, and 82%. Patients with grade 0/I meningioma showed 3- and 5-year PFS rates of 98.4% and 95.6%. Patients with grade II or III meningiomas showed 3-year PFS rates of 36%. 93.8% of patients showed local tumor control. Multivariate analysis did not indicate any significant prognostic factors. Conclusion. FSRT may play an important role as a noninvasive and safe method in the clinical management of older patients with meningioma

Significance of tumor mutation burden and immune infiltration in thymic epithelial tumors

Background: Thymic epithelial tumors (TETs) are relatively rare malignant thoracic tumors. Tumor mutation burden (TMB) and immune infiltration play important roles in tumorigenesis. Methods: Research data was obtained using the Cancer Genome Atlas (TCGA) database to evaluate the landscape of tumor mutations, related factors, and relationship of prognosis. The CIBERSORT algorithm was used to evaluate immune cell infiltration in TETs and its relationship with TMB. Immune-related differentially expressed genes (irDEGs) were identified. Hub irDEGs independently related to prognosis were analyzed using univariate and multivariate Cox proportional hazard models. A survival signature was constructed from hub irDEGs. Results A total of 122 patients were included in this study. GTF2I was the most common gene mutation. Higher TMB was significantly associated with the later stage, more advanced pathological type, and older age. The overall survival (OS) of patients in the low-TMB group was significantly better. There was no significant correlation between TMB levels and PD-L1 expression. Enrichment analysis showed that DEGs were mainly involved in the P13K-Akt signaling pathway. There were significant differences in macrophage and other types of immune cell infiltration between the high- and low-TMB groups. CCR5, FASLG, and CD79A independently relating to prognosis were screened from 391 irDEGs. The low-risk group had a significantly better prognosis than the high-risk group based on the signature, which has a good predictive effect on OS. Conclusions: In this study, TETs patients with high TMB had a significantly poor prognosis and an immune-related gene signature was found to effectively evaluate the long-term prognosis

Prognostic indices in stereotactic radiotherapy of brain metastases of non- small cell lung cancer

Background Our purpose was to analyze the long-term clinical outcome and to identify prognostic factors after Linac-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) on patients with brain metastases (BM) from non-small cell lung cancer (NSCLC). Materials and Methods We performed a retrospective analysis of survival on 90 patients who underwent SRS or FSRT of intracranial NSCLC metastases between 04/2004 and 05/2014 that had not undergone prior surgery or whole brain radiotherapy (WBRT) for BM. Follow-up data was analyzed until May 2015. Potential prognostic factors were examined in univariable and multivariable analyses. The Golden Grading System (GGS), the disease-specific graded prognostic assessment (DS-GPA), the RADES II prognostic index as well as the NSCLC-specific index proposed by Rades et al. in 2013 (NSCLC-RADES) were calculated and their predictive values were tested in univariable analysis. Results The median follow-up time of the surviving patients was 14 months. The overall survival (OS) rate was 51 % after 6 months and 29.9 % after 12 months. Statistically significant factors of better OS after univariable analysis were lower International Union Against Cancer (UICC) stage at first diagnosis, histology of adenocarcinoma, prior surgery of the primary tumor and lower total BM volume. After multivariable analysis adenocarcinoma histology remained a significant factor; higher Karnofsky Performance Score (KPS) and the presence of extracranial metastases (ECM) were also significant. The RADES II and the NSCLC-RADES indices were significant predictors of OS. However, the NSCLC-RADES failed to differentiate between intermediate- and low-risk patients. The DS-GPA and GGS were not statistically significant predictors of survival in univariable analysis. Conclusion The ideal prognostic index has not been defined yet. We believe that more specific indices will be developed in the future. Our results indicate that the histologic subtype of NSCLC could add to the prognostic value of specialized future indices. The RADES II index had the highest predictive value in the examined patient cohort

Adjuvant radiotherapy improves progression-free survival in intracranial atypical meningioma

BACKGROUND: Meningiomas are the most common primary tumors of the central nervous system. In patients with WHO grade I meningiomas no adjuvant therapy is recommended after resection. In case of anaplastic meningiomas (WHO grade III), adjuvant fractionated radiotherapy is generally recommended, regardless of the extent of surgical resection. For atypical meningiomas (WHO grade II) optimal postoperative management has not been clearly defined yet. METHODS: We conducted a retrospective analysis of patients treated for intracranial atypical meningioma at Charité Universitätsmedizin Berlin from March 1999 to October 2018. Considering the individual circumstances (risk of recurrence, anatomical location, etc.), patients were either advised to follow a wait-and-see approach or to undergo adjuvant radiotherapy. Primary endpoint was progression-free survival (PFS). RESULTS: This analysis included 99 patients with atypical meningioma (WHO grade II). Nineteen patients received adjuvant RT after primary tumor resection (intervention group). The remaining 80 patients did not receive any further adjuvant therapy after surgical resection (control group). Median follow-up was 37 months. Median PFS after primary resection was significantly longer in the intervention group than in the control group (64 m vs. 37 m, p = 0.009, HR = 0.204, 95% CI = 0.062-0.668). The influence of adjuvant RT was confirmed in multivariable analysis (p = 0.041, HR = 0.192, 95% CI = 0.039-0.932). CONCLUSIONS: Our study adds to the evidence that RT can improve PFS in patients with atypical meningioma

Accelerated hyperfractionation plus temozolomide in glioblastoma

Introduction Hyperfractionated (HFRT) or accelerated hyperfractionated radiotherapy (AHFRT) have been discussed as a potential treatment for glioblastoma based on a hypothesized reduction of late radiation injury and prevention of repopulation. HFRT and AHFRT have been examined extensively in the pre-Temozolomide era with inconclusive results. In this study we examined the role of accelerated hyperfractionation in the Temozolomide era. Materials and methods Sixty-four patients who underwent AHFRT (62 of which received Temozolomide) were compared to 67 patients who underwent normofractionated radiotherapy (NFRT) (64 of which received TMZ) between 02/2009 and 10/2014. Follow-up data were analyzed until 01/2015. Results Median progression-free survival (PFS) was 6 months for the entire cohort. For patients treated with NFRT median PFS was 7 months, for patients treated with AHFRT median PFS was 6 months. Median overall survival (OS) was 13 months for all patients. For patients treated with NFRT median OS was 15 months, for patients treated with AHFRT median OS was 10 months. The fractionation regimen was not a predictor of PFS or OS in univariable- or multivariable analysis. There was no difference in acute toxicity profiles between the two treatment groups. Conclusions Univariable and multivariable analysis did not show significant differences between NFRT and AHFRT fractionation regimens in terms of PFS or OS. The benefits are immanent: the regimen does significantly shorten hospitalization time in a patient collective with highly impaired life expectancy. We propose that the role of AHFRT + TMZ should be further examined in future prospective trials

secondary results of a randomized phase III trial (SAKK 10/94)

Background To analyze the impact of weight loss before and during chemoradiation on survival outcomes in patients with locally advanced head and neck cancer. Methods From 07/1994-07/2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiation therapy alone or the same radiation therapy combined with two cycles of concomitant cisplatin. The primary endpoint was time to any treatment failure (TTF); secondary endpoints were locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Patient weight was measured 6 months before treatment, at treatment start and treatment end. Results The proportion of patients with >5% weight loss was 32% before, and 51% during treatment, and the proportion of patients with >10% weight loss was 12% before, and 17% during treatment. After a median follow-up of 9.5 years (range, 0.1 – 15.4 years) weight loss before treatment was associated with decreased TTF, LRRFS, DMFS, cancer specific survival and OS in a multivariable analysis. However, weight loss during treatment was not associated with survival outcomes. Conclusions Weight loss before and during chemoradiation was commonly observed. Weight loss before but not during treatment was associated with worse survival

Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy - a case series

<p>Abstract</p> <p>Introduction</p> <p>Magnetic resonance imaging (MRI) and computed tomography (CT) with ⁶⁸Ga-DOTATOC positron emission tomography (⁶⁸Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy.</p> <p>Methods</p> <p>Fifty patients with 56 meningiomas of the SB underwent MRI, CT, and ⁶⁸Ga-DOTATOC PET/CT prior to fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma extension, visible on MRI ± CT (MRI/CT) <it>or </it>PET, and were evaluated further. The respective findings were reviewed independently, analyzed with respect to correlations, and compared with each other.</p> <p>Results</p> <p>Within the study group, SB transgression was associated with bony changes visible by CT in 14 patients (81%). Tumorous changes of the foramen ovale and rotundum were evident in 13 and 8 cases, respectively, which were accompanied by skeletal muscular invasion in 8 lesions. We analysed six designated anatomical sites of the SB in each of the 16 patients. Of the 96 sites, 42 had infiltration that was delineable by MRI/CT and PET in 35 cases and by PET only in 7 cases. The mean infracranial volume that was delineable in PET was 10.1 ± 10.6 cm³, which was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm³).</p> <p>Conclusions</p> <p>⁶⁸Ga-DOTATOC-PET allows detection and assessment of the extent of infracranial meningioma invasion. This method seems to be useful for planning fractionated stereotactic radiation when used in addition to conventional imaging modalities that are often inconclusive in the SB region.</p

Image-guided high presicion radiotherapy in clinical management of solid tumors

Die klinische Radioonkologie erfährt seit einigen Jahren rapide und fortwährende Fortschritte der Technologie. Auf der Seite der Hardware scheint es eine hohe Kompetition und Innovation zu geben, dessen Ende momentan nicht absehbar ist. In einer Dekade sind mehrere vom Grund auf innovative Beschleunigermodelle und mittel- und kleinvolumige Geräte präsentiert: Novalis, TomoTherapy, Cybernife, Clinac, Trilogy, TrueBeam, Synergy, Leksell GammKnife, sowie Intrabeam, und viele andere. Seitens der Software, Algorithmen und Rechenleistung sind die Entwicklungen ebenfalls ohne historischen Vergleich. Diese explizit radiotherapeutischen Optionen werden vorangetrieben durch die ständigen Transformationen der Bildgebungstechnologien (MRT, CT, und vor allem PET). Die Synergie der beiden Domänen beherbergt enorme Potenziale für die Onkologie in Richtungen von 4 dimensionalen Systemen der Bildgebung und der Therapie, die die bekannten Limitationen der jetzigen Standard-Radiotherapie überwinden könnten: Bewegung der Zielläsionen und der tumortragenden Organe oder Unterschiede der Ortsauflösung der CT, MRT, PET und andere Verfahren, die in Kombination kompensiert werden könnten. Die Themen heutiger klinischer Radioonkologie sind eng verschränkt mit dem Begriff der „Präzision“. Unter allen klinischen Umständen muss die Präzision messbar, optimierbar, reproduzierbar und beeinflussbar sein. Die Präzision inkludiert die Planung inklusive aller Bildgebungsmethoden, Planungssoftware, Pretests; sowie die Ausführung inklusive der Lagerung, Monitoring einerseits und Strahlenarrangements und Sicherheit anderseits. Bildgeführte hochpräzise Radiotherapie erfasst zunehmend weitere Bereiche der (radio)onkologischen Therapie. Eine kritische Evaluation neuer technologischer Optionen ist unbedingt notwendig, um sie zu richtiger Indikation für den richtigen Patienten einzusetzten. IGRT, im erweiterten Sinn, ist ein Schritt in die richtige Richtung. Die in dieser Schrift erörterten Messungen, Prüfungen und Analysen sind ein Beitrag zum Verständnis konkreter Probleme der Präzision im klinischen Alltag und zugleich ein konzeptueller Faktor. Technologie allein ist weder ein Zweck für sich noch die einzige Treibkraft medizinischer Handlung. Das Ziel bleibt die qualitative Verbesserung der Therapie und deren Resultate für unsere Patienten. Im Sinne einer patienten-orientierten Medizin sollen die neuen Modalitäten der Radiotherapie ihren Beitrag dazu leisten.Radiation oncology is experiencing major advances in technology. On the hardware level, there is a sharp competition in innovation without predictable end. In last decade, a large array of radiotherapy machines have been introduced to the market (Novalis, TomoTherapy, Cyberknife etc). On the software level, rapid progress has been done. Besides inherent radiation oncology technologies, diagnostic tools had become essential (MRT, PET). The synergy of those machnines and technologies induce potential advances in the field toward 4dimensional imaging and radiotehrapy execution. It is transgressing the conventional areas of radiation onoclogy. Radiation oncology is, today, interlaced strongly with the term "presicion". Under clinical conditions, this has to be achived by measurements, must enable reproduction. Presicion includes planing procedures and preplaning, involving software, imaging tools, pretests. And, it has to be true for the execution of therapy in terms of monitoring of positioning and patient safety. The research work presented in this "habilitation" is a contribution to the body of knowledge on image-guided radiotherapy