Markus W. Gross

In vitro chemo- and radio-resistance in small cell lung cancer correlates with cell adhesion and constitutive activation of AKT and MAP kinase pathways.

Most small cell lung cancer (SCLC) patients relapse within 12 months of starting combination chemotherapy plus radio-therapy, due to the development of acquired chemo- and radio-resistance. This phenomenon relates to the induction of tumour differentiation, resulting in apoptosis-resistant, morphologically variant (v-SCLC) cells, which lack the neuroendocrine expression of classic (c-) SCLC cells. In this study spontaneously adherent SCLC sublines were shown by differential gene expression analysis to provide an in vitro model of variant differentiation in SCLC, with down-regulation of neuroendocrine markers and up-regulation of epithelial differentiation markers cyclin D1, endothelin, the cell adhesion molecules CD 44 and integrin subunits α2, β3 and β4. The sensitivity of adherent SCLC sublines to etoposide, cyclophosphamide and gamma radiation was significantly diminished relative to parent suspension cell lines. Western blot analysis using phosphorylation-specific antibodies to Akt and MAP kinase revealed markedly elevated activation in adherent SCLC sublines, paralleled by increased levels of phosphorylated Bad protein and activated NF-κB. Subcultivation of the adherent sublines on uncoated surfaces reversed their adherent phenotype immediately and under these conditions Akt activity reverted to low levels. These results suggest that c-SCLC cells can differentiate spontaneously to v-SCLC and that the associated cellular adhesion may trigger Akt-dependent inhibition of apoptosis in SCLC cells, thus leading to acquired chemo- and radio-resistance.

Hypofractionated stereotactic reirradiation of recurrent glioblastomas : a beneficial treatment option after high-dose radiotherapy?

Background and Purpose:Recurrent malignant gliomas have a very poor prognosis. This trial aimed to evaluate the benefits of reirradiation in case of recurrent glioblastoma multiforme (GBM) using hypofractionated stereotactic radiotherapy (hFSRT) after primary high-dose percutaneous irradiation.Patients and Methods:Between 1998 and 2008, 53 patients with recurrent GBM were treated by hFSRT based on CT and MR imaging. At the time of recurrence, a median total dose of 30 Gy (20–60 Gy) was delivered in median fractions of 3 Gy/day (2–5Gy).Results:The reirradiation was well tolerated (no acute or late toxicity > grade 2), despite the relatively large median tumor volume (35.01 ml). Karnofsky Performance Score was the strongest predictor for survival after reirradiation (p = 0.0159). Tumor volume (p = 0.4690), patient age (p = 0.4301), second operation (p = 0.6930), and chemotherapy (p = 0.1466) at the time of reirradiation did not affect survival. After hFSRT, the median survival was 9 months, and the 1-year progression-free survival (PFS) amounted to 22%.The median overall survival from initial diagnosis was 27 months. 1-year survival from first diagnosis was 83%, 2-year survival 45%. The median time to progression from the end of initial irradiation to recurrence was 12 months. 1-year PFS before reirradiation was 40%.Conclusion:hFSRT as a secondary treatment of recurrent GBM is a feasible and effective treatment option. Only minor side effects were observed with prolonged life expectancy of 9 months.Hintergrund und Ziel:Die Prognose im Rezidivfall eines malignen Glioms ist schlecht. Diese Studie hatte zum Ziel, den Stellenwert einer hypofraktionierten stereotaktischen Rebestrahlung (hFSRT) bei rezidiviertem Glioblastom (GBM) nach perkutaner hochkonformaler Radiotherapie zu evaluieren.Patienten und Methodik:Zwischen 1998 und 2008 wurden 53 Patienten mit einem rezidivierten GBM stereotaktisch rebestrahlt. Die mediane Gesamtherddosis betrug 30 Gy (20–60 Gy), die mediane Einzelherddosis 3 Gy/Tag (2–5 Gy).Ergebnisse:Trotz großer Tumorvolumen von median 35,01 ml wurde nach hFSRT keine Akut- oder Spättoxizität > Grad 2 beobachtet. Der Karnofsky-Perfomance-Score war der einzige determinante Faktor hinsichtlich des Gesamtüberlebens nach hFSRT (p = 0,0159). Hingegen beeinflussten Tumorvolumen (p = 0,4690), Patientenalter (p = 0,4301), Zweitoperationen (p = 0,6930) oder Chemotherapie (p = 0,1466) das Gesamtüberleben nach hFSRT nicht. Das mediane Gesamtüberleben nach hFSRT betrug 9 Monate, das progressionsfreie 1-Jahres-Überleben (PFS) 22%. Das mediane Gesamtüberleben nach initialer Diagnosestellung eines GBM lag bei 27 Monaten, das 1- bzw. 2-Jahres-Gesamtüberleben bei 83% bzw. 45%. Der mediane Zeitpunkt bis zum ersten Rezidiv nach initialer Bestrahlung betrug 12 Monate, das 1-Jahres-PFS nach initialer Bestrahlung bis zum ersten Rezidiv 40%.Schlussfolgerung:Die hFSRT ist eine geeignete und effektive Behandlungsoption für rezidivierte GBM. Das mediane Gesamtüberleben nach hFSRT konnte bei geringer Nebenwirkungsrate um 9 Monate verlängert werden.

Hypofractionated Stereotactic Reirradiation of Recurrent Glioblastomas

Background and Purpose:Recurrent malignant gliomas have a very poor prognosis. This trial aimed to evaluate the benefits of reirradiation in case of recurrent glioblastoma multiforme (GBM) using hypofractionated stereotactic radiotherapy (hFSRT) after primary high-dose percutaneous irradiation.Patients and Methods:Between 1998 and 2008, 53 patients with recurrent GBM were treated by hFSRT based on CT and MR imaging. At the time of recurrence, a median total dose of 30 Gy (20–60 Gy) was delivered in median fractions of 3 Gy/day (2–5Gy).Results:The reirradiation was well tolerated (no acute or late toxicity > grade 2), despite the relatively large median tumor volume (35.01 ml). Karnofsky Performance Score was the strongest predictor for survival after reirradiation (p = 0.0159). Tumor volume (p = 0.4690), patient age (p = 0.4301), second operation (p = 0.6930), and chemotherapy (p = 0.1466) at the time of reirradiation did not affect survival. After hFSRT, the median survival was 9 months, and the 1-year progression-free survival (PFS) amounted to 22%.The median overall survival from initial diagnosis was 27 months. 1-year survival from first diagnosis was 83%, 2-year survival 45%. The median time to progression from the end of initial irradiation to recurrence was 12 months. 1-year PFS before reirradiation was 40%.Conclusion:hFSRT as a secondary treatment of recurrent GBM is a feasible and effective treatment option. Only minor side effects were observed with prolonged life expectancy of 9 months.Hintergrund und Ziel:Die Prognose im Rezidivfall eines malignen Glioms ist schlecht. Diese Studie hatte zum Ziel, den Stellenwert einer hypofraktionierten stereotaktischen Rebestrahlung (hFSRT) bei rezidiviertem Glioblastom (GBM) nach perkutaner hochkonformaler Radiotherapie zu evaluieren.Patienten und Methodik:Zwischen 1998 und 2008 wurden 53 Patienten mit einem rezidivierten GBM stereotaktisch rebestrahlt. Die mediane Gesamtherddosis betrug 30 Gy (20–60 Gy), die mediane Einzelherddosis 3 Gy/Tag (2–5 Gy).Ergebnisse:Trotz großer Tumorvolumen von median 35,01 ml wurde nach hFSRT keine Akut- oder Spättoxizität > Grad 2 beobachtet. Der Karnofsky-Perfomance-Score war der einzige determinante Faktor hinsichtlich des Gesamtüberlebens nach hFSRT (p = 0,0159). Hingegen beeinflussten Tumorvolumen (p = 0,4690), Patientenalter (p = 0,4301), Zweitoperationen (p = 0,6930) oder Chemotherapie (p = 0,1466) das Gesamtüberleben nach hFSRT nicht. Das mediane Gesamtüberleben nach hFSRT betrug 9 Monate, das progressionsfreie 1-Jahres-Überleben (PFS) 22%. Das mediane Gesamtüberleben nach initialer Diagnosestellung eines GBM lag bei 27 Monaten, das 1- bzw. 2-Jahres-Gesamtüberleben bei 83% bzw. 45%. Der mediane Zeitpunkt bis zum ersten Rezidiv nach initialer Bestrahlung betrug 12 Monate, das 1-Jahres-PFS nach initialer Bestrahlung bis zum ersten Rezidiv 40%.Schlussfolgerung:Die hFSRT ist eine geeignete und effektive Behandlungsoption für rezidivierte GBM. Das mediane Gesamtüberleben nach hFSRT konnte bei geringer Nebenwirkungsrate um 9 Monate verlängert werden.

First experience with I-123-alpha-methyl-tyrosine spect in the 3-D radiation treatment planning of brain gliomas

PURPOSE This study compares the results of iodine-123-alpha-methyl-tyrosine single photon computed emission tomography (IMT-SPECT) with magnetic resonance imaging (MRI) in tumor volume definition of brain gliomas. Furthermore, it evaluates the influences of the information provided from IMT-SPECT for three-dimensional (3D) conformal treatment planning. METHODS AND MATERIALS In 30 patients with nonresected, histologically proven brain gliomas (glioblastoma-13 patients, astrocytoma Grade III-12 patients, astrocytoma Grade II-3 patients, oligodendroglioma Grade III-1 patient, oligodendroglioma Grade II-1 patient), IMT-SPECT and MRI were performed pretherapeutically in the same week. A special software system allowed the coregistration of the IMT-SPECT and MRI data. The gross tumor volume (GTV) defined on the IMT-SPECT/T2-MRI fusion images (GTV-IMT/T2) was compared with the GTV-T2, defined on the T2-MRI alone. On the IMT-SPECT/T1Gd-MRI overlays, the volume of the IMT tumor uptake (GTV-IMT) was compared with the volume of the gadolinium (Gd) enhancement (GTV-T1Gd). The initial planning target volume (PTV) and the boost volume (BV) outlined on the IMT-SPECT/T2-MRI co-images were analyzed comparatively to the PTV and BV delineated using the T2-MRI alone. RESULTS In all 30 patients a higher IMT uptake of tumor areas, compared to the normal brain tissue was observed. Mean GTV-IMT, mean GTV-T2, and mean GTV-T1Gd were 43, 82, and 16 cm(3), respectively. IMT tumor uptake outside the contrast enhancement regions was observed in all patients. Mean relative increase of tumor volume defined on the fusion images, GTV-IMT/T1Gd versus GTV-T1Gd alone was 78%. IMT tumor uptake areas outside the GTV-T2 were registered in 7 patients (23%). In these patients, the mean increase GTV-IMT/T2 was 33% higher than GTV-T2, defined according to the T2-MRI data alone. The additional information provided by IMT-SPECT modified minimally the initial PTV (mean relative increase PTV-IMT/T2 versus PTV-T2, 5%) but significantly the BV (mean relative increase BV-IMT/T2 versus BV-T2, 37%). CONCLUSION In a significant number of patients, the IMT-SPECT investigation improves tumor detection and delineation in the planning process. This has important consequences in the 3D conformal treatment planning, especially in the delineation of BV and in dose escalation studies.

Stereotactic radiotherapy of meningiomas: symptomatology, acute and late toxicity.

Background and Purpose:Stereotactic radiosurgery (SRS) is well established in the treatment of skull base meningiomas, but this therapy approach is limited to small tumors only. The fractionated stereotactic radiotherapy (SRT) offers an alternative treatment option. This study aims at local control, symptomatology, and toxicity.Patients and Methods:Between 1997–2003, 224 patients were treated with SRT (n = 183), hypofractionated SRT (n = 30), and SRS (n = 11). 95/224 were treated with SRT/SRS alone. 129/224 patients underwent previous operations. Freedom from progression and overall survival, toxicity, and symptomatology were evaluated systematically. Additionally, tumor volume (TV) shrinkage was analyzed three-dimensionally within the planning system.Results:The median follow-up was 36 months (range, 12–100 months). Overall survival and freedom from progression for 5 years were 92.9% and 96.9%. Quantitative TV reduction was 26.2% and 30.3% 12 and 18 months after SRT/SRS (p < 0.0001). 95.9% of the patients improved their symptoms or were stable. Clinically significant acute toxicity (CTC III°) was rarely seen (2.5%). Clinically significant late morbidity (III°–IV°) or new cranial nerve palsies did not occur.Conclusion:SRT offers an additional treatment option of high efficacy with only few side effects. In the case of large tumor size (> 4 ml) and adjacent critical structures (< 2 mm), SRT is highly recommended.Hintergrund und Ziel:Die stereotaktische Radiochirurgie (SRS) ist in der Behandlung von Schädelbasismeningeomen fest etabliert. Ihr Einsatz ist jedoch auf kleine Tumoren begrenzt. Die stereotaktisch fraktionierte Radiotherapie (SRT) bietet eine Behandlungsalternative an. Ziel dieser Untersuchung war, die lokale Kontrolle, Symptomatologie und die Toxizität zu evaluieren.Patienten und Methodik:Zwischen 1997 und 2003 wurden 224 Patienten stereotaktisch fraktioniert (n = 183), stereotaktisch hypofraktioniert (n = 30) und radiochirurgisch (n = 11) behandelt. 95/224 wurden primär bestrahlt, 129/224 waren voroperiert. Progressionsfreies und Gesamtüberleben, Toxizität und Symptomatologie wurden systematisch erfasst. Zusätzlich wurde die Tumorvolumenreduktion quantitativ mit dem Planungssystem ermittelt.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 36 Monate (12–100 Monate). Das 5-Jahres-Gesamtüberleben lag bei 92,9%, das progressionsfreie Überleben bei 96,9%. Die quantitative Tumorvolumenreduktion betrug 12 und 18 Monate nach SRT/SRS 26,2% und 30,3% (p < 0,0001). Bei 95,9% der Patienten waren die Symptome kontrolliert oder gebessert. Klinisch signifikante Akuttoxizität (CTC III°) trat selten auf (2,5%). Klinisch signifikante Spättoxizität (III°–IV°) oder neu aufgetretene neurologische Defizite wurden nicht beobachtet.Schlussfolgerung:Die SRT ist eine effektive und nebenwirkungsarme Therapie. Im Fall eines großen Tumorvolumens (> 4 ml) und nahegelegener Risikostrukturen (< 2 mm) ist eine SRT empfehlenswert.

Significant tumor volume reduction of meningiomas after stereotactic radiotherapy: results of a prospective multicenter study.

OBJECTIVEStereotactic radiosurgery (SRS) is well established in the treatment of cranial base meningiomas. Fractionated stereotactic radiotherapy (SRT) offers an additional treatment option. Data for radiological regression differ, ranging from 13 to 61%. Therefore, the aims of this prospective study were to quantitatively analyze tumor volume (TV) shrinkage and to calculate determining factors. METHODSEighty-four patients were examined under equal conditions before and after SRT. Fat-saturated axial T1-weighted contrast-enhanced magnetic resonance imaging scans with 1- to 3-mm slice thickness were used. After image fusion, TV was drawn in each slice to analyze TV shrinkage three-dimensionally by the planning system. RESULTSMean TV had shrunk by 33% at 24 months (P = 0.02) and by 36% at 36 months (P = 0.0007) after SRT. With regard to half-year intervals, TV reduction decreased continuously towards a steady state (P < 0.0001). Younger age (P = 0.001) and smaller TV (P = 0.01) are determining factors. There was no correlation between TV reduction, prescribed dose, histological classification, sex, or previous operations. CONCLUSIONMeningiomas shrink significantly after SRT. TV shrinkage declines towards a steady state, which is not yet defined. Younger age and smaller TV are determining factors. Previous operations, sex, prescribed dose, or histological subtypes do not affect TV shrinkage. Eighteen to 24 months after irradiation, when symptoms are clinically stable, is the best time for the first magnetic resonance imaging scans evaluating tumor control and shrinkage.

Fractionated stereotactic radiotherapy of glomus jugulare tumors. Local control, toxicity, symptomatology, and quality of life.

Background and Purpose:For glomus jugulare tumors, the goal of treatment is microsurgical excision. To minimize postoperative neurologic deficits, stereotactic radiosurgery (SRS) was performed as an alternative treatment option. Stereotactic fractionated radiotherapy (SRT) could be a further alternative. This study aims at the assessment of local control, side effects, and quality of life (QoL).Patients and Methods:Between 1999–2005, 17 patients were treated with SRT. 11/17 underwent previous operations. 6/17 received primary SRT. Treatment was delivered by a linear accelerator with 6-MV photons. Median cumulative dose was 57.0 Gy. Local control, radiologic regression, toxicity, and symptomatology were evaluated half-yearly by clinical examination and MRI scans. QoL was assessed by Short Form-36 (SF-36).Results:Median follow-up was 40 months. Freedom from progression and overall survival for 5 years were 100% and 93.8%. Radiologic regression was seen in 5/16 cases, 11/16 patients were stable. Median tumor shrinkage was 17.9% (p = 0.14). Severe acute toxicity (grade 3–4) or any late toxicity was never seen. Main symptoms improved in 9/16 patients, 7/16 were stable. QoL was not affected in patients receiving primary SRT.Conclusion:SRT offers an additional treatment option of high efficacy with less side effects, especially in cases of large tumors, morbidity, or recurrences after incomplete resections.Hintergrund und Ziel:Standardtherapie von Glomus-jugulare-Tumoren ist die mikrochirurgische Resektion. Zur Vermeidung postoperativer neurologischer Defizite wurde die stereotaktische Radiochirurgie (SRS) als Behandlungsalternative etabliert. Die stereotaktisch-fraktionierte Radiotherapie (SRT) könnte eine weitere Alternative darstellen. Ziel dieser Studie ist die Evaluation der lokalen Kontrolle, Nebenwirkungen und Lebensqualität.Patienten und Methodik:Zwischen 1999 und 2005 wurden 17 Patienten stereotaktisch-fraktioniert bestrahlt. 11/17 waren voroperiert, 6/17 wurden primär bestrahlt. Die Bestrahlung erfolgte mit einem Linearbeschleuniger mit 6-MV-Photonen. Die mediane Gesamtdosis betrug 57,0 Gy. Die lokale Kontrolle, radiologische Regression, Toxizität und Symptomatologie wurden halbjährlich mittels klinischer Untersuchungen und MRT-Kontrollen erfasst. Die Lebensqualität wurde mit dem Fragebogen Short Form-36 (SF-36) evaluiert.Ergebnisse:Die mediane Nachbeobachtungszeit lag bei 40 Monaten. Das 5-Jahres-Gesamtüberleben betrug 93,8%, das progressionsfreie Überleben 100%. Radiologische Regression trat in 5/16 Fällen auf, in 11/16 war der Tumor kontrolliert. Die mediane Tumorschrumpfung betrug 17,9% (p = 0,14). Schwere Akuttoxizität (CTC Grad 3–4) oder jegliche Spättoxizität wurde nicht beobachtet. In 9/16 Fällen konnten die Hauptsymptome gebessert werden, in 7/16 waren sie stabil. Die Lebensqualität primär mit SRT behandelter Patienten war nicht beeinträchtigt.Schlussfolgerung:Die SRT bietet eine zusätzliche Option von hoher Effektivität mit geringer Nebenwirkungswahrscheinlichkeit. Das gilt insbesondere für große Tumoren, für morbide Patienten und im Rezidivfall nach inkompletter Resektion.

Fractionated Stereotactic Radiotherapy of Glomus Jugulare Tumors

Background and Purpose:For glomus jugulare tumors, the goal of treatment is microsurgical excision. To minimize postoperative neurologic deficits, stereotactic radiosurgery (SRS) was performed as an alternative treatment option. Stereotactic fractionated radiotherapy (SRT) could be a further alternative. This study aims at the assessment of local control, side effects, and quality of life (QoL).Patients and Methods:Between 1999–2005, 17 patients were treated with SRT. 11/17 underwent previous operations. 6/17 received primary SRT. Treatment was delivered by a linear accelerator with 6-MV photons. Median cumulative dose was 57.0 Gy. Local control, radiologic regression, toxicity, and symptomatology were evaluated half-yearly by clinical examination and MRI scans. QoL was assessed by Short Form-36 (SF-36).Results:Median follow-up was 40 months. Freedom from progression and overall survival for 5 years were 100% and 93.8%. Radiologic regression was seen in 5/16 cases, 11/16 patients were stable. Median tumor shrinkage was 17.9% (p = 0.14). Severe acute toxicity (grade 3–4) or any late toxicity was never seen. Main symptoms improved in 9/16 patients, 7/16 were stable. QoL was not affected in patients receiving primary SRT.Conclusion:SRT offers an additional treatment option of high efficacy with less side effects, especially in cases of large tumors, morbidity, or recurrences after incomplete resections.Hintergrund und Ziel:Standardtherapie von Glomus-jugulare-Tumoren ist die mikrochirurgische Resektion. Zur Vermeidung postoperativer neurologischer Defizite wurde die stereotaktische Radiochirurgie (SRS) als Behandlungsalternative etabliert. Die stereotaktisch-fraktionierte Radiotherapie (SRT) könnte eine weitere Alternative darstellen. Ziel dieser Studie ist die Evaluation der lokalen Kontrolle, Nebenwirkungen und Lebensqualität.Patienten und Methodik:Zwischen 1999 und 2005 wurden 17 Patienten stereotaktisch-fraktioniert bestrahlt. 11/17 waren voroperiert, 6/17 wurden primär bestrahlt. Die Bestrahlung erfolgte mit einem Linearbeschleuniger mit 6-MV-Photonen. Die mediane Gesamtdosis betrug 57,0 Gy. Die lokale Kontrolle, radiologische Regression, Toxizität und Symptomatologie wurden halbjährlich mittels klinischer Untersuchungen und MRT-Kontrollen erfasst. Die Lebensqualität wurde mit dem Fragebogen Short Form-36 (SF-36) evaluiert.Ergebnisse:Die mediane Nachbeobachtungszeit lag bei 40 Monaten. Das 5-Jahres-Gesamtüberleben betrug 93,8%, das progressionsfreie Überleben 100%. Radiologische Regression trat in 5/16 Fällen auf, in 11/16 war der Tumor kontrolliert. Die mediane Tumorschrumpfung betrug 17,9% (p = 0,14). Schwere Akuttoxizität (CTC Grad 3–4) oder jegliche Spättoxizität wurde nicht beobachtet. In 9/16 Fällen konnten die Hauptsymptome gebessert werden, in 7/16 waren sie stabil. Die Lebensqualität primär mit SRT behandelter Patienten war nicht beeinträchtigt.Schlussfolgerung:Die SRT bietet eine zusätzliche Option von hoher Effektivität mit geringer Nebenwirkungswahrscheinlichkeit. Das gilt insbesondere für große Tumoren, für morbide Patienten und im Rezidivfall nach inkompletter Resektion.

STEREOTACTIC RADIOTHERAPY FOR THE TREATMENT OF NONACOUSTIC SCHWANNOMAS

OBJECTIVENonacoustic schwannomas are rare tumors in contrast to the most common neuromas of Cranial Nerve VIII. The current treatment of choice in these cases is microsurgical resection, but the risk of postoperative complications is high, especially in cavernous sinus-invading tumors. In many of these cases, it is not possible to achieve complete tumor removal, resulting in the probability of recurrences. For those patients, radiosurgery (RS) or stereotactic radiotherapy (SRT) can offer an alternate treatment. METHODSWithin a 5-year period (2000–2005), 19 intracranial nonacoustic neuromas were treated with SRT-13 trigeminal neuromas, five neuromas of the lower cranial nerves (jugular foramen), and one located in the orbital region. Of these cases, there were nine women and 10 men who were, on average, 54 years of age (range, 33–83 yr). Eight patients had previously undergone surgery elsewhere and showed progressive tumor growth. All 19 patients were treated with SRT: 15 with normal fractions of 1.8–2 Gy single dose up to 54–59.4 Gy. Their irregular tumor volume ranged from 4.2 to 43.1 ccm (average: 14.1 ccm). Hypofractionation with 6 to 7 × 5 Gy was applied in four cases with an average tumor volume of 4.1 ccm (2.2–6.2 ccm). Clinical results and the efficacy for tumor control with an average follow-up of 35 months (11–63 mo) were evaluated. RESULTSLocal tumor control rate was 95% (18 of 19 cases): one patient previously operated on had a recurrence of tumor progression after SRT, followed by a second subtotal resection. A tumor regression was proved in 11 cases (one neuroma disappeared and four patients had tumor shrinkage of more than 50%, the other six experienced shrinkage between 20% and 40%). Within the first 6 months, two patients developed temporarily increased tumor volume as well as a confirmed reaction to irradiation. In one of these two cases, there were mild side effects according to CTC Grade I. No patient experienced a new or increased neurological deficit. Improvement of their cranial nerve disturbances was achieved in 11 of 19 patients and the other eight showed no clinical changes. The mostly moderate trigeminal pain decreased slowly. CONCLUSIONSRT is a low-risk and effective treatment option for intracranial neuromas. Particularly in cases of sinus cavernous-invading trigeminal and in jugular foramen tumors, SRT can be the treatment of choice. Concerning tumor regression, SRT is as effective as RS.

Vemurafenib-Induced Radiation Recall Dermatitis: Case Report and Review of the Literature

The cutaneous effects of BRAF (serine/threonine protein kinase B-raf) inhibitors such as vemurafenib remain poorly defined. Rash, squamous cell carcinoma, keratoacanthoma and photosensitivity are the most common grade 2 or 3 adverse events observed in clinical trials. We here report the case of a patient with a BRAF V600E mutated metastatic melanoma who developed severe radiation recall dermatitis 6 weeks after completing radiotherapy. Vemurafenib treatment had been initiated 1 week before the development of dermatitis because of rapidly progressing disease. Upon topical treatment of the affected skin areas, clinical symptoms regressed over a period of 2 months, although vemurafenib was continuously administered. As our case goes in line with other reports, we believe that physicians should be aware of this additional cutaneous side effect of vemurafenib and that continuation of the treatment is safe when close clinical control and interdisciplinary management can be provided.