Single versus multiple fraction stereotactic radiosurgery for medium-sized brain metastases (4-14 cc in volume): reducing or fractionating the radiosurgery dose?

Background and purpose: Stereotactic radiosurgery (SRS) of brain metastases (BM) and resection cavities is a widely used and effective treatment modality. Based on target lesion size and anatomical location, single fraction SRS (SF-SRS) or multiple fraction SRS (MF-SRS) are applied. Current clinical recommendations conditionally recommend either reduced dose SF-SRS or MF-SRS for medium-sized BM (2-2.9 cm in diameter). Despite excellent local control rates, SRS carries the risk of radionecrosis (RN). The purpose of this study was to assess the 12-months local control (LC) rate and 12-months RN rate of this specific patient population. Materials and methods: This single-center retrospective study included 54 patients with medium-sized intact BM (n=28) or resection cavities (n=30) treated with either SF-SRS or MF-SRS. Follow-up MRI was used to determine LC and RN using a modification of the "Brain Tumor Reporting and Data System" (BT-RADS) scoring system. Results: The 12-month LC rate following treatment of intact BM was 66.7% for SF-SRS and 60.0% for MF-SRS (p=1.000). For resection cavities, the 12-month LC rate was 92.9%% after SF-SRS and 46.2% after MF-SRS (p=0.013). For intact BM, RN rate was 17.6% for SF-SRS and 20.0% for MF-SRS (p=1.000). For resection cavities, RN rate was 28.6% for SF-SRS and 20.0% for MF-SRS (p=1.000). Conclusion: Patients with intact BM showed no statistically significant differences in 12-months LC and RN rate following SF-SRS or MF-SRS. In patients with resection cavities the 12-months LC rate was significantly better following SF-SRS, with no increase in the RNFS.

Treatment and related morbidity of nasal cavity and paranasal sinus cancers.

Introduction: Sinonasal malignancies are rare and histologically heterogeneous cancers of the nasal cavity and sinuses. The treatment of choice is usually surgery and, if necessary, adjuvant radiotherapy. In this study, we aimed to investigate treatment modalities and associated morbidity. Methods: A consecutive case series of solid sinonasal cancer treated at our tertiary referral center was analyzed. We performed a retrospective chart review and statistical analysis. Results: A total of 156 patients with sinonasal cancer were enrolled in the present study. Male patients were more frequently affected (62%) and the median age was 64 years. Squamous cell carcinoma, adenocarcinoma and malignant melanoma (MM) were the most common histopathological entities. Surgery was the primary treatment modality for 73% of curatively treated patients. Primary radiotherapy alone or in combination with systemic treatment was less frequent. Median overall (OS) and recurrence-free survival (RFS) was 164 months and 71.3 months, respectively. Multivariate analysis revealed negative associations of histology (MM) and skull base involvement on RFS and age, skull base involvement and the type of primary therapy (radiochemotherapy) on OS. Postoperative 30-day morbidity was low, with most patients (84%) experiencing no reported events. Radiotherapy was generally well-tolerated, despite most of patients experienced acute toxicity such as dermatitis (80.6%) or mucositis (72.1%). However, only one event of acute toxicity > grade 3 was reported. Long term morbidity was most frequently reported as pain (23%), dry mucosa (19%) and anosmia (14%). Conclusion: We observed negative associations of histology (MM) and skull base involvement on RFS and age, skull base involvement and the type of primary therapy (radiochemotherapy) on OS. Acute treatment-related morbidity was generally low for surgical patients and considerable for irradiated patients. Moreover, a consistent part of the cohort displayed long term morbidity.

Accurate prediction of isocitrate dehydrogenase -mutation status of gliomas using SLOW-editing magnetic resonance spectroscopic imaging at 7 T MR.

Background: 2-hydroxy-glutarate (2HG) is a metabolite that accumulates in isocitrate dehydrogenase (IDH)-mutated gliomas and can be detected noninvasively using MR spectroscopy. However, due to the low concentration of 2HG, established magnetic resonance spectroscopic imaging (MRSI) techniques at the low field have limitations with respect to signal-to-noise and to the spatial resolution that can be obtained within clinically acceptable measurement times. Recently a tailored editing method for 2HG detection at 7 Tesla (7 T) named SLOW-EPSI was developed. The underlying prospective study aimed to compare SLOW-EPSI to established techniques at 7 T and 3 T for IDH-mutation status determination. Methods: The applied sequences were MEGA-SVS and MEGA-CSI at both field strengths and SLOW-EPSI at 7 T only. Measurements were performed on a MAGNETOM-Terra 7 T MR-scanner in clinical mode using a Nova 1Tx32Rx head coil and on a 3 T MAGNETOM-Prisma scanner with a standard 32-channel head coil. Results: Fourteen patients with suspected glioma were enrolled. Histopathological confirmation was available in 12 patients. IDH mutation was confirmed in 9 out of 12 cases and 3 cases were characterized as IDH wildtype. SLOW-EPSI at 7 T showed the highest accuracy for IDH-status prediction (91.7% accuracy, 11 of the 12 predictions correct with 1 false negative case). At 7 T, MEGA-CSI had an accuracy of 58.3% and MEGA-SVS had an accuracy of 75%. At 3 T, MEGA-CSI showed an accuracy of 63.6% and MEGA-SVS of 33.3%. The co-edited cystathionine was detected in 2 out of 3 oligodendroglioma cases with 1p/19q codeletion. Conclusions: Depending on the pulse sequence, spectral editing can be a powerful tool for the noninvasive determination of the IDH status. SLOW-editing EPSI sequence is the preferable pulse sequence when used at 7 T for IDH-status characterization.

VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial.

BACKGROUND: Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap. METHODS: In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness - breathiness - hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported. DISCUSSION: To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506.