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

Background 2-Hydroxy-glutarate (2HG) is a metabolite that accumulates in IDH-mutated gliomas and can be detected non-invasively using MR-spectroscopy. However, due to the low concentration of 2HG, established magnetic resonance spectroscopic imaging (MRSI) techniques at low-field have limitations with respect to signal-to-noise and to spatial resolution that can be obtained within clinically acceptable measurement-times. Recently a tailored editing-method for 2HG detection at 7T named SLOW-EPSI was developed. The underlying prospective study aimed to compare SLOW-EPSI to established techniques at 7T and 3T for IDH-mutation status determination. Methods The applied sequences were MEGA-SVS and MEGA-CSI at both field strengths and SLOW-EPSI at 7T only. Measurements were performed on a MAGNETOM-Terra 7T MR-scanner in clinical-mode using a Nova 1Tx32Rx head-coil and on a 3T 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 7T showed highest accuracy for IDH-status prediction (91.7% accuracy, 11 of 12 predictions correct with 1 false negative case). At 7T, MEGA-CSI had an accuracy of 58.3% and MEGA-SVS an accuracy of 75%. At 3T, 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 co-deletion. Conclusion Depending on the pulse sequence, spectral editing can be a powerful tool for noninvasive determination of the IDH-status. SLOW-editing EPSI sequence is the preferable pulse sequence when used at 7T for IDH-status characterization.