Therapy Resistance of Glioblastoma in Relation to the Subventricular Zone: What Is the Role of Radiotherapy?

Glioblastoma is a highly heterogeneous primary malignant brain tumor with marked inter-/intratumoral diversity and a poor prognosis. It may contain a population of neural stem cells (NSC) and glioblastoma stem cells that have the capacity for migration, self-renewal and differentiation. While both may contribute to resistance to therapy, NSCs may also play a role in brain tissue repair. The subventricular zone (SVZ) is the main reservoir of NSCs. This study investigated the impact of bilateral SVZ radiation doses on patient outcomes. We included 147 patients. SVZs were delineated and the dose administered was extracted from dose-volume histograms. Tumors were classified based on their spatial relationship to the SVZ. The dose and outcome correlations were analyzed using the Kaplan-Meier and Cox proportional hazards regression methods. Median progression-free survival (PFS) was 7 months (range: 4-11 months) and median overall survival (OS) was 14 months (range: 9-23 months). Patients with an ipsilateral SVZ who received ≥50 Gy showed significantly better PFS (8 versus 6 months; p < 0.001) and OS (16 versus 11 months; p < 0.001). Furthermore, lower doses (<32 Gy) to the contralateral SVZ were associated with improved PFS (8 versus 6 months; p = 0.030) and OS (15 versus 11 months; p = 0.001). Targeting the potential tumorigenic cells in the ipsilateral SVZ while sparing contralateral NSCs correlated with an improved outcome. Further studies should address the optimization of dose distribution with modern radiotherapy techniques for the areas surrounding infiltrated and healthy SVZs

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 [study protocol].

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

Oncologic outcome with versus without target volume compartmentalization in postoperative radiotherapy for oral cavity squamous cell carcinoma.

BACKGROUND AND PURPOSE The volume treated with postoperative radiation therapy (PORT) in patients with oral cavity squamous cell carcinoma (OCSCC) is a mediator of toxicity affecting quality of life. Current guidelines only allow for very limited reduction of PORT volumes. This study investigated the safety and efficacy of de-intensified PORT for patients with OCSCC by refined compartmentalization of the treatment volume. MATERIALS AND METHODS This retrospective cohort study identified 103 OCSCC patients treated surgically from 2014 to 2019 with a loco-regional risk profile qualifying for PORT according to guidelines. PORT was administered only to the at-risk compartment and according to a refined compartmentalization concept (CC). Oncological outcome of this CC cohort was compared to a historical cohort (HC) of 98 patients treated before the CC was implemented. RESULTS Median follow-up time was 4.5 and 4.8 years in the CC and HC cohorts, respectively. In the CC cohort, a total of 72 of 103 patients (70%) had a pathological risk profile that allowed for further compartmentalization and, hence, received a reduced treatment volume or omission of PORT altogether. Loco-regional control at 3 and 5 years was 77% and 73% in the CC cohort versus 78% and 73% in the HC (p = 0.93), progression-free survival was 72% and 64% versus75% and 68% (p = 0.58), respectively. Similarly, no statistically significant difference was seen in other outcome measures. CONCLUSIONS De-intensified PORT limiting the treatment volume to the at-risk compartment or avoiding PORT altogether for low-risk patients with OCSCC does not seem to compromise disease control in this retrospective comparison. Based on these hypothesis-generating findings, a prospective study is being planned

Impact of pretreatment second look 18FDG-PET/CT on stage and treatment changes in head and neck cancer.

Background Patients diagnosed with locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) regularly undergo staging with 18F-FDG PET/CT in our center. In cases of delays in radiotherapy (RT) planning CT more than 4 weeks after initial PET/CT or clinically suspected progress, PET/CT is repeated for restaging and as an RT planning reference. Our aim was to determine the impact of second-look PET/CT on stage migration, treatment change and RT planning. Methods Consequent treatment changes were categorized as minor and major. Minor changes were defined as PET/CT-based modifications of RT plans, e.g., the addition of anatomical compartments, changes in high- and low-risk dose levels or both. Major changes included changes from curative to palliative treatment intent and alterations of interdisciplinary treatment plans, such as the addition of induction chemotherapy, switch to primary surgery, no treatment and/or the necessity of additional diagnostic work-up resulting in the postponement or cancellation of treatment. Results Thirty-two newly diagnosed LAHNSCC patients who were treated between 2014 and 2018 underwent second-look PET/CT (median interval 42.5 days). Second-look PET/CT led to locoregional and distant upstaging in 3/32 and 1/32 patients, respectively. In 1/32 patients (3%), second-look PET/CT led to a palliative approach with systemic treatment. New lymph node metastases were discovered in 16 patients, 6 of whom also showed significant progression of the primary tumor, resulting in minor changes in 16 of the remaining 31 patients (52%) who were treated curatively. Conclusion If RT treatment planning of LAHNSCC was delayed by more than 4 weeks after initial PET/CT staging or when progression was clinically suspected, a second look at 18FDG-PET/CT was performed. This led to changes in treatment planning in more than half of the cases, which is expected to directly influence oncologic outcomes