RESUMO
Background: To study neoadjuvant chemoradiotherapy (nCRT) and potential predictive factors for response in locally advanced oral cavity cancer (LA-OCC). Methods: The INVERT trial is an ongoing single-center, prospective phase 2, proof-of-principle trial. Operable patients with stage III-IVA squamous cell carcinomas of the oral cavity were eligible and received nCRT consisting of 60 Gy with concomitant cisplatin and 5-fluorouracil. Surgery was scheduled 6-8 weeks after completion of nCRT. Explorative, multiplex immunohistochemistry (IHC) was performed on pretreatment tumor specimen, and diffusion-weighted magnetic resonance imaging (DW-MRI) was conducted prior to, during nCRT (day 15), and before surgery to identify potential predictive biomarkers and imaging features. Primary endpoint was the pathological complete response (pCR) rate. Results: Seventeen patients with stage IVA OCC were included in this interim analysis. All patients completed nCRT. One patient died from pneumonia 10 weeks after nCRT before surgery. Complete tumor resection (R0) was achieved in 16/17 patients, of whom 7 (41%, 95% CI: 18-67%) showed pCR. According to the Clavien-Dindo classification, grade 3a and 3b complications were found in 4 (25%) and 5 (31%) patients, respectively; grade 4-5 complications did not occur. Increased changes in the apparent diffusion coefficient signal intensities between MRI at day 15 of nCRT and before surgery were associated with better response (p=0.022). Higher abundances of programmed cell death protein 1 (PD1) positive cytotoxic T-cells (p=0.012), PD1+ macrophages (p=0.046), and cancer-associated fibroblasts (CAFs, p=0.036) were associated with incomplete response to nCRT. Conclusion: nCRT for LA-OCC followed by radical surgery is feasible and shows high response rates. Larger patient cohorts from randomized trials are needed to further investigate nCRT and predictive biomarkers such as changes in DW-MRI signal intensities, tumor infiltrating immune cells, and CAFs.
RESUMO
BACKGROUND: Despite oversized latissimus dorsi free flap reconstruction in the head and neck area, esthetic and functional problems continue to exist due to the well-known occurrence of transplant shrinkage. The purpose of this study was to acquire an estimation of the volume and time of the shrinkage process. MATERIALS AND METHODS: The assessment of volume loss was performed using a 3D evaluation of two postoperative CT scans. A retrospective review was conducted on all latissimus dorsi free flap reconstructions performed between 2004 and 2013. Inclusion criteria for the assessment were: resection of an oral carcinoma and microsurgical defect coverage with latissimus dorsi free flap; a first postoperative CT (CT1) performed between 3 weeks and a maximum of 3 months after reconstruction surgery; and an additional CT scan (CT2) performed at least one year postoperatively. The exclusion criterion was surgical intervention in the local area between the acquisition of CT1 and CT2. The effect of adjuvant radiation therapy was considered. Volume determination of the transplant was carried out in CT1 and CT2 by manual segmentation of the graft. RESULTS: Fifteen patients were recruited. 3D evaluation showed an average volume loss of 34.4%. In the consideration of postoperative radiotherapy the volume reduction was 39.2% in patients with radiotherapy and 31.3% in patients without radiotherapy. CONCLUSION: The reconstruction flap volume required for overcorrection of the surgical defect was investigated. This study indicates that a volume loss of more than 30% could be expected one or more years after latissimus dorsi free flap reconstruction. Clinical trial number DRKS00007534.
