Brachytherapy and osteoradionecrosis in patients with base of tongue cancer.

BACKGROUND: Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden. AIMS: Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival. MATERIAL AND METHODS: We used data from the Swedish Head and Neck Cancer Register between 2008-2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions. RESULTS: Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p = .012), whereas overall survival did not differ (HR = 0.95, p = .782). CONCLUSIONS AND SIGNIFICANCE: Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.

Mandibular resection in patients with head and neck cancer: acute and long-term complications after reconstruction.

BACKGROUND: The treatment of head and neck cancer is an intensive multimodal treatment that has a great impact on the individual patient. AIMS/OBJECTIVES: This study aimed to evaluate acute and long-term complications associated with mandibular resections and reconstructions. MATERIAL AND METHODS: We retrospectively retrieved data on complications and recurrences among patients that underwent mandibular resections and reconstructions for treating oral cavity cancer (n = 190 patients) and osteoradionecrosis (ORN, n = 72). Reconstructions included composite grafts (n = 177), soft tissue flaps (n = 61), or primary closure without any graft (n = 24). RESULTS: Forty-two patients that underwent reconstructions with composite grafts displayed serious complications (Clavien-Dindo ≥ IIIa). The complication rates were similar between patients treated for oral cavity cancer and patients treated for ORN. Patients that underwent a primary closure without any graft, had a significantly lower risk of complications compared to patients that underwent the other treatments. After hospitalization, 181 patients (69%) had at least one complication. CONCLUSIONS: A majority of patients undergoing resection and reconstruction due to oral cancer/ORN suffered from postoperative complications regardless of indication, comorbidity status or reconstruction technique. The risk of Clavien-Dindo grade IIIa-V events was significantly lower for patients treated with primary closure without grafts. SIGNIFICANCE: The results from this study clarifies the importance of in-depth analyse prior to decision of treatment for patients with head and neck cancer.

Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer.

Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depend on the patient's radiosensitivity. Currently, there is no assay available that can reliably predict the individual's response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls.. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual's risk of experiencing radiation-induced toxicity.

Quality of life after microvascular mandibular reconstruction for osteoradionecrosis-A prospective study.

BACKGROUND: Reconstructive surgery for mandibular osteoradionecrosis is increasing; however, evidence regarding the impact on health-related quality of life is lacking. The current exploratory study prospectively investigates whether resection with reconstruction is associated with changes in HRQoL parameters for these patients. METHODS: Seventeen patients underwent microvascular reconstruction for mandibular osteoradionecrosis between 2012 and 2015, and 16 completed the EORTC quality of life questionnaires QLQ-C30 and QLQ-H&N35 1 month before and 1 year after surgery. RESULTS: Increases in emotional (P = 0.01) and social functioning (P = 0.004) were observed, together with improvements in the fatigue (P = 0.04), appetite loss (P = 0.02) and pain (P = 0.02) scores, as evaluated by the QLQ-C30. Pain reduction was further confirmed by the QLQ-H&N35 (P = 0.04), which also showed improved scores for feeling ill (P = 0.001) and sexual difficulties (P = 0.04). CONCLUSION: This exploratory study suggests that microvascular reconstruction after mandibular osteoradionecrosis may improve HRQoL, with an emphasis on pain reduction; however, further studies are needed.

Influence of genetic background and oxidative stress response on risk of mandibular osteoradionecrosis after radiotherapy of head and neck cancer.

BACKGROUND: Osteoradionecrosis (ORN) of the mandible is a severe complication of head and neck radiotherapy (RT) treatment, where the impact of individual radiosensitivity has been a suggested explanation. METHODS: A cohort of patients with stage II/III ORN was compared to matched controls. Blood was collected and irradiated in vitro to study the capacity to handle radiation-induced oxidative stress. Patients were also genotyped for 8 single-nucleotide polymorphisms (SNPs) in genes involved in the oxidative stress response. RESULTS: A difference in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) levels was found between the patient cohorts (p = 0.01). The SNP rs1695 in glutathione s-transferase p1 (GSTP1) was also found to be more frequent in the patients with ORN (p = .02). Multivariate analysis of the clinical and biological factors revealed concomitant brachytherapy plus the 2 biomarkers to be significant factors which influense risk of mandibular osteoradionecrosis after radiotherapy of head and neck cancer. CONCLUSION: The current study indicates that oxidative stress response contributes to individual radiosensitivity and healthy tissue damage caused by RT and may be predicted by biomarker analysis.

Rapid prototyped patient specific implants for reconstruction of orbital wall defects.

Defects of orbital walls can be reconstructed using implants. The authors report a safe and accurate method to reconstruct bone defects in the orbital area using patient specific implants. A detailed process description of computer aided design (CAD) reconstructive surgery (CRS) is introduced in this prospective study. The 3D volumetric virtual implant was design using MSCT data and PTCProEngineer™ 3D software. The intact orbital cavity of twelve patients was mirrored to the injured side. Specific ledges steered the implant into correct place. Postoperatively the position was assessed using image fusion. One implant (8%) was rejected due to chemical impurities, two (16%) had a false shape due to incorrect CAD. Data of thin bone did not transfer correctly to CAD and resulted in error. One implant (8%) was placed incorrectly. Duration of the CRS was in average 1.17 h, correspondingly 1.57 h using intraoperative bending technique. The CRS process has several critical stages, which are related to converting data and to incompatibility between software. The CRS process has several steps that need further studies. The data of thin bone may be lost and disturb an otherwise very precise technique. The risk of incorporating impurities into the implant must be carefully controlled.