Anti-epileptic drug use during adjuvant chemo-radiotherapy is associated with poorer survival in patients with glioblastoma: A nationwide population-based cohort study.

INTRODUCTION: There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome. MATERIAL AND METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862). CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.

Deep learning model for pleural effusion detection via active learning and pseudo-labeling: a multisite study.

BACKGROUND: The study aimed to develop and validate a deep learning-based Computer Aided Triage (CADt) algorithm for detecting pleural effusion in chest radiographs using an active learning (AL) framework. This is aimed at addressing the critical need for a clinical grade algorithm that can timely diagnose pleural effusion, which affects approximately 1.5 million people annually in the United States. METHODS: In this multisite study, 10,599 chest radiographs from 2006 to 2018 were retrospectively collected from an institution in Taiwan to train the deep learning algorithm. The AL framework utilized significantly reduced the need for expert annotations. For external validation, the algorithm was tested on a multisite dataset of 600 chest radiographs from 22 clinical sites in the United States and Taiwan, which were annotated by three U.S. board-certified radiologists. RESULTS: The CADt algorithm demonstrated high effectiveness in identifying pleural effusion, achieving a sensitivity of 0.95 (95% CI: [0.92, 0.97]) and a specificity of 0.97 (95% CI: [0.95, 0.99]). The area under the receiver operating characteristic curve (AUC) was 0.97 (95% DeLong's CI: [0.95, 0.99]). Subgroup analyses showed that the algorithm maintained robust performance across various demographics and clinical settings. CONCLUSION: This study presents a novel approach in developing clinical grade CADt solutions for the diagnosis of pleural effusion. The AL-based CADt algorithm not only achieved high accuracy in detecting pleural effusion but also significantly reduced the workload required for clinical experts in annotating medical data. This method enhances the feasibility of employing advanced technological solutions for prompt and accurate diagnosis in medical settings.

Diet Outcome in Patients With Hypopharyngeal Defects Repaired With Different Reconstruction Flaps: A Comparative Study.

OBJECTIVES: To assess potential risk factors influencing diet outcomes after reconstruction of subtotal hypopharyngeal defects using free patch- or tube-shaped anterolateral thigh (ALT) fasciocutaneous flaps. STUDY DESIGN: Retrospective cohort study. SETTING: First-level referral hospital. METHODS: Between January 2011 and December 2020, we studied hypopharyngeal cancer patients who underwent the reconstruction of hypopharyngeal defects using free patch- or tube-shaped ALT fasciocutaneous flaps. The choice between patch- or tube-shaped ALT flaps depended on the defect's nature, favoring patch-shaped for subtotal defects and tube-shaped for circumferential defects. A restricted diet was characterized by a history of enterostomy or endoscopic esophageal dilation treatment postreconstruction. We analyzed patients with restricted diets at 1- and 3-year follow-up visits. RESULTS: Ninety-eight patients were enrolled; 39 patch-shaped flaps, and 59 tube-shaped flaps. No significances were noted in demographics, postoperative radiotherapy (RT) or chemotherapy, rates of free flap reoperation/salvage, or complications. However, a significant difference emerged in diet outcomes at the 1-year follow-up (P = .005). The rate of a restricted diet was 6.08 times higher in patients with tube-shaped flaps compared to patch-shaped flaps (95% confidence interval [CI]: 1.95-18.94). Stratifying based on postoperative RT revealed a 5.47 times higher rate of a restricted diet in tube-shaped flap recipients compared to patch-shaped flap recipients (95% CI: 1.44-20.48). No significances were observed in 5-year survival rates. CONCLUSION: Concerning postoperative RT, patch-shaped flaps exhibited a lower incidence of a restricted diet compared to tube-shaped flaps. Preservation of the posterior mucosa may play a crucial role in preventing RT-induced esophageal stricture.

Association of radiation dose to cardiac substructures with major ischaemic events following breast cancer radiotherapy.

BACKGROUND AND AIMS: Patients with left-sided breast cancer receive a higher mean heart dose (MHD) after radiotherapy, with subsequent risk of ischaemic heart disease. However, the optimum dosimetric predictor among cardiac substructures has not yet been determined. METHODS AND RESULTS: This study retrospectively reviewed 2158 women with breast cancer receiving adjuvant radiotherapy. The primary endpoint was a major ischaemic event. The dose-volume parameters of each delineated cardiac substructure were calculated. The risk factors for major ischaemic events and the association between MHD and major ischaemic events were analysed by Cox regression. The optimum dose-volume predictors among cardiac substructures were explored in multivariable models by comparing performance metrics of each model. At a median follow-up of 7.9 years (interquartile range 5.6-10.8 years), 89 patients developed major ischaemic events. The cumulative incidence rate of major ischaemic events was significantly higher in left-sided disease (P = 0.044). Overall, MHD increased the risk of major ischaemic events by 6.2% per Gy (hazard ratio 1.062, 95% confidence interval 1.01-1.12; P = 0.012). The model containing the volume of the left ventricle receiving 25 Gy (LV V25) with the cut-point of 4% presented with the best goodness of fit and discrimination performance in left-sided breast cancer. Age, chronic kidney disease, and hyperlipidaemia were also significant risk factors. CONCLUSION: Risk of major ischaemic events exist in the era of modern radiotherapy. LV V25 ≥ 4% appeared to be the optimum parameter and was superior to MHD in predicting major ischaemic events. This dose constraint could aid in achieving better heart protection in breast cancer radiotherapy, though a further validation study is warranted.

Developing an AI-assisted planning pipeline for hippocampal avoidance whole brain radiotherapy.

BACKGROUND AND PURPOSE: Hippocampal avoidance whole brain radiotherapy (HA-WBRT) is effective for controlling disease and preserving neuro-cognitive function for brain metastases. However, contouring and planning of HA-WBRT is complex and time-consuming. We designed and evaluated a pipeline using deep learning tools for a fully automated treatment planning workflow to generate HA-WBRT radiotherapy plans. MATERIALS AND METHODS: We retrospectively collected 50 adult patients who received HA-WBRT. Using RTOG- 0933 clinical trial protocol guidelines, all organs-at-risk (OARs) and the clinical target volume (CTV) were contoured by experienced radiation oncologists. A deep-learning segmentation model was designed and trained. Next, we developed a volumetric-modulated arc therapy (VMAT) auto-planning algorithm for 30 Gy in 10 fractions. Automated segmentations were evaluated using the Dice similarity coefficient (DSC) and 95th-percentile Hausdorff distance (95 % HD). Auto-plans were evaluated by the percentage of PTV volume that receives 30 Gy (V30Gy), conformity index (CI), and homogeneity index (HI) of planning target volume (PTV) and the minimum dose (D100%) and maximum dose (Dmax) for the hippocampus, Dmax for the lens, eyes, optic nerve, brain stem, and chiasm. RESULTS: We developed a deep-learning segmentation model and an auto-planning script. For the 10 cases in the independent test set, the overall average DSC and 95 % HD of contours were greater than 0.8 and less than 7 mm, respectively. All auto-plans met the RTOG- 0933 criteria. The HA-WBRT plan automatically created time was about 10 min. CONCLUSIONS: An artificial intelligence (AI)-assisted pipeline using deep learning tools can rapidly and accurately generate clinically acceptable HA-WBRT plans with minimal manual intervention and increase efficiency of this treatment for brain metastases.

Tumor Volume Reduction Rate to Induction Chemotherapy is a Prognostic Factor for Locally Advanced Head and Neck Squamous Cell Carcinoma: A Retrospective Cohort Study.

Introduction: Aim of this retrospective cohort study is to evaluate the prognostic value of tumor volume reduction rate status post-induction chemotherapy in locally advanced head and neck squamous cell carcinoma. Methods: Patients newly diagnosed from year 2007 to 2016 at a single center were included in this retrospective study. All patients had received induction Taxotere, Platinum, Fluorouracil followed by daily definitive intensity-modulated radiotherapy for 70 Gy in 35 fractions concurrent with or without cisplatin-based chemotherapy. Tumor volume reduction rate was measured and calculated by contrast-enhanced computed tomography images at diagnosis, and after at least 1 cycle of induction chemotherapy, and analyzed though a univariate and multivariate Cox regression model. Results: Ninety patients of the primary cancer sites at hypopharynx (31/90, 34.4%), oropharynx (29/90, 32.2%), oral cavity (19/90, 21.1%), and larynx (11/90, 12.2%) were included in this study, with a median follow-up time interval of 3.9 years. In multivariate Cox regression analysis, the tumor volume reduction rate of the primary tumor (TVRR-T) was also an independently significant prognostic factor for disease-free survival (DFS) (hazard ratio 0.77, 95% confidence interval 0.62-0.97; P-value = .02). Other factors including patient's age at diagnosis, the primary cancer site, and RECIST (Response Evaluation Criteria in Solid Tumors), were not significantly related. At a cutoff value using 50% in Kaplan-Meier survival analysis, the DFS was higher with TVRR-T ≥ 50% group (log-rank test, P = .024), and a trend of improved overall survival. (log-rank test, P = .069). Conclusion: TVRR-T is a probable prognostic factor for DFS. With a cut-off point of 50%, TVRR-T may indicate better DFS.

Both combined or sequential use with immune checkpoint inhibitors on cetuximab-treated patients with recurrent or metastatic head and neck squamous cell carcinoma improve the overall survival.

BACKGROUND: After the introduction of ICI treatment, data about feasibility and activity of a cetuximab-containing first-line therapy in patients with recurrent and/or metastatic head and neck cancer (R/M HNSCC) are still not available. We sought to analyze the clinical outcomes in the real-world setting. MATERIAL METHODS: This retrospective study was conducted at two tertiary medical centers in Taiwan. Patients with R/M HNSCC receiving cetuximab-containing first-line therapy were included between January 2017 and July 2019. The study endpoints were the response, Progression-Free Survival (PFS), and Overall Survival (OS). Subgroup analyses were conducted to evaluate survival outcomes by platinum resistance and the use of immunotherapy. RESULTS: We identified 290 patients treated with cetuximab-containing first-line therapy. The most primary tumor site was oral cavity cancer (59.3%). 44% of patients were resistant to platinum. The median PFS and OS were 5.0 months and 9.1 months, respectively, for the total population. In patients with platinum resistance, the median OS was 10.4 months with ICIs versus 6.3 months without ICIs; p = 0.01. In patients with platinum sensitivity, the median OS was 20.6 months with ICIs versus 9.1 months without ICs; p < 0.01. OS benefit with ICIs was similar between patients who received ICIs after progression on Cetuximab and receiving Cetuximab in combination with ICIs. Independent favorable prognostic factors for OS were platinum-sensitive, better response to cetuximab, and ICIs use. CONCLUSION: ICIs are indicated to improve OS in R/M HNSCC receiving cetuximab-containing first-line therapy, even in platinum-resistant populations. The reduction in risk of death with ICIs was similar regarding the combination or sequencing of cetuximab.

Usefulness of multi-labelling artificial intelligence in detecting rhythm disorders and acute ST-elevation myocardial infarction on 12-lead electrocardiogram.

Aims: To develop an artificial intelligence-based approach with multi-labelling capability to identify both ST-elevation myocardial infarction (STEMI) and 12 heart rhythms based on 12-lead electrocardiograms (ECGs). Methods and results: We trained, validated, and tested a long short-term memory (LSTM) model for the multi-label diagnosis of 13 ECG patterns (STEMI + 12 rhythm classes) using 60 537 clinical ECGs from 35 981 patients recorded between 15 January 2009 and 31 December 2018. In addition to the internal test above, we conducted a real-world external test, comparing the LSTM model with board-certified physicians of different specialties using a separate dataset of 308 ECGs covering all 13 ECG diagnoses. In the internal test, the area under the curves (AUCs) of the LSTM model in classifying the 13 ECG patterns ranged between 0.939 and 0.999. For the external test, the LSTM model for multi-labelling of the 13 ECG patterns evaluated by AUC was 0.987 ± 0.021, which was superior to those of cardiologists (0.898 ± 0.113, P < 0.001), emergency physicians (0.820 ± 0.134, P < 0.001), internists (0.765 ± 0.155, P < 0.001), and a commercial algorithm (0.845 ± 0.121, P < 0.001). Of note, the LSTM model achieved an accuracy of 0.987, AUC of 0.997, and precision, recall, and F 1 score of 0.952, 0.870, and 0.909, respectively, in detecting STEMI. Conclusions: We demonstrated the usefulness of an LSTM model in the multi-labelling detection of both rhythm classes and STEMI in competitive testing against board-certified physicians. This AI tool exceeding the cardiologist-level performance in detecting STEMI and rhythm classes on 12-lead ECG may be useful in prioritizing chest pain triage and expediting clinical decision-making in healthcare.

Automated Hypofractionated IMRT treatment planning for early-stage breast Cancer.

BACKGROUND: Hypofractionated whole-breast irradiation is a standard adjuvant therapy for early-stage breast cancer. This study evaluates the plan quality and efficacy of an in-house-developed automated radiotherapy treatment planning algorithm for hypofractionated whole-breast radiotherapy. METHODS: A cohort of 99 node-negative left-sided breast cancer patients completed hypofractionated whole-breast irradiation with six-field IMRT for 42.56 Gy in 16 daily fractions from year 2016 to 2018 at a tertiary center were re-planned with an in-house-developed algorithm. The automated plan-generating C#-based program is developed in a Varian ESAPI research mode. The dose-volume histogram (DVH) and other dosimetric parameters of the automated and manual plans were directly compared. RESULTS: The average time for generating an autoplan was 5 to 6 min, while the manual planning time ranged from 1 to 1.5 h. There was only a small difference in both the gantry angles and the collimator angles between the autoplans and the manual plans (ranging from 2.2 to 5.3 degrees). Autoplans and manual plans performed similarly well in hotspot volume and PTV coverage, with the autoplans performing slightly better in the ipsilateral-lung-sparing dose parameters but were inferior in contralateral-breast-sparing. The autoplan dosimetric quality did not vary with different breast sizes, but for manual plans, there was worse ipsilateral-lung-sparing (V4Gy) in larger or medium-sized breasts than in smaller breasts. Autoplans were generally superior than manual plans in CI (1.24 ± 0.06 vs. 1.30 ± 0.09, p < 0.01) and MU (1010 ± 46 vs. 1205 ± 187, p < 0.01). CONCLUSIONS: Our study presents a well-designed standardized fully automated planning algorithm for optimized whole-breast radiotherapy treatment plan generation. A large cohort of 99 patients were re-planned and retrospectively analyzed. The automated plans demonstrated similar or even better dosimetric quality and efficacy in comparison with the manual plans. Our result suggested that the autoplanning algorithm has great clinical applicability potential.

Increased risk of pelvic fracture after radiotherapy in rectal cancer survivors: A propensity matched study.

To determine whether radiotherapy (RT) can increase pelvic fracture risk in rectal cancer survivors. Rectal cancer patients who underwent curative surgery between 1996 and 2011 in Taiwan were retrospectively studied using the National Health Insurance Research Database (NHIRD) of Taiwan. ICD-9 Codes 808, 805.4-805.7, 806.4-806.7, and 820 (including pelvic, sacrum, lumbar, and femoral neck fracture) were defined as pelvic fracture. Propensity scores for RT, age, and sex were used to perform one-to-one matches between the RT and non-RT group. Risks of pelvic and arm fractures were compared by multivariable Cox regression. Of the 32 689 patients, 7807 (23.9%) received RT, and 1616 suffered from a pelvic fracture (incidence rate: 1.17/100 person-years). The median time to pelvic fracture was 2.47 years. After matching, 6952 patients each in the RT and non-RT groups were analyzed. RT was associated with an increased risk of pelvic fractures in the multivariable Cox model (hazard ratio (HR): 1.246, 95% confidence interval (CI): 1.037-1.495, P = 0.019) but not with arm fractures (HR: 1.013, 95% CI: 0.814-1.259, P = 0.911). Subgroup analyses revealed that RT was associated with a higher pelvic fracture rate in women (HR: 1.431, 95% CI: 1.117-1.834) but not in men, and the interaction between sex and RT was significant (P = 0.03). The HR of pelvic fracture increased 2-4 years after RT (HR: 1.707, 95% CI: 1.150-2.534, P = 0.008). An increased risk of pelvic fracture is noted in rectal cancer survivors, especially women, who receive RT.

Second primary malignancy risk after radiotherapy in rectal cancer survivors.

AIM: To investigate second primary malignancy (SPM) risk after radiotherapy in rectal cancer survivors. METHODS: We used Taiwan's National Health Insurance Research Database to identify rectal cancer patients between 1996 and 2011. Surgery-alone, preoperative short course, preoperative long course, and post-operative radiotherapy groups were defined. The overall and site-specific SPM incidence rates were compared among the radiotherapy groups by multivariate Cox regression, taking chemotherapy and comorbidities into account. Sensitivity tests were performed for attained-year adjustment and long-term survivors analysis. RESULTS: A total of 28220 patients were analyzed. The 10-year cumulative SPM incidence was 7.8% [95% confidence interval (CI): 7.2%-8.2%] using a competing risk model. The most common sites of SPM were the lung, liver, and prostate. Radiotherapy was not associated with increased SPM risk in multi-variate Cox model (hazard ratio = 1.05, 95%CI: 0.91-1.21, P = 0.494). The SPM hazard remained unchanged in 10-year-survivors. In addition, no SPM risk difference was found between the preoperative radiotherapy and postoperative radiotherapy groups. CONCLUSION: In this large population-based cohort study, we demonstrated that radiotherapy had no increase in SPM.

A simple method for determining dosimetric leaf gap with cross-field dose width for rounded leaf-end multileaf collimator systems.

PURPOSE: The dosimetric leaf gap (DLG) and multileaf collimator (MLC) transmission are two important systematic parameters used to model the rounded MLC leaf ends effect when commissioning an Eclipse treatment planning system (TPS). Determining the optimal DLG is a time consuming process. This study develops a simple and reliable method for determining the DLG using the cross-field dose width. METHODS AND MATERIALS: A Varian TrueBeam linac with 6 MV, 10 MV, 6 MV flattening filter free (FFF) and 10 MV FFF photon beams and equipped with the 120 Millennium MLC and the Eclipse™ TPS was used in this study. Integral sliding fields and static slit MLC field doses with different gap widths were measured with an ionization chamber and GAFCHROMIC EBT3 films, respectively. Measurements were performed for different beam energies and at depths of 5 and 10 cm. DLGs were derived from a linear extrapolation to zero dose and intercepting at the gap width axis. In the ion chamber measurements method, the average MLC leaf transmission to the gap reading for each gap (RgT) were calculated with nominal and cross-field dose widths, respectively. The cross-field dose widths were determined according to the dose profile measured with EBT3 films. Additionally, the optimal DLG values were determined using plan dose measurements, as the value that produced the closest agreement between the planned and measured doses. DLGs derived from the nominal and cross-field dose width, the film measurements, and the optimal process, were obtained and compared. RESULTS: The DLG values are insensitive to the variations in depth (within 0.07 mm). DLGs derived from nominal gap widths showed a significantly lower values (with difference about 0.5 mm) than that from cross-field dose widths and from film measurements and from plan optimal values. The method in deriving DLGs by correcting the nominal gap widths to the cross-field dose widths has shown good agreements to the plan optimal values (with difference within 0.21 mm). CONCLUSIONS: The DLG values derived from the cross-field dose width method were consistent with the values derived from film measurements and from the plan optimal process. A simple and reliable method to determine DLG for rounded leaf-end MLC systems was established. This method provides a referable DLG value required during TPS commissioning.

Combined Yttrium-90 microsphere selective internal radiation therapy and external beam radiotherapy in patients with hepatocellular carcinoma: From clinical aspects to dosimetry.

PURPOSE: Selective internal radiation therapy (SIRT) is an effective treatment strategy for unresectable hepatocellular carcinoma (HCC) patients. However, the prognoses of patients with portal vein thrombosis, extra-hepatic metastases, or residual tumors remain poor when treated with SIRT alone. In these patients, sequential external beam radiotherapy (EBRT) may offer a chance of salvage. Here, we reported the clinical outcomes and the detailed dosimetry analysis of 22 patients treated with combination therapy. METHODS: Between October 2011 and May 2015, 22 consecutive patients who underwent EBRT after yttrium-90 (90Y) SIRT were included in this study. The post-SIRT 90Y bremsstrahlung SPECT/CT of each patient was transferred to dose distribution by adopting the local deposition hypothesis. The patient-specific 3-dimensional biological effective dose distribution of combined SIRT and EBRT was generated. The overall survival and safety were evaluated. The relationship between dosimetric parameters and liver toxicity was analyzed. RESULTS: The mean administered activity of SIRT was 1.50 GBq (range: 0.5-2.8). The mean prescribed dose of EBRT was 42.3 Gy (range: 15-63) in 14 fractions (range: 5-15) and was targeted to the residual liver tumor in 12 patients (55%), portal vein thrombosis in 11 patients (50%), and perihilar lymphadenopathies in 4 patients (18%). The overall 1-, 2-, and 3-year survival rates were 59.8%, 47.9%, and 47.9%, respectively. Overall, 8 patients (36%) developed > grade 2 liver toxicities, and the Child-Pugh score prior to EBRT strongly affected the toxicity risk. A dosimetry analysis restricted to 18 Child-Pugh A/B patients showed that the V100 (The fraction of normal liver exposed to more than 100 Gy) to V140 significance differed between patients who did or did not experience hepatotoxicity. The V110 was the strongest predictor of hepatotoxicity (18.6±11.6% vs 29.5±5.8%; P = 0.030). CONCLUSION: Combined therapy is feasible and safe if patients are carefully selected. Specifically, 3-dimensional dosimetry is crucial for the evaluation of efficacy and toxicity. The normal liver V100 to V140 values of the combined dose should be as low as possible to minimize the risk of liver toxicity.

Definitive Radiotherapy for Older Patients with Prostate Cancer: Experience of a Medical Center in Taiwan.

Whether age predicts treatment outcome of prostate cancer remains controversial. With the aging of the world population, properly understanding the effect of age may facilitate both treatment decision-making and defining the natural history of prostate cancer. Consecutive 581 patients with locally-confined adenocarcinoma of the prostate who received radical definitive radiotherapy(RT) (76-78 Gy) between 2004 and 2015 at a medical center in Taiwan were reviewed retrospectively. Median age was 78 years. The median follow-up was 66 months. The 5-year biochemical failure-free survival(BFFS), distant metastasis-free survival(DMFS), disease-specific survival(DSS), and overall survival(OS) rates were 84.9%, 93.8%, 97.8%, and 86.6%, respectively, for all patients. Comparing those above and below the age of 80, no difference in 5-year BFFS, DMFS, or DSS was found. Multivariate Cox regression analysis showed that tumor stage, Gleason score, initial PSA, and latency before RT were significant risk factors of BFFS. The latency before RT was significantly longer in the older group than in the under 80 group. Delay to start RT might explain the previous finding of inferior disease control in older patients in other studies. With the exception of OS, no other differences in outcomes or toxicities were observed in older patients.

Risk factors for osteonecrosis of the jaw in oral cancer patients after surgery and eventual adjuvant treatment: The potential role of chemotherapy.

BACKGROUND AND PURPOSE: To identify the risk factors for osteonecrosis of the jaw (ONJ) in oral cancer patients after surgery with and without adjuvant therapy in a nationwide, population-based study. MATERIAL AND METHODS: Using the Taiwan National Health Insurance Research Dataset, we recruited patients with newly diagnosed oral cancer between 1997 and 2011. All of them underwent primary surgery. Data regarding demographic characteristics; tooth extractions; medications; and cancer treatments, including types of mandibular surgery, radiotherapy and platinum-based chemotherapy, were collected for analysis. RESULTS: We identified 25,858 patients who suffered 2802 ONJ events. The ONJ incidence rate was 3.45 per 100 person-years. Lip cancer was associated with the highest risk of ONJ, followed by buccal mucosa, gum, mouth floor and tongue cancer. Using a time-dependent Cox regression model, multivariable analysis demonstrated that mandibulotomy (hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.01-1.55; p<0.001), radiotherapy (HR, 1.39; 95% CI, 1.26-1.54; p<0.001) and platinum-based chemotherapy (HR, 1.94; 95% CI, 1.56-2.41; p<0.001) were significant risk factors for ONJ. In the subgroup analysis of patients receiving radiotherapy and patients not receiving radiotherapy, platinum-based chemotherapy remained a risk factor for ONJ. CONCLUSIONS: Mandibulotomy, radiotherapy and platinum-based chemotherapy were associated with an increased ONJ risk. Chemotherapy was a risk factor regardless of whether radiotherapy was administered.

Risk factors for and the role of dental extractions in osteoradionecrosis of the jaws: A national-based cohort study.

BACKGROUND: The purpose of this study was to investigate the risk factors, especially the use of certain drugs and the dental procedures, for osteoradionecrosis of the jaw (ORNJ) in patients with head and neck cancer undergoing irradiation as their primary treatment. METHODS: The cohort was composed of 23,527 patients with head and neck cancer. Cox proportional hazard models were used for risk factors analysis. RESULTS: The overall incidence of ORNJ is 3.93 per 100 person-years. Buccal cancer carried the highest ORNJ risk. The use of steroids had a protective effect. Preradiotherapy extraction posed no excess risk, whereas postradiotherapy extraction was associated with gradually increased risk of ORNJ over time that peaked at 4 to 5 years. CONCLUSION: ORNJ warrants life-long attention for head and neck cancer survivors. The present study strongly confirms the role of preirradiation dental extractions. Meanwhile, efforts should be made to prevent posttreatment extractions, especially in the first posttreatment 4 years. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1313-1321, 2017.

Adrenocortical carcinoma initially presenting with hypokalemia and hypertension mimicking hyperaldosteronism: a case report.

BACKGROUND: Adrenocortical carcinoma is a rare malignancy and rare cause of Cushing's syndrome. CASE PRESENTATION: A 65-year-old seemingly well male patient was referred to our clinic under the suspicion of hyperaldosteronism due to hypertension combined with hypokalemia. However, his serum aldosterone and plasma renin activity were within normal limits. Instead, Cushing's syndrome was diagnosed by elevated urine free cortisol and a non-suppressible dexamethasone test. Abdominal computed tomography showed a 7.8 × 4.8 cm mass lesion at the right adrenal gland with liver invasion. Etomidate infusion was performed to reduce his cortisol level before the patient received a right adrenalectomy and liver wedge resection. The pathology report showed adrenocortical carcinoma with liver and lymph node metastasis. According to the European Network for the Study of Adrenal Tumors (ENSAT) staging system, the tumor was classified as T4N1M1, stage IV. Recurrent hypercortisolism was found shortly after surgery. The patient died of Fournier's gangrene with septic shock on the 59th day after diagnosis. CONCLUSIONS: We report a case of rapidly progressive stage IV adrenocortical carcinoma with initial presentations of hypokaelmia and hypertension, mimicking hyperaldosteronism.