ImportanceThe association of primary tumor volume with outcomes in T3 glottic cancers treated with radiotherapy with concurrent chemotherapy remains unclear, with some evidence suggesting worse locoregional control in larger tumors.ObjectiveTo evaluate the association of primary tumor volume with oncologic outcomes in patients with T3 N0-N3 M0 glottic cancer treated with primary (chemo)radiotherapy in a large multi-institutional study.Design, Setting, and ParticipantsThis multi-institutional retrospective cohort study involved 7 Canadian cancer centers from 2002 to 2018. Tumor volume was measured by expert neuroradiologists on diagnostic imaging. Clinical and outcome data were extracted from electronic medical records. Overall survival (OS) and disease-free survival (DFS) outcomes were assessed with marginal Cox regression. Laryngectomy-free survival (LFS) was modeled as a secondary analysis. Patients diagnosed with cT3 N0-N3 M0 glottic cancers from 2002 to 2018 and treated with curative intent intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Overall, 319 patients met study inclusion criteria.ExposuresTumor volume as measured on diagnostic imaging by expert neuroradiologists.Main Outcomes and MeasuresPrimary outcomes were OS and DFS; LFS was assessed as a secondary analysis, and late toxic effects as an exploratory analysis determined before start of the study.ResultsThe mean (SD) age of participants was 66 (12) years and 279 (88%) were men. Overall, 268 patients (84%) had N0 disease, and 150 (47%) received concurrent systemic therapy. The mean (SD) tumor volume was 4.04 (3.92) cm3. With a mean (SD) follow-up of 3.85 (3.04) years, there were 91 (29%) local, 35 (11%) regional, and 38 (12%) distant failures. Increasing tumor volume (per 1-cm3 increase) was associated with significantly worse adjusted OS (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11) and DFS (HR, 1.04; 95% CI, 1.01-1.07). A total of 62 patients (19%) underwent laryngectomies with 54 (87%) of these within 800 days after treatment. Concurrent systemic therapy was associated with improved LFS (subdistribution HR, 0.63; 95% CI, 0.53-0.76).Conclusions and RelevanceIncreasing tumor volumes in cT3 glottic cancers was associated with worse OS and DFS, and systemic therapy was associated with improved LFS. In absence of randomized clinical trial evidence, patients with poor pretreatment laryngeal function or those ineligible for systemic therapy may be considered for primary surgical resection with postoperative radiotherapy.
Background Hyperparathyroid crisis, or “parathyroid storm” is a rare manifestation of primary hyperparathyroidism, characterized by sudden onset of symptomatic, severe hypercalcemia (> 3.5 mmol/L). Hemorrhage into a parathyroid adenoma has rarely been reported as an inciting or associated event. We present a case of hemorrhage into a longstanding adenoma presenting with acute onset of profound hypercalcemia and associated complications. Case presentation A 60-year-old male presented to hospital with sudden onset of confusion, muscle weakness, and ataxia. Initial labs showed serum calcium 4.79 mmol/L, parathyroid hormone 2043 ng/L; creatinine 364 μmol/L. Review of the patient’s medical history indicated a 4-year history of recurrent nephrolithiasis, but no prior documented calcium levels. The hypercalcemia did not respond to 5 days of aggressive medical management with fluid resuscitation, denosumab and calcitonin, and later pamidronate and cinacalcet. He continued to deteriorate, requiring intubation and continuous renal replacement therapy. Imaging demonstrated 4.8 cm cystic right paratracheal mass; Technetium (Tc99m) Sestamibi scintigraphy was non-localizing. Urgent parathyroidectomy was completed, revealing a 5 × 3.3 × 1.8 cm hemorrhagic, atypical hypercellular parathyroid. Unfortunately, the patient died from complications from anticoagulation therapy for treatment of deep vein thrombosis 4 weeks after admission. His renal function had not recovered at the time of his death. Conclusion This case gives potential insight into the etiology of hyperparathyroid crisis, and the difficulty in achieving control of hypercalcemia with medical means. Surgical intervention is the definitive management in these cases and should be considered urgently. Graphical Abstract
Background The study objectives were: provide longitudinal data on upper aerodigestive tract function and late complications following IMRT for nasopharyngeal carcinoma, and elucidate factors that might predict a worse outcome. The hypotheses were: (1) Despite advances such as IMRT, radiation will cause significant functional decline and late complications that often progress or arise years after treatment. (2) Larger radiation volume will be associated with poorer outcomes. Methods Longitudinal, observational cohort study of nasopharyngeal carcinoma patients with retrospective analysis of prospectively collected, population-based data. Late sequelae and validated measures of overall performance, speech, and swallowing were documented pre-treatment and 3,6,12, 24, 36 and ≥ 60-months post-treatment. Results Forty-two patients treated curatively with radiation (N = 9) or chemoradiation (N = 33) were followed for a median 74 months. Functional outcomes showed an initial nadir at 3 months associated with acute effects of treatment, followed by initial recovery. There was subsequent functional decline years post-treatment with advancing dysphagia/aspiration, trismus, muscle spasm, and hypoglossal nerve palsy. Univariable regression analysis revealed that increasing high-dose radiation volumes (PTV 70 Gy) were associated with increased likelihood of less than solid diet (Performance Status Scale (PSS)—Normalcy of Diet score < 50; p = 0.04), and reduced PSS—Understandability of Speech (p = 0.005). The probability of poor outcome increased with time. Eleven percent of patients were tube feed dependent at ≥ 5 years. Conclusions Despite improvements in radiation delivery, late effects of radiation remain common. Higher radiation volumes are associated with poorer outcomes that worsen over time. Graphical Abstract
Objective To assess whether multiple injections of a powerful antioxidant can improve established sensorineural hearing loss in guinea pigs. Study Design Animal study. Setting Animal science laboratory, University of Manitoba. Methods A total of 16 guinea pigs were used in our study: 8 underwent unilateral intracochlear neomycin injection, and 8 underwent unilateral saline to serve as controls. After a period of 3 weeks for hearing loss to stabilize, 4 guinea pigs from each group received weekly intraperitoneal injections of N-acetylcysteine (NAC) for 4 weeks. Click auditory brainstem response (ABR) testing was conducted at baseline, weekly after the start of NAC injections, and after the last injection. Pure tone ABR tests were conducted prior to intracochlear injections and at completion of the study. Results Click ABR thresholds were significantly worse in ears treated with neomycin ( P < .001), as expected, but not significantly different when treated with NAC ( P = .664). Thresholds for pure tone ABR were also not statistically different in neomycin-treated ears with or without NAC ( P > .99). Conclusions The aggressive antioxidant therapy performed in this study was not successful in improving established hearing loss via an antioxidant regimen that is known to change the oxidation-reduction potential in the cochlea.
e18044 Background: Organ preservation approaches to treatment of locally advanced larynx cancers are widely used and consist of radiotherapy (RT) with or without concurrent systemic therapy (CRT). Analyses of the National Cancer Database point to decreasing survival as CRT became widely adopted in place of total laryngectomy (TL). Tumor volume in T3 laryngeal tumors has been postulated as one variable to explain this finding, with higher volume associated with lower local control based on small sample size studies largely in pre-intensity modulated radiotherapy (IMRT) era, and low volume T3 tumors being associated with improved local control with CRT. We sought to validate these findings in a contemporary cohort of T3 larynx patients treated with IMRT. Methods: This was a national, multicentre retrospective cohort study of patients diagnosed with American Joint Committee on Cancer (AJCC) T3 N0-3 M0 glottic and supraglottic cancers who underwent curative intent IMRT with or without systemic treatment from 2002-2018. Tumor volumes were calculated using a validated standardized approach by a Neuroradiologist. Primary predictor was tumor volume, primary outcome was local control (LC), and secondary outcomes included overall survival (OS), as well as late grade 3+ toxicities. Kaplan Meier estimates and log-rank tests were used for survival analyses, with Cox proportional hazards used for univariable analyses. Results: 246 patients met inclusion criteria, 147 glottic and 99 supraglottic cancers. At baseline, glottic patients were more likely to be male (p < 0.01), have a fixed vocal cord (p < 0.01), not have pre-epiglottic space invasion ( < 0.01), be cN0 (p < 0.01), and have lower grade tumors (p < 0.01). Mean tumor volumes for glottic and supraglottic tumors were 5.0 (4.2-5.8) cc and 13.0 (10.3–15.6) cc respectively. Univariable analysis showed systemic therapy was associated with improved local failure (HR 0.49, 95%CI 0.24 – 0.99, p = 0.05). Within the glottic cohort, tumor volume was not associated with local failure (HR 1.09, 95%CI 0.71 – 1.67, p = 0.38), however having a local failure event was associated with increased feeding tube dependence (HR 2.52, 95%CI 1.05 – 6.02, p = 0.04). Median local failure free survival in the overall cohort was 28.5 months, with median OS 23.2 months. There was a trend towards improved local control in the supraglottic cohort compared to glottic patients (log-rank p = 0.08), but the supraglottic cohort had significantly worse overall survival (log-rank p = 0.02). Conclusions: In this retrospective cohort study, there were baseline and outcome differences between patients with T3 glottic and supraglottic larynx cancer, with worse overall survival in supraglottic patients. Tumor volume was not associated with local control in the glottic cohort. These findings are pending further validation in a larger cohort and will be analyzed separately for supraglottic tumors.
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