Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.
Background This study evaluates the contemporary care for patients with locally recurrent nasopharyngeal carcinoma after failure of the primary course of intensity modulated radiotherapy. Methods Eligible patients were identified through the Hong Kong Cancer Registry database. Patterns of care and treatment outcomes were analyzed. Results Two hundred seventy‐two patients with locally recurrent tumors were identified. Of them, 30.9% received surgery, whereas 35.7% received re‐irradiation (re‐RT). The 5‐year overall survival (OS) for the whole group was 30.2%. Old age and advanced rT classification were adverse prognostic factors, whereas surgery (mainly in resectable recurrence) was associated with favorable survival outcome. The 5‐year OS rates for patients who received surgery and re‐RT were 56.3% and 21.8%, respectively. Conclusions Early detection of resectable recurrence is of paramount importance as surgery for resectable tumors offers the potential to achieve excellent outcomes. Re‐RT could be considered in selected patients with unresectable disease and favorable prognostic features.
Purpose To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base. Materials and Methods Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with <3 months of follow-up, receiving <45 GyRBE or nonconventional fractionation, and/or no follow-up magnetic resonance imaging (MRI) were excluded. TLN was determined using MRI and graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Clinical (gender, age, comorbidities, concurrent chemotherapy, smoking, radiation techniques) and dose-volume parameters were analyzed for TLN correlation. The receiver operating characteristic curve and area under the curve (AUC) were performed to determine the cutoff points of significant dose-volume parameters. Results Between 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2–69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume [aV]); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm3 volume receiving the maximum dose (D0.5cm3, D1cm3, and D2cm3, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm3 gave the highest AUC (0.935) among dose parameters. The 11-cm3 cutoff value for aV50 and 62 GyRBE for D2cm3 showed maximum specificity and sensitivity. Conclusion The estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm3, D2cm3 ≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy.
Substantial risk of SPT, especially for in-field sarcoma and tongue cancers, exists after definitive IMRT for NPC. SPT severely negates longevity of NPC survivors. High awareness and careful surveillance is warranted for this late lethal complication.
asopharyngeal carcinoma (NPC) accounts for 0.6% of all cancers diagnosed worldwide and is an endemic disease in Southeast Asia. 1 Nasopharyngeal carcinoma is highly sensitive to radiotherapy and chemotherapy and is typically treated with definitive radiotherapy alone for stage I, chemoradiotherapy for stage II, and chemoradiotherapy with induction or adjuvant chemotherapy for stage III to IVA. With modern radiotherapy techniques and effective systemic chemotherapy, prognosis of NPC has improved remarkably in the past 2 decades. Since the wide adoption of intensity-modulated radiotherapy (IMRT) following results of the Radiation Therapy Oncology Group 0225 trial, 2 there has been improvement in target conformity and short-term and long-term toxic effects compared with conventional techniques. However, late sequelae of treatment still occur because of the significant dose delivered to the surrounding healthy tissues. Furthermore, the use of cisplatin in extended cycles also increases the risk of cumulative platinum toxic effects. Recently, studies 3-6 have attempted to individualize treatments in NPC to limit toxicity without compromising efficacy. Alternative dosing, schedules, and substitutes for cisplatin have been proposed. Radiation doses, elective nodal irradiation vol-umes, and postinduction radiation target delineation have also evolved. This article aims to review strategies and propose future directions for deescalating systemic or radiotherapy in NPC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.