Causal effects of endometriosis on cancer risk: A Mendelian randomization study.

Endometriosis has been reported in epidemiological studies to be associated with certain types of cancer. However, the presence of reverse causality and residual confounding due to common risk factors introduces uncertainty regarding the extent to which endometriosis itself contributes to the development of cancer. We performed the Mendelian randomization (MR) to investigate the causal associations between endometriosis and 34 different types of cancers. The results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for ovarian cancer (OR = 3.2913; p-value = .0320). The genetic liabilities to endometriosis had causal associations with the decreased risk for skin cancer (OR = 0.9973; p-value = .0219), hematological cancer (OR = 0.9953; p-value = .0175) and ER- breast cancer (OR = 0.6960; p-value = .0381). The causal association of the above combinations were robust by test of heterogeneity and pleiotropy. Together, our study suggests that endometriosis had causal effect on cancer risk.

Causal effects of endometriosis on SLE, RA and SS risk: evidence from meta-analysis and Mendelian randomization.

BACKGROUND: Endometriosis is an underdiagnosed disorder that affects an estimated 6-10% of women of reproductive age. Endometriosis has been reported in epidemiological studies to be associated with autoimmune diseases. However, the relationship remains controversial. METHODS: A meta-analysis of observational studies was undertaken to evaluate the risk of autoimmune diseases in patients with endometriosis. The relevant studies were retrieved via the databases Medline, Embase and Web of Science until July 20, 2023. Mendelian randomization (MR) was subsequently utilized to scrutinize the causal influence of genetic predisposition toward endometriosis on three autoimmune diseases. RESULTS: The meta-analysis findings revealed a relationship between endometriosis and the onset of SLE (cohort studies: RR = 1.77, 95% confidence interval (CI): 1.47-2.13, I2 = 0%; Case-control and cross-sectional studies: OR = 5.23, 95% CI: 0.74-36.98, I2 = 98%), RA (cohort studies: RR = 2.18, 95% CI: 1.85-2.55, I2 = 92%; Case-control and cross-sectional studies: OR = 1.40, 95% CI: 1.19-1.64, I2 = 0%) and SS (cohort studies: RR = 1.49, 95% CI: 1.34-1.66, I2 = 0%). Similarly, in our MR study, the results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for SLE (OR = 1.915, 95% CI: 1.204-3.045, p = 0.006) and RA (OR = 1.005, 95% CI: 1.001-1.009, p = 0.014). CONCLUSIONS: Both our meta-analysis and MR study indicate that endometriosis increases the risk of autoimmune diseases. These findings not only broaden our understanding of the genetic mechanisms underlying the comorbidity of endometriosis and autoimmune diseases, but also offer a new strategy for autoimmune disease prevention.

Difference after radiotherapy observed in patients with nasopharyngeal carcinoma.

To evaluate the shrinkage rate of small cervical lymph nodes (SCLNs) at different levels in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy retrospectively. 96 adult patients with NPC who underwent intensity-modulated radiotherapy (IMRT) at our institution were analyzed and followed-up. Evaluation of the response (shrinking rate) of SCLNs was determined by the bidimensional tumor area. Binary logistic regression was conducted to explore the risk factors associated with the shrinking rate of SCLNs. Of the 96 patients included in this study, 1,194 SCLNs were identified. Among the SCLNs, 28.6% were level IIb and 21.3% were level IIa. SCLNs at level IIa (96.1%), tended to have a response effect of no change (NC) with shrinking rate <50% (odds ratio [OR]=0.007; 95% CI: 0.003-0.021, P=5.287×10-25). Conversely, the most proportionate share of SCLNs for shrinking rate ≥50% (complete response (CR) or partial response (PR)) was observed at level IIb (67.2%) (OR=6.104; 95% CI: 3.267-11.407, P=1.420×10-8). There was no significant difference of shrinking rate between irradiation doses of 60Gy and 63Gy. Most SCLNs at level IIa were not shrunk after radiotherapy. The irradiation dose of SCLNs at level IIa should be not more than 60Gy to reduce side effects.

Postoperative Radiotherapy Omitting Level â £ for Locally Advanced Supraglottic and Glottic Laryngeal Carcinoma.

BACKGROUND: Cervical lymph nodes metastases are one of the most significant prognostic factors in patients with laryngeal carcinoma, whether treatment by surgery or by radiotherapy. The current study retrospected the postoperative radiotherapy of locally advanced supraglottic and glottic laryngeal carcinoma (at a greater risk of lymph node metastasis) to determine the effect of radiotherapy excluding cervical level Ⅳ lymph nodes. METHODS: Patients of supraglottic type and glottic type were irradiated with level Ⅳ from January 2012 to June 2013, without level Ⅳ from July 2013 to December 2014, according to physicians' decision. Ninety-three patients were selective neck irradiation (SNI) of levels Ⅱ-Ⅳ (Group A) and 87 patients were SNI of levels Ⅱ and Ⅲ (Group B). The comparison between Group A and Group B was made with observation of clinical risk of recurrence and radiation complications, as well as overall survival (OS), progress-free survival (PFS) and regional nodal recurrence-free survival. RESULTS: No remarkable difference was observed in the distribution of recurrence, levels of relapse, OS, PFS and regional nodal recurrence-free survival between the 2 groups (p > 0.05). Mean radiation dose at level Ⅳ, thyroid and cervical esophagus showed significant difference between the 2 therapeutic groups (p < 0.01). As regard radiation complications, no significant difference was found in radiation dermatitis of any grade between the 2 groups (p > 0.05). However, there was remarkable difference in clinical hypothyroidism and radiation esophagitis between Group A and Group B (p < 0.05). CONCLUSIONS: Radiotherapy after surgery omitting level Ⅳ may improve the quality of life in patients with locally advanced supraglottic and glottic laryngeal carcinoma, won't worsen the prognosis as well.

A dosimetric study on radiation-induced hypothyroidism following intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma.

The objective of the present study was to investigate the association between thyroid gland-dosimetric parameters and hypothyroidism induced by intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma (NPC). A total of 52 patients with NPC treated in the Department of Radiation Oncology of The Affiliated Hospital of Xuzhou Medical University, from May 2008 to December 2016 were retrospectively enrolled in the present study and divided into two groups based on thyroid function: The euthyroid and hypothyroid groups. The association between hypothyroidism and clinical or dosimetric parameters were analyzed. Females had a significantly increased probability of suffering from radiation-induced hypothyroidism (RIHT), compared with males (P=0.010). The occurrence of RIHT was significantly negatively associated with thyroid volume prior to radiotherapy (P=0.048). Furthermore, the mean dose (Dmean) and V50 in the hypothyroidism group were significantly increased, compared with the euthyroidism group (P=0.017 and P=0.023, respectively). During the treatment optimization period, dose constraints associated with the thyroid gland demonstrated a significantly protective effect on thyroid function compared with the unconstrained group (P=0.034). According to the receiver operating characteristic curves, the threshold value was 5,160 cGy for Dmean and 54.5% for V50. The 3-year cumulative incidence of RIHT was 67.8% when the Dmean value was >5,160 cGy and 44.6% when the Dmean was <5,160 cGy (log rank test, P=0.036). Furthermore, the 3-year cumulative incidence was 66.1% when the V50 was >54.5%, and 29.9% when the V50 was <54.5% (log rank test, P=0.025). In conclusion, RIHT is associated with radiation dose, particularly with Dmean and V50 of the thyroid gland. Dose constraints associated with the thyroid gland significantly reduced the incidence of hypothyroidism compared with the unconstrained group.

A Randomized Pilot Trial Comparing Position Emission Tomography (PET)-Guided Dose Escalation Radiotherapy to Conventional Radiotherapy in Chemoradiotherapy Treatment of Locally Advanced Nasopharyngeal Carcinoma.

BACKGROUND: This pilot trial is designed to determine whether PET/CT-guided radiotherapy dose escalation can improve local control while minimizing toxicity for the treatment of locally advanced nasopharyngeal carcinoma. METHODS: 67 patients were randomized into the three treatment arms: conventional chemoradiotherapy (group A), CT-guided dose escalation chemoradiotherapy (group B) and PET/CT-guided dose escalation chemoradiotherapy (group C). Radiotherapy was delivered using the simultaneous modulated accelerated radiation therapy (SMART) technique in the dose-escalation treatment arms. Patients received concurrent and adjuvant chemotherapy. RESULTS: The use of PET/CT significantly changed the treatment volume delineation of the gross tumor volume. 3-year local progression-free (LPF) survival rates of three groups were 83.3%, 90.9% and 100%, respectively. The 3-year regional progression-free survival (RPFS) rates were 95.8%, 95.5% and 100%, respectively. The 3-year disease free survival (DFS) rates were 79.2%, 86.4% and 95.2%, respectively. The 3-year overall survival (OS) rates were 83.3%, 90.9% and 95.2%, respectively. The 3-year disease-free survival (DFS) rates were 79.2%, 86.4% and 95.2%, respectively. No patient had grade 4 late toxicity. CONCLUSIONS: PET/CT-guided dose escalation radiotherapy is well-tolerated and appears to be superior to conventional chemoradiotherapy for locally advanced NPC. TRIAL REGISTRATION: ClinicalTrials.gov NCT02089204.

Low­dose radiation­induced apoptosis in human leukemia K562 cells through mitochondrial pathways.

High­dose total body irradiation (TBI) has an established role as preparative regimen for bone­marrow transplantation in the treatment of chronic myelogenous leukemia (CML), but this regimen still has a relatively high rate of acute and late toxicity. Low­dose radiation (LDR) induces apoptosis of tumor cells and has numerous beneficial effects on normal tissues, including radiation homeostasis and adaptive response. Based on the previous evidence, in the present study, K562 cells were exposed to LDR, high­dose radiation (HDR), and LDR in combination with HDR to investigate the possible mechanism of the apoptotic effect and hypersensitivity induced by LDR. The apoptotic rate increased in all radiation groups in a time­dependent manner. An upregulation of Bax protein expression and a downregulation of Bcl­xl in a dose­dependent manner in human leukemia K562 cells was observed. However, the expression of p53 protein did not change in all of the radiation cell groups. The mitochondrial membrane potential (ΔΨm) in K562 cells decreased in all of the radiation cell groups in a dose­dependent manner. Furthermore, the decrease of ΔΨm was enhanced in the LDR/HDR group compared with that in the LDR or HDR groups. The activity of caspase­3 was enhanced in all of the radiation groups. In the LDR/HDR group, the activity of caspase­3 was higher than that in the HDR or LDR groups. The present study provided preliminary experimental evidence of LDR being beneficial in combination with TBI in the treatment of CML.

Dosimetric verification for primary focal hypermetabolism of nasopharyngeal carcinoma patients treated with dynamic intensity-modulated radiation therapy.

OBJECTIVE: To make sure the feasibility with (18F)FDG PET/CT to guided dynamic intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma patients, by dosimetric verification before treatment. METHODS: Chose 11 patients in III~IVA nasopharyngeal carcinoma treated with functional image-guided IMRT and absolute and relative dosimetric verification by Varian 23EX LA, ionization chamber, 2DICA of I'mRT Matrixx and IBA detachable phantom. Drawing outline and making treatment plan were by different imaging techniques (CT and (18F)FDG PET/CT). The dose distributions of the various regional were realized by SMART. RESULTS: The absolute mean errors of interest area were 2.39%±0.66 using 0.6 cc ice chamber. Results using DTA method, the average relative dose measurements within our protocol (3%, 3 mm) were 87.64% at 300 MU/min in all filed. CONCLUSIONS: Dosimetric verification before IMRT is obligatory and necessary. Ionization chamber and 2DICA of I'mRT Matrixx was the effective dosimetric verification tool for primary focal hyper metabolism in functional image-guided dynamic IMRT for nasopharyngeal carcinoma. Our preliminary evidence indicates that functional image-guided dynamic IMRT is feasible.