Objective To investigate the clinical outcomes and toxicity in patients
with locally advanced cervical cancer treated with supplementary
applicator guided-intensity modulated radiation therapy (IMRT) based on
conventional intracavitary brachytherapy (IC/IMRT). Population Large
high risk clinical target volume (HR-CTV) volume (>40cc) at
the time of brachytherapy cervical cancer patients were recruited.
Methods This study is a retrospective analysis of 76 patients with
locally advanced cervical cancer (FIGO IIB-IVA) treated with concurrent
chemo-radiotherapy followed by IC/IMRT between June 2010 and October
2016. External radiotherapy (45 Gy in 25 fractions) with cisplatin
chemotherapy treated before IC/IMRT. The prescription dose for HR-CTV
and IR-CTV were 6 Gy and 5 Gy per fraction for 5 fractions respectively.
Results: Mean HR-CTV was 65.8±23.6 cc at the time of brachytherapy. D90
for HR-CTV and IR-CTV were 88.7±3.6 Gy and 78.1±2.5 Gy. D2cc for
bladder, rectum, sigmoid and small intestine were 71.8±3.8 Gy, 64.6±4.9
Gy, 63.9±5.3 Gy and 56.7±8.7 Gy respectively. Median follow-up was 85
months (47.9-124.2 months). Five-year local recurrence free survival
rate, metastasis recurrence free survival rate, disease free survival
rate and cancer special survival rate were 87.6%, 82.4%, 70.9% and
76.3%, respectively. The grade 1+2 gastrointestinal and urinary late
toxicities were 15.8% and 21.1%, while grade 3 late toxicities were
3.9% and 5.2%, respectively. Neither acute nor late grade 4
gastrointestinal or urinary toxicities were seen. Conclusions: The
combination of ICBT with an applicator-guided supplementary IMRT boost
achieved an excellent local control and overall survival with low
toxicity for bulky residual cervical tumor
Background
Radioresistance remains a major clinical challenge in cervical cancer therapy. Salicylic acid (SA)-mediated direct activation of AMP–activated protein kinase (AMPK) is critical to radiosensitivity. However, limited data exists regarding the combination of SA and radiotherapy, even though there are several indications that this might be a promising treatment strategy. This study aimed to investigate the radiosensitizing effect of SA on human cervical cancer cells and its potential molecular mechanism.
Methods
Cervical cancer cells were treated with SA and ionizing radiation. The expression of γ-H2AX was evaluated by immunofluorescence (IF) assay. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to detect the protein level of AMPK/TSC2/mTOR pathway.
Results
SA inhibited basal proliferation of cervical cancer cells in a dose and time dependent manner. In addition, SA increased radiation-induced DNA damage, promoted apoptosis, triggered a redistribution of cell cycle from G2-M phase to G1-S phase of cervical cancer cells, and hence increased cell sensitivity to radiation. Moreover, SA treatment elevated the expression levels of p-AMPKα and p-TSC2, whereas the level of p-mTOR was significantly decreased.
Conclusion
SA enhances the radiosensitivity of cervical cancer cells by targeting AMPK/TSC2/mTOR signaling pathway, and might serve as a promising therapeutic strategy to improve the efficacy of radiotherapy for cervical cancer.
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