Regional heating of the pelvic area with mEHT significantly increased the peri-tumour temperature and improved the blood flow in cervical cancer. This is the first demonstration that the blood flow in cervical cancer is increased by regional hyperthermia. Such increases in temperature and blood flow may account for the clinical observations that hyperthermia improves the response of cervical cancer to radiotherapy or chemotherapy.
The survival of patients with recurrent cervical cancer following irradiation remains poor. Chemotherapy combined with hyperthermia has been demonstrated to improve the response rate. The present study was performed to evaluate the effect of modulated electro-hyperthermia combined with conventional chemotherapy compared with chemotherapy alone on recurrent cervical cancer previously treated with irradiation. A total of 20 patients were treated with chemotherapy alone, and 18 were treated with chemotherapy combined with modulated electro-hyperthermia. A single patient was treated with chemo-radiotherapy as primary treatment and then relapsed; the tumor was inoperable and radio-refractory upon recurrence. Local metastases, including metastasis of the para-aortic lymph nodes and adjacent pelvic lymph nodes were included, but distant metastases were excluded. Modulated electro-hyperthermia was performed three times per week beginning at chemotherapy initiation, and patients underwent a total of 36 sessions. The overall response (complete remission + partial remission + stable disease/progressive disease) to treatment was significantly greater in the group of patients who underwent chemotherapy combined with modulated electro-hyperthermia (P=0.0461), and at the evaluation conducted at the last follow-up visit, the response rate was significantly higher (P=0.0218). Additionally, severe complications were not reported. In the present study, of patients with recurrent cervical cancer previously treated with irradiation, the overall response rate for patients treated with chemotherapy combined with modulated electro-hyperthermia was significantly greater than that for those treated with chemotherapy alone.
Background
Early diagnosis and continuous monitoring are necessary for an efficient management of cervical cancers (CC). Liquid biopsy, such as detecting circulating tumor DNA (ctDNA) from blood, is a simple, non-invasive method for testing and monitoring cancer markers. However, tumor-specific alterations in ctDNA have not been extensively investigated or compared to other circulating biomarkers in the diagnosis and monitoring of the CC. Therfore, Next-generation sequencing (NGS) analysis with blood samples can be a new approach for highly accurate diagnosis and monitoring of the CC.
Method
Using a bioinformatics approach, we designed a panel of 24 genes associated with CC to detect and characterize patterns of somatic single-nucleotide variations, indels, and copy number variations. Our NGS CC panel covers most of the genes in The Cancer Genome Atlas (TCGA) as well as additional cancer driver and tumor suppressor genes. We profiled the variants in ctDNA from 24 CC patients who were being treated with systemic chemotherapy and local radiotherapy at the Jeonbuk National University Hospital, Korea.
Result
Eighteen out of 24 genes in our NGS CC panel had mutations across the 24 CC patients, including somatic alterations of mutated genes (
ZFHX3–
83%,
KMT2C-
79%
, KMT2D-
79%, NSD1–67%,
ATM-
38% and
RNF213
–27%). We demonstrated that the
RNF213
mutation could be used potentially used as a monitoring marker for response to chemo- and radiotherapy.
Conclusion
We developed our NGS CC panel and demostrated that our NGS panel can be useful for the diagnosis and monitoring of the CC, since the panel detected the common somatic variations in CC patients and we observed how these genetic variations change according to the treatment pattern of the patient.
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