Identifying Molecular Changes in Early Cervical Cancer Samples of Patients That Developed Metastasis

Cervical cancer is one of the most common cancers in women worldwide. Patients diagnosed with early-stage cervical cancer have a good prognosis, however, 10-20% suffer from local or distant recurrent disease after primary treatment. Treatment options for recurrent cervical cancer are limited. Therefore, it is crucial to identify factors that can predict patients with an increased risk of recurrence to optimize treatment to prevent the recurrence of cervical cancer. We aimed to identify biomarkers in early-stage primary cervical cancer which recurred after surgery. Formalin-Fixed, Paraffin-Embedded surgical specimens of 34 patients with early-stage cervical cancer (FIGO 2009 stage 1B1) and 7 healthy controls were analyzed. Targeted gene expression profiling using the PanCancer IO 360 panel of NanoString Technology was performed. The findings were confirmed by performing immunohistochemistry stainings. Various genes, namely GLS, CD36, WNT5a, HRAS, DDB2, PIK3R2, and CDH2 were found to be differentially highly expressed in primary cervical cancer samples of patients who developed distant recurrence. In addition, The relative infiltration score of CD8+ T cells, CD80+CD86+ macrophages, CD163+MRC1+ macrophages, and FOXP3+IL2RA+ regulatory T cells were significantly higher in this group of samples. In contrast, no significant differences in gene expression and relative immune infiltration were found in samples of patients who developed local recurrence. The infiltration of CD8 and FOXP3 cells were validated by immunohistochemistry using all samples included in the study. We identified molecular alterations in primary cervical cancer samples from patients who developed recurrent disease. These findings can be utilized towards developing a molecular signature for the early detection of patients with a high risk to develop metastasis.

Đánh giá thời gian sống thêm không tiến triển ung thư cổ tử cung tái phát - di căn điều trị phác đồ có platinum tại Bệnh viện K

TÓM TẮT Mục tiêu: Đánh giá thời gian sống thêm không tiến triển và một số yếu tố liên quan của bệnh nhân ung thư cổ tử cung tái phát di căn được điều trị phác đồ phác đồ hóa chất có Platinum. Phương pháp: Mô tả hồi cứu kết hợp tiến cứu, đối tượng nghiên cứu là 89 bệnh nhân được chẩn đoán ung thư cổ tử cung tái phát, tiến triển, di căn được điều trị phác đồ hóa chất Paclitaxel - Cisplatin hoặc Paclitaxel - Carboplatin tại bệnh viện K từ tháng 1/2019 - 4/2021. Kết quả: Thời gian sống thêm không bệnh tiến triển trung vị là 5,2 ± 1,7 tháng. Số vị trí di căn và đáp ứng với điều trị ảnh hưởng đến thời gian sống thêm không tiến triển. Kết luận: Phác đồ cho kết quả tốt và tương đối an toàn. ABSTRACT ASSESSMENT OF PROGRESSION - FREE SURVIVALIN METASTATIC RECURRENT CERVICAL CANCERTREATED BY PLATINUM - BASED CHEMOTHERAPY AT K HOSPITAL Objectives: To evaluate the progression - free survival and explore some related factors of patients with metastatic recurrent cervical cancer treated with platinum - based chemotherapy. Methods: A combined prospective and retrospective descriptive study was carried out in eighty - nine patients with recurrent, progressive, metastatic cervical cancer treated with Paclitaxel - Cisplatin or Paclitaxel - Carboplatin at the K hospital from 1/2019 - 4/2021. Results: The median progression - free survival time was 5.2 ± 1.7 months. The number of metastatic sitesand response to treatment affect progression - free survival. Conclusions: The regimen is effective and relatively safe. Keywords: Recurrent metastatic cervical cancer, platinum.

Radioactive 125I Seed Implantation for Recurrent Cervical Carcinoma After Surgery and Radiotherapy: A Case Report

Background: The prognosis of cervical cancer is remarkable, but there are still instances of pelvic and/or extrapelvic recurrence after radical hysterectomy with platinum-based chemoradiotherapy. Sixty percent of the patients with radiotherapy (RT) failure have pelvic recurrence, and 80% of them relapse within two years after treatment. Recurrent cervical cancer seriously affects the prognosis and survival rate of patients. Due to the dose limitation for normal tissue, it is difficult to deliver a sufficient number of doses to recurrent lesions through reirradiation. With the rapid development of brachytherapy technologies such as three-dimensional afterloading brachytherapy, interstitial brachytherapy and radioactive 125I seed implantation, the overall survival (OS) of patients with recurrent cervical cancer has been improving. In the present study, a case in which the patient was successfully treated with radioactive 125I seed implantation is reported.Case presentation: The patient, a 47-year-old woman, was initially diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer and received preoperative radiotherapy, radical hysterectomy, pelvic lymph node dissection and postoperative radiotherapy. After 95 months of follow-up, retroperitoneal lymph node metastasis and edema of the left lower limb . The size of the retroperitoneal lesion was 2.3 × 2.0 cm, and the size of the left supraclavicle lesion was 2.0 × 1.5 cm. Radioactive 125I seed implantation was performed for retroperitoneal lymph node metastasis and left supraclavicular metastasis. Paclitaxel and cisplatin chemotherapy were given after the operation. Three months after implantation, the size of the retroperitoneal focus was 1.5 × 1.1 cm, and the size of the left supraclavicular lesion was 1.0 × 0.6 cm. Thirteen months after implantation, according to the RECIST standard, the therapeutic effect reached CR. At the time of submission, the patient's progression-free survival was 6 years and 4 months.Conclusions: CT-guided 125I seed implantation is a safe, effective, and minimally invasive method for treating patients with recurrent cervical cancer after radiotherapy. The response of this patient indicates that 125I seed implantation can be used as a complementary treatment for recurrent cervical cancer after chemoradiotherapy and may also prove to be reliable for comprehensive treatment of cervical cancer.

Salvage Radiotherapy Strategy and Its Prognostic Significance for Patients With Locally Recurrent Cervical Cancer After Radical Resection: a Retrospective 10-year Analysis

Background: Salvage radiotherapy modes for treating patients with local cervical cancer recurrence after radical surgery are controversial. Therefore, we aimed to evaluate the clinical efficacy and prognostic significance of two radiotherapy modes—involved-field radiotherapy combined with regional lymph nodes (regional radiotherapy) and involved-field radiotherapy alone (local radiotherapy)—in these patients.Methods: We retrospectively enrolled patients with local recurrence who underwent radical surgery without radiotherapy for early-stage cervical cancer from January 2010 to January 2020. Clinical outcomes were analyzed using the Kaplan–Meier method and a Cox proportional hazards model.Results: Forty-four patients underwent intensity-modulated radiotherapy (IMRT)-based salvage treatment. The 5-year overall survival and progression-free survival rates were 64% and 60.2%, respectively. Sixteen of 18 patients with stump recurrence and 15 of 26 patients with pelvic and abdominal cavity recurrence received regional radiotherapy, while others received local radiotherapy. Univariate analysis showed that patients with stump recurrence, who underwent regional radiotherapy, and with a lower systemic inflammation response index (SIRI) had better prognosis than their counterparts. Patients aged < 51 years, with stump recurrence, recurrence time ≤ 24 months, recurrence site=1, and a lower SIRI who received regional radiotherapy had a better prognosis than patients who received local radiotherapy. SIRI correlated with the recurrence site and radiotherapy mode.Conclusion: Locally recurrent cervical cancer treated with IMRT-based salvage therapy has a good prognosis. Recurrence site, SIRI, and the radiotherapy mode significantly influenced prognosis. Regional radiotherapy may be suitable for patients with stump recurrence, recurrence time ≤ 24 months, and one recurrence site.

PD-1 Inhibitor Maintenance Therapy Combined Iodine-125 Seed Implantation Successfully Salvage Recurrent Cervical Cancer after CCRT: A Case Report

Cervical cancer is the fourth most common cancer in females worldwide. Patients with stage III and IV cervical cancer based on the Federation of Gynecology and Obstetrics (FIGO) classification have higher recurrence rates. Because of organs at risk (OAR) protection and the low indication rate of salvage surgery, the choice of treatment is always challenging. Systemic chemotherapy is palliative and can be performed in conjunction with surgery or radiotherapy; however, it has no significant benefit to survival. Brachytherapy and stereotactic body radiotherapy (SBRT) are characterized by extremely high radiation doses applied to tumor cells while sparing the normal tissues. Several studies have investigated the efficacy of these technologies in recurrent cervical cancer and showed promising results. The immune checkpoint inhibitors approach was also investigated and showed promising results too. Herein, we report a case of a patient with cervical cancer that recurred five months after adjuvant chemotherapy and concurrent chemoradiotherapy. The disease prognosis after interstitial implantation brachytherapy (IIB) was determined. Then, the patient underwent radioactive 125I-seed implantation combined with PD-1 inhibitor treatment. The patient exhibited a partial response after seed implantation, and up to now, the duration of this partial response was 24 months.

Chinese Expert Consensus on Iodine125 Seed Implantation for Recurrent Cervical Cancer in 2021

The treatment modality for recurrent cervical cancer (rCC) is limited, and the prognosis of these patients is poor. Seed implantation could be an important component of rCC management in the context of dose boost or salvage therapy after surgery or radiotherapy, which is characterized by a minimally invasive, high local dose, and rapidly does fall, sparing normal tissue. For patients with good performance status and lateral pelvic wall recurrence with an available puncture path, seed implantation was recommended, as well as for selected central pelvic recurrence and extra-pelvic recurrence. The combination of brachytherapy treatment planning system and CT guidance was needed, and three-dimensional printing templates could greatly improve the accuracy, efficiency, and quality of seed implantation to achieve a potential ablative effect and provide an efficient treatment for rCC. However, the recommendations of seed implantation were mainly based on retrospective articles and lack high-quality evidence, and multicenter prospective randomized studies are needed. In this consensus on iodine125 seed implantation for rCC, indication selection, technical process and requirements, dosimetry criteria, radiation protection, combined systemic therapy, and outcomes of seed implantation for rCC are discussed.