Treatment Of Recurrent Cervical Cancer Research Articles

Efficacy of nimotuzumab in combination with immunotherapy for a young recurrent cervical cancer patient: a case report and literature review.

Cervical cancer is one of the most common malignant tumors in women, and more than one-third of the patients have already developed to a locally advanced stage at initial diagnosis. After standard concurrent chemoradiotherapy, recurrence still occurs in 29-38% of patients with locally advanced cervical cancer (LACC), and the 5-year survival rate of patients with recurrence is only 3.8-13.0%, resulting in a poor prognosis and limited therapeutic choices. Currently, the recommended first-line systemic treatment for recurrent metastatic cervical cancer involves cisplatin or carboplatin in combination with paclitaxel-based chemotherapy, supplemented with the antivascular agent bevacizumab and the immune checkpoint inhibitor pembrolizumab. The use of these drugs, however, is limited due to side effects such as myelosuppression, gastrointestinal perforation, and bleeding, so new treatment modalities need to be explored. Anti-EGFR (epithelial growth factor receptor, anti-surface growth factor receptor antibody) targeted drugs have been demonstrated to have a significant radiosensitizing effect on synchronous chemoradiotherapy in LACC and are now considered to have potential for the treatment of recurrent cervical cancer. We represented a LACC patient who relapsed 6 months after concurrent chemoradiotherapy. The patient received six cycles of nimotuzumab combined with camrelizumab, and the efficacy was evaluated to be partial remission after two or four cycles of treatment, with progression-free survival up to 9 months, without significant side effects. Until March 2024, the patient was still undergoing treatment. Promising efficacy and tolerable side effects of nimotuzumab in combination with camrelizumab were observed in this case.

Cervical cancer treatment update: A Society of Gynecologic Oncology clinical practice statement

Cervical cancer is the most commonly diagnosed gynecologic cancer worldwide. Although the incidence has declined with increased screening and higher uptake of human papillomavirus (HPV) vaccination in high-income countries, this disease remains the second highest cause of cancer mortality among women in low- and middle-income countries. In this clinical practice statement, we describe therapies for cervical cancer by treatment setting, as well as quality of life, financial toxicity, and disparities associated with this disease. In addition to chemotherapy and radiation, therapeutic strategies for cervical cancer include immune checkpoint blockade, antiangiogenics, and antibody-drug conjugates. Optimal treatment for recurrent cervical cancer remains an area of unmet need, necessitating further exploration of rational and innovative treatment approaches, including cell and immune-based therapies. Importantly, development of effective therapies for cervical cancer must incorporate strategies to ensure universal equitable access to HPV vaccination, screening, and treatment. Important consequences of the disease and treatment that impact quality of life must also be addressed. Patients with cervical cancer are at increased risk for financial toxicity, which can lead to downstream detrimental effects on physical, financial, and career outcomes. Underrepresentation of racial and ethnic minorities in gynecologic oncology clinical trials highlights the urgent need for collaborative and focused initiatives to bridge the significant divide and alleviate inequalities in the prevention and treatment of cervical cancer.

Re-irradiation for recurrent cervical cancer: A single institutional experience

PurposeSalvage treatment of recurrent cervical cancer of patients with a history of radiotherapy is currently a major clinical challenge. The purpose of our study was to retrospectively analyze clinical outcomes of radiation in patients with recurrent cancer who have previously received radiotherapy at our hospital and further explore the efficacy and safety of this treatment modality. MethodsAll consecutive patients who underwent re-irradiation were included in our department between January 2015 and December 2017. All the patients received Volumetric Modulated Arc Therapy (VMAT) alone or VMAT followed by three dimensional–image-guided brachytherapy (3D-IGBT). The volume and dose for re-irradiation depended on previous radiation fields, dosimetry and recurrence sites. All patients received systemic chemotherapy before or after re-irradiation. ResultsFifty patients were included in our study. The median time from primary radiotherapy to re-irradiation was 12 months. Local recurrence, which was the most common failure following primary treatment, was present in 25 patients (50.0 %) while regional recurrence, loco-regional recurrence and distant recurrence combined in-filed recurrence was present in 8 (16.0 %), 9 (18.0 %) and 8 patients (16.0 %). Re-irradiation dose to lymph nodes was 45 Gy with or without a boost up to 55–60 Gy, and to the gross mass was 36–45 Gy with or without a boost up to 45–61 Gy. The median follow-up period was 22 (range,4–59) months. The 3-year local control (LC), progression-free survival (PFS), and overall survival (OS) rates were 58.0, 38.7, and 44.4 %, respectively. The median time of PFS and OS was 14 and 26 months, respectively. The interval between two successive radiotherapies beyond 12 months was significantly associated with better LC and PFS (p ≤ 0.05), but without the benefit of OS (p > 0.05). Serum SCC antigen level less than 1.5 ng/ml had a significantly better impact on PFS (p ≤ 0.05). Overall, 14 patients (28 %) experienced ≥ grade 3 acute toxicities, while 9 (18 %) experienced ≥ grade 3 late toxicities. ConclusionsRe-irradiation with VMAT is an effective and safe salvage treatment option with a reasonably good clinical outcome and toxicity profile in selected patients. In our experience, recurrent cancer patients with an interval between two successive radiotherapy courses beyond 12 months and with a serum SCC-Ag level less than 1.5 ng/ml, had improved outcomes.

Efficacy and safety of PD-1 inhibitor combined with concurrent chemoradiotherapy in locally advanced cervical cancer with pelvic and/or para-aortic lymph node metastases: a retrospective cohort study.

The prognosis remains poor after standard chemoradiotherapy in locally advanced cervical cancer patients with pelvic and/or para-aortic lymph node metastases. Programmed cell death receptor-1 (PD-1) inhibitors have been recommended as the first-line treatment for recurrent cervical cancer. The efficacy of PD-1 inhibitor combined with concurrent chemoradiotherapy in locally advanced cervical cancer was still uncertain. This study aimed to explore the efficacy and safety of PD-1 inhibitors combined with concurrent chemoradiotherapy in locally advanced cervical cancer patients with pelvic and/or para-aortic lymph node metastases. This retrospective study included patients with pelvic and/or para-aortic lymph node positive diseases [International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA] who had received PD-1 inhibitors plus chemoradiotherapy/radiotherapy between April 1, 2020, and March 31, 2022 at the Hunan Cancer Hospital. The baseline clinicopathological characteristics, treatment, and clinical outcomes were collected. The major clinical outcomes were objective response rate (ORR), progression-free survival (PFS), and treatment-related adverse events (TRAEs). A total of 29 patients were included. The mean age was 55.8 [standard deviation (SD): 8.8] years. Most patients had stage IIIA-IIIB disease (72.4%) and squamous cell carcinoma (93.1%). All patients had lymph node metastases, including 24 (82.8%) with multiple metastases and 11 (37.9%) with para-aortic lymph node metastases. Among the 29 patients, 18 received sintilimab and 11 received camrelizumab concurrently with chemoradiotherapy or radiotherapy. The ORR was 96.6% [95% confidence interval (CI): 0.828, 0.993] at 3 months after radiotherapy (including 15 complete responses and 13 partial responses). At the data cutoff (August 31, 2022), the median follow-up was 14 (range, 5-30) months. The median PFS was not mature. The estimated 1- and 2-year PFS rates were 85.3% (95% CI: 60.1%, 95.2%) and 76.8% (95% CI: 47.0%, 91.2%), respectively. TRAEs of any grade occurred in 27 (93.1%) patients, most commonly as a decrease in white blood counts (82.8%), anemia (58.6%), and fatigue (48.3%). TRAEs of grade 3 or greater occurred in eight (27.6%) patients. There were no treatment-related deaths. PD-1 inhibitor combined with concurrent chemoradiotherapy showed potential benefit in term of tumor response and PFS in locally advanced cervical cancer patients with pelvic and/or para-aortic lymph node metastases.

Re-Irradiation with Intensity-Modulated Radiation Therapy for the Treatment of Recurrent Cervical Cancer in the Pelvis: An Analysis of Outcomes and Toxicity.

Background and Objectives: Treatment options for most patients with recurrent cervical cancer within the previously irradiated field are limited. This study aimed to investigate the feasibility and safety of re-irradiation using intensity-modulated radiation therapy (IMRT) for patients with cervical cancer who experienced intrapelvic recurrence. Materials and Methods: We retrospectively analyzed 22 patients with recurrent cervical cancer who were treated with re-irradiation for intrapelvic recurrence using IMRT between July 2006 and July 2020. The irradiation dose and volume were determined based on the range considered safe for the tumor size, location, and previous irradiation dose. Results: The median follow-up period was 15 months (range: 3-120) and the overall response rate was 63.6%. Of the symptomatic patients, 90% experienced symptom relief after treatment. The 1- and 2-year local progression-free survival (LPFS) rates were 36.8% and 30.7%, respectively, whereas the 1- and 2-year overall survival (OS) rates were 68.2% and 25.0%, respectively. Multivariate analysis revealed that the interval between irradiations and gross tumor volume (GTV) were significant prognostic factors for LPFS. The response to re-irradiation showed borderline statistical significance for LPFS. The GTV and response to re-irradiation were also independent prognostic factors for OS. Grade 3 late toxicities were observed in 4 (18.2%) of the 22 patients. Recto- or vesico-vaginal fistula occurred in four patients. The irradiation dose was associated with fistula formation with borderline significance. Conclusions: Re-irradiation using IMRT is a safe and effective treatment strategy for patients with recurrent cervical cancer who previously received RT. Interval between irradiations, tumor size, response to re-irradiation, and radiation dose were the main factors affecting efficacy and safety.

Experience of cytokine therapy in the treatment of recurrent cervical cancer

Cervical cancer is the most common malignant tumor of the female genital organs. In general, the prognosis in patients with advanced cervical cancer is unfavorable. The option of choice for stage IV of the disease and relapses is systemic platinum-containing chemotherapy. Its effectiveness is about 20-26%, life expectancy is 12 to 13 months. Undoubtedly, the search and development of new methods of treating this disease is an extremely urgent task. Immuno-oncology has emerged as a potential new strategy to improve the treatment outcomes of patients with malignant neoplasms. Much attention in research is focused on the opportunity of using interleukin-2, tumor necrosis factor (TNF) and interferon-gamma (IFNγ) for tumor immunotherapy, since these cytokines play a special role in antitumor protection. Due to the active search for new hybrid molecules based on TNFα, some domestically developed recombinant antitumor drugs are implicated into modern practice of clinical oncologists, in particular, “Refnot” (TNFα-thymosin-α1) and “Ingaron” (IFNγ preparation). We analyzed the result of combined treatment (standard polychemotherapy at the 1st line augmented with cytokinotherapy including Refnot + Ingaron therapy) in one patient with recurrent cervical cancer. According to the control examination, upon completion of the polychemotherapy course, a complete tumor response was registered according to the Recist 1.1 criteria. The patient continued to receive cytokines as supporting therapy. Currently, according to control quarterly examinations, a complete regression of recurrent tumor persists from the end of polychemotherapy to 28 months of observation. One should note that when monitoring the state of the immune system during therapy with Refnot and Ingaron, we noted an increase in absolute and relative numbers of T cells to normal levels along with higher cytotoxic and antitumor potential of NK cells without increasing their number. The patient well tolerates the therapy, improved quality of life is documented, and there are no clinically significant side effects. Hence, the therapy with “Refnot” (TNFα-thymosin-α1) and “Ingaron” (IFNγ) in this clinical case proved to be a safe method of maintenance therapy with a positive therapeutic effect thus allowing effective control of recurrent cervical cancer for more than 2 years, as well as significantly improve quality of life of the patient. This type of therapy may be recommended for usage in clinical oncology.

Modern Opportunities of Stereotaxic Radiation Therapy in the Treatment of Recurrent Cervical Cancer (Cc)

Сervical cancer is the first in the structure of oncogynecological pathology, while in the last decade there has been a steady increase in the incidence of cervical cancer.

Efficacy and safety of intensity Modulated Radiation therapy combined with Concurrent Chemoradiotherapy in the treatment of Recurrent Cervical Cancer.

To evaluate the clinical value of intensity modulated radiation therapy (IMRT) combined with concurrent chemoradiotherapy in the treatment of recurrent cervical cancer. This was a retrospective study. Eighty patients with recurrent cervical cancer were recruited and randomly divided into two groups: the experimental group and the control group, with 40 cases in each group at The Fourth Hospital of Hebei Medical University from April, 2017 to April, 2022. Patients in the control group were only given IMRT, while those in the experimental group were given concurrent chemoradiotherapy with paclitaxel and cisplatin based on IMRT. All patients were evaluated for clinical efficacy, adverse drug reactions, and differences in the levels of SCC-Ag, CEA and CA724 and other tumor markers before and after treatment. The total effective rate in the experimental group was significantly better than in the control group (p=0.02). The incidence of adverse reactions was 40% in the experimental group and 32.5% in the control group, with no statistically significant difference (p=0.48). After treatment, the levels of tumor markers in the experimental group were significantly lower than those in the control group, with a statistically significant difference (p=0.00). The three years survival rate was 80% in the experimental group and 55% in the control group (p=0.03). The five years survival rate was 65% in the experimental group and 42.5% in the control group, with a statistically significant difference (p=0.04). Intensity modulated radiation therapy (IMRT) combined with concurrent chemoradiotherapy is a safe and effective regimen for recurrent cervical cancer, boasting significant clinical efficacy, reduced tumor markers, no significant increase in adverse reactions, and significantly improved three-years and five years survival rate.

Clinical study of interstitial brachytherapy for 72 cases of recurrent cervical cancer.

To determine the application value of interstitial brachytherapy in the treatment of recurrent cervical cancer. A retrospective analysis was conducted on the clinical data of 72 patients with recurrent cervical cancer admitted to The Fourth Hospital of Hebei Medical University from September 2017 to April 2022. They were divided into two groups according to different brachytherapy methods: conventional after-load radiotherapy group and interstitial brachytherapy group. After treatment, regular outpatient reviews or telephone follow-ups were conducted to evaluate the efficacy, related toxic and side effects and prognostic factors. The short-term efficacy of the interstitial brachytherapy group was significantly higher than that of the interstitial brachytherapy group (p<0.05). The one-year LC and two-year LC of the interstitial brachytherapy group were 94% and 90.6%, respectively, while those of the conventional after-load group were 74.5% and 67.8%, respectively, with a statistically significant difference (p<0.05). The clinical efficacy of peripheral recurrence was 13.9% in the interstitial brachytherapy group, and that in the conventional after-load group was 2.7%, with a statistically significant difference (p<0.05). There was a statistically significant difference in late toxic and side effects between the two groups (p<0.05). Prognostic factors: Multivariate analysis of the COX regression model showed that only the maximum tumor diameter was an independent prognostic factor for OS and PFS, while the recurrence site and brachytherapy method were the independent prognostic factors for LC. Interstitial brachytherapy radiotherapy touts various benefits in the treatment of patients with recurrent cervical cancer, such as good short-term efficacy, high local control rate, reduced incidence of advanced bladder and rectal toxicity, and improved quality of life.

Cemiplimab as Second-Line Therapy for Patients with Recurrent Cervical Cancer: A United States-based Cost-effectiveness Analysis.

The efficacy of cemiplimab in recurrent cervical cancer has been demonstrated in the clinical trial EMPOWER-Cervical 1.However, its high price makes patients and clinicians hesitate to use it. Therefore, we designed a study to evaluate its cost-effectiveness. We developed a Markov model based on phase III clinical trials to calculate the cost, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) over 20years with a willingness-to-pay (WTP) threshold of $150,000/QALY. The economic data included were obtained from official US government websites and published literature. Sensitivity analysis was used to determine the uncertainties associated with the model, and a subgroup analysis was performed. Compared with chemotherapy, cemiplimab produced an additional 0.597 QALYs (0.751 LYs), resulting in an ICER of $111,211.471/QALY in the United States.The cost of cemiplimab is the most influential factor in the model. The results of these models were robust in all sensitivity analyses. From the American public payers' perspective, subgroup analysis showed cemiplimab was a cost-effective regimen in patients with squamous cell carcinoma, adenocarcinoma, or programmed cell death ligand 1 (PD-L1)≥1%. From the American public payers' perspective, cemiplimab is a cost-effective treatment option for second-line treatment of recurrent cervical cancer. Meanwhile, cemiplimab was a cost-effective treatment for patients with PD-L1≥1 and all histological types.

A novel point-of-care ethyl cellulose ethanol ablative therapy for the enhancement of paclitaxel in local recurrent cervical cancer treatment (308.5)

<b>Objectives:</b> Cervical cancer is a leading cause of global cancer mortality. Low- and middle-income countries (LMICs) suffer nearly 90% of the disease burden; this is largely due to the unavailability of technologies for cervical cancer treatment. A local ablation is a promising option for patients with recurrent localized cervical cancer who are not surgical candidates and progress despite systemic therapy and radiation. We developed a low-cost polymer-assisted ethanol ablative therapy, ethyl-cellulose ethanol (ECE) ablation, which overcomes the main shortcoming of traditional ethanol ablation: off-target ethanol leakage. The effectiveness of ECE ablation has been previously demonstrated in pre-clinical head and neck and breast cancer models. Here, we investigated the effects of paclitaxel, either locally or systemically administered, and local ablation with ECE in a preclinical model of cervical cancer. <b>Methods:</b> A syngeneic cervicovaginal tumor model was established in C57BL/6 mice using TC1-Luc, HPV16 E6/E7+ cells expressing luciferase. To determine whether ECE enhances the antitumor effect of paclitaxel, tumor-bearing mice were randomized for treatment with systemic intraperitoneal paclitaxel (P_ip) alone, local intratumoral paclitaxel (P_it) alone, P_ip + ECE, or P_it + ECE therapy (<i>n</i> = 5 per group). Tumors were monitored with calipers and bioluminescence imaging via a Perkin-Elmer <i>in vivo</i> imaging system (IVIS); tumors were imaged on days 1, 2, 3, 7, and 14. Paclitaxel therapy was administered one day prior to ECE at a 20 mg/kg dose either intraperitoneally or intratumorally. ECE was performed via intratumoral injection of 100 µL ethanol ethyl cellulose under IVIS image guidance. Mice were monitored until day 60 at the end of the study. Fig. 1 <b>Results:</b> Representative IVIS images of TC-1 Luc tumors treated with ECE + P_ip, ECE+ P_it, P_ip, and P_it on days 1 (pre-treatment), 7, and 14 post-implantation are shown in Figure 1A. Tumor growth measured by total radiance intensity (integral of light signal intensity throughout the tumor area) showed that both ECE + P_ip and ECE + P_it had significantly decreased tumor growth compared to P_ip, and P_it groups, as shown in Figure 1B (p < 0.05). Overall, mice treated with ECE + P_it performed best with significantly lower total radiance compared to ECE + P_ip, P_ip, and P_it groups. Mice in the ECE + P_ip, ECE+ P_it, P_ip, and P_it groups were observed until tumor burden was reached or the end of the study (day 60). Tumor volumes were significantly decreased in both ECE + P_ip and ECE + P_it compared to P_ip and P_it groups, as shown in Figure 1C. Additionally, mice treated with the ECE + P_it group lived significantly longer than ECE + P_ip, P_ip, and P_it groups. Survival was significantly improved with P_it compared to P_ip and with ECE + P_it compared to ECE + P_ip (p < 0.05). Mice treated with ECE + P_ip lived significantly longer than mice treated with P_ip (p < 0.05), as shown in Figure 1D. At the end of the study, fewer mice had tumors detectable via IVIS after treatment in the ECE + P_it (1 out of 5 mice), compared to ECE + P_ip (5 out of 5 mice), P_ip (5 out of 5 mice), and P_it (5 out of 5 mice) groups. <b>Conclusions:</b> The antitumor effect of paclitaxel is enhanced when paired with ECE ablation in a pre-clinical model of HPV-positive cancer. This proof-of-concept study lays the groundwork for future translational work using paclitaxel in combination with ECE ablation to increase the accessibility of low-cost treatment for recurrent cervical cancer.

Pembrolizumab in pretreated advanced, metastatic cervical, vulvar, vaginal carcinoma (325)

<b>Objectives:</b> Recurrent, pretreated cervical carcinoma is a notoriously difficult-to-treat disease with a poor prognosis. Pembrolizumab was granted accelerated approval by the FDA in June 2018 in the setting of pretreated, recurrent, or metastatic cervical cancer based on preliminary results of the phase II basket trial KEYNOTE-158. While the reported objective response rate was only 12%, many patients exhibited a durable response, with some remaining on treatment for >12 months. We sought to examine the real-world incorporation and utilization of this treatment option and evaluate patient outcomes in an academic and safety-net county hospital system. <b>Methods:</b> Based upon timing of accelerated FDA approval and to allow for lead-in, review of institutional data identified women with pretreated recurrent, persistent, or metastatic cervical, vaginal, or vulvar carcinoma who were planned to receive pembrolizumab from 2017 to 2021. Demographics and clinical-pathologic data were collected. Duration of treatment, treatment-related adverse events, and clinical outcomes were analyzed. Patients with uterine and ovarian primary tumors, PD-L1 negative status, and those who did not receive a single cycle of treatment were excluded. <b>Results:</b> Fifty-two patients were identified, of whom 20 were included in the analysis. The median number of prior systemic lines of treatment was 1 (max 4). The objective response rate was 11.7%, with a clinical benefit rate of 47%. Overall, the median duration of treatment (mDOT) was 2.1 months (two cycles, IQR: 1-8). Among patients with progression of disease or death, mDOT was 2.1 months (two cycles, IQR: 2-3). Twenty-five percent of patients received at least ten cycles, all of whom presently remain on treatment (mDOT 13 months). Treatment was generally well-tolerated, with 25% experiencing any toxicity (majority G2 hypothyroidism). One patient suffered grade 3+ toxicity - immune-mediated colitis, which resulted in cessation of treatment after one cycle. The most common reasons for non-initiation of treatment with pembrolizumab included a loss to follow-up, PD-L1 negative tumors, or enrollment in clinical trials. <b>Conclusions:</b> Pembrolizumab is generally well-tolerated in the treatment of recurrent cervical cancer, and real-world experience is compared favorably with published clinical trial outcomes data. One- quarter of patients experienced a durable response of > 10 months with minimal toxicity.

Many years of experience in the treatment of recurrent cervical cancer

Background. The incidence of cervical cancer (CC) in the world is 500,000 new cases per year. In the structure of mortality from malignant neoplasms in women under 45 years of age, CC ranks 1st. Aim. To conduct a multivariate analysis of CC relapses, taking into account the results of primary treatment of CC patients for the subsequent choice of treatment methods for CC recurrences.Methods. Retrospective analysis of 105 case histories of patients for the period 2011–2021 who were treated at the Meshalkin National Medical Research Center and received therapy for recurrences of CC. Results. Stage I — 19 (18.1%), II — 32 (30.5%), III — 50 (47.6%), IV — 4 (3.8%). Primary methods of treatment: combined radiotherapy — 51 (49%), surgical method — 18 (17%), chemoradiotherapy — 18 (17%), surgery in combination with adjuvant radiotherapy — 15 (14%), polychemotherapy (with palliative purpose) — 1 (1%). In the structure of types of relapses: locoregional relapses — 42 (39%), local relapses — 31 (29%), metastatic hematogenous — 22 (20%), metastatic lymphogenous — 13 (12%). Late relapses (more than 12 months) — 65 (62%), early (6–12 months) — 22 (21%), progression (up to 6 months) — 18 (17%). Localizations for the occurrence of distant cervical cancer metastases: bones — 11 (39.3%), lungs — 10 (35.7%), brain — 3 (10.7%), liver — 4 (14.3%), lymphogenous metastases: supraclavicular lymph nodes — 5 (35.7%), inguinal lymph nodes — 8 (57.1%), abdominal lymph nodes — 1 (7.2%).Conclusion. In 62% there were late relapses, in 48% — in patients with initial stages, more frequent and longer follow-up with an oncogynecologist is indicated. Patients need treatment by an oncologist, radiologist, neurosurgeon, chemotherapist regardless of the stage, timing of occurrence, localization of relapses.

The Role of DAPK1 in the Cell Cycle Regulation of Cervical Cancer Cells and in Response to Topotecan.

Cervical cancer is one of the most serious health conditions, with nearly 500,000 women developing the disease each year worldwide. At present, the treatment of recurrent cervical cancer remains largely ineffective, and efforts in cancer drug development are currently focused on critical serine/threonine kinases, such as death-associated protein kinase 1 (DAPK1) and polo-like kinase 1 (PLK1). In the current study, we aimed at exploring the cell cycle roles of DAPK1 and PLK1 in cervical cancer cells. To achive this goal, we used multiple methods including western blotting and assays for studying kinase activity, apoptosis, cell cycle, cell proliferation, immunofluorescence and proximity ligation. The present study demonstrated that, in cervical cancer cells, the enzymatic activity of DAPK1 was regulated in a cell cycle-specific manner. NIMA-related kinases, CDKs, PLKs and Aurora kinases regulate the function of centrosomes by orchestrating the separation of chromosomes during cell division. The present study added DAPK1 to this group of protein kinases due to its localization at centrosomes during mitosis. It was shown that DAPK1 was autophosphorylated at Ser308 in the G2 phase and during mitosis. From prophase to metaphase, the colocalization of PLK1 and DAPK1 at centrosomes was observed. Furthermore, the interaction of both these kinases could be demonstrated using proximity ligations assays and immunoprecipitations. DAPK1 was found to be a substrate of PLK1. Topotecan is an effective drug used for the treatment of cervical cancer. Therefore, the current study examined the role of DAPK1 in topotecan-induced cervical cancer cell death, and it was identified that RNA interference-based silencing of DAPK1 decreased the apoptotic effect of topotecan. Thus, these findings suggested that DAPK1 could be a biomarker and a potential target for the response to topotecan during the therapy of patients with cervical cancer.

Combination of weekly paclitaxel-carboplatin plus standard bevacizumab as neoadjuvant treatment in stage IB–IIB cervical cancer

ObjectiveIn this study we investigated response rates of bevacizumab in addition to weekly paclitaxel and carboplatin in neoadjuvant setting in cervical cancer stage IB–IIB.MethodsIn this retrospective study we included patients...

Selection of Treatment Regimens for Recurrent Cervical Cancer.

ObjectiveThe selection of individualized treatment for recurrent cervical cancer is challenging. This study aimed to investigate the impact of various therapies on survival outcomes after recurrence.MethodsEligible patients were diagnosed with recurrent cervical cancer between March 2012 and April 2018. Postrecurrence progression-free survival (PFS) and overall survival (OS) were investigated in the whole cohort and in subgroups, categorized by recurrence site and prior radiotherapy history, using a multivariate model that incorporated treatment for primary and recurrent tumors, histological pathology, and FIGO staging.ResultsTwo hundred and sixty recurrent cervical cancer patients were included. As of March 1, 2020, the median postrecurrence PFS and OS were 7.0 (range 0-94) and 24.0 (1.8-149.1) months, respectively. In a multivariate model measured by PFS, radiotherapy was superior to other therapies for the whole cohort (p=0.029) and recurrence only within the pelvic cavity (p=0.005), but the advantages of radiotherapy disappeared in patients with a history of radiotherapy (p values >0.05). For recurrence only beyond the pelvic cavity, combination therapy resulted in improved PFS (p=0.028). For recurrence both within and beyond the pelvic cavity, no therapy regimen provided additional PFS benefits (p values >0.05). Radiotherapy and combination therapy were also associated with improved postrecurrence OS for recurrence within the pelvic cavity (p=0.034) and only beyond the pelvic cavity (p=0.017), respectively.ConclusionsIn cervical cancer patients, postrecurrence radiotherapy can improve PFS and OS for patients with recurrence within the pelvic cavity and without prior radiotherapy. For recurrence beyond the pelvic cavity or cases with a history of radiotherapy, combination or individualized therapy may provide potential survival benefits.

ASO Authors Reflections: Vaginectomy as Surgical Treatment of Recurrent Cervical Cancer.

ASO Authors Reflections: Vaginectomy as Surgical Treatment of Recurrent Cervical Cancer.

Is a Vaginectomy Enough or is a Pelvic Exenteration Always Required for Surgical Treatment of Recurrent Cervical Cancer? A Propensity-Matched Study.

Reporting the perioperative and survival outcomes of vaginectomy with respect to a matched series of pelvic exenteration (PE) in women with isolated recurrent cervical cancer. The records of vaginal recurrent cervical cancer patients admitted at Fondazione Policlinico "Agostino Gemelli" IRCCS in Rome from January 2010 to June 2019 were retrospectively analyzed. A propensity-matched score analysis was performed by age, clinical stage, disease-free interval, and R0 resection. Postsurgical complications and survival rates were evaluated. Fifteen women underwent vaginectomy, and 30 patients were submitted to PE. No statistical differences were observed between the two groups at baseline characteristics. The vaginectomy procedures were successfully performed in all women, and no case required conversion to PE. Moreover, a higher rate of major postoperative complications after PE with respect to vaginectomy (p = 0.027) was recorded. Among them, three women required reoperation within 30 postoperative days, and four experienced two or more complications. Twenty-five (55.6%) women experienced recurrence: 8 of 25 (32.0%) in the vaginectomy group, and 17 of 25 (68%) in the PE group, with a median progression-free survival of 20months and 13months, respectively (p = 0.169). In total, 5 of 15 (33.3%) died of disease in the vaginectomy group and 13/30 (43.3%) in the PE group, with a median overall survival of 39 and 18months for vaginectomy and PE, respectively (p = 0.161). The vaginectomy seems to allow for salvage treatment, such as radiotherapy and/or PE, but with a minimal impact on the quality of life in appropriately selected women with local recurrent cervical cancer.

Advances in immunotherapy for cervical cancer.

Novel therapies are needed for the treatment of recurrent cervical cancer. The best chemotherapy regimen to date has a response rate of 48% with an overall survival of 17 months, with limited options for second-line chemotherapy. Immunotherapy can induce a strong immune response in cervical cancer due to retained viral antigens and is reviewed in this article. Current clinical trials include treatment with Listeria that elicits an immune response against the E7 oncoprotein and active vaccines against the E7 oncoprotein. Although the response rates to programmed cell death 1 (PD-1) inhibition alone have been modest, the landmark survival reported in these trials suggests the activity of these agents may not be measured by RECIST criteria. The KEYNOTE-158 trial has led to the approval of pembrolizumab in recurrent programmed cell death ligand 1 (PD-L1) positive cervical cancer. Combinations of programmed cell death 1 and anticytotoxic T-lymphocyte-associated protein 4 inhibitors (CTLA4) inhibitors have shown promising and durable activity. There is active research with new combinations of checkpoint inhibitors, as well as combinations of these drugs with chemotherapy and radiation, and other novel approaches. Immune therapy has broad activity in cervical cancer. Responses to immunotherapy can be dramatic and durable. Continued work to find the optimal combination and setting for immunotherapy is ongoing.

High-dose-rate intracavitary brachytherapy for recurrent cervical cancer in the vaginal stump after hysterectomy.

ABSTRACTThis study aimed to evaluate the treatment outcomes of patients who received high-dose-rate intracavitary brachytherapy (HDR-BT) using Iridium-192 with or without external beam radiotherapy as definitive treatment for recurrent cervical cancer after hysterectomy. Thirty-six patients with local recurrence after hysterectomy received radiotherapy including HDR-BT from 2005 to 2013. Overall survival, local control rate, and progression-free survival were estimated retrospectively via the Kaplan-Meier method. Late adverse events were also scored using the Common Terminology Criteria for Adverse Events (version 3.0). Median follow-up time was 38 (range, 7.4–101.3) months. The 3-year estimates of overall survival, local control rate, and progression-free survival were 100.0%, 82.8%, and 76.8%, respectively. Two patients (5.6%) had grade 2 lymphedema, but no other adverse events greater than grade 2 were reported. In conclusion, HDR-BT was an effective treatment modality for patients with cervical cancer recurrence in the vaginal stump.