The Current Trend of Fertility Preservation in Patients with Cervical Cancer.

Although the incidence of most cancers increases with age, a considerable number of patients receive a diagnosis of cancer during their reproductive years. Young women wishing to get pregnant after cancer treatment should be provided consultation for fertility preservation and possible options. In patients with cervical cancer, hysterectomy is often inevitable because the uterus is located too close to the cervix. For young patients with cervical cancer who desire to get pregnant and whose lesion is confined to the cervix, sparing the uterus and, partially, the cervix should be prioritized as much as possible, while simultaneously ensuring favorable oncologic outcomes. In this review, we explore how to choose an adequate fertility-preserving procedure to achieve a balance between favorable oncologic outcomes and fertility and management during pregnancy after a radical trachelectomy in women with early-stage cervical cancer. For patients who require hysterectomy or radiation, evaluation of the ovarian condition and laparoscopic ovarian transposition followed by the use of artificial reproduction techniques and pregnancy by surrogacy should be discussed as options to achieve a successful pregnancy.

Consistency in human papillomavirus type detection between self-collected vaginal specimens and physician-sampled cervical specimens.

With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.

Case report: Malignant transformation of ovarian endometrioma during long term use of dienogest in a young lady.

Endometriosis is a benign disease, which is also regarded as a precursor to ovarian malignancy. Dienogest is a progestin treatment for endometriosis with efficacy and tolerability. A 35-year-old Taiwanese lady with ovarian endometrioma had taken dienogest for the last 5 years. During sonographic follow-up, surgery was suggested owing to suspicious of malignant transformation of ovarian endometrioma. While she hesitated and turned to receive two cycles of oocyte retrieval because of nulliparity. Meanwhile, more papillary growth in the ovarian endometrioma with intratumor flow was found during follow-up. Laparoscopic enucleation was performed later, and pathology revealed clear cell carcinoma with peritoneal involvement, at least FIGO stage IIB. She then underwent debulking surgery to grossly no residual tumor and received adjuvant chemotherapy with no tumor recurrence in post-operative 17-months follow-up. Considering fertility preservation, conservative treatment of ovarian endometrioma is typically indicated for those women who have not yet completed childbearing. However, malignant transformation may still occur despite long-term progestin treatment. Therefore, careful image follow-up is still indispensable.

Maintenance Chemotherapy in Patients with Platinum-Sensitive Relapsed Epithelial Ovarian Cancer after Second-Line Chemotherapy.

(1) Background: Our aim was to evaluate the efficacy and adverse effects of maintenance chemotherapy in platinum-sensitive recurrent epithelial ovarian cancer after second-line chemotherapy. (2) Methods: A total of 72 patients from a single institute who had been diagnosed with platinum-sensitive recurrent ovarian cancer and had experienced either complete or partial response after six cycles of second-line chemotherapy were divided into a standard group (n = 31) with six cycles or a maintenance group (n = 41) with more than six cycles. We then compared patient characteristics and survival outcomes between these two groups. (3) Results: In all patients, after primary management for the first recurrence, the maintenance group showed worse survival outcomes. Patients who had not undergone either surgery or radiotherapy were divided into complete response and partial response groups after six cycles of chemotherapy. In patients with partial response, maintenance chemotherapy led to a significant improvement in PFS (median, 3.6 vs. 6.7 months, p = 0.007), but no significant change in in OS. The median cycle number of maintenance chemotherapy was four. (4) Conclusions: Maintenance chemotherapy may still play an important role in patients with platinum-sensitive recurrent ovarian cancer, particularly in selected patient groups.

Long-term outcome of minimally invasive staging surgery for clinical stage I endometrial cancer: A single institute experience in Taiwan.

BACKGROUND: Endometrial cancer is the most common gynecological cancer in developed countries. With recent advances in equipment and knowledge, minimally invasive surgery (MIS) is widely accepted for the treatment of endometrial cancer. This study had the largest number of cases to date in Taiwan, comparing outcomes between MIS and laparotomy staging surgery using real-world data with long-term follow-up. METHODS: We retrospectively reviewed patients with clinical stage 1 endometrial cancer from 2009 to 2020 in our institute. All patients underwent comprehensive surgical staging procedures by MIS or laparotomy. The safety, morbidity, progression-free survival (PFS), and overall survival (OS) rates of the two groups were compared. Clinical and pathologic factors were compared with Chi-square and Fisher Exact test. PFS and OS were estimated by the Kaplan-Meier method. Differences between survival curves were analyzed using the log-rank test. A p value of <0.05 was considered statistically significant. Using Cox proportional hazards models, all factors found to be significantly associated with risk of recurrence on univariate analyses were then assessed together through multivariable models, resulting in a final oncologic outcome between MIS and laparotomy. RESULTS: A total of 665 cases (412 cases in MIS group and 253 cases in laparotomy group) were enrolled for data analysis. Median operation time was shorter in MIS group (244 and 265 minutes, p < 0.001). Median blood loss was also less (75 and 430 mL, p < 0.001). Median postoperative hospitalization duration was longer in the laparotomy group (2 and 7 days, p = 0.001). After adjusting presurgery risk factors, the PFS and OS were no significant difference in MIS and laparotomy groups. CONCLUSION: Using real-world data with long-term follow-up, we could confirm excellent PFS and OS in selective patients with clinical stage 1 endometrial carcinoma who received MIS, and the surgical time, hospital day, and blood loss were also less.

Efficacy and toxicities of doxorubicin plus ifosfamide in the second-line treatment of uterine leiomyosarcoma.

Purpose: Uterine leiomyosarcoma is a rare and aggressive tumor known for its drug resistance and metastatic potential. The standard first-line treatment typically involves anthracycline-based chemotherapy or a combination of gemcitabine and docetaxel; however, there is currently no established second-line treatment. Therefore, the aim of this study was to evaluate the efficacy and toxicity of doxorubicin plus ifosfamide as a potential second-line treatment for uterine leiomyosarcoma. Materials and methods: This is a retrospective, single-center, single-arm study. We reviewed the tumor registry data from January 2010 to December 2022 and identified patients with uterine leiomyosarcoma who had previously received first-line salvage or adjuvant treatment involving gemcitabine and taxotere, and later experienced tumor recurrence. Patients who met these criteria were included in the study. The primary endpoint was the efficacy of doxorubicin and ifosfamide as a second-line treatment for uterine leiomyosarcoma, as measured by progression-free survival, 1-year overall survival, and response rate. The secondary endpoint was the adverse events associated with this regimen. Results: Fifty-two patients were diagnosed with uterine leiomyosarcoma during the study period, nine of whom were included in the data analysis. All patients had previously received gemcitabine-docetaxel as first-line adjuvant therapy, with a median progression-free survival period of 8.4 months. Doxorubicin-ifosfamide was administered as second-line treatment, with a median progression-free survival of 6.0 months (range: 2.7-79.9 months). The clinical benefit rate of the second-line treatment was 66.7%, with a median overall survival of 33.0 months, and a 1-year overall survival rate of 83.3%. Previous reports have shown that the median progression-free survival for second-line treatments using other regimens ranged from 1.4-5.6 months. The most common adverse event was myelosuppression, with five patients requiring granulocyte colony-stimulating factor and one patient requiring a blood transfusion. No patient discontinued treatment due to unmanageable adverse events. Conclusion: Use of doxorubicin with ifosfamide may be a promising and reasonable second-line treatment with manageable adverse events for patients with uterine leiomyosarcoma.

The relationships between stress, coping strategies, and quality of life among gynecologic cancer survivors.

Many studies have reported that gynecologic cancer diagnosis, surgery, adjuvant therapy, and survivorship can be extremely stressful for many people during their cancer journey, and most cancer survivors have experienced stress after cancer, which impacts their quality of life. Importantly, healthy stress management will assist patients in overcoming obstacles in their lives and enhance both the quality of life and the cancer adjustment process. This study aimed to investigate the relationships between stress, coping strategies, and quality of life among gynecologic cancer survivors and to assess the mediating effects of coping on the relationship between quality of life and stress. A series of regression models and Sobel test were conducted to investigate whether coping strategies mediated the relationship between stress and quality of life. Stress was a predictor of quality of life. Acceptance was the mediator between stress and quality of life. Tailored programs that foster coping strategies, such as the strategy of acceptance, to reduce stress and maintain quality of life in this vulnerable group need to be developed.

Methoxyhispolon Methyl Ether, a Hispolon Analog, Thwarts the SRC/STAT3/BCL-2 Axis to Provoke Human Triple-Negative Breast Cancer Cell Apoptosis In Vitro.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with few treatment options. A promising TNBC treatment approach is targeting the oncogenic signaling pathways pivotal to TNBC initiation and progression. Deregulated activation of signal transducer and activator of transcription 3 (STAT3) is fundamental to driving TNBC malignant transformation, highlighting STAT3 as a promising TNBC therapeutic target. Methoxyhispolon Methyl Ether (MHME) is an analog of Hispolon, an anti-cancer polyphenol found in the medicinal mushroom Phellinus linteus. Still, MHME's anti-cancer effects and mechanisms remain unknown. Herein, we present the first report about MHME's anti-TNBC effect and its action mechanism. We first revealed that MHME is proapoptotic and cytotoxic against human TNBC cell lines HS578T, MDA-MB-231, and MDA-MB-463 and displayed a more potent cytotoxicity than Hispolon's. Mechanistically, MHME suppressed both constitutive and interleukin 6 (IL-6)-induced activation of STAT3 represented by the extent of tyrosine 705-phosphorylated STAT3 (p-STAT3). Notably, MHME-evoked apoptosis and clonogenicity impairment were abrogated in TNBC cells overexpressing a dominant-active mutant of STAT3 (STAT3-C); supporting the blockade of STAT3 activation is an integral mechanism of MHME's cytotoxic action on TNBC cells. Moreover, MHME downregulated BCL-2 in a STAT3-dependent manner, and TNBC cells overexpressing BCL-2 were refractory to MHME-induced apoptosis, indicating that BCL-2 downregulation is responsible for MHME's proapoptotic effect on TNBC cells. Finally, MHME suppressed SRC activation, while v-src overexpression rescued p-STAT3 levels and downregulated apoptosis in MHME-treated TNBC cells. Collectively, we conclude that MHME provokes TNBC cell apoptosis through the blockade of the SRC/STAT3/BCL-2 pro-survival axis. Our findings suggest the potential of applying MHME as a TNBC chemotherapy agent.

Can HPV Test on Random Urine Replace Self-HPV Test on Vaginal Self-Samples or Clinician-Collected Cervical Samples?

Objective: This study investigated whether random urine (RU) samples can be used to accurately identify human papillomavirus (HPV) and whether these samples can replace self-collected vaginal samples in HPV tests. Methods: A total of 167 patients with abnormal Pap smears were recruited. The patients provided self-collected vaginal and RU samples for HPV testing. Clinicians obtained cervical samples from the patients. Colposcopy examination and cervical biopsy were performed. Hybrid Capture II (HC II) and Cervista tests were used to detect HPV in the RU samples. Results: The results of tests on clinician-collected cervical samples were used as the benchmark. The sensitivities of the Cervista tests on vaginal samples and the HC II and Cervista tests on RU samples were 75.00%, 49.07%, and 44.44%, respectively. After we adjusted the HPV detection cutoff value for urine samples based on values in the receiver operating characteristic curve, the sensitivities of the HC II and Cervista tests increased to 63.89% and 58.33%, respectively. In 167 patients, 59 had cervix biopsies showing CIN2 or worse (CIN2+). For CIN2+, the sensitivity was 47.5% and 50.8% in the HC II and Cervista tests on RU samples, respectively. Conclusion: HPV tests on RU samples had approximately 60% sensitivity to HPV tests on clinician-collected cervical samples after the cutoff values were adjusted. For CIN2+, the sensitivity was only approximately 50%. Further studies and improvements in urine-based HPV testing are needed to establish it as a more convenient and accessible method for detecting HPV and cervical dysplasia in patients.

Iron metabolism and ferroptosis: A pathway for understanding preeclampsia.

Preeclampsia (PE) is a serious medical condition that poses a significant health risk to women and children worldwide, particularly in the middle- and low-income countries. It is a complex syndrome that occurs as a result of abnormal pregnancy. Hypertension is the most common symptom of PE, with proteinuria and specific organ systems as detrimental targets. PE's pathogenesis is diverse, and its symptoms can overlap with other diseases. In early pregnancy, when the placenta takes over control, oxidative stress may be closely associated with ferroptosis, a type of cell death caused by intracellular iron accumulation. Ferroptosis in the placenta is defined by redox-active iron availability, loss of antioxidant capacity and phospholipids containing polyunsaturated fatty acids (PUFA) oxidation. Recent studies suggest a compelling potential link between ferroptosis and PE. In this article, we comprehensively review the current understanding of PE and discuss one of its emerging underlying mechanisms, the ferroptosis pathway. We also provide perspective and analysis on the implications of this process in the diagnosis, prevention, and treatment of preeclampsia. We aim to bridge the gap between clinicians and basic scientists in understanding this harmful disease and challenge the research community to put more effort into this exciting new area.

Ultrafast absorption mechanism of oil-emulsified micelles onto ferrous absorbents with dielectrophoresis force in the presence of polarization.

Absorption and desorption rates were generally dependent on the concentration gradient from bulk to absorbents. A novel methodology based on a capacitor with an alternating electric field (AEF) is developed to accelerate the absorption and desorption rates with the frequency manipulation. Ferrous polystyrene microspheres (PISMs) are synthesized as absorbents, which could enhance the complex permittivities as well as dielectric properties. Theoretically, the attractive force and viscous force predominately determine the particle and micelles movement in the medium under an AEF. Oil-emulsified micelles (OEM) with various viscosities were selected as absorbates. Both the OEM and microspherical absorbents assembled through the external attractive force in the presence of the AEF. When the attractive force is equal to viscous force in the medium at the characteristic frequency, the optimal absorption rate could be obtained. The absorption rate constants of pseudo-first-order for OEMs under the polarization at 50 V and 120 kHz of frequency are ca. 10 times higher than that in absence of the polarization. The desorption rate as well as recycling efficiency could be also improved at 800 kHz. The ferrous PISMs with high complex permittivity prevented the damage from the AEF, which could be recycled 10 times of absorption and desorption with frequency manipulation under the AEF. Our methodology provides novel insights for ultrafast wastewater treatment.

Early-Stage, BRCA-Associated Ovarian Cancer Detected by Papanicolaou Smear: A Case Report.

Historically known as a "silent killer", ovarian cancer is often diagnosed at an advanced stage. We describe an unusual case of stage I, ovarian, high-grade serous carcinoma detected by a routine Papanicolaou (PAP) smear, with no abnormal physical, imaging, or laboratory findings. A 53-year-old woman with newly diagnosed triple-negative breast cancer received a screening Pap smear, which showed malignant cells not coming from the breast or uterine cervix. Pelvic examination, cervical biopsy, and gynecologic ultrasonography found no abnormality. Endometrial curettage yielded free-floating adenocarcinoma cells. The immunohistochemical stain result indicated ovary or fallopian tube cancer. Complete cytoreductive surgery was performed, and high-grade serous carcinoma of bilateral ovaries, FIGO stage IB, was diagnosed. Although extremely rare, when malignant cells not originating from the uterine cervix are detected on a Pap smear, it may lead to an early diagnosis of ovarian cancers, and this warrants further comprehensive workup.

Sertindole, an Antipsychotic Drug, Curbs the STAT3/BCL-xL Axis to Elicit Human Bladder Cancer Cell Apoptosis In Vitro.

Bladder cancer is the leading urinary tract malignancy. Epidemiological evidence has linked lower cancer incidence in schizophrenia patients to long-term medication, highlighting the anticancer potential of antipsychotics. Sertindole is an atypical antipsychotic agent with reported anticancer action on breast and gastric cancers. Yet, sertindole's effect on bladder cancer remains unaddressed. We herein present the first evidence of sertindole's antiproliferative effect and mechanisms of action on human bladder cancer cells. Sertindole was cytotoxic against bladder cancer cells while less cytotoxic to normal urothelial cells. Apoptosis was a primary cause of sertindole's cytotoxicity, as the pan-caspase inhibitor z-VAD-fmk rescued cells from sertindole-induced killing. Mechanistically, sertindole inhibited the activation of signal transducer and activator of transcription 3 (STAT3), an oncogenic driver of bladder cancer, as sertindole lowered the levels of tyrosine 705-phosphorylated STAT3 along with that of STAT3's target gene BCL-xL. Notably, ectopic expression of the dominant-active STAT3 mutant impaired sertindole-induced apoptosis in addition to restoring BCL-xL expression. Moreover, bladder cancer cells overexpressing BCL-xL were refractory to sertindole's proapoptotic action, arguing that sertindole represses STAT3 to downregulate BCL-xL, culminating in the induction of apoptosis. Overall, the current study indicated sertindole exerts bladder cancer cytotoxicity by provoking apoptosis through targeted inhibition of the antiapoptotic STAT3/BCL-xL signaling axis. These findings implicate the potential to repurpose sertindole as a therapeutic strategy for bladder cancer.

Targeting HSF1 for cancer treatment: mechanisms and inhibitor development.

Heat Shock Factor 1 (HSF1) is a master regulator of heat shock responsive signaling. In addition to playing critical roles in cellular heat shock response, emerging evidence suggests that HSF1 also regulates a non-heat shock responsive transcriptional network to handle metabolic, chemical, and genetic stress. The function of HSF1 in cellular transformation and cancer development has been extensively studied in recent years. Due to important roles for HSF1 for coping with various stressful cellular states, research on HSF1 has been very active. New functions and molecular mechanisms underlying these functions have been continuously discovered, providing new targets for novel cancer treatment strategies. In this article, we review the essential roles and mechanisms of HSF1 action in cancer cells, focusing more on recently discovered functions and their underlying mechanisms to reflect the new advances in cancer biology. In addition, we emphasize new advances with regard to HSF1 inhibitors for cancer drug development.

An Open Dataset of Annotated Metaphase Cell Images for Chromosome Identification.

Chromosomes are a principal target of clinical cytogenetic studies. While chromosomal analysis is an integral part of prenatal care, the conventional manual identification of chromosomes in images is time-consuming and costly. This study developed a chromosome detector that uses deep learning and that achieved an accuracy of 98.88% in chromosomal identification. Specifically, we compiled and made available a large and publicly accessible database containing chromosome images and annotations for training chromosome detectors. The database contains five thousand 24 chromosome class annotations and 2,000 single chromosome annotations. This database also contains examples of chromosome variations. Our database provides a reference for researchers in this field and may help expedite the development of clinical applications.

Improved Progression-Free Survival Associated with Tumor-Infiltrating Lymphocytes in High-Grade Endometrial Cancer.

Tumor-infiltrating lymphocytes (TILs) have emerged as a prognostic marker in endometrial cancer (EC). However, the role of TILs in EC with distinct histology grades and molecular types (such as mismatch repair [MMR] deficiency) has not yet been made clear. We retrospectively included 237 patients with primary EC who underwent a standard staging operation of laparoscopic or laparotomy total hysterectomy and bilateral salpingo-oophorectomy for analyses. An independent pathologist who was blind to the study patients' information reviewed the pathologic slides to assess TILs according to the method introduced by the International Immuno-Oncology Biomarkers Working Group in 2017. The outcomes of interest included both progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method was used to determine the curves of PFS and OS according to TILs, and also in the relevant subgroups (low-grade vs. high-grade, MMR-proficient vs. MMR-deficient). After a median follow-up duration of 1.82 years, 18 patients had experienced either disease progression or death. Overall, TILs (+) were not associated with PFS or OS. We did observe, however, that TILs (+) were associated with a better PFS (p = 0.045) in patients with high-grade EC, but not in those with low-grade tumors (p = 0.733). The effect of TILs on PFS was not observed in patients with MMR-proficient (p = 0.347) or MMR-deficient (p = 0.168) EC. TILs were associated with a better PFS in patients with high-grade EC. Our results suggest that TILs may be a potential prognostic marker in these patients.

Long-Term Efficacy and Toxicity of Intensity-Modulated Radiotherapy in Bulky Cervical Cancer.

Treatment of bulky cervical cancer is associated with both high adverse effects and local recurrence rates with traditional box method radiotherapy. Intensity-modulated radiotherapy (IMRT) has been adopted for the treatment of cervical cancer in order to deliver more precise radiation doses to the target region. We retrospectively enrolled a total of 98 patients with cervical cancer ≥4 cm who completed IMRT and point A-based brachytherapy treatment. The median follow-up time of the cohort was 6.84 years, with the 5-year OS and DFS being 66.33% and 75.12%, respectively. In addition, 7.14% of patients experienced local recurrence, 12.24% had distant recurrence, 6.12% had both local and distant recurrence, and 3.06% had persistent disease. In the univariate analysis, lymph node metastasis, higher creatinine levels, higher initial CA-125 and receiving chemotherapy other than cisplatin were all associated with a worse PFS. A tumor size ≥6 cm was associated with an increased incidence of higher grade of acute diarrhea. Grade 3 late radiation proctitis and cystitis developed in 11.22% and 13.27% of patients, respectively. The local recurrence rates and overall efficiencies were not inferior to other studies involving traditional pelvic external beam radiation therapy with concurrent chemotherapy. The safety and efficacy of IMRT for bulky cervical cancer were acceptable.

Performance Enhancement of Electrochemiluminescence with the Immunosensor Controlled Using Magnetized Masks for the Determination of Epithelial Cancer Biomarker EpCAM.

The performance of an electrochemiluminescence (ECL) immunosensor was improved with a particle gradient. SiO2-coated magnetic beads were adopted as nanocarriers for gradient manipulation and immobilized with the primary antibody. Cadmium telluride quantum dots were coated with a layer of protein G for conjugation and orientation of the secondary antibody as signal labels. ECL immunosensor gradients on the electrode were formed by magnetolithography (ML) with magnetized nickel masks of column and stripe arrays. The immunosensor generally aggregated as an island on the substrate, leading to a decrease of efficiency in the characteristic signals. Stripe arrays of magnetized nickel were designed to generate cylindrical magnetic flux on the substrate to improve the particle manipulation with the gradient. Various gradients of the sandwich-structured immunosensor substantially affected the electrochemical performance. Compared to the gradient-free immunosensor, the gradient of the immunosensor generated by ML using a 3 µm stripe array mask enhanced the ECL intensity ∼2.2 times. The results of quantification of epithelial cell adhesion molecules (EpCAM) with the gradient immunosensor showed a broad linear range (15-420 pg mL-1), a low limit of detection (5.5 pg mL-1), and high reliability for EpCAM-spiked serum samples, indicating that the immunosensor gradient substantially enhances the performance of the ECL assay.

Long-term treatment outcomes/toxicities of definite chemoradiotherapy (intensity-modulated radiation therapy) for early-stage "bulky" cervical cancer and survival impact of histological subtype.

BACKGROUND: To investigate the long-term treatment outcomes of early stage bulky cervical cancer treated with definite chemoradiotherapy (CCRT) using intensity-modulated radiotherapy (IMRT) followed by intracavity brachytherapy (ICRT) and the impact of histologic subtype on survival. METHODS: From 2004 to 2016, 126 patients with FIGO stage IB2-IIB bulky (≥4 cm) cervical cancer treated with CCRT followed by ICRT were retrospectively reviewed. Long-term treatment-related acute/late toxicities and treatment outcomes including overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were reported. Different histologic subtype between squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC)) of uterine cervix were also compared. RESULTS: Median follow-up time for alive patients was 117 months. The 5-year OS, LRRFS and DMFS were 75.3%, 87.8% and 75.6%, respectively. The most common ≥ grade 3 acute toxicity was hematologic toxicity (41.3%). The rates of ≥ grade 3 late toxicities were 4% of proctitis, 0.8% of urethral stricture and 0.8% of radiation dermatitis (peri-anal skin necrosis and gangrene). The 5-year OS/LRRFS/DMFS for SCC and AC/ASC were 81.7%/93.7%/81.5% and 51.9%/65.8%/53.5%, respectively (all log-rank p < 0.05). The AC/ASC histology was an independent prognostic factor for worse OS, LRRFS, and DMFS (All p < 0.05). CONCLUSION: After long-term follow up, definite CCRT using IMRT followed by ICRT is a feasible treatment with favorable acute and late treatment toxicities for patients with early stage bulky cervical cancer. This treatment outcomes were excellent for "bulky" FIGO stage IB2-IIB SCC of the uterine cervix but seemed insufficient for AC/ASC of uterine cervix.