Brachytherapy is a critical component of locally advanced cervical cancer treatment, and patients ineligible for brachytherapy historically have poor outcomes. Delivery of boost with stereotactic body radiation therapy (SBRT) has been studied, though toxicity is a concern. Recent case reports have explored adaptive radiation boost, which can adjust plans for inter-fraction motion using magnetic resonance guidance. Herein, we report the first patient with locally advanced cervical cancer ineligible for brachytherapy who was treated with a cone-beam computed tomography (CBCT)-guided adaptive boost following completion of chemoradiation. A 71-year-old female with locally advanced cervical cancer was treated with chemoradiation and was deemed ineligible for a brachytherapy boost due to tumor size, geometry, and a fistula with a tumor in the bladder. She was prescribed a boost to the primary tumor of 25 Gy in five fractions using CBCT-guided adaptive radiation following the completion of chemoradiation. A simulation was performed using a non-contrast CT fused with a mid-chemoradiation magnetic resonance imaging (MRI) scan to create an initial plan. For each treatment fraction, kilovoltage CBCTs were acquired, contours of organs at risk (OARs) were adjusted to reflect anatomy-of-the-day, and an adapted plan was generated. The initial and adapted plans were compared using dose-volume histogram objectives, and the adapted plan was used if it resolved OAR constraint violations or improved target coverage. The use of the initial treatment plan would have resulted in constraint violations for the rectum, sigmoid, and bladder in all fractions. The adapted plans achieved hard constraints in all fractions for all four critical OARs. The mean total treatment time across all five fractions was 58 minutes. This case demonstrates the feasibility of a CBCT-guided adaptive boost approach and the dosimetric benefits of plan adaptation in this setting. Though larger-scale and longer-term data are needed, CBCT-guided adaptive radiation may present a feasible alternative modality to deliver boost doses for brachytherapy-ineligible patients.

UNASSIGNED: For locally advanced cervical cancer (LACC), treatment response to radiotherapy (RT) can vary significantly even among those with the same stage classification of International Federation of Gynecology and Obstetrics (FIGO). This study investigated the value of ADC metric for forecasting end-of-treatment outcomes in LACC patients referred for RT.
UNASSIGNED: Eighty patients with pathologically confirmed cervical squamous cell carcinoma with (SCC) were included in the research. Abdominal or pelvic MRI scans were conducted at least three times for all participants: before RT, three weeks after beginning of RT and approximately two months after RT was finalized. Calculated apparent diffusion coefficient (ADC) values of the LACC include: pre-ADC, interim-ADC, ΔADC and Δ%ADC. Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, subjects were calculated and subsequently categorized into good responders group (complete response) and poor responders group (progressive disease, stable disease or partial response).
UNASSIGNED: Compared to good-responders, subjects of poor-responder group showed significantly lower values of interim-ADC, ΔADC, and Δ%ADC (all P < 0.05). To distinguish between good and poor responders, the optimal cutoff values of interim-ADC, ΔADC, and Δ%ADC were determined to be 1.067 × 10-3 mm2/sec, 0.209 × 10-3 mm2/sec, and 30.74 % using the ROC curve, with corresponding sensitivities of 83.78 %, 86.49 %, 75.68 %, and specificities of 88.37 %, 86.49 %, 75.68 %, respectively. Multivariate logistic regression revealed that the baseline tumor diameter and interim-ADC were significant prognostic factors for treatment response with an odds ratio (OR) of 0.105 (95 % confidence interval [95 % CI] 0.018-0.616) for baseline tumor diameter and 42.896 (95 % CI 8.205-224.262) for interim-ADC.
UNASSIGNED: The interim-ADC value and baseline tumor diameter surfaced as possible indicative factors for predicting the response to RT in patients with LACC.

Despite the introduction of targeted vaccines and screening protocols, locally advanced cervical cancer represents a median proportion of 37% among all cervical carcinomas. Compared to early stages, it presents significantly lower cure rates, with a 5-year disease-free survival rate of 68% and a 5-year overall survival rate of 74%. According to current guidelines, definitive radiotherapy with concomitant chemotherapy represents the gold standard for locally advanced cervical cancer treatment. However, a significant number of patients relapse and die from metastatic disease. The aim of this narrative review is to examine the recent advancements in treating locally advanced cervical cancer, exploring new frontiers in therapeutic approaches. The PubMed database and clinical trial registries were searched to identify relevant articles published on locally advanced cervical cancer treatment up to March 2024, mainly focusing on papers published in the last decade. Abstracts presented at major international congresses that bring relevant evidence were included. Progress achieved in refining radiotherapy techniques, recent evidence regarding neoadjuvant treatment preceding surgery or concurrent chemoradiotherapy, and key findings concerning adjuvant treatment are thoroughly explored. Furthermore, a comprehensive review of prominent phase II and phase III trials examining the integration of immune checkpoint inhibitors is conducted, analyzing the various contexts in which they are applied. In light of the new evidence that has emerged in recent years and is discussed in this article, the appropriate selection of the most suitable therapeutic approach for each patient remains a complex but crucial issue.

Squamous cell carcinomas (SCCs) are the most prevalent malignant tumors affecting the cervix. The superficial spread of SCC along the inner surface of the uterus, replacing the endometrium with malignant cells, is a rare subtype of cervical cancer. We present the case of a 55-year-old woman who complained of per-vaginal white discharge and generalized weakness for one month. Clinical examination revealed a bulky and fibrosed cervical os. A cervical biopsy confirmed the diagnosis of poorly differentiated nonkeratinizing SCC. MRI showed an endocervical infiltrative, heterogeneously enhancing mass lesion involving the cervix, along with cervical stenosis and hydrometra. Irregular thickening with nodular enhancing deposits showing morphology similar to the cervical lesion and restricted diffusion were noted along the endometrial lining contiguous with the cervical lesion. The patient underwent a radical hysterectomy, and histopathological examination revealed poorly differentiated nonkeratinizing squamous cell cervical carcinoma with contiguous squamous cell extension into the uterine endometrium, confirming the diagnosis of superficially spreading cervical SCC. Establishing the continuity of the lesion on imaging and histopathological testing is critical to confirm the presence of a superficial spread of cervical cancer and rule out contemporaneous endometrial cancer.

BACKGROUND: The treatment of choice for patients with locally advanced cervical cancer (LACC) is definitive concurrent radio chemotherapy which consists of external beam radiotherapy (EBRT) and concurrent platinum-based chemotherapy (CCRT), with the possible addition of brachytherapy (BT). However, the benefits of adjuvant surgery after neoadjuvant treatments remain a debated issue and a still open question in the literature. This meta-analysis aims to provide an updated view on the controversial topic, focusing on comparing surgery after any adjuvant treatment and standard treatment.
METHODS: Following the recommendations in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, the PubMed and Embase databases were systematically searched in April 2023 for early publications. No limitations on the country were applied. Only English articles were considered. The comparative studies containing data about disease-free survival (DFS) and/or overall survival (OS) were included in the meta-analysis.
RESULTS: The CCRT + surgery group showed a significantly better DFS than CCRT (RR 0.69 [95% CI 0.58-0.81] p < 0.01) and a better OS (RR 0.70 [95% CI 0.55-0.89] p < 0.01). Nine studies comparing neoadjuvant chemotherapy (NACT) plus surgery and CCRT were also enrolled. The NACT + surgery group showed a significantly better DFS than CCRT (RR 0.66 [95% CI 0.45-0.97] p < 0.01) and a better OS (RR 0.56 [95% CI 0.38-0.83] p < 0.01). In the sub-analysis of three randomized control trials, the surgery group documented a non-significantly better DFS and OS than CCRT (OR 1.10 [95% CI 0.67-1.80] p = 0.72; I2 = 69% p = 0.72; OR 1.09 [95% CI 0.63-1.91] p = 0.75; I2 = 13% p = 0.32).
CONCLUSIONS: The results provide updated findings about the efficacy of neoadjuvant treatments, indicating significantly improved DFS and OS in patients undergoing hysterectomy after CCRT or NACT compared with patients undergoing standard treatments.

UNASSIGNED: Organ motion (OM) and volumetric changes pose challenges in radiotherapy (RT) for locally advanced cervical cancer (LACC). Magnetic Resonance-guided Radiotherapy (MRgRT) combines improved MRI contrast with adaptive RT plans for daily anatomical changes. Our goal was to analyze cervico-uterine structure (CUS) changes during RT to develop strategies for managing OM.
UNASSIGNED: LACC patients received chemoradiation by MRIdian system with a simultaneous integrated boost (SIB) protocol. Prescription doses of 55-50.6 Gy at PTV1 and 45-39.6 Gy at PTV2 were given in 22 and 25 fractions. Daily MRI scans were co-registered with planning scans and CUS changes were assessed.Six PTVs were created by adding 0.5, 0.7, 1, 1.3, 1.5, and 2 cm margins to the CUS, based on the simulation MRI. Adequate margins were determined to include 95 % of the CUSs throughout the entire treatment in 95 % of patients.
UNASSIGNED: Analysis of 15 LACC patients and 372 MR scans showed a 31 % median CUS volume decrease. Asymmetric margins of 2 cm cranially, 0.5 cm caudally, 1.5 cm posteriorly, 2 cm anteriorly, and 1.5 cm on both sides were optimal for PTV, adapting to CUS variations. Post-14th fraction, smaller margins of 0.7 cm cranially, 0.5 cm caudally, 1.3 cm posteriorly, 1.3 cm anteriorly, and 1.3 cm on both sides sufficed.
UNASSIGNED: CUS mobility varies during RT, suggesting reduced PTV margins after the third week. MRgRT with adaptive strategies optimizes dose delivery, emphasizing the importance of streamlined IGRT with reduced PTV margins using a tailored MRgRT workflow with hybrid MRI-guided systems.

Neoadjuvant chemotherapy (NACT) is a viable therapeutic option for women diagnosed locally advanced cervical cancer (LACC). However, the factors influencing pathological response are still controversial. We collected pair specimens of 185 LACC patients before and after receiving NACT and conducted histological evaluation. 8 fresh tissues pre-treatment were selected from the entire cohort to conducted immune gene expression profiling. A novel pathological grading system was established by comprehensively assessing the percentages of viable tumor, inflammatory stroma, fibrotic stroma, and necrosis in the tumor bed. Then, 185 patients were categorized into either the good pathological response (GPR) group or the poor pathological response (PPR) group post-NACT, with 134 patients (72.4%, 134/185) achieving GPR. Increasing tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating lymphocytes volume (TILV) pre-treatment were correlated with GPR, with TILV emerging as an independent predictive factor for GPR. Additionally, CIBERSORT analysis revealed noteworthy differences in the expression of immune makers between cPR and non-cPR group. Furthermore, a significantly heightened density of CD8 + T cells and a reduced density of FOXP3 + T cells were observed in GPR than PPR. Importantly, patients exhibiting GPR or inflammatory type demonstrated improved overall survival and disease-free survival. Notably, stromal type was an independent prognostic factor in multivariate analysis. Our study indicates the elevated TILV in pre-treatment specimens may predict a favorable response to NACT, while identifying stromal type in post-treatment specimens as an independent prognostic factor. Moreover, we proposed this pathological grading system in NACT patients, which may offer a more comprehensive understanding of treatment response and prognosis.

OBJECTIVE: Analyzing dose distributions to regional lymph-node metastases (RLNMs) in locally advanced cervical cancer (LACC) patients undergoing intracavitary and interstitial hybrid brachytherapy (IC/IS).
METHODS: Dose distributions of eleven LACC patients with 38 RLNMs, and who received 38 IC/IS sessions were analyzed in EQD2, considering RLNM positions and ipsilateral interstitial needles; these RLNMs, excepting the para-aortic region, were classified into four groups.
RESULTS: RLNMs had a median of two ipsilateral interstitial needles per session. Significant differences were observed in total RLNM D90, depending on whether the position was cranial or caudal of the uterine base (85.5 vs. 378.9 cGy, p < 0.0001), and whether the RLNM D90 was associated with a number of ipsilateral interstitial needles between 0-1 or 2 or more (68.4 vs. 112.2 cGy, p = 0.006) per session. At each session, Group 1 RLNMs (cranial of the uterine base, 0-1 ipsilateral interstitial needle) had a mean D90 of 21.1 cGy; Group 2 (cranial, 2 or more), 73.8; Group 3 (caudal, 0-1), 94.7; and Group 4 (caudal, 2 or more), 136.1.
CONCLUSIONS: RLNMs located caudal of the uterine base associated with two or more ipsilateral interstitial needles in IC/IS had a higher dose contribution, which should be considered when calculating the RLNMs\' dose of external beam boost irradiation.

Cancer is a disease in which abnormal cells divide uncontrollably, destroying tissues. A malignant tumor arises from cells in the cervix, the lower portion of the uterus (womb) that links the uterus to the vagina (birth canal), and is known as cervical cancer. One of the most significant global community health problems is cancer, which sees a daily increase in the number of sufferers. Therefore, it is crucial to expand our understanding of the molecular pathophysiology of cervical cancer and to suggest new therapeutic goals as well as new techniques for early detection of the illness. Since early diagnosis of pathologies can dramatically increase a patient\'s chance of survival, prognosis, and recurrence. This article aims to educate readers about some essential concepts surrounding cervical cancer, including the various types of cervical cancer, the stages of cancer, as well as their etiology, epidemiology, pathogenesis, management, and treatment, and its relationship with pregnancy. All of these concepts are essential for any individual studying medicine or working in the medical industry to understand. We intend to summarize the information that is currently available and the recommended courses of action for treating cervical cancer and its association with pregnancy in this review. Research priorities and controversies are also noted.

Locally advanced cervical cancers are often treated with palliative intent due to concerns that the tumor is too far advanced or too large to be treated curatively. Also, patients greater than 65 years of age with cervical cancer are sometimes regarded as being too old or too frail to be cured with combined radiation and chemotherapy. These patients are often treated with radiation alone or with palliative therapy. Understanding the treatment modalities for cervical cancer is essential, as they can be complex and unique to each patient\'s specific diagnosis. This case report aims to describe the dramatic response to treatment with combined radiation and chemotherapy for a patient greater than 65 years of age with pelvis-filling cervical cancer with right-sided hydronephrosis. After a five-week course of concurrent chemoradiation, the cervical mass radiographically completely disappeared, with no evidence of disease noted on pelvic MRI.