Search Results (87)

Background: Following the results of the Laparoscopic Approach to Carcinoma of the Cervix (LACC) trial, doubts have arisen about the safety of laparoscopy in the treatment of endometrial cancer. Methods: A retrospective multicenter cohort study which included all endometrial cancer (EC) patients who underwent a hysterectomy in Emilia Romagna hospitals from 2000 to 2019. All cases were revised and classified according to the 2009 International Federation of Gynaecology and Obstetrics (FIGO) staging system. The different impacts of the surgical approach on survival were stratified according to the recurrence risk from the 2016 European Society for Medical Oncology (ESMO)–European Society of Gynaecological Oncology (ESGO) classification system. The clinical characteristics and oncological outcome of patients treated by laparoscopy were compared with those treated by laparotomy. Results: A total of 2402 EC patients were included in the study. The use of laparoscopy has increased over the years, reaching 81% of procedures in 2019. Laparoscopy reduced complications and hospital stay. Laparoscopy was preferred to treat low, intermediate, and intermediate/high-risk patients. Laparoscopy showed no adverse effects on overall survival (OS) in any recurrence risk class. Particularly in high-risk EC patients, laparoscopy was associated with an increased OS in comparison with women treated by laparotomy regardless of the use of adjuvant therapy. Conclusions: Laparoscopy should always be chosen to treat EC of any risk class. The goal is to ensure correct treatment and oncological safety regardless of the surgical approach. Full article

The recommended treatment for early-stage cervical cancer (FIGO 2018 stages IA–IB2 and selected IIA1) is surgery, followed by either observation or adjuvant therapy, based on individual risk factors. Surgical management has evolved from extensive radical procedures to more conservative strategies, allowing for fertility-preserving options in appropriately selected patients. In 2018, a landmark study (LACC trial) evaluated the surgical approach to radical hysterectomy, comparing open vs. minimally invasive surgery. The results demonstrated that minimally invasive surgery was associated with worse disease-free and overall survival, leading to guidelines changes that recommend the open radical hysterectomy as the new standard of care. More recently, results from the prospective randomized SHAPE trial demonstrated that in well-selected patients with low-risk early-stage cervical cancer, recurrence rates are comparable between simple hysterectomy and radical hysterectomy. An ongoing study, the CONTESSA trial, is evaluating the role of neoadjuvant chemotherapy in the setting of fertility preservation for lesions measuring 2–4 cm. In addition, ongoing studies are evaluating different surgical approaches for both simple hysterectomy (LASH trial) and radical hysterectomy (ROCC/GOG-3043 and RACC trials), with a focus on comparing oncologic outcomes. Attention has also turned to refining lymph node assessment. Sentinel lymph node biopsy has become a standard staging strategy with reduced morbidity. The SENTICOL I-II and SENTIX/ENGOT-Cx2 trials support its safety and diagnostic accuracy in early-stage disease. This article offers a comprehensive overview of recently published prospective trials that have shaped clinical practice in the management of early-stage cervical cancer. It focuses on surgical approaches and radicality, the role of sentinel lymph node mapping, and fertility-sparing treatments. The review further draws attention to ongoing investigations and novel studies that may influence future directions in the field. Full article

Background/Objectives: Recent advancements in the treatment of LACC have focused on improving outcomes through systemic treatment intensification. Therefore, this review aims to analyze the brachytherapy (BT) techniques employed in recent studies that are likely to change upcoming clinical guidelines, and to discuss the evolving role of IGABT in optimizing patient outcomes. Methods: This review focuses on BT practices reported across main phase III trials—OUTBACK, INTERLACE, CALLA, and KEYNOTE A18—compared with the EMBRACE I study. Analyzed parameters include BT modality, dose prescription techniques, imaging guidance, and overall treatment time (OTT). Results: In EMBRACE I, MRI-based IGABT was mandatory, with 43% of patients receiving an intracavitary/interstitial (IC/IS) applicator; cumulative EQD2 D90 HR-CTV was 90 Gy with a median OTT of 46 days. The OUTBACK trial relied predominantly on point A-based BT, with limited use of volume-based BT (28%). The INTERLACE trial reported mixed BT approaches: 70% point A-based, 30% volume-based, and 20% 2D BT. A median cervical dose of 79.4 Gy was reported. CALLA maintained strong protocol adherence, with 60% volume-based BT and a median tumor EQD2 dose of 83 Gy, although lower in the Japan cohort. In the KEYNOTE A 18 cohort, volume-based BT was performed in 88% of patients, with a median D90 HR-CTV dose of 87 Gy; IC/IS applicators were used in 23% of cases. Conclusions: Across these major studies, the following consistent pattern emerges: the quality and technique of BT impact survival outcomes and toxicity profile in LACC. MRI-based IGABT—with the use of IC/IS applicators when needed—is essential. Full article

Cervical cancer remains a significant health challenge globally, with locally advanced cervical cancer (LACC) representing a particularly complex subset due to its diverse definitions and varied treatment approaches. The absence of randomized controlled trials comparing the upfront radical surgery followed by concurrent chemoradiotherapy (CCRT) or chemotherapy alone for clearly defined risk factors for LACC hinders the development of standardized treatment protocols, leading to disparities in patient outcomes across different healthcare settings. This paper seeks to underline the necessity of a consensus on the definition of LACC and aims to comprehensively and critically review the existing literature trying to harmonize treatment strategies and improve prognostic outcomes. Our analysis suggests a multimodal approach for treating FIGO IB3, IIA2, and selected IIB cases at facilities capable of delivering highly curative nerve-sparing surgical interventions, with the goal of bridging the gap in current treatment methodologies. Preliminary findings suggest that adopting a standardized definition could facilitate more consistent treatment outcomes and enhance comparative research. Full article

Background/Objective: This study aimed to assess the prognostic significance of pretreatment nutritional and systemic inflammatory indices (IIs), and body composition parameters in patients with locally advanced cervical cancer (LACC) treated with chemoradiation and brachytherapy. The goal was to identify key predictors of clinical outcomes, such as local control (LC), metastasis-free survival (MFS), disease-free survival (DFS), and overall survival (OS), using machine learning techniques. Materials and methods: A retrospective analysis of 173 patients with LACC treated between 2007 and 2021 was conducted. The study utilized machine learning techniques, including LASSO regression and Classification and Regression Tree (CART) analysis, to identify significant predictors of outcomes. Clinical data, tumor-related parameters, and treatment factors, along with IIs and body composition metrics (e.g., sarcopenic obesity), were incorporated into the models. Model performance was evaluated using ROC curves and AUC values. Results: Among 173 patients, hemoglobin (Hb) levels, ECOG performance status, and total protein emerged as primary prognostic indicators across multiple endpoints. For 2-year LC, patients with Hb > 11.9 g/dL had a rate of 95.1% compared to 73.6% in those with lower levels, with further stratification by ECOG status, ANRI, and total protein refining predictions. For 5-year LC, rates were 83.1% for Hb > 11.5 g/dL and 43.3% for lower levels. For 2-year MFS, ECOG 0 patients had an 88.1% rate compared to 73.8% for ECOG ≥ 1. In 2-year OS, Hb > 11.9 g/dL predicted a 95.1% rate, while ≤11.9 g/dL correlated with 74.0%. IIs (ANRI, SIRI, MLR) demonstrated predictive value only within specific patient subgroups defined by the primary prognostic indicators. The model showed strong predictive accuracy, with AUCs ranging from 0.656 for 2-year MFS to 0.851 for 2-year OS. Conclusions: These findings underscore the value of integrating traditional prognostic factors with emerging markers to enhance risk stratification in LACC. The use of machine learning techniques like LASSO and CART demonstrated strong predictive capabilities, highlighting their potential to refine individualized treatment strategies. Prospective validation of these models is warranted to confirm their utility in clinical practice. Full article

Background and Objectives: Recent studies have supported the non-inferiority of the minimally invasive treatment approach over the open approach. However, they have also underlined its inferiority regarding its oncological results, while preserving the short-term benefits. The direct effects of these results were represented by indication changes in international guidelines on the application of minimally invasive surgery for treating early-stage cervical cancer. Material and metods: Herein, a literature review, including studies between 1992 and 2017, was performed. Results: The results show that the studies published during this period supported the non-inferiority of the minimally invasive treatment approach for early-stage cervical cancer compared with the open approach. However, the studies included were unicentric, non-randomized and relied on a reduced number of patients. The results of the Laparoscopic Approach to Cervical Cancer [LACC] trial could not have been considered, since only studies published between 1992 and 2017 were included. This trial firmly supported the advantages of the minimally invasive approach in treating early-stage cervical cancer. The literature published after 2018 highlighted the necessity for new clinical studies, randomized and prospective ones, to cover the defects of this study and to verify (or not) its results. Conclusions: the studies published after 2018 mainly focused on the deficiencies of the LACC trial and also on developing new methods that could improve this surgical technique, thus enhancing the safety of the minimally invasive approach in treating early-stage cervical cancer. However, none of the included studies succeeded to provide enough evidence to oppose the results obtained in the LACC trial. Therefore, in order to clarify the state of this surgical approach, the results of three ongoing randomized clinical trials are expected. Full article

This study investigates the clinical efficacy of MRI-based adaptive brachytherapy (IGABT) using combined intracavitary and interstitial techniques in the curative treatment of patients with advanced cervical cancer (LACC). A retrospective analysis was conducted on 149 LACC patients treated at a single center. The therapeutic protocol included intensity-modulated external beam radiotherapy (IMRT) and IGABT. Dosimetric parameters were evaluated for relevance for local control (LC), progression-free survival (PFS), and overall survival (OS) using Kaplan–Meier estimation, Cox regression, and log-rank test. Patients predominantly presented with stage III/IV tumors (81%, FIGO 2018). The median high-risk clinical target volume (hrCTV) was 34 cm³, with a median D90% dose of 88.9 GyEQD2. At 24 months, OS, PFS, and LC rates were 86%, 57%, and 81%, respectively. FIGO stage, tumor volume, and histology were significant predictors of PFS. Higher total hrCTV doses were strongly correlated with improved LC and PFS, emphasizing the importance of precise dosimetric optimization in IGABT and confirming the critical role of IGABT in achieving very good LC rates for LACC. The reported LC rates are comparable to landmark studies, such as INTERLACE and KEYNOTE-A18. This study validates the effectiveness of MRI-guided IGABT in enhancing local tumor control in advanced-stage cervical cancer while providing insights into the prognostic implications of dosimetric parameters such as hrCTV and point A. Future research should address the persistent challenge of distant metastases by exploring the integration of novel systemic treatment options. Full article

Background/Objectives: The optimal treatment for locally advanced cervical cancer (LACC) is debated. The proposed treatments are concomitant chemoradiotherapy plus brachytherapy (cCTRT-B) or neoadjuvant chemotherapy (NACT) followed by radical surgery (RS). The prediction NACT response is crucial for identifying responder patients who may benefit from subsequent radical surgery. The aim of this study was to find ultrasound characteristics to predict the response to NACT in patients with LACC. Methods: Consecutive patients with diagnoses of LACC were prospectively enrolled. According to FIGO staging criteria, all IB2-IIIC patients underwent three cycles of platinum-based NACT followed by radical surgery. Patients were evaluated by pelvic ultrasound one week before NACT (T0) and three weeks after the last cycle of chemotherapy (T1). The parameters analysed were volume of the lesion, tumor/uterus volume ratio, parametrial infiltration, color score, resistance (RIUA) and pulsatility (PIUA) indices of uterine arteries (UA). Results: From July 2019 to April 2023, 40 patients were enrolled. A significant decrease in tumor volume (p < 0.01) and a reduced parametrial infiltration after NACT were observed (p < 0.01). The results of the unadjusted and adjusted logistic models showed that age and RIUA positively affect the estimated probability of treatment response (p < 0.01). According to the univariate and multivariate model, RIUA greater than 0.72 ensures 87% sensitivity and 70% specificity with 82.5% accuracy in predicting tumor reduction. Conclusions: Patients over 54 with a RIUA above 0.72 are more likely to respond to NACT. Pelvic ultrasound proved to be a useful tool for predicting NACT response in LACC patients. Full article

Background/Objectives: Neoadjuvant chemotherapy followed by concurrent chemoradiation therapy (NACT + CCRT) and adjuvant chemotherapy following CCRT (CCRT + ACT) have inconsistent effects on the survival of women with locally advanced cervical cancer (LACC) compared to CCRT. Moreover, the effects of NACT + CCRT and CCRT + ACT have not been clearly compared. This study compared the effects of NACT + CCRT and CCRT + ACT on survival using a network meta-analysis to select the optimal treatment in women with LACC. Methods: The PubMed, Medline, and Embase databases were searched, and six randomized controlled trials assessing the progression-free survival (PFS) and overall survival (OS) in women with newly diagnosed LACC treated with NACT + CCRT, CCRT + ACT, or CCRT alone (controls) were identified. A network meta-analysis was conducted. Results: Indirect comparisons showed no significant differences in PFS and OS between NACT + CCRT and CCRT + ACT. Direct comparisons also showed similar PFS and OS between NACT + CCRT and CCRT and between CCRT + ACT and CCRT. CCRT + ACT exhibited the highest surface under the cumulative ranking curve (SUCRA) value as a better treatment option for the PFS and OS (CCRT + ACT vs. NACT + CCRT vs. CCRT: 72% vs. 26.8% vs. 51.2% in PFS and 64.3% vs. 45.1% vs. 40.7% in OS). Conclusions: In women with LACC, NACT + CCRT had no different effects on the PFS and OS compared to CCRT + ACT, despite the relatively higher SUCRA value observed for CCRT + ACT. Further studies are warranted to clarify the effects of these strategies. Full article

Approximately 36% of patients with cervical cancer present with regional nodal metastasis at diagnosis, which is associated with adverse survival outcomes after definitive treatment. In the modern era of chemoradiotherapy (CRT) and image-guided adaptive brachytherapy (IGABT), where excellent local control is achieved for patients with locally advanced cervical cancer (LACC), nodal failure remains a major challenge to cure. To optimize treatment outcomes for node-positive LACC and reduce the incidence of nodal failure, various treatment approaches have been explored, including methods of surgical nodal staging or dissection, RT dose escalation strategies, such as intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to involved nodes, and elective treatment of subclinical para-aortic (PAO) disease. Additionally, there is growing interest in emerging precision RT techniques, such as magnetic resonance-guided radiotherapy (MRgRT) and proton therapy, which may allow for further improvement in the therapeutic ratio. This review outlines the various methods of detection of nodal metastasis, treatment options for node-positive LACC, techniques of nodal radiotherapy and their clinical evidence in efficacy and toxicity profiles. Furthermore, recent advances in systemic therapy and promising novel therapeutic directions that may shape the management of node-positive LACC are discussed. Full article

Background: Cervical cancer is the most important cancer type found in women throughout the world. Numerous research studies are being performed to investigate the effectiveness of different strategies for the imaging and treatment of locally advanced cervical cancer, which are showing favorable outcomes. Brachytherapy is characterized by the application of very high radiation doses to target tumor cells with the least exposure to normal tissues. Methods: In the present case study, we report a 43-year-old female patient suffering from cervical cancer belonging to urban origin, with no personal pathological history, who presented herself to the gynecology department of the Bihor County Emergency Clinical hospital with vaginal bleeding. The histopathological examination of the cervix showed squamous cell carcinoma. The treatment was performed with neoadjuvant chemotherapy and concurrent chemoradiotherapy. Results: According to the clinical and histopathological examination, a diagnosis of non-keratinizing squamous carcinoma of the uterine cervix at FIGO stage III C1 was established. Radio-chemotherapy was performed, as well as periodic imaging assessments with a CT of the chest, pelvis, and abdomen, without local and distant relapse. FDG PET imaging was performed for the management and follow-up of cervical cancer by retrieving the SUVmax value. Conclusions: The post-therapeutic complications are represented by the vaginal stenosis installed 6 months after the end of the radiotherapeutic treatment. Full article

Background/Objectives: Cervical cancer is a significant global health concern, with high incidence and mortality rates, especially in less-developed regions. [¹⁸F]FDG PET/CT is now indicated at various stages of management, but its analysis is essentially based on SUVmax, a measure of [¹⁸F]FDG uptake. Radiomics, by extracting a multitude of parameters, promises to improve the diagnostic and prognostic performance of the examination. However, studies remain heterogeneous, both in terms of patient numbers and methods, so a synthesis is needed. Methods: This systematic review was conducted following PRISMA-P guidelines and registered in PROSPERO (CRD42024584123). Eligible studies on PET/CT radiomics in cervical cancer were identified through PubMed and Scopus and assessed for quality using the Radiomics Quality Score (RQS v2.0), with data extraction focusing on study design, population characteristics, radiomic methods, and model performances. Results: The review identified 22 studies on radiomics in cervical cancer, 19 of which focused specifically on locally advanced cervical cancer (LACC) and assessed various clinical outcomes, such as survival, relapse, treatment response, and lymph node involvement prediction. They reported significant associations between prognostic indicators and radiomic features, indicating the potential of radiomics to improve the predictive accuracy for patient outcomes in LACC; however, the overall quality of the studies was relatively moderate, with a median RQS of 12/36. Conclusions: While radiomic analysis in cervical cancer presents promising opportunities for survival prediction and personalized care, further well-designed studies are essential to provide stronger evidence for its clinical utility. Full article

Background: The aim is to propose a model for predicting occult paraaortic lymph node (PALN) involvement in locally advanced cervical cancer (LACC) patients by including parameters such as reconstruction detection technology (use of time-of-flight) and parameters related to the primary tumor. This model will then be compared with the scores used in routine clinical practice; Methods: This retrospective observational cohort study included patients diagnosed with LACC who underwent ¹⁸F-FDG PET/CT prior to PALN surgical staging between February 2012 and May 2020. The following parameters were collected on PET/CT: tumor SUVmax, tumor MTV, number of common and distal pelvic node involvements. A multivariate regression analysis estimating the probability of PALN involvement was performed, with optimal thresholds determined via ROC curves; Results: In total, 71 patients met the inclusion criteria. Occult PALN involvement was detected in 12.7% of patients. A derived multivariate PET model selected four variables: number of common and distal iliac lymph nodes (OR 5.9 and 2.7, respectively), tumor-to-liver SUV ratio (OR 0.9) and the use of time-of-flight technology (OR 21.4 if no time-of-flight available). At the optimal threshold, a sensitivity of 77.8% and specificity of 88.7% was found. The model’s performances varied significantly between patients whose PET/CT used time-of-flight and those whose PET/CT did not. No significant differences were found between our model and the one used in clinical practice (p = 0.55); Conclusions: This study shows that PET/CT technology influences the ability to detect occult PALN involvement in LACC. This parameter should be considered in the regular revision of PET-based scores. Full article

Objectives: This study aimed to assess the capacity of longitudinal FDG-PET radiomics for early distinguishing between locally advanced cervical cancer (LACC) patients who responded to treatment and those who did not. Methods: FDG-PET scans were obtained before and midway through concurrent chemoradiation for a study cohort of patients with LACC. Radiomics features related to image textures were extracted from the primary tumor volumes and stratified for relevance to treatment response status with the aid of random forest recursive feature elimination. Predictive models based on the k-nearest neighbors time series classifier were developed using the top-selected features to differentiate between responders and non-responders. The performance of the developed models was evaluated using receiver operating characteristic (ROC) curve analysis and n-fold cross-validation. Results: The top radiomics features extracted from scans taken midway through treatment showed significant differences between the two responder groups (p-values < 0.0005). In contrast, those from pretreatment scans did not exhibit significant differences. The AUC of the mean ROC curve for the predictive model based on the top features from pretreatment scans was 0.8529, while it reached 0.9420 for those derived midway through treatment scans. Conclusions: The study highlights the potential of longitudinal FDG-PET radiomics extracted midway through treatment for predicting response to chemoradiation in LACC patients and emphasizes that interim PET scans could be crucial in personalized medicine, ultimately enhancing therapeutic outcomes for LACC. Full article

Ganoderma lingzhi, a species of white rot fungus, possesses the highest abundance of lignocellulose-degrading enzymes among these fungi, as well as a relatively high carbon conversion rate. Corn straw, as an important sustainable resource, is used as a substrate for the liquid culture of G. lingzhi. However, little is known about the genes encoding the lignocellulose degradation and polysaccharide and triterpenoid biosynthetic pathways involved in this process. This paper employs transcriptomics to uncover the key genes involved in lignocellulose degradation and the synthesis of polysaccharides and triterpenoids during the liquid fermentation of G. lingzhi using corn straw as the substrate, as well as their associations. Carbohydrate-Active enzymes analysis of differential genes in the sequencing results was used to analyze the genes related to lignocellulose degradation. Among these, 43 core genes encoding CAZymes were obtained after 0 to 5 days of fermentation, and 25 core genes encoding CAZymes were obtained after 5 to 12 days of fermentation. The differential expression levels of DN3690_c0_g1 (EGL), DN3627_c0_g2 (XYN), DN4778_c0_g1 (XYN), DN2037_c0_g1 (LACC), and DN277_c2_g1 (MnP) were used to identify the key genes. The polysaccharide synthesis metabolic pathway favored mannitol synthesis, and the expression of triterpene precursor-metabolizing enzyme genes revealed higher expression levels of key enzyme genes such as ACAT, HMGS, and MPK. A correlation clustering analysis of genes related to lignocellulose degradation, polysaccharide, and triterpene anabolism during liquid fermentation showed that lignocellulose degradation genes mainly influenced arabinose and mannitol anabolism, as well as the synthesis of triterpene precursors. Full article