Search Results (67)

Background/Objectives: Surgery is the standard treatment for early-stage endometrial cancer (EC); however, some patients are medically inoperable due to comorbidities or morbid obesity. Definitive image-guided brachytherapy (BT) with or without external beam radiotherapy (EBRT) is a curative alternative, although comparative data with surgery remains limited. This study compared cancer-specific survival (CSS) at 2 and 5 years in high-risk surgical patients with early-stage EC (FIGO 2009 I–II), treated with definitive radiotherapy or surgery. Secondary endpoints included overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), and toxicity. Methods: Retrospective comparative study including 72 patients treated between 2011 and 2023: 36 medically inoperable treated with BT +/− EBRT and 36 matched undergoing surgery. Survival outcomes were estimated using Kaplan–Meier methods and compared using log-rank tests. Results: Median age was 74 years and mean BMI was 38.1 kg/m²; 75% were morbidly obese, with endometrioid carcinoma being the predominant histology (88.9%). Five-year CSS was 97.2% in the radiotherapy group versus 91.7% in the surgery group (p = 0.39). Five-year RFS was identical in both groups (86.1%), with recurrence rates of 13.9%. Five-year OS was lower in the radiotherapy group (66.7% vs. 77.8%; p = 0.3), without statistical significance. Grade ≥3 radiotherapy-related toxicity occurred in 19.4%, whereas severe surgical complications occurred in 8.3%. Conclusions: Definitive BT ± EBRT is an effective and well-tolerated curative option for medically inoperable early-stage EC, with survival and recurrence outcomes comparable to surgery, supporting its role as a valid therapeutic alternative in high-risk surgical patients. Full article

The treatment of locally advanced cervical cancer is based on concomitant cisplatin-based chemoradiotherapy followed by brachytherapy. The quality of this treatment is essential to optimize results. In particular, intensity-modulated radiotherapy followed by image-guided brachytherapy achieves 90% local control regardless of the stage of the disease. More recently, several randomized trials have changed the management of these tumors: The INTERLACE trial evaluated the benefits of neoadjuvant chemotherapy with carboplatin and paclitaxel and demonstrated a survival benefit for this approach. This trial has been the subject of considerable criticism. The KEYNOTE A.18 trial evaluated the addition of pembrolizumab to standard treatment: an improvement in overall survival was demonstrated for patients with stage III-IV disease (FIGO 2014 classification). The CALLA trial, which evaluated the addition of durvalumab, was negative. This review summarizes the biological rationale for this immunotherapy, its results, and the quality criteria for chemoradiotherapy. It describes the various trials in detail, puts their results into context, and discusses the relevance of this new treatment based on the patients’ baseline characteristics. Based on this critical analysis, patients with stage III-IVA cervical cancer (FIGO 2014 classification) should receive, in addition to standard chemoradiotherapy, concomitant treatment with pembrolizumab followed by two years of maintenance therapy. Full article

Background/Objectives: Cervical cancer remains a leading cause of cancer morbidity and mortality worldwide. Although chemoradiation followed by brachytherapy is the curative-intent standard for locally advanced disease, outcomes remain heterogeneous and recurrence and distant metastasis persist. In parallel, immune checkpoint inhibitors (ICIs) and antibody–drug conjugates (ADCs) have expanded systemic options in recurrent or metastatic settings and created new opportunities for multimodality. This review aims to integrate treatment-relevant cervical cancer biology and biomarkers to clarify how chemoradiation, immunotherapy, and ADCs can be optimally selected, sequenced, and combined across disease states. Methods: We conducted a structured narrative, evidence-based literature synthesis focusing on cervical cancer management. The review encompassed: (i) the molecular and immune mechanisms underlying human papillomavirus (HPV)-driven carcinogenesis; (ii) contemporary diagnostic and staging approaches, including advanced imaging modalities and histopathological evaluation; and (iii) clinical and translational evidence supporting the optimization of chemoradiation, immune checkpoint inhibition, and antibody–drug conjugates, with emphasis on clinically validated or emerging biomarkers that are relevant to patient stratification and mechanistically rational combination or sequencing strategies. A systematic search of PubMed/MEDLINE, Embase, and major oncology conference proceedings was performed. Priority was given to peer-reviewed original research articles, high-impact clinical trials (Phase II–III), meta-analyses, and consensus guidelines published within the past 10 years to ensure contemporary relevance. Articles published prior to this period were generally excluded to maintain clinical currency; however, seminal studies that established foundational therapeutic standards, mechanistic paradigms, or landmark treatment milestones were intentionally retained due to their enduring influence on current practice. Exclusion criteria included non-peer-reviewed sources, case reports with limited generalizability, non-English publications, and studies lacking methodological rigor or clinical relevance to cervical cancer management. Preclinical studies were included selectively when directly informing therapeutic mechanisms, biomarker development, or translational rationale. This approach was designed to balance historical context with up-to-date clinical applicability, ensuring both scientific rigor and contemporary relevance. Results: Chemoradiation and brachytherapy remain essential for local control, while ICIs can restore antitumor T-cell activity in biomarker-enriched contexts. ADCs enable target-directed delivery of potent cytotoxins and may promote immunogenic cell death, supporting immunotherapy and radiation. However, key challenges include resistance mechanisms, toxicity management, and patient identification for the most beneficial combined multimodality. Conclusions: A biology- and biomarker-informed framework can guide more rational integration of multimodality therapy in cervical cancer. Future progress will depend on validated predictive biomarkers, optimized sequencing/combination strategies, and trials that balance efficacy with short- and long-term toxicity. Full article

Background/Objectives: Image-guided adaptive brachytherapy (IGABT) has transformed the standard of care for locally advanced cervical cancer (LACC), enabling volumetric target definition and dose–volume histogram (DVH)-based planning to improve pelvic tumor control while limiting severe late toxicity. Methods: A comprehensive literature search of PubMed/MEDLINE and Embase was done for articles published up to August 2024, using combinations of the following keywords and Medical Subject Heading (MeSH) terms: “cervical cancer”, “endometrial cancer”, “vaginal cancer”, “uterine neoplasms”, “brachytherapy”, “high-dose-rate”, “image-guided”, “MRI-guided”, “3D brachytherapy”, “IGABT”, “interstitial”, “locoregional control”, “toxicity”, “quality of life”, and “patient-reported outcomes”. Results: We summarized the contemporary evidence on IGABT for cervical, endometrial, and primary or recurrent vaginal cancers, focusing on local control, survival, late morbidity, and patient-reported outcomes. We described the key target volume concepts (gross tumor volume, high- and intermediate-risk clinical target volumes), and the role of MRI-, CT-, and ultrasound-based planning with intracavitary, intracavitary–interstitial, and interstitial applicators. Conclusions: Image-guided adaptive brachytherapy has redefined the standard of care for the management of locally advanced cervical cancer. Through the integration of volumetric target concepts, DVH-based dose reporting, and advanced imaging, IGABT has enabled consistent dose escalation to the residual tumor while accounting for organ-at-risk constraints, resulting in high local control rates and reduced severe morbidity compared with historical 2D brachytherapy. Full article

Pelvic recurrence following radiotherapy for cervical cancer presents a major therapeutic challenge with historically poor prognosis and limited options. This review comprehensively examines the evolving landscape of management strategies for this condition, encompassing both local and systemic approaches. We discuss the roles of salvage surgery and advanced re-irradiation techniques, including stereotactic body radiotherapy and image-guided brachytherapy, highlighting their potential and associated toxicities. A significant focus is placed on the revolution in systemic therapy, particularly the integration of targeted agents—such as anti-angiogenic drugs, PARP inhibitors, and tyrosine kinase inhibitors—and immunotherapy, chiefly immune checkpoint inhibitors like pembrolizumab and cemiplimab. These modalities have demonstrated substantial improvements in survival outcomes in clinical trials. The review underscores the critical shift towards personalized medicine, where treatment selection is increasingly guided by molecular profiling. Finally, we explore future directions, including combination strategies, novel immunotherapies, and emerging technologies, which collectively promise to transform the management of recurrent cervical cancer from palliative control towards the goals of durable remission and functional cure. Full article

Background: Locally advanced cervical cancer (LACC) represents a significant challenge in oncology, requiring accurate assessment of local extent and metastatic spread. Multiparametric magnetic resonance imaging (mpMRI) has assumed a central role in the loco-regional characterization of the tumor due to its high soft-tissue resolution and the ability to integrate functional information. Objectives: In this narrative review, we explore the use of mpMRI in the diagnosis, staging, and treatment response of LACC, comparing its performance with that of PET/CT, which remains complementary for remote staging. The potential of whole-body magnetic resonance imaging (WB-MRI) and hybrid PET/MRI techniques is also analyzed, as well as the emerging applications of radiomics and artificial intelligence. The paper also discusses technical limitations, interpretative variability, and the importance of protocol standardization. The goal is to provide an updated and translational summary of imaging in LACC, with implications for clinical practice and future research. Methods: Prospective and retrospective studies, systematic reviews, and meta-analyses on adult patients with cervical cancer were included. Results: Fifty-two studies were included. MRI demonstrated a sensitivity and specificity greater than 80% for parametrial and bladder invasion, but limited sensitivity (45–60%) for lymph node disease, lower than PET/CT. Multiparametric MRI was useful in early prediction of response to chemotherapy and radiotherapy and in distinguishing residual disease from fibrosis. The integration of MRI into Image-Guided Adaptive Brachytherapy (IGABT) resulted in improved oncological outcomes and reduced toxicity. The applications of radiomics and AI demonstrated enormous potential in predicting therapeutic response and lymph node status in the MRI study, but multicenter validation is still needed. Conclusions: MRI is the cornerstone of the local–regional staging of advanced cervical cancer; it has become an essential and crucial tool in treatment planning. Its use, combined with PET/CT for lymph node assessment and metastatic disease staging, is now the standard of care. Future prospects include the use of whole-body MRI and the development of predictive models based on radiomics and artificial intelligence. Full article

In recent years, several randomized controlled trials have been published regarding cervical cancer therapy and significantly changed the treatment landscape. Recent advances have improved the treatment options and allow personalized treatment concepts with escalation of treatment in high-risk disease and de-escalation with reduction in morbidity in selected low-risk patients. This review aims to provide a comprehensive analysis of the latest landmark studies that are poised to significantly influence clinical practice. Personalized treatment concepts with careful patient selection allow de-escalation in the surgical treatment of cervical cancer. In low-risk cervical cancer patients (lesions of ≤2 cm with limited stromal invasion), simple hysterectomy (SH) was non-inferior to radical hysterectomy in terms of 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention and improved sexual health and quality of life. Furthermore, sentinel lymphadenectomy is constantly replacing systematic pelvic lymphadenectomy in patients with low-risk cervical cancer. In addition, further studies are necessary to clarify the role of postoperative therapy for patients with intermediate-risk cervical cancer. Starting in 2008, the EMBRACE studies assess the role of Image guided adaptive brachytherapy (IGABT) in LACC in addition to modern external beam radiotherapy concurrent to chemotherapy. The publication of the results of the EMBRACE I prospective study established MRI guided IGABT as state-of-the-art brachytherapy for LACC. EMBRACE II and additional prospective studies emerging from this consortium will address important questions in modern radiotherapy for LACC. Immune checkpoint inhibitors (CPIs) have been evaluated across various clinical settings and are expected to be utilized in numerous scenarios due to several positive randomized trials. Particularly, the combination of platinum-based chemotherapy and pembrolizumab, with or without bevacizumab, has been established as the new standard treatment for primary metastatic or recurrent PD-L1 positive high-risk cervical cancer. In locally advanced cervical cancer, two new treatment escalation regimens—neoadjuvant chemotherapy and adjuvant CPI therapy—have been evaluated in addition to chemoradiation. Furthermore, antibody-drug conjugates, such as tisotumab-vedotin, represent a promising future therapeutic option for recurrent cervical cancer. Full article

Objective: To investigate the survival prediction probability of the nomogram from retro-EMBRACE and the T-score in patients with locally advanced cervical cancer (LACC). Materials and Methods: A total of 204 patients with LACC who underwent curative chemoradiotherapy and brachytherapy (BT) between 2010 and 2021 were included in our single-center retrospective study. Clinical records, examinations, and magnetic resonance images (MRI) before and after external beam radiotherapy (EBRT) were retrospectively reviewed to obtain information on age, tumor size, parametrial involvement, ureteral involvement, bladder invasion, uterine involvement, high-risk clinical target volume at the first brachytherapy application, lymph node involvement, vaginal involvement, recurrence, metastasis, and last follow-up. The 5-year overall survival probabilities of the patients were determined by nomogram. T-score was calculated separately at diagnosis (TS_D) and brachytherapy (TS_BT), and their effects on local recurrence-free survival, disease-free survival, and overall survival were analyzed. Results: The median age was 52 (29–89). The 5-year survival rate of the patients was calculated to be 90.18%. The median nomogram’s survival estimate for 60 months was 70.35% (20.9–87.1). The median TS_D and TS_BT were 5.5 (1–16) and 1 (0–6), respectively. According to the multivariate Cox regression models, TS_D (HR = 1.203, 95% CI 1.021–1.417, p = 0.024) was significantly associated with local recurrence-free survival. Conclusions: This study demonstrated that the nomogram’s predictions for 60-month overall survival are underestimates. Prognosis can be estimated using the TS_D, which can be easily obtained with a clinical examination and detailed MRI examination. Full article

Purpose: To present the findings of our preliminary experience using daily image-guided radiotherapy (IGRT) supported by implanted fiducial markers (FMs) in the radiotherapy of the vaginal cuff, in a cohort of post-surgery endometrial cancer patients. Methods: Patients with vaginal cuff cancer requiring adjuvant radiation with external beams were enrolled. Five patients underwent radiation therapy targeting the pelvic disease and positive lymph nodes, with doses of 50.4 Gy in twenty-eight fractions and a subsequent stereotactic boost on the vaginal vault at a dose of 5 Gy in a single fraction. One patient was administered 30 Gy in five fractions to the vaginal vault. These patients underwent external beam RT following the implantation of three 0.40 × 10 mm gold fiducial markers (FMs). Our IGRT strategy involved real-time 2D kV image-based monitoring of the fiducial markers during the treatment delivery as a surrogate of the vaginal cuff. To explore the potential role of FMs throughout the treatment process, we analyzed cine movies of the 2D kV-triggered images during delivery, as well as the image registration between pre- and post-treatment CBCT scans and the planning CT (pCT). Each CBCT used to trigger fraction delivery was segmented to define the rectum, bladder, and vaginal cuff. We calculated a standard metric to assess the similarity among the images (Dice index). Results: All the patients completed radiotherapy and experienced good tolerance without any reported acute or long-term toxicity. We did not observe any loss of FMs during or before treatment. A total of twenty CBCTs were analyzed across ten fractions. The observed trend showed a relatively emptier bladder compared to the simulation phase, with the bladder filling during the delivery. This resulted in a final median Dice similarity coefficient (DSC) of 0.90, indicating strong performance. The rectum reproducibility revealed greater variability, negatively affecting the quality of the delivery. Only in two patients, FMs showed intrafractional shift > 5 mm, probably associated with considerable rectal volume changes. Target coverage was preserved due to a safe CTV-to-PTV margin (10 mm). Conclusions: In our preliminary study, CBCT in combination with the use of fiducial markers to guide the delivery proved to be a feasible method for IGRT both before and during the treatment of post-operative gynecological cancer. In particular, this approach seems to be promising in selected patients to facilitate the use of SBRT instead of BRT (brachytherapy), thanks to margin reduction and adaptive strategies to optimize dose delivery while minimizing toxicity. A larger sample of patients is needed to confirm our results. Full article

Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, it is imperative that alternative therapies are effective for non-surgical patients. There are several thermal ablative techniques, including radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), microwave ablation (MWA), alcohol ablation, stereotactic body radiotherapy (SBRT), cryoablation, irreversible electroporation (IRE), biliary intraluminal brachytherapy, and biliary photodynamic therapy (PDT). Emerging literature in animal models and human patients has demonstrated that endoscopic ultrasound (EUS)-guided RFA (EUS-RFA) prevents tumor progression through coagulative necrosis, protein denaturation, and activation of anticancer immunity in local and distant tumor tissue (abscopal effect). RFA treatment has been shown to not only reduce tumor-associated immunosuppressive cells but also increase functional T cells in distant tumor cells not treated with RFA. The remarkable ability to reduce tumor progression and promote tumor microenvironment (TME) remodeling makes RFA a very promising non-surgical therapy technique that has the potential to reduce mortality in this patient population. EUS-RFA offers superior precision and safety compared to other ablation techniques for pancreatic and biliary cancers, due to real-time imaging capabilities and minimally invasive nature. Future research should focus on optimizing RFA protocols, exploring combination therapies with chemotherapy or immunotherapy, and expanding its use in patients with metastatic disease. This review article will explore the current data and underlying pathophysiology of EUS-RFA while also highlighting the role of ablative therapies as a whole in immune activation response. Full article

Background/Objectives: Image-guided adaptive brachytherapy is a standard modality in the treatment of locally advanced cervical cancer. However, the availability of isotope-based brachytherapy is limited in countries with lower resources. The objective of this study is to report the first institutional dosimetric and clinical data on intracavitary electronic brachytherapy. Methods: A total of 25 patients with histologically proven cervical cancer stage IB-IVA were treated with concurrent chemoradiotherapy and electronic brachytherapy. The patients were followed up for a median of 12 months (range 6–24). Toxicity was evaluated by the radiation oncologist and gynecologist on each visit and scored by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: All patients completed the treatment successfully with a median overall treatment time (OTT) of 52 days (range 39–89). The desired target coverage was achieved in all patients, and the dose limits for the organs at risk were achieved in 88% of the patients. No Grade 3 toxicities occurred. A total of 84% of the patients achieved local control in the cervix, and a complete response was noted in 72% of the patients. Conclusions: Electronic brachytherapy provides the option to deliver a high dose of radiation to the uterine cervix without leading to severe toxicity. Further improvements to the treatment protocol could provide better locoregional and systemic control of the disease. Studies with larger cohorts and longer follow-up are necessary. Full article

Radiotherapy (RT) has undergone transformative advancements since its inception over a century ago. This review highlights the most promising and impactful innovations shaping the current and future landscape of RT. Key technological advances include adaptive radiotherapy (ART), which tailors treatment to daily anatomical changes using integrated imaging and artificial intelligence (AI), and advanced image guidance systems, such as MR-LINACs, PET-LINACs, and surface-guided radiotherapy (SGRT), which enhance targeting precision and minimize collateral damage. AI and data science further support RT through automation, improved segmentation, dose prediction, and treatment planning. Emerging biological and targeted therapies, including boron neutron capture therapy (BNCT), radioimmunotherapy, and theranostics, represent the convergence of molecular targeting and radiotherapy, offering personalized treatment strategies. Particle therapies, notably proton and heavy ion RT, exploit the Bragg peak for precise tumor targeting while reducing normal tissue exposure. FLASH RT, delivering ultra-high dose rates, demonstrates promise in sparing normal tissue while maintaining tumor control, though clinical validation is ongoing. Spatially fractionated RT (SFRT), stereotactic techniques and brachytherapy are evolving to treat challenging tumor types with enhanced conformality and efficacy. Innovations such as 3D printing, Auger therapy, and hyperthermia are also contributing to individualized and site-specific solutions. Across these modalities, the integration of imaging, AI, and novel physics and biology-driven approaches is redefining the possibilities of cancer treatment. This review underscores the multidisciplinary and translational nature of modern RT, where physics, engineering, biology, and informatics intersect to improve patient outcomes. While many approaches are in various stages of clinical adoption and investigation, their collective impact promises to redefine the therapeutic boundaries of radiation oncology in the coming decade. 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

Background: Cervical cancer treatment with advanced radiotherapy techniques benefits from image guidance, particularly when anatomical changes occur during therapy. This case emphasizes the need for adaptive radiotherapy when target volume shifts significantly. Methods: A 70-year-old woman with International Federation of Gynecology and Obstetrics (FIGO) IIIC2 9th edition cervical squamous cell carcinoma presented with a distended uterine cavity due to fluid accumulation. She underwent definitive chemoradiotherapy using Volumetric Modulated Arc Therapy (VMAT) and weekly cisplatin. Results: Daily Cone Beam Computed Tomography (CBCT) imaging revealed progressive uterine shrinkage as intrauterine fluid drained, significantly altering target volume and organ-at-risk (OAR) positioning. These changes necessitated two re-planning CT scans during external beam radiotherapy to maintain accurate dosing and avoid OAR toxicity. The patient completed treatment, including image-guided brachytherapy, without complications. Adaptive planning ensured adequate tumor coverage and minimized normal tissue exposure. Conclusions: This case highlights the critical role of daily CBCT in detecting anatomical changes during radiotherapy. Adaptive re-planning, though rarely required more than once, was essential here to preserve treatment accuracy. CBCT should be considered a standard verification tool in cervical cancer radiotherapy, particularly in cases involving intrauterine fluid. 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