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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.
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The current review described a 55-year woman using 28 months to finish her surgery-based radiation-free multimodality treatment journey to fight International Federation of Gynaecology & Obstetrics (FIGO) 2018 clinical stage IIA2 (cT2aN0M0) squamous cell carcinoma (SCC) of the cervix. She received six cycles of perioperative adjuvant therapy, including three cycles of neoadjuvant therapy (NAT) and three cycles of postoperative adjuvant therapy by using combination of dose-dense chemotherapy (CT, weekly paclitaxel 80 mg/m2+triweekly cisplatin 40 mg/m2), immunotherapy (IO, triweekly pembrolizumab 200 mg) and half-dose anti-angiogenic agent (triweekly bevacizumab 7.5 mg/kg) plus interval radical surgery (radical hysterectomy + bilateral salpingo-oophorectomy + bilateral pelvic lymph node dissection + para-aortic lymph node sampling) and following maintenance therapy with monthly 22 cycles of half-dose of IO (pembrolizumab 100 mg) and concomitant 4 cycles of single-agent CT (paclitaxel 175 mg/m2) and 18 cycles of half-dose anti-angiogenic agent (bevacizumab 7.5 mg/kg). During the cervical SCC fighting journey, two unwanted adverse events (AEs) occurred. One was pseudo-progressive disease during the NAT treatment and pathology-confirmed upgrading FIGO stage IIIC1p (ypT2a1N1M0) after radical surgery and the other was the occurrence of hypothyroidism during the post operative adjuvant therapy. Based on this case we presented, we review the recent trend in the management of women with locally advanced cervical cancer (LACC) using the radiation-free but surgery-based multimodality strategy and highlight the strengths and limitations about perioperative adjuvant therapy with dose-dense CT + IO + half-dose anti-angiogenic agent and maintenance treatment of half-dose IO combining with short-term single agent CT and following long-term half-dose anti-angiogenic agent. All underscore the possibility that women with LACC have an opportunity to receive surgery-based RT-free multi-modality strategy to manage their diseases with satisfactory results. Additionally, the evolving role of IO plus CT with/without anti-angiogenic agent functioning as either primary treatment or adjuvant therapy for the treatment of advanced CC has been in process continuously. Moreover, the patient's positive response to IO, pembrolizumab as an example, both during the primary and maintenance therapy, highlights the importance of integrating IO into CT regimens for CC, especially in cases where conventional therapies, RT as an example, are insufficient or who do not want to receive RT-based treatment. The sustained disease-free status of the patient over several years reinforces the potential of IO to significantly increase long-term survival outcomes in CC patients, particularly for those with LACC.
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Carcinoma de Células Escamosas , Histerectomía , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/patología , Persona de Mediana Edad , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Histerectomía/métodos , Terapia Neoadyuvante/métodos , Paclitaxel/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estadificación de Neoplasias , Terapia Combinada , Bevacizumab/administración & dosificación , Bevacizumab/uso terapéutico , Quimioterapia Adyuvante/métodos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Cisplatino/administración & dosificación , Escisión del Ganglio LinfáticoRESUMEN
PURPOSE: To provide risk estimations for vaginal morbidity with regard to vaginal dilation (summarizing the use of dilators and/or sexual activity) in locally advanced cervical cancer patients (LACC) treated with definitive radiochemotherapy and image-guided adaptive brachytherapy (IGABT) within the prospective, multi-institutional EMBRACE-I study. MATERIAL/METHODS: Physician-assessed vaginal morbidity (CTCAEv3.0), use of vaginal dilators and patient-reported sexual activity (EORTC-CX24) were prospectively assessed at baseline and during regular follow-up. Frequency analysis for vaginal dilation was performed in a sub-cohort of patients with ≥3 follow-ups. Regular dilation was defined if reported in ≥50% of follow-ups, no/infrequent dilation if reported in <50%. Actuarial estimates were calculated with Kaplan-Meier method; comparisons evaluated with the log-rank test. Univariate and multivariable Cox proportional hazard regression were used to evaluate risk factors for vaginal stenosis G≥2. RESULTS: The EMBRACE-I study included a total of 1416 patients (2008-2015); 882 were evaluated in the present report with a median follow-up of 60 months. Of those, 565 (64%) reported regular dilation. This was associated with a significantly lower 5-year risk of vaginal stenosis G≥2 compared to no/infrequent dilation (23% vs. 37%, p≤0.001). This univariate finding was confirmed by multivariable analysis, after adjusting for other risk factors (HR=0.630, p=0.001). Regular vaginal dilation was also associated with a significantly higher risk for vaginal dryness G≥1 (72% vs. 67%, p=0.028) and bleeding G≥1 (61% vs. 34%, p≤0.001). CONCLUSION: Vaginal stenosis represents irreversible fibrotic changes that can cause pain during gynecological examination and dyspareunia in LACC survivors. Regular vaginal dilation (defined as the use of dilators and/or sexual activity) is associated with a significantly lower risk for G≥2 vaginal stenosis, suggesting a potential improvement of vaginal patency. It is also associated with a significantly higher risk for mild G≥1 dryness and bleeding (no higher risk for G≥2), which both can be clinically managed.
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Introduction: Residual or recurrent cervical cancer post-CCRT is a challenging clinical issue, even though there has been much effort in recent decades to increase patient survival after radiation. There is a paucity of literature regarding the role of hysterectomy in recurrent/residual disease after radiation in LACC patients. Such a procedure is controversial and not routinely performed because of difficulties in obtaining tumor-free margins and the high rate of associated morbidity. Aims and Objectives: Evaluate outcomes and morbidities in patients who had undergone hysterectomy for residual or recurrent disease after radiation in LACC patients. Material and Methods: This is a prospective observational study on radiotherapy-treated LACC patients (IIB-III) with residual disease or recurrent disease who have undergone adjuvant hysterectomy. This study has been conducted at AHPGIC, Cuttack, with a sample size of 30 patients. Results: 18/30 patients underwent extrafascial hysterectomy, and rest 12 patients had radical hysterectomy. No significant difference in complications, achieving tumor free margins or recurrences post adjuvant hysterectomy based on the radicality of surgery was observed. 5 cases of recurrences post-adjuvant hysterectomy were detected. Some of the factors which had significant association with recurrences post adjuvant hysterectomy were non squamous histology, no preoperative brachytherapy, deep stromal invasion and positive surgical margins. Median follow-up time was 14 months (12-27 months). Conclusion: This study shows that adjuvant hysterectomy is feasible with good outcome and acceptable morbidity after chemoradiotherapy in cervical cancer patients "If selection of patients for adjuvant hysterectomy is appropriate."
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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.
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Background: 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. Methods: 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). Results: 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. Conclusion: The interim-ADC value and baseline tumor diameter surfaced as possible indicative factors for predicting the response to RT in patients with LACC.
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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.
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INTRODUCTION: Cervical cancer is the fourth most dangerous malignancy worldwide in women and is diagnosed at the advanced stages in most cases. Oncological and surgical modalities when precisely employed together can prove to be helpful for determining the proper diagnosis and treatment strategies. Neoadjuvant chemotherapy (NACT) has been found to have a role in reducing tumor size and has evolved as a treatment regimen for locally advanced cervical cancer (LACC). The present study aimed to analyze the treatment strategies either with neoadjuvant platinum-based chemotherapy (NACT) administration or not and pathological responses in patients with LACC. METHODS: We reviewed 100 patients of LACC from October 2018 to December 2022 at Bihor County Emergency Clinical Hospital. About 43 patients underwent radiation therapy in addition to NACT administration (NACT+/other) and 57 underwent other treatment regimens without neoadjuvant treatment (NACT-/ other). Various demographic parameters, FIGO staging, histological status, surgical interventions, and survival rate (local disease-free survival (LDFS) and disease-free survival (DFS)) were accessed in both groups. Statistical analysis was performed to analyze the significance of various parameters studied. RESULTS: The mean age range of the studied sample was 57.05 ± 12.51 in NACT+/other and 60.4±12.32 in NACT-/other. Among 100 patients, 90 cases of squamous carcinoma, eight of adenocarcinoma, and two cases of adenosquamous carcinoma were analyzed and treated. At stage IIIC1, 11 patients were accessed while 15 patients were at clinical stage IIIC2, and among these, 25.58% received neoadjuvant oncological treatment and very limited mediastinal disease. DFS rates are greater in the patients who have undergone surgery in the NACT+/other group, while in the LDFS, there is better survival in the case of surgery without any NACT treatment (NACT-/other). CONCLUSIONS: The effect of NACT can be suggested as another important treatment strategy and result in a good response in terms of DFS and LDFS in patients with LACC. This approach aims to reduce tumor size preoperatively, facilitating surgical removal and potentially improving patient outcomes compared to other treatment modalities. Thus, it can be concluded that NACT may be considered an important strategy to be opted for the treatment of LACC.
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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). CONCLUSION: 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.
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PURPOSE: 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. CONCLUSION: 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.
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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.
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Linfocitos Infiltrantes de Tumor , Terapia Neoadyuvante , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Persona de Mediana Edad , Linfocitos Infiltrantes de Tumor/inmunología , Adulto , Resultado del Tratamiento , Anciano , Supervivencia sin EnfermedadRESUMEN
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.
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Introduction: 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. Materials and methods: 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. Results: 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. Conclusion: 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.
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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.
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Background and Purpose: Automatic segmentation methods have greatly changed the RadioTherapy (RT) workflow, but still need to be extended to target volumes. In this paper, Deep Learning (DL) models were compared for Gross Tumor Volume (GTV) segmentation in locally advanced cervical cancer, and a novel investigation into failure detection was introduced by utilizing radiomic features. Methods and materials: We trained eight DL models (UNet, VNet, SegResNet, SegResNetVAE) for 2D and 3D segmentation. Ensembling individually trained models during cross-validation generated the final segmentation. To detect failures, binary classifiers were trained using radiomic features extracted from segmented GTVs as inputs, aiming to classify contours based on whether their Dice Similarity Coefficient ( DSC ) < T and DSC ⩾ T . Two distinct cohorts of T2-Weighted (T2W) pre-RT MR images captured in 2D sequences were used: one retrospective cohort consisting of 115 LACC patients from 30 scanners, and the other prospective cohort, comprising 51 patients from 7 scanners, used for testing. Results: Segmentation by 2D-SegResNet achieved the best DSC, Surface DSC ( SDSC 3 mm ), and 95th Hausdorff Distance (95HD): DSC = 0.72 ± 0.16, SDSC 3 mm =0.66 ± 0.17, and 95HD = 14.6 ± 9.0 mm without missing segmentation ( M =0) on the test cohort. Failure detection could generate precision ( P = 0.88 ), recall ( R = 0.75 ), F1-score ( F = 0.81 ), and accuracy ( A = 0.86 ) using Logistic Regression (LR) classifier on the test cohort with a threshold T = 0.67 on DSC values. Conclusions: Our study revealed that segmentation accuracy varies slightly among different DL methods, with 2D networks outperforming 3D networks in 2D MRI sequences. Doctors found the time-saving aspect advantageous. The proposed failure detection could guide doctors in sensitive cases.
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Cervical cancer (CC) remains among the most frequent cancers worldwide despite advances in screening and the development of vaccines against human papillomavirus (HPV), involved in virtually all cases of CC. In mid-income countries, a substantial proportion of the cases are diagnosed in advanced stages, and around 40% of them are diagnosed in women under 49 years, just below the global median age. This suggests that members of this age group share common risk factors, such as chronic inflammation. In this work, we studied samples from 46 patients below 45 years old, searching for a miRNA profile regulating cancer pathways. We found 615 differentially expressed miRNAs between tumor samples and healthy tissues. Through bioinformatic analysis, we found that several of them targeted elements of the JAK/STAT pathway and other inflammation-related pathways. We validated the interactions of miR-30a and miR-34c with JAK1 and STAT3, respectively, through dual-luciferase and expression assays in cervical carcinoma-derived cell lines. Finally, through knockdown experiments, we observed that these miRNAs decreased viability and promoted proliferation in HeLa cells. This work contributes to understanding the mechanisms through which HPV regulates inflammation, in addition to its canonical oncogenic function, and brings attention to the JAK/STAT signaling pathway as a possible diagnostic marker for CC patients younger than 45 years. To our knowledge to date, there has been no previous description of a panel of miRNAs or even ncRNAs in young women with locally advanced cervical cancer.
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Regulación Neoplásica de la Expresión Génica , Inflamación , MicroARNs , Factor de Transcripción STAT3 , Transducción de Señal , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , MicroARNs/genética , MicroARNs/metabolismo , Transducción de Señal/genética , Adulto , Inflamación/genética , Inflamación/patología , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Células HeLa , Janus Quinasa 1/metabolismo , Janus Quinasa 1/genética , Proliferación Celular/genética , Línea Celular Tumoral , Persona de Mediana EdadRESUMEN
Cervical cancer is the 4th most diagnosed cancer in women. At a locally advanced stage, standard treatment combines chemotherapy, radiotherapy and a brachytherapy boost. Brachytherapy is a radiotherapy modality, often unknown, which allows the delivery of a very targeted high dose because it's given directly in contact with the tumor. This technique has proven its effectiveness in the treatment of locally advanced cervical cancer. It represents a major advantage because, despite technical advances, there is currently no alternative yielding equivalent results.
Le cancer du col utérin est le 4ème cancer féminin le plus diagnostiqué. à un stade localement avancé, la prise en charge standard relève d'un traitement associant de la chimiothérapie, de la radiothérapie et une curiethérapie de clôture. La curiethérapie est une modalité de radiothérapie, souvent méconnue du grand public, qui permet de délivrer une dose élevée de façon très ciblée, car celle-ci est donnée directement au contact de la tumeur. Cette technique a prouvé son efficacité et son caractère indispensable dans le traitement du cancer du col utérin localement avancé. Elle représente un atout majeur car, malgré l'évolution des techniques de radiothérapie externe plus modernes, il n'y a, à ce jour, aucune alternative équivalente.
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Braquiterapia , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapia , Braquiterapia/métodos , Femenino , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). METHODS: Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). RESULTS: A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314-0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343-0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). CONCLUSIONS: In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.
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Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia , Cisplatino , Paclitaxel , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Femenino , Persona de Mediana Edad , Quimioradioterapia/métodos , Quimioradioterapia/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Adulto , Anciano , Resultado del Tratamiento , Supervivencia sin ProgresiónRESUMEN
OBJECTIVE: This investigation aimed to develop and validate a novel oxidative stress score for prognostic prediction in locally advanced cervical cancer (LACC) patients receiving chemoradiotherapy. METHODS: A total of 301 LACC patients were enrolled and randomly divided into a training and a validation set. The association between oxidative stress parameters and prognosis was analyzed for oxidative stress score (OSS) establishment. A Cox regression model was conducted for overall survival (OS) and progression-free survival (PFS). A nomogram prediction model was developed using independent prognostic factors from the training set and validated in the validation set. RESULTS: A novel OSS was established with four oxidative stress parameters, including albumin, total bilirubin, blood urea nitrogen, and lactate dehydrogenase. Multivariate regression analysis identified OSS as an independent prognostic factor for OS (p = 0.001) and PFS (p < 0.001). A predictive nomogram based on the OSS was established and validated. The C-indexes of the nomogram in the training set were 0.772 for OS and 0.781 for PFS, while in the validation set the C-indexes were 0.642 for OS and 0.621 for PFS. CONCLUSION: This study confirmed that preoperative OSS could serve as a useful independent prognostic factor in LACC patients who received CCRT.
Asunto(s)
Biomarcadores de Tumor , Quimioradioterapia , Nomogramas , Estrés Oxidativo , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Pronóstico , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Adulto , Anciano , Bilirrubina/sangre , Nitrógeno de la Urea Sanguínea , Supervivencia sin Progresión , L-Lactato Deshidrogenasa/sangre , Modelos de Riesgos ProporcionalesRESUMEN
PROPOSE: To evaluate the advantage of the manual adaptive plans comparing to the scheduled plans, and explored clinical factors predicting patients suitable for adaptive strategy. METHODS AND MATERIALS: Eighty two patients with weekly online cone-beam computed tomography (CBCT) were enrolled. The re-CT simulation was performed after 15 fractions and a manual adaptive plan was developed if a significant deviation of the planning target volume (PTV) was found. To evaluate the dosimetric benefit, D98, homogeneity index (HI) and conformity index (CI) for the planning target volume (PTV), as well as D2cc of the bowel, bladder, sigmoid and rectum were compared between manual adaptive plans and scheduled ones. The clinical factors influencing target motion during radiotherapy were analyzed by chi-square test and logistic regression analysis. RESULTS: The CI and HI of the manual adaptive plans were significantly superior to the scheduled ones (P = 0.0002, 0.003, respectively), demonstrating a better dose coverage of the target volume. Compared to the scheduled plans, D98 of the manual adaptive plans increased by 3.3% (P = 0.0002), the average of D2cc to the rectum, bladder decreased 0.358 Gy (P = 0.000034) and 0.240 Gy (P = 0.03), respectively. In addition, the chi-square test demonstrated that age, primary tumor volume, and parametrial infiltration were the clinical factors influencing target motion during radiotherapy. Multivariate analysis further identified the large tumor volume (≥ 50cm3, OR = 3.254, P = 0.039) and parametrial infiltration (OR = 3.376, P = 0.018) as the independent risk factors. CONCLUSION: We found the most significant organ motion happened after 15 fractions during treatment. The manual adaptive plans improved the dose coverage and decreased the OAR doses. Patients with bulky mass or with parametrial infiltration were highly suggested to adaptive strategy during definitive radiotherapy due to the significant organ motion.