Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer.
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ABSTRACT:
SUBMITTER: Kokka F
PROVIDER: S-EPMC9394583 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Publications
Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer.
Kokka Fani F Bryant Andrew A Olaitan Adeola A Brockbank Elly E Powell Melanie M Oram David D
The Cochrane database of systematic reviews 20220822
<h4>Background</h4>This is an update of the Cochrane Review published in Issue 4, 2015. Cervical cancer is one of the most frequent cause of death from gynaecological cancers worldwide. Many new cervical cancer cases in low-income countries present at an advanced stage. Standard care in Europe and the US for locally advanced cervical cancer (LACC) is chemoradiotherapy. In low-income countries, with limited access to radiotherapy, LACC may be treated with chemotherapy and hysterectomy. It is not ...[more]
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Project description:This study is to compare the survival outcomes of laparoscopic radical hysterectomy (LRH) to those of abdominal radical hysterectomy (ARH) for patients with locally advanced cervical cancer (LACC). Patients with the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 to IIB LACC who underwent radical hysterectomy between 2001 and 2015 were identified. The disease-free survival (DFS) and overall survival (OS) were compared according to the surgical approach and were adjusted based on clinicopathologic characteristics. A total of 396 patients were included in the study, with 179 (45.2%) and 217 (54.8%) patients in the ARH and LRH groups, respectively. The LRH group showed a significantly lower amount of estimated blood loss, lower blood transfusion rate and shorter length of hospital stay. Overall, there were no significant differences in the 5-year DFS and 5-year OS between the LRH and ARH groups with the Kaplan-Meier method. However, multivariate analyses identified LRH as an independent prognostic factor for a poor DFS (hazard ratio [HR] 2.5; 95% confidence interval [95% CI] 0.19 to 0.87; p = 0.02). The analysis of stage IB2 disease and the squamous subtype (61.9% and 87.9% of all participants, respectively) reached the same conclusion. When stratifying by FIGO stage, the patients with IB2 (n = 348) in the ARH group had a significantly better DFS (HR 0.14, 95% CI 0.05-0.42, p < 0.01) and OS (HR 0.17, 95% CI 0.04-0.67, p = 0.11) than those in the LRH group in the Cox regression model. However, no differences were found in patient with stage IIA1, IIA2, or IIB in Cox regression model. When stratifying by histological types, for the patients with squamous carcinomas (n = 375), in Cox model, ARH had a significantly superior DFS compared with those who underwent LRH (HR 0.45, 95% CI 0.25-0.82, p = 0.01), but the OS was not statistically significant (HR 0.57, 95% CI 0.27-1.20, p = 0.14). However, no differences were found in patient with adenocarcinoma and adenosquamous carcinomas in the Cox model. Therefore, ARH was associated with a higher DFS than LRH in patients with LACC, especially in patients with stage IB2 disease or the squamous subtype.
| S-EPMC6890871 | biostudies-literature
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| S-EPMC6543111 | biostudies-literature
Project description:Cervical cancer represents a significant portion of the global cancer burden for women, with low- and middle-income countries carrying the bulk of this burden. Additionally, underserved populations in countries with sufficient resources may have a higher incidence of cervical cancer and poorer outcomes. Concurrent chemoradiotherapy is the standard-of-care treatment for locally advanced cervical cancer, which includes patients with stage IB3 to IVA disease, and it is effective for many patients; however, cervical cancer-related mortality remains high. The critical nature of cervical cancer treatment is underscored by the recent launch of the World Health Organization global initiative to accelerate the elimination of cervical cancer using a triple-intervention strategy of increased vaccination, screening, and treatment. The initiative calls for 90% of all patients diagnosed with cervical cancer to receive the appropriate treatment, but to reach this global goal there are significant barriers related to radiotherapy that must be addressed. We discuss and review evidence of the lack of adherence to guideline-recommended treatment, brachytherapy underutilization, limited access to radiotherapy in low- and middle-income countries, as well as regional limitations within high-income countries, as the major barriers to radiotherapy treatment for locally advanced cervical cancer. We further review ways these barriers are currently being addressed and, in some cases, make additional recommendations to address these issues. Finally, despite receiving recommended treatments, many patients with locally advanced cervical cancer have a poor prognosis. With effective administration of current standards of care, the global community will be able to shift focus to advancing treatment efficacy for these patients. We review several types of therapies under clinical investigation that are additions to concurrent chemoradiotherapy, including immune checkpoint inhibitors, antiangiogenic agents, DNA repair inhibitors, human papillomavirus vaccines, and radiosensitizing nanoparticles.
| S-EPMC8921593 | biostudies-literature
Project description:Background and objectiveTo assess the efficacy of a Risk-Adapted Ablative Radiotherapy (RAdAR) approach, after intensive induction chemotherapy, in patients with locally advanced pancreatic cancer (LAPC).Material and methodsPatients with LAPC who received RAdAR following induction chemotherapy from January 2017 to December 2019 were included in this observational study. The RAdAR approach consisted of an anatomy- and simultaneous integrated boost (SIB)-based dose prescription strategy. RAdAR was delivered with stereotactic ablative radiation therapy (SAbR), administering 30 Gy in 5 fractions to the tumor volume (PTVt) and 50 Gy SIB (BED10 100 Gy) to the vascular involvement, or with (hypo-)fractionated ablative radiotherapy (HART) prescribing 50.4 Gy in 28 fractions to the PTVt, with a vascular SIB of 78.4 Gy (BED10 100 Gy). Primary end points were freedom from local progression (FFLP), overall survival (OS), and progression-free survival (PFS).ResultsSixty-four LAPC patients were included. Induction chemotherapy consisted of gemcitabine/nab-paclitaxel in 60.9% and FOLFIRINOX in 39.1% of cases. SAbR was used in 52 (81.2%) patients, and HART in 12 (18.8%). After RAdAR, surgery was performed in 17 (26.6%) patients. Median follow-up was 16.1 months. Overall local control (LC) rate was 78.1%, with no difference between resected and non-resected patients (2-year FFLP 75.3% vs 56.4%; p = 0.112). Median OS and PFS were 29.7 months and 8.7 months, respectively, for the entire cohort. Resected patients had a better median OS (not reached versus 26.1 months; p = 0.0001) and PFS (19 versus 5.6 months; p < 0.0001) compared to non-resected patients. In non-resected patients, no significant difference was found between SAbR and HART for median FFLP (28.1 versus 18.5 months; p = 0.614), OS (27.4 versus 25.3 months; p = 0.624), and PFS (5.7 versus 4.3 months; p = 0.486). One patient (1.6%) experienced acute grade 4 gastro-intestinal bleeding. No other acute or late grade ≥ 3 toxicities were observed.ConclusionsThe RAdAR approach, following intensive induction chemotherapy, is an effective radiation treatment strategy for selected LAPC patients, representing a promising therapeutic option in a multimodality treatment regimen.
| S-EPMC8093383 | biostudies-literature
Project description:BackgroundSurvival with locally advanced bladder cancer (LABC) following radical cystectomy (RC) remains poor. Although adjuvant chemotherapy (AC) is standard of care, one small, randomized trial has suggested a potential survival benefit when combined with post-operative radiotherapy (PORT).ObjectiveWe examined the association of AC + PORT with overall survival (OS) in patients with LABC after RC.MethodsUsing a prior phase 2 trial to inform design, we conducted observational analyses to emulate a hypothetical target trial of patients aged 18-79 years with pT3-4 Nany M0 or pTany N1-3 M0 urothelial bladder carcinoma following RC who were treated with AC (multiagent chemotherapy within 3 months of RC) with or without PORT (≥45 Gy to the pelvis) from 2006-2015 in the NCDB. Patients who received preoperative chemotherapy or radiotherapy were excluded. The associations of treatment with OS were evaluated using multivariable Cox regression.Results1,684 patients were included, with 66 receiving AC + PORT and 1,618 AC alone. Compared to patients treated with AC alone, those treated with AC + PORT were more likely to have pT4 disease (52% vs 26%; p < 0.01), positive surgical margins (44% vs 17%; p < 0.01), and be treated at a non-academic facility (75% vs 53%; p < 0.01). Crude 5-year OS was 19% for AC + PORT versus 36% for AC alone (p = 0.01). Adjusted 5-year OS was 33% for AC + PORT versus 36% for AC alone (p = 0.49). After adjusting for baseline characteristics including pathologic features, AC + PORT was not associated with improved OS compared to AC alone (HR 1.11; 95% CI 0.82-1.51).ConclusionsAlthough infrequently utilized, the addition of radiotherapy to AC is not associated with improved OS in LABC. These results highlight the need for prospective trials to better define the potential benefits from PORT with regard to symptomatic progression and oncologic outcomes.
| S-EPMC11181795 | biostudies-literature
Project description: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.
| S-EPMC11247755 | biostudies-literature
Project description:AimTo investigate and compare overall survival (OS), disease-free survival (DFS) and toxicity of women who underwent either chemoradiotherapy with or without prior lymph node debulking or upfront chemotherapy followed by radiotherapy and hyperthermia (triple therapy) for locally advanced cervical cancer (LACC) to identify a potential role for triple therapy.MethodsWomen with histologically proven LACC and with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 and IIA2 to IVA were included. Cox regression analyses were used for calculating hazard ratios and to adjust for confounding variables. A multivariable logistic regression analysis was used to examine the influence of covariates on toxicity.ResultsA total of 370 patients were included of whom 58% (n = 213) received chemoradiotherapy (CRT), 18% (n = 66) received node-debulking followed by chemoradiotherapy (LND-CRT) and 25% (n = 91) received triple therapy (TT). Five-year OS was comparable between the three treatment groups, with 53% (95% confidence interval 46-59%) in the CRT group, 45% (33-56%) in the LND-CRT group and 53% (40-64%) in the TT group (p = 0.472). In the adjusted analysis, 5-year OS and DFS were comparable between the three treatment groups. No chemotherapy-related differences in toxicity were observed.ConclusionThis study suggests that the toxicity and survival of TT is similar to CRT or LND-CRT.
| S-EPMC10854526 | biostudies-literature
Project description:BackgroundHigh Programmed death ligand 1 (PD-L1) expression are thought to be necessary to PD-1/PD-L1 axis blockades in many tumors. The aim of the study was to explore the variation of PD-L1 expression after neoadjuvant chemotherapy (NAC) in cervical squamous cell carcinoma (SCC) and its clinical implications.MethodsA total of 142 paired SCC specimens before and after platinum-based NAC were obtained from cervical cancer patients. The expression of PD-L1 and CD3+, CD4+, CD8+ tumor infiltrating lymphocytes (TILs) was detected by immunohistochemistry and the association between TILs, chemotherapy response, clinical outcome and PD-L1 expression was evaluated.ResultsThe fraction of patients with high PD-L1 expression was significantly increased from 32.4 to 46.5% after NAC (χ2 = 5.897, p = 0.015), while the increase of CD3+, CD4+, CD8+ TILs was not significant. High PD-L1 expression was not associated with CD3+, CD4+, CD8+ TILs before NAC, however CD8+ TILs infiltration was positively associated with high PD-L1 expression after NAC (r = 0.205, p = 0.014). The decreased PD-L1 expression was more observed in patients with clinical response to NAC (χ2 = 6.890, p = 0.009). A longer DFS was seen in patients with decreased PD-L1 expression than those with elevated or stable PD-L1 expression (p = 0.048, 95% CI: 0.091-0.987), while the difference was not significant in multivariate analysis (p = 0.113, 95% CI: 0.108-1.266).ConclusionsCisplatin based chemotherapy can increase PD-L1 expression in cervical cancer. The increased PD-L1 expression and a lymphocyte predominant microenvironment after chemotherapy provide a rational for use of PD-1/PD-L1 axis-inhibitor in the neoadjuvant setting.
| S-EPMC7271386 | biostudies-literature
Project description:The benefit of adjuvant hysterectomy after definitive concurrent chemoradiotherapy (CCRT) for locally-advanced cervical cancer (LACC) is controversial. The purpose of the present study was to systematically search the literature and perform a meta-analysis to compare overall survival (OS) and disease-free survival (DFS) between patients subjected to CCRT with hysterectomy and those who underwent CCRT alone. The PubMed, Scopus, Embase and Google scholar databases were searched. A meta-analysis to determine hazard ratios (HRs) and odds ratios (ORs) with meta-regression was performed for the following moderators: Disease stage, histology and proportion of radical hysterectomy. Data from 14 studies were included. The results indicated that patients who received CCRT with hysterectomy had significantly better OS (HR, 0.72; 95% CI, 0.56 to 0.91; I2=19%; P=0.007) and DFS (HR, 0.72; 95% CI, 0.56 to 0.93; I2=27%; P=0.01) than those treated with CCRT alone. However, in a subgroup analysis by study type, the results were significant only for retrospective studies but not for randomized controlled trials (RCTs). However, only 2 RCTs were included with small sample size, heterogeneity and low overall quality. Subgroup analyses based on the use of brachytherapy in the CCRT with hysterectomy group demonstrated no difference in OS and DFS between the two groups. Regarding the absolute numbers of death and recurrence events, no significant difference in mortality (OR, 0.91; 95% CI, 0.62 to 1.33; I2=0%; P=0.64) was determined between the two groups, but a significantly reduced incidence of recurrence was observed in the CCRT with hysterectomy group (OR, 0.61; 95% CI, 0.47-0.79; I2=29%; P=0.0002). The meta-regression results point to a significant influence of the proportion of stage II patients on OS. Despite the overall analysis indicating improved OS and DFS with the use of adjuvant hysterectomy after CCRT, subgroup analysis based on similar treatment protocols failed to demonstrate any significant benefit of hysterectomy in LACC. However, the results indicated that the recurrence rate may be higher in patients undergoing CCRT without hysterectomy. The limited quality of the studies included and selection bias from retrospective studies restrict the possibility to draw strong conclusions.
| S-EPMC7798101 | biostudies-literature
Project description:BackgroundThere is no agreed upon standard of care for borderline-resectable pancreatic cancer (BRPC) or locally-advanced pancreatic cancer (LAPC) patients regarding the benefit of chemotherapy or radiation alone or in combination.Patients and methodsWe completed a retrospective cohort analysis of BRPC and LAPC patients at a cancer center with expertise in multi-disciplinary pancreatic ductal adenocarcinoma (PDAC) treatment over a 5-year period from 03/01/2014 to 03/01/2019 (cut-off date). The total evaluable newly diagnosed, treatment naïve, BRPC, and LAPC patients with adequate organ function and ability to obtain treatment after multidisciplinary review was 52 patients. After analysis, patients were evaluated for rates of resection, extent of resection (R0 or R1), median progression-free survival (mPFS), and median overall survival (mOS).ResultsPatients were treated with chemotherapy alone (gemcitabine and nab-paclitaxel = 77% (20/26); FOLFIRINOX = 19% (5/26); single agent gemcitabine 3.8% (1/26)), or chemotherapy followed by chemoradiation (gemcitabine +5 Gy × 5 weeks), or chemoradiation alone prior to re-staging and potential resection. Of the 29% (15/52) of patients who went on to surgical resection, 73% (11/15) achieved R0 resection. An R0 resection was achieved in 35% (9/26) of patients treated with chemotherapy alone, 7.6% (1/13) in a patient treated with chemotherapy followed by radiation, and 7.6% (1/13) with concurrent chemoradiotherapy alone. Chemotherapy alone achieved a mPFS of 16.4 months (p < 0.0025) and mOS of 26.2 months (p < 0.0001), chemotherapy followed by chemoradiation was 13.0 months and 14.9 months respectively, while concurrent chemoradiotherapy was 6.9 months and 7.3 months.Conclusions and relevanceBRPC and LAPC patients capable of surgery after only receiving neoadjuvant treatment with chemotherapy had higher rates of R0 resection with prolonged median PFS and OS compared with any patient needing combination chemotherapy with radiotherapy.
| S-EPMC10134275 | biostudies-literature