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 certain if this improves survival. It is important to assess the value of hysterectomy with radiotherapy or chemotherapy, or both, as an alternative.To determine whether hysterectomy, in addition to standard treatment with radiotherapy or chemotherapy, or both, in women with LACC (Stage IB2 to III) is safe and effective compared with standard treatment alone.We searched CENTRAL, MEDLINE via Ovid, Embase via Ovid, LILACS, trial registries and the grey literature up to 3 February 2022.We searched for randomised controlled trials (RCTs) that compared treatments involving hysterectomy versus radiotherapy or chemotherapy, or both, in women with LACC International Federation of Gynecology and Obstetrics (FIGO) Stages IB2 to III.We used standard methodological procedures expected by Cochrane. We independently assessed study eligibility, extracted data and assessed the risk of bias. Where possible, we synthesised overall (OS) and progression-free (PFS) or disease-free (DFS) survival in a meta-analysis using a random-effects model. Adverse events (AEs) were incompletely reported and we described the results of single trials in narrative form. We used the GRADE approach to assess the certainty of the evidence.From the searches we identified 968 studies. After deduplication, title and abstract screening, and full-text assessment, we included 11 RCTs (2683 women) of varying methodological quality. This update identified four new RCTs and three ongoing RCTs. The included studies compared: hysterectomy (simple or radical) with radiotherapy or chemoradiotherapy or neoadjuvant chemotherapy (NACT) versus radiotherapy alone or chemoradiotherapy (CCRT) alone or CCRT and brachytherapy. There is also one ongoing study comparing three groups: hysterectomy with CCRT versus hysterectomy with NACT versus CCRT. There were two comparison groups for which we were able to do a meta-analysis. Hysterectomy (radical) with neoadjuvant chemotherapy versus chemoradiotherapy alone Two RCTs with similar design characteristics (620 and 633 participants) found no difference in five-year OS between NACT with hysterectomy versus CCRT. Meta-analysis assessing 1253 participants found no evidence of a difference in risk of death (OS) between women who received NACT plus hysterectomy and those who received CCRT alone (HR 0.94, 95% CI 0.76 to 1.16; moderate-certainty evidence). In both studies, the five-year DFS in the NACT plus surgery group was worse (57%) compared with the CCRT group (65.6%), mostly for Stage IIB. Results of single trials reported no apparent difference in long-term severe complications, grade 3 acute toxicity and severe late toxicity between groups (very low-quality evidence). Hysterectomy (simple or radical) with neoadjuvant chemotherapy versus radiotherapy alone Meta-analysis of three trials of NACT with hysterectomy versus radiotherapy alone, assessing 571 participants, found that women who received NACT plus hysterectomy had less risk of death (OS) than those who received radiotherapy alone (HR 0.71, 95% CI 0.55 to 0.93; I2 = 0%; moderate-quality evidence). However, a significant number of participants who received NACT plus hysterectomy also had radiotherapy. There was no difference in the proportion of women with disease progression or recurrence (DFS and PFS) between NACT plus hysterectomy and radiotherapy groups (RR 0.75, 95% CI 0.53 to 1.05; I2 = 20%; moderate-quality evidence). The certainty of the evidence was low or very-low for all other comparisons for all outcomes. None of the trials reported quality of life outcomes.From the available RCTs, we found insufficient evidence that hysterectomy with radiotherapy, with or without chemotherapy, improves the survival of women with LACC who are treated with radiotherapy or CCRT alone. The overall certainty of the evidence was variable across the different outcomes and was universally downgraded due to concerns about risk of bias. The certainty of the evidence for NACT and radical hysterectomy versus radiotherapy alone for survival outcomes was moderate. The same occurred for the comparison involving NACT and hysterectomy compared with CCRT alone. Evidence from other comparisons was generally sparse and of low or very low-certainty. This was mainly based on poor reporting and sparseness of data where results were based on single trials. More trials assessing medical management with and without hysterectomy may test the robustness of the findings of this review as further research is likely to have an important impact on our confidence in the estimate of effect. 

Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer

Objective The aim of the present study was to retrospectively evaluate the toxicity and efficacy of post-operative small pelvic intensity-modulated radiotherapy in early-stage cervical cancer patients with intermediate-risk factors Methods Between 2012 and 2016, 151 patients who had cervical cancer (International Federation of Gynecology and Obstetrics stage I-IIA) with intermediate-risk factors were treated with post-operative small pelvic intensity-modulated radiotherapy The median dose of 504 Gy in 28 fractions with small pelvic intensity-modulated radiotherapy was prescribed to the planning target volume The intensity-modulated radiotherapy technique used was conventional fixed-field intensity-modulated radiotherapy or helical tomotherapy Results The median follow-up was 37 months The 3-year disease-free survival and overall survival rates were 89 and 96%, respectively A total of 144 patients (953%) were alive at the last follow-up In total, 6 patients (39%) had recurrence: locoregional recurrence in 3 patients (2%), distant metastasis in 2 (13%), and both in 1 (06%) Diarrhoea was the most common acute toxicity There were no patients suffering from acute or late grade ≥ 3 toxicity Only 4 patients (26%) had late grade 2 toxicities Conclusions For early-stage cervical cancer patients with intermediate-risk factors, post-operative small pelvic intensity-modulated radiotherapy was safe and well tolerated The rates of acute and late toxicities were quite satisfactory

Post-operative small pelvic intensity-modulated radiation therapy for early-stage cervical cancer with intermediate-risk factors: efficacy and toxicity.

Background Although hematologic review criteria for general hospitals have been established, they may be insufficient for cancer hospitals. This study aimed to establish the appropriate review criteria for hematology analyzers in cancer hospitals. Methods A total of 1003 samples from our hospital were randomly selected for blood smear preparation and microscopic review. The review criteria of the International Consensus Group for Hematology Review (ICGH) and Chinese consensus group were used to obtain the review, true-negative (TN), true-positive (TP), false-negative (FN), and false-positive (FP) rates, as well as the triggered rules. Our review criteria were established by comparing flag or numeric value information of TP and FP samples, adjusting rules to obtain better efficiency, a low slide review rate, and an acceptable FN rate. Results Overall, 197 (19.64%) samples showed positive smear findings. Compared to the ICGH criteria, the slide review rate of the newly established criteria declined from 51.25% to 39.28%, and the TP and TN rates increased from 17.85% and 46.06% to 23.13% and 55.83%, respectively. The FN rate of the newly established criteria was 3.69%. Another set of samples used to validate the newly established criteria yielded the review, FN, and FP rates as 33.49%, 1.86%, and 25.58%, respectively. Conclusion The newly established review criteria for hematology analyzers enabled the prompt identification, smear, and further verification of doubtful specimens, without a significant increase in the workload, thus improving the efficiency of the review process. This study provided data support for other cancer hospitals to establish review criteria.

Establishment of improved review criteria for hematology analyzers in cancer hospitals.

Cancer develops through an imbalance in the cell cycle regulators, resulting in persistent proliferation and escaping apoptosis. Essential oils (EOs) are gaining popularity as a potential natural-based anticancer agent. This research aimed to evaluate cytotoxic activity by induction of apoptosis in Syzygium aromaticum , Melaleuca cajuputi , and Cymbopogon nardus EOs against the HeLa human cervical cancer cell lines. HeLa cell cultures were treated with EOs from three plants separately at 30, 60, and 120 μg/ml and 0 μg/ml as control. The trypan blue exclusion test was conducted to examine cell viability and determine the inhibitory concentration (IC 50 ) value. Cytotoxicity activity was evaluated using Annexin V (AV) and propidium iodide (PI) flow cytometry. The EOs of the three herbs significantly decrease HeLa cells’ viability at 24 and 48 hours after treatment in comparison to the control. AV–PI analysis displayed significant induction of late-stage apoptosis in a dose-dependent relationship. The 48 hour IC 50 values of EOs were 18.06 µg/ml ( S. aromaticum ), 26.25 µg/ml ( M. cajuputi ), and 28.03 µg/ml ( C. nardus ). The EOs of S. aromaticum , M. cajuputi , and C. nardus have potential anticancer activity with their cytotoxic effects on HeLa cells and could be explored further as a cervical cancer treatment.

/pdf/proapoptotic-activity-of-essential-oils-from-syzygium-3sfsotxd.pdf

Proapoptotic activity of essential oils from Syzygium aromaticum, Melaleuca cajuputi, and Cymbopogon nardus on HeLa human cervical cancer cells

Locally advanced cancer cervix: a systematic review and metaanalysis of 17 randomized trials to explore the therapeutic evidence for concurrent chemoradiotherapy over radiotherapy alone

Purpose The toxicity of postoperative radiotherapy for cervical cancer affects patients' quality of life. We evaluated acute toxicity in postoperative intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) as well as the influence of dosimetric parameters and concomitant chemotherapy. Methods A total of 45 patients with early operable cervical cancer underwent postoperative IMRT with 40-45 Gy. The control group of 50 patients was treated with 3DCRT. Brachytherapy and concomitant cisplatin chemotherapy were performed in all patients according to pathologic and histologic findings. The patients were monitored for acute gastrointestinal, urological and hematological toxicity classified according to the RTOG acute radiation morbidity scoring criteria. We also analyzed the influence of dosimetric parameters on acute toxicity. Results Significant differences were found in overall acute toxicity (p=0.018), acute genitourinary toxicity (p=0.029), anemia (p=0.043) and neutropenia (p=0.027) but not in acute gastrointestinal toxicity between the IMRT and 3DCRT groups. In all patients, regarding chemotherapy administration, differences were found between the chemoradiotherapy and radiotherapy group as far as overall acute toxicity (CHRT vs RT; p=0.011) and hematological toxicity were concerned (p=0.001). Patients with ≥3 cycles of chemotherapy showed increased hematologic toxicity. In the IMRT group according to the administration of chemotherapy (chemoradiotherapy vs radiotherapy), statistically significant difference for leukopenia (p=0.009) was found and in the 3DCRT group for anemia (p=0.021) and neutropenia (p=0.029). According to chemotherapy administration (chemoradiotherapy vs radiotherapy), a statistically significant difference in leukopenia (p=0.009) was found in the IMRT group while in the 3DCRT group the differences were in anemia (p=0.021) and neutropenia (p=0.029). Conclusion IMRT is associated with lower acute toxicity and better dosimetric parameters in organs at risk (OAR) compared to 3DCRT. Higher hematological toxicity occurred when concomitant chemotherapy was performed, regardless of RT technique. Further reduction of toxicity is expected with protocol and technical improvement and research of gene-related toxicity.

Acute toxicity of postoperative intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for cervical cancer: The role of concomitant chemotherapy.

Purpose To analyze the dose distribution achieved during 2D radiography-based brachytherapy (BRT) planning, by using a 3D MRI-based BRT replanning evaluation, in patients with advanced cervical carcinoma, treated with definitive concomitant chemoradiation (CCRT). Methods The curative CCRT was applied to 30 patients with advanced cervical carcinoma. For each patient, 2D radiography-based planning and a 3D MRI-based BRT replanning were performed. Applying the same source positions and dwell times in both planning methods, it was possible to use the MRI replanning to evaluate the dose distribution, maximum organs at risk (OAR) doses and target volume coverage, that was obtained during 2D BRT planning. Results A statistically significant difference for bladder and rectum maximum doses, between 2D planning (Bmax, Rmax) and 3D replanning (D0.1ccm, D1ccm, D2ccm) was found, except between Bmax and bladder D2ccm dose (p=0.07), and Rmax and rectal D2ccm dose in the group of patients with symmetrical rectum position regarding the applicator system (p=0.47). MRI evaluation of the HR-CTV volume, according to the 2D planning achieved dose distribution, revealed total EQD2 HR-CTV doses: D90 (107.15±22.06 Gy) and D100 (80.66±14.58 Gy). Conclusion 2D radiography-based BRT planning can provide a good estimation for the bladder and rectum 3D D2ccm dose with a significant statistical difference for the doses in the smaller OAR volumes (D0.1ccm, D1ccm). Inability to visualize tumor tissue during 2D BRT planning provides no option in tailoring the dose distribution to the tumor volume and patient anatomy, leading to potential under/over-treatment in some patients.

3D MRI-based evaluation of the 2D brachytherapy planning in patients with advanced cervical cancer: An analysis of the delivered dose.

Purpose Within implementation of intensity-modulated radiotherapy (IMRT) in the postoperative irradiation of cervical cancer we evaluated and compared IMRT and three-dimensional conformal radiotherapy (3DCRT) dosimetric parameters for target volumes and organs at risk (OAR). Methods We randomized 95 patients with cervical cancer, UICC stage I-III, in groups depending of the type of external beam postoperative radiotherapy. Forty-five patients were treated with IMRT and 50 with 3DCRT. All patients underwent brachytherapy, and according to risk factors some of the patients had concomitant cisplatin chemotherapy. The study was done in a period of three years from December 2015. Analysis of dosimetric parameters for target volume coverage and OARs was performed. Results IMRT plans showed better conformity compared to 3DCRT plans, represented with homogenity index and conformity index, with higher maximum dose (PTV105 and D2). Both plans achieved adequate planning target volume coverage described with PTV95. Statistically significant difference between groups was found for bladder, rectum and bowel high dose regions: bladder V45 (p=0.000), rectum V40 (p=0.043) and V45 (p=0.000), bowel V45 (p=0.000), and bone marrow dosimetric parameters V20-V45; all were better in IMRT plans. Significant difference was found for volume of patient body normal tissue receiving dose of 20Gy, which was higher in IMRT. Conclusion IMRT is a highly conformal technique. Satisfactory target volume coverage was achieved with both techniques, with better sparing of OARs in the IMRT group. With this technique improvement, we expect better quality of life in cervical cancer patients with good prognosis.

Implementation of intensity-modulated radiotherapy and comparison with three-dimensional conformal radiotherapy in the postoperative treatment of cervical cancer.

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Acute toxicity of postoperative intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for cervical cancer: The role of concomitant chemotherapy.

3D MRI-based evaluation of the 2D brachytherapy planning in patients with advanced cervical cancer: An analysis of the delivered dose.

Implementation of intensity-modulated radiotherapy and comparison with three-dimensional conformal radiotherapy in the postoperative treatment of cervical cancer.