• adjuvant chemotherapy
• cervical cancer
• definitive radiotherapy
• distant metastases
• guidelines
• image-guided brachytherapy
• neoadjuvant chemotherapy

• Cervical cancer
• Dose escalation
• Gynecologic brachytherapy
• Nterstitial brachytherapy
• Tumor control probability
• Vaginal Cancer

• Lymph node relapse
• extended nodal radiotherapy (ENRT)
• gynecologic tumors
• positron emission tomography (PET) guidance
• simultaneous integrated boost
• stereotactic body radiotherapy

• cervical cancer
• immunotherapy
• intensity-modulated radiotherapy
• nodal control
• radiotherapy
• simultaneous integrated boost

• CHEMOTHERAPY
• Gynaecological oncology
• Patients
• RADIOTHERAPY
• Uterine Cervical Neoplasms

• Adult
• Aged
• Female
• Humans
• Middle Aged
• Brachytherapy/methods
• Brachytherapy/adverse effects
• Clinical Trials, Phase III as Topic
• Disease-Free Survival
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Multicenter Studies as Topic
• Pelvis
• Randomized Controlled Trials as Topic
• Uterine Cervical Neoplasms/pathology
• Uterine Cervical Neoplasms/radiotherapy

• Tata Memorial Centre, Mumbai

• PET‐CT
• carcinoma cervix
• patient‐reported outcome measures
• tomotherapy

• Humans
• Female
• Positron Emission Tomography Computed Tomography/methods
• Uterine Cervical Neoplasms/therapy
• Uterine Cervical Neoplasms/diagnostic imaging
• Middle Aged
• Chemoradiotherapy/methods
• Fluorodeoxyglucose F18
• Radiopharmaceuticals/therapeutic use
• Prospective Studies
• Adult
• Aged
• Patient Reported Outcome Measures
• Radiotherapy, Intensity-Modulated/methods
• Cisplatin/therapeutic use
• Treatment Outcome
• Radiotherapy, Image-Guided/methods

• 6242-P6/RGCB/PMD/DBT/RMPA/2015 Department of Biotechnology, Ministry of Science and Technology, India

• IGABT
• intracavitary and interstitial hybrid brachytherapy
• locally advanced cervical cancer
• optimal lymph-node boost dosage
• point B
• regional lymph-node metastases

• 22K07779, 23H02869, and 23K07171 the Ministry of Education, Culture, Sports, Science and Technology of Japan

• Bulky
• Case report
• Cervical cancer
• Lymph node
• Para-aortic
• Radiotherapy

• Adaptive Radiotherapy
• Artificial Intelligence
• Cone-beam CT
• Deformable Image Registration

• Definitive
• External beam radiotherapy
• Intensity-modulated radiation therapy
• Postoperative
• Uterine cervical neoplasms

• Female
• Humans
• Radiotherapy, Intensity-Modulated/adverse effects
• Radiotherapy, Intensity-Modulated/methods
• Uterine Cervical Neoplasms/pathology
• Radiotherapy Dosage
• Radiotherapy, Conformal/methods

• cervical cancer
• image-guided brachytherapy
• nodal control
• radiotherapy
• simultaneous integrated boost
• volumetric modulated arc therapy

• Boost
• Cervical cancer
• Chemoradiotherapy
• IMRT
• Lymph nodes
• VMAT

• Female
• Humans
• Uterine Cervical Neoplasms/drug therapy
• Uterine Cervical Neoplasms/pathology
• Retrospective Studies
• Neoplasm Staging
• Chemoradiotherapy/adverse effects
• Chemoradiotherapy/methods
• Lymph Nodes/pathology
• Radiotherapy, Intensity-Modulated/methods

• cervical cancer
• lymph nodes
• radiotherapy, intensity-modulated

• Female
• Humans
• Positron Emission Tomography Computed Tomography
• Uterine Cervical Neoplasms/surgery
• Uterine Cervical Neoplasms/pathology
• Lymphatic Metastasis/pathology
• Neoplasm Recurrence, Local/pathology
• Lymph Node Excision/methods
• Lymph Nodes/surgery
• Lymph Nodes/pathology
• Neoplasm Staging
• Retrospective Studies

• Adjuvant chemotherapy
• Cervical cancer
• IMRT

Dose escalation for positive node maybe improve the regional control of patients with node-positive cervical cancer, but the optimal dose for nodes of different sizes remains controversial. The purpose of this study was to explore the individualized dose escalation for lymph nodes (LNs) with different sizes in the definitive radiotherapy of cervical cancer.

A total of 1002 cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO 2009) stage IB1–IVA, who were treated by definitively radiotherapy between September 2013 and December 2016 were enrolled. All LNs identified by computed tomography/magnetic resonance imaging (CT/MRI) were assigned into three groups according to the short diameters of < 1 cm, 1–2 cm or ≥ 2 cm at pretreatment.

In total, 580 patients with 1310 LNs were detected. The nodal control rate in groups of LNs < 1 cm, 1–2 cm and ≥ 2 cm was 99.4%, 96%, and 75.9%, respectively (P = 0.000). Among LNs < 1 cm, the control, overall survival (OS) and progression-free survival (PFS) rates did not significantly differ among three dose-based groups (≤ 50.4 Gy, 50.4–60 Gy, > 60 Gy) (control rate, 99.4% vs. 99.3% vs. 100%, P = 0.647) (5-year OS, 76.2% vs. 79% vs. 81.6%, P = 0.682) (5-year PFS, 74.1% vs. 73.9% vs. 78.9% P = 0.713). Among LNs of 1–2 cm, the control and PFS rates were significantly higher in the group of dose ≥ 55 Gy than the group of dose < 55 Gy (control rate, 98% vs. 93.6%, P = 0.028) (5-year PFS, 69.6% vs. 56.7%, P = 0.025). However, this did not cause a significant difference for 5-year OS rate (72.6% vs. 68.3%, P = 0.5). Among LNs ≥ 2 cm, the control, OS, and PFS rates were higher in the group of dose ≥ 55 Gy than the group of dose < 55 Gy, while no significant difference was found (control rate, 82.1% vs. 63.2%, P = 0.107) (5-year OS, 60.6% vs. 37.5%, P = 0.141) (5-year PFS, 51.5% vs.37.5%, P = 0.232).

Radiation dose escalation is not necessary for LNs < 1 cm, and dose escalation of 55 Gy is enough for LNs of 1–2 cm.

• Dose escalation
• Lymph node
• Radiotherapy
• Uterine cervical neoplasms

• Extended-field irradiation
• Locally advanced cervical cancer
• Para-aortic lymph node

Regional control is occasionally unsatisfactory in cervical cancer, with the optimal radiation dose for nodal metastases in definitive radiotherapy (RT) with concurrent chemotherapy (CRT) remaining controversial. We investigated dose-response relationship for nodal local control in cervical cancer.

We identified 115 patients with 417 metastatic nodes who received definitive CRT for cervical cancer with nodal metastases. External beam radiation therapy and brachytherapy plans were summated to determine total dose received by each node. Prognostic factors of nodal control and dose-response relationship were investigated using Cox-regression and restricted cubic spline function.

The 2-year progression-free survival rate was 69.4%. Among 43 patients with failures, 17 patients (37.5%) had regional failure included in first failure sites of which all except one were in-field only regional failures. Total 30 nodes showed recurrence at initial metastatic site after treatment. Neutrophil-to-lymphocyte ratio (NLR) ≥3.1, total radiation dose (minimum dose received by 98% of the target volume in equivalent dose in 2 Gy per fractions), and initial nodal volume ≥5.29 mL were poor prognostic factors (all p<0.050) of nodal local control. Restricted cubic spline functions revealed strongest dose-response relationship in high NLR (NLR ≥3.1) and initial nodal volume ≥5.29 mL subgroup.

Initial nodal volume, radiation dose_, and NLR were significant factors of nodal local control in cervical cancer; a stronger dose-response relationship was seen in bulky nodes with high NLR. Clinicians may consider these factors when determining the RT dose and the need for boost to nodal metastases in cervical cancer.

One-third of cervical cancer with nodal metastases had regional failure as first failure, mostly in-field failures. Neutrophil-to-lymphocyte ratio (NLR) ≥3.1, radiation dose, and initial nodal volume ≥5.29 mL were significant factors of nodal control. The strongest radiation dose-response was found in bulky nodes with a high NLR.

• Brachytherapy
• Cervical Cancer
• Dose
• Lymph Node
• Nodal Control
• Radiotherapy

• Cervical cancer
• hypofractionation
• intensity-modulated radiotherapy
• nodal boost
• simultaneous integrated boost

This study aimed to assess the prognostic factors of overall survival (OS) in patients with stage IIB–IVA cervix carcinoma (CC) who underwent external beam radiation therapy (EBRT) and brachytherapy (BRT) and to compare the prognostic accuracy of the 2014 and 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system using the Surveillance, Epidemiology, and End Results (SEER) database.

Patients with a histopathological diagnosis of CC between 2004 and 2016 were included. The primary endpoint was OS. The prognostic significance for OS was analyzed by the Cox regression model. Prognostic accuracy in evaluating 3- and 5-year OS in different staging systems was evaluated using time-dependent receiver operating characteristic (tdROC) curves.

A total of 2585 patients with stage IIB–IVA CC, staged according to the 2014 FIGO staging system, were included in the study. The 3- and 5-year OS rates were 63.9% and 56.6%, respectively, with a median OS of 98 months. Independent variables, such as older age at diagnosis, histological grades apart from well or moderately differentiated, large tumor size, advanced tumor stages classified according to the 2014 and 2018 FIGO staging systems and treatment without chemotherapy or unknown were associated with a worse OS. A tdROC analysis conducted using DeLong’s tests revealed no significant difference in the prediction of 3- and 5-year OS between the 2014 and 2018 FIGO staging systems (P = 0.912 and 0.863, respectively).

Both 2014 and 2018 FIGO staging systems were strong prognostic factors for OS. No significant risk classification was observed for stage IIIC1 disease in the revised 2018 FIGO staging system for patients who underwent EBRT and BRT.

• Surveillance, Epidemiology, and End Results database
• prognostic analysis
• risk factors
• staging
• survival

Background: Over the past two decades, there has been significant advancement in the management of cervical cancer, particularly in the domain of definitive chemoradiotherapy for locally advanced cervical cancer (LACC). Indeed, radiation treatment paradigms have shifted from a two-dimensional (2D) approach solely based on anatomical bony landmarks, to an image-guided three-dimensional (3D) approach, with the goal of delivering doses more precisely to clinical targets with an increased sparing of organs-at-risk. Methods: This is a narrative review on the advances in radiation technologies for the treatment of cervical cancer. Using the PubMed database, we identified articles published in English up until November 18, 2021 on the treatment of LACC with external beam radiotherapy (EBRT) and brachytherapy. A search of the Clinicaltrials.gov and Clinicaltrialsregister.eu retrieved information on ongoing clinical trials on the topic of combined immunotherapy and radiotherapy in cervical cancer. Results: We highlight the historical evolution from the use of 2D radiotherapy to 3D-conformal radiotherapy, and then intensity modulated radiotherapy (IMRT) for the delivery of EBRT. We also discuss advances in brachytherapy, notably the transition to 3D image-guided adaptive brachytherapy (3D-IGABT). In this context, we highlight large cohort studies that were recently constructed and have shown significant improvement in local control and treatment-related toxicities with 3D-IGABT. Finally, we discuss other advances in the field, notably the use of stereotactic body radiotherapy (SBRT) as a substitute to brachytherapy, and the addition of immunotherapy to chemoradiation. Conclusions: The use of IG-IMRT and 3D-IGABT have considerably improved treatment outcomes and toxicity profiles for patients with LACC, and are now considered the gold standard in many countries. The use of SBRT boost as a replacement for brachytherapy has been associated with increased toxicity and decreased efficacy and should be used with caution in the context of clinical trials. New experimental approaches include the addition of immunotherapy to chemoradiation regimens.

• Extended-field radiotherapy
• locally advanced cervical cancer
• neoadjuvant chemotherapy
• para-aortic lymph node

• FIGO stage
• cervical cancer
• concurrent chemoradiotherapy
• lymph node
• prognosis
• surgery

• AUC
• Appropriate Use Criteria
• Appropriateness Criteria
• Imaging
• Recurrence
• Staging
• Vaginal carcinoma

• Female
• Follow-Up Studies
• Humans
• Magnetic Resonance Imaging
• Neoplasm Recurrence, Local
• Positron Emission Tomography Computed Tomography
• Societies, Medical
• United States
• Vaginal Neoplasms/diagnostic imaging

• Dose fractionation, Radiation
• Lymphadenopathy
• Radiation dosage

• (Para-aortic) nodal failure
• EMBRACE
• Risk factors

Globally, cervical cancer has the fourth highest cancer incidence and mortality in women. Cervical cancer is unique because it has effective prevention, screening, and treatment options. This review discusses the current cervical cancer advances with a focus on locally advanced cervical cancer. Topics discussed include diagnostic imaging principles, surgical management with adjuvant therapy and definitive concurrent chemoradiotherapy. Emphasis is given on current advances and future research directions in radiation therapy (RT) with an emphasis on three-dimensional brachytherapy, intensity-modulated RT, image-guided RT, proton RT and hyperthermia.

• Chemotherapy
• hyperthermia
• image-guided brachytherapy
• intensity-modulated radiation therapy
• locally advanced cervical cancer
• proton therapy

• angiogenesis inhibitors
• cervical cancer
• chemotherapy
• immunotherapy
• radiotherapy

To investigate the safety and outcomes of elective para-aortic (PA) nodal irradiation utilizing modern treatment techniques for patients with node positive cervical cancer.

Patients with pelvic lymph node positive cervical cancer who received radiation were included. All patients received radiation therapy (RT) to either a traditional pelvic field or an extended field to electively cover the PA nodes. Factors associated with survival were identified using a Cox proportional hazards model, and toxicities between groups were compared with a chi-square test.

96 patients were identified with a mean follow up of 40 months. The incidence of acute grade ≥ 2 toxicity was 31% in the elective PA nodal RT group and 15% in the pelvic field group (Chi-square p = 0.067. There was no significant difference in rates of grade ≥ 3 acute or late toxicities between the two groups (p>0.05). The KM estimated 5-year OS was not statistically different for those receiving elective PA nodal irradiation compared to a pelvic only field, 54% vs. 73% respectively (log-rank p = 0.11).

Elective PA nodal RT can safely be delivered utilizing modern planning techniques without a significant increase in severe (grade ≥ 3) acute or late toxicities, at the cost of a possible small increase in non-severe (grade 2) acute toxicities. In this series there was no survival benefit observed with the receipt of elective PA nodal RT, however, this benefit may have been obscured by the higher risk features of this population. While prospective randomized trials utilizing a risk adapted approach to elective PA nodal coverage are the only way to fully evaluate the benefit of elective PA nodal coverage, these trials are unlikely to be performed and instead we must rely on interpretation of results of risk adapted approaches like those used in ongoing clinical trials and retrospective data.

• brachytherapy
• cervical cancer
• chemoradiation (CRT)
• para-aortic nodal irradiation
• radiation therapy

• brachytherapy
• consensus
• radiotherapy
• uterine cervical neoplasms

• cervical cancer
• radiation
• radiotherapy dosage
• radiotherapy, image-guided
• radiotherapy, intensity-modulated

• Adult
• Female
• Humans
• Lymph Nodes/radiation effects
• Middle Aged
• Radiotherapy Dosage/standards
• Uterine Cervical Neoplasms/radiotherapy

• Cervical cancer
• Guideline
• PET/CT
• Positron emission tomography
• Radiation oncology
• Treatment planning
• [18F]FDG

• Female
• Fluorodeoxyglucose F18
• Humans
• Neoplasm Staging
• Positron Emission Tomography Computed Tomography
• Positron-Emission Tomography
• Radiopharmaceuticals
• Uterine Cervical Neoplasms/diagnostic imaging
• Uterine Cervical Neoplasms/pathology
• Uterine Cervical Neoplasms/radiotherapy

• Amsterdam UMC (University of Amsterdam)

• Chronic toxicity
• Grade 2 and above Acute G.I or GU Toxicity
• Improved therapeutic Index
• Pelvic lymph node positive locally advanced cervical cancer
• Prophylactic para aortic extended field SIB-VMAT

We sought dosimetric predictors of a decreasing estimated glomerular filtration rate (eGFR) in gynecological oncology patients receiving extended-field radiation therapy (EFRT).

Between July 2012 and April 2020, 98 consecutive cervical or endometrial cancer patients underwent EFRT or whole-pelvis radiation therapy (WPRT) with concurrent cisplatin chemotherapy in our institution. To explore the effect of concurrent cisplatin chemotherapy on renal function, the renal function of the WPRT patients was examined. Of the 98 patients, 34 cervical or endometrial cancer patients underwent EFRT including extended-field intensity-modulated radiation therapy (EF-IMRT) and 64 cervical cancer patients underwent WPRT with cisplatin. Of the 34 EFRT patients, 32 underwent concurrent cisplatin chemotherapy. Excluding patients exhibiting recurrences within 6 months, 31 EFRT patients were analyzed in terms of the dose-volume kidney histograms (the percentages of kidney volumes receiving 12, 16, 20, and 24 Gy) and the post- to pre-treatment eGFR ratios. We calculated Pearson correlation coefficients between the renal dose volume and the percentage eGFR reductions of the 31 EFRT patients, and those treated via EF-IMRT. Renal dose constraint significance was evaluated using the Mann–Whitney U test.

The eGFR value after WPRT with cisplatin remained largely unchanged for 12 months, unlike that after EFRT. In EFRT patients, a strong correlation was evident between the KV_20Gy dose and the post- to pre-treatment eGFR ratio (correlation coefficients − 0.80 for all patients and − 0.74 for EF-IMRT patients). In EF-IMRT patients, the kidney volume receiving 20 Gy tended to correlate negatively with the eGFR reduction. The Mann–Whitney U test showed that patients with KV_20Gy values < 10% retained significantly better renal function than did patients with KV_20Gy values > 10% (P = 0.002).

Imposition of a severe kidney dose constraint during EF-IMRT may reduce nephrotic toxicity. Future prospective investigations of kidney-sparing EF-IMRT are required.

• Extended-field radiation therapy
• Gynecological oncology
• Nephrotoxicity

The Korean Radiation Oncology Group conducted a nationwide questionnaire survey to evaluate the patterns of clinical practice for patients with cervical cancer receiving definitive radiation therapy (RT) in South Korea.

Practicing radiation oncologists from 93 centers in South Korea were administered a questionnaire survey via e-mail. The survey focused on demographic characteristics, diagnostic evaluation, indications for definitive RT, RT techniques, RT field and dose prescription, lymph node (LN) boost RT, brachytherapy, and chemotherapy.

The response rate was 62.4% (58/93 institutions). Of the 2,134 patients treated at the radiation oncology department in 2019, 48.8% underwent definitive RT. The selection of patients for definitive concurrent chemoradiation therapy and RT field, and RT dose prescription varied greatly. The upper border of the pelvis was commonly used as the bony landmark for external beam RT (81%–88% of respondents). Most (96.6%) centers performed LN boost RT with median total doses of 59 Gy and 59.2 Gy for pelvic and retroperitoneal LN, respectively. With 50% of the centers offering brachytherapy, image-guided brachytherapy and volume-based prescription were applied in 48.3% and 37.9%, respectively. Upfront concurrent chemoradiation therapy with varying prescription doses was considered by 60.4% respondents in cases of supraclavicular LN metastasis.

Most differences were noted in the indications for treatment, RT field, and prescription dose. This finding can serve as a reference for establishing practical RT guidelines for the management of locally advanced cervical cancer.

• Cervical Cancer
• Practice Patterns
• Radiation Therapy
• Survey

Cervical cancer remains a major health challenge in low- to middle-income countries. We present the experiences of two centers practicing in variable resource environments to determine predictors of improved radiochemotherapy treatment.

This comparative review describes cervical cancer presentation and treatment with concurrent chemoradiotherapy with high-dose-rate brachytherapy between 2014 and 2017 at the National Radiotherapy Oncology and Nuclear Medicine Center (NRONMC) in Korle-Bu Teaching Hospital, Accra, Ghana, and Moffitt Cancer Center (MCC), Tampa, FL.

Median follow-up for this study was 16.9 months. NRONMC patients presented with predominantly stage III disease (42% v 16%; P = .002). MCC patients received para-aortic node irradiation (16%) and interstitial brachytherapy implants (19%). Median treatment duration was longer for NRONMC patients compared with MCC patients (59 v 52 days; P < .0001), and treatment duration ≥ 55 days predicted worse survival on multivariable analysis (MVA; P = .02). Stage ≥ III disease predicted poorer local control on MVA. There was a difference in local control among patients with stage III disease (58% v 91%; P = .03) but not in survival between MCC and NRONMC. No significant difference in local control was observed for stage IB, IIA, and IIB disease.

Although there were significant differences in disease presentation between the two centers, treatment outcomes were similar for patients with early-stage disease. Longer treatment duration and stage ≥ III disease predicted poor outcomes.

• COVID-2019
• Evidence-based oncology
• Pandemic
• Radiation oncology

• COVID-19/prevention & control
• Humans
• India
• Pandemics/prevention & control
• Radiation Oncology
• SARS-CoV-2/pathogenicity

• Dose response
• locally advanced endometrial cancer
• lymph node
• nodal boost
• pre-operative chemoradiotherapy

• cervical cancer
• lymph nodes
• surgical procedures, operative

• Female
• Humans
• Lymph Nodes/pathology
• Neoplasm Staging
• Survival Analysis
• Uterine Cervical Neoplasms/diagnostic imaging
• Uterine Cervical Neoplasms/mortality
• Uterine Cervical Neoplasms/therapy