Health-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study

doi:10.1016/j.ijrobp.2015.12.363

International Journal of Radiation OncologyBiologyPhysics

Volume 94, Issue 5, 1 April 2016, Pages 1088-1098

https://doi.org/10.1016/j.ijrobp.2015.12.363 Get rights and content

Purpose

This study analyzed functioning and symptom scores for longitudinal quality of life (QoL) from patients with locally advanced cervical cancer who underwent definitive chemoradiation therapy with image guided adaptive brachytherapy in the EMBRACE study.

Methods and Materials

In total, 744 patients at a median follow-up of 21 months were included. QoL was prospectively assessed using European Organization for Research and Treatment of Cancer Quality of Life core module 30 (EORTC QLQ-C30) and EORTC cervical cancer module 24 (CX24) questionnaires at baseline, then every 3 months during the first year, every 6 months in the second and third years, and finally yearly thereafter in patients with no evidence of disease. Outcomes were evaluated over time and compared to those from an age-matched female reference population.

Results

General QoL and emotional and social functioning were impaired at baseline but improved during the first 6 months after treatment, to reach a level comparable to that of the reference population, whereas cognitive functioning remained impaired. Both social and role functioning showed the lowest scores at baseline but which increased after treatment to reach a plateau at 6 months and then declined slightly at 3 and 4 years. The overall symptom experience was elevated at baseline and decreased to a level within the range of that of the reference population. Similarly, tumor-related symptoms (eg, pain, appetite loss, and constipation), which were present before treatment, decreased substantially at the first follow-up after treatment. Several treatment-related symptoms developed either immediately after and persisted over time (diarrhea, menopausal symptoms, peripheral neuropathy, and sexual functioning problems) or developed gradually after treatment (lymphedema and dyspnea).

Conclusions

This longitudinal prospective QoL analysis showed that patients' general QoL and functioning were impaired before treatment compared to those of reference data. Several tumor-related symptoms resolved after treatment, and functioning and general QoL returned to that of the level of the reference population, indicating a transient impact of diagnosis and treatment. However, several treatment-related symptoms and problems did develop and persist, either immediately or gradually after treatment.

Introduction

In the definitive treatment of locally advanced cervical cancer (LACC), patients treated with chemoradiation therapy, implementation of image guided adaptive brachytherapy (IGABT) based on repeated volumetric imaging for dose optimization showed, in several single-institution reports, substantially improved local control and survival rates with decreased severe treatment-related side effects 1, 2, 3, 4. Parallel to this more favorable outcome, mild to moderate morbidity is currently the focus of research, as it can have considerable impact on patients' well being and health-related quality of life (QoL).

Previous studies in cervical cancer survivors reported that QoL of patients treated with (definitive) radiation therapy was decreased compared to that of the general female population 5, 6. In addition, QoL was reduced to a higher degree after radiation therapy in LACC than after surgery alone in early-stage cervical cancer 6, 7, 8. However, in most of these QoL studies, treatment components and combinations are heterogeneous and not well described 6, 9, 10. Furthermore, long-term QoL following IGABT has not been reported.

The currently ongoing international, prospective, observational EMBRACE study on IGABT in LACC aims to validate the feasibility and high efficacy of IGABT in a multi-institutional setting and to provide benchmark data for treatment parameters with regard to disease outcome, morbidity and QoL (www.embracestudy.dk).

Therefore, the objective of this EMBRACE analysis was to evaluate longitudinal health-related QoL regarding functioning and symptom scores after definitive chemoradiation therapy with IGABT in a large and homogenously treated cohort of LACC patients and to compare these outcomes to those of a previously published age-matched female reference population.

Section snippets

Patients

Patients with primary biopsy-proven squamous-, adeno-, or adenosquamous carcinoma of the uterine cervix, International Federation of Gynecology and Obstetrics (FIGO) stages IB to IVA (and stage IVB with para-aortic metastatic nodes below [lumbar] L1-L2 only) treated with curative intent with definitive chemoradiation therapy including IGABT were included in the EMBRACE study. The study was approved in all participating centers by the respective National Ethics Committees.

Treatment

Patients were treated

Results

At closure of the database for this analysis, October 31, 2014, 1205 patients were registered at the EMBRACE website; 1140 patients had a clinical baseline assessment, and baseline EORTC QLQ responses were available for 920 patients. Of those, 744 patients with baseline from 21 centers and at least 1 additional EORTC QLQ follow-up were included in this analysis. In each follow-up assessment, the mean number of EORTC QLQ responses missing in patients with a completed clinical assessment is 7%

Discussion

The aim of this EMBRACE analysis was to report prospectively assessed, longitudinal QoL, and symptoms in disease-free locally advanced cervical cancer patients after definitive chemoradiation therapy with IGABT and to compare results to those in an age-matched general population.

The primary findings of this study were that general QoL and emotional and social functioning were impaired at baseline but improved during the first 6 months after treatment, reaching a level comparable to that of the

Conclusions

In conclusion, this large prospective QoL analysis showed that patients' functioning and general QoL are impaired at baseline compared to reference data; tumor-related symptoms resolve after treatment and functioning and general QoL returns to the level of the RP indicating a transient impact of diagnosis and treatment on these more general scales. However, several treatment-related symptoms did develop and persisted, either immediately after or gradually after treatment.

Radiation therapy is a

Acknowledgments

The EMBRACE Collaborative Group included Jacob Lindegaard, Kari Tanderup, and Lars Fokdal, Department of Oncology, Aarhus University Hospital, Denmark; Elzbieta Van Der Steen Banasik, Department of Radiotherapy, Arnhem, The Netherlands; Christine Haie-Meder, Isabelle Dumas, and Cyrus Chargari, Department of Radiotherapy, Gustave-Roussy, Villejuif, France; Remi A. Nout, Department of Radiation Oncology, Leiden University Medical Center, The Netherlands; Erik Van Limbergen, Department of

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Systematic Review of the Literature on Multiple Co-occurring Symptoms in Patients Receiving Treatment for Gynecologic Cancers
2024, Seminars in Oncology Nursing
Patients with gynecologic cancers experience a very high symptom burden that has a negative impact on their quality of life. This systematic review aims to identify the common co-occurring symptoms, the prevalence of common symptoms, common instruments used to measure symptoms, associated risk factors, and the symptom burden in patients with gynecologic cancers.
A search of four databases (ie, PubMed, Embase, Web of Science, and CINAHL) was done from January 1, 2012, through September 5, 2022. A qualitative synthesis of the extant literature was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA 2020).
A total of 118 studies met the prespecified inclusion criteria. Ninety-six symptoms were assessed across these studies. The top six symptoms and their grand mean prevalence rates were lack of energy (64.4%), fatigue (62.1%), abdominal pain (53.3%), depression (52.6%), concentration dysfunction (52.0%), and drowsiness (51.9%). Numerous methodologic challenges were evident across studies. Future research needs to develop a disease-specific symptom assessment measure, evaluate for risk factors associated with a higher symptom burden, and determine the impact of multiple symptoms on patient outcomes.
The results are relevant for oncology clinicians to assess patients with gynecologic cancers for the presence of common symptoms and risk factors for higher symptom burden in the patients and to offer effective management interventions.
Time-action and patient experience analyses of locally advanced cervical cancer brachytherapy
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Although MRI-based image guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC) has resulted in favorable outcomes, it can be logistically complex and time consuming compared to 2D image-based brachytherapy, and both physically and emotionally intensive for patients. This prospective study aims to perform time-action and patient experience analyses during IGABT to guide further improvements.
LACC patients treated with IGABT were included for the time-action (56 patients) and patient experience (29 patients) analyses. Times per treatment step were reported on a standardized form. For the patient experience analysis, a baseline health status was established with the EQ-5D-5L questionnaire and the perceived pain, anxiety and duration for each treatment step were assessed with the NRS-11.
The median total procedure time from arrival until discharge was 530 (IQR: 480–565) minutes. Treatment planning (delineation, reconstruction, optimization) required the most time and took 175 (IQR: 145–195) minutes. Highest perceived pain was reported during applicator removal and treatment planning, anxiety during applicator removal, and duration during image acquisition and treatment planning. Perceived pain, anxiety and duration were correlated. Higher pre-treatment pain and anxiety scores were associated with higher perceived pain, anxiety and duration.
This study highlights the complexity, duration and impact on patient experience of the current IGABT workflow. Patient reported pre-treatment pain and anxiety can help identify patients that may benefit from additional support. Research and implementation of measures aiming at shortening the overall procedure duration, which may include logistical, staffing and technological aspects, should be prioritized.
Overall Severe Morbidity After Chemo-Radiation Therapy and Magnetic Resonance Imaging-Guided Adaptive Brachytherapy in Locally Advanced Cervical Cancer: Results From the EMBRACE-I Study
2023, International Journal of Radiation Oncology Biology Physics
To evaluate overall severe late morbidity (grade ≥3) in patients with locally advanced cervical cancer treated with chemo-radiation therapy and magnetic resonance image guided adaptive brachytherapy within the prospective EMBRACE-I study, and to compare the results with published literature after standard radiograph based brachytherapy (BT).
From 2008 to 2015 the EMBRACE-I study enrolled 1416 patients. Morbidity was assessed (Common Terminology Criteria for Adverse Events version 3.0) every 3 months the 1st year, every 6 months the second and third year, and yearly thereafter and 1251 patients had available follow-up on late morbidity. Morbidity events (grade 3-5) were summarized as the maximum grade during follow-up (crude incidence rates) and actuarial estimates at 3 and 5 years. To compare with the published literature on standard radiograph based BT, Common Terminology Criteria for Adverse Events scores from the EMBRACE-I study were retrospectively converted into a corresponding score in the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer system.
In total, 534 severe events occurred in 270 patients; 429 events were grade 3 and 105 were grade 4 events. Actuarial estimates for grade ≥3 gastrointestinal (GI), genitourinary (GU), vaginal and fistula events at 5 years were 8.5% (95% confidence interval [CI], 6.9%-10.6%), 6.8% (95% CI, 5.4%-8.6%), 5.7% (95% CI, 4.3%-7.6%), and 3.2% (95% CI, 2.2%-4.5%), respectively. The 5-year actuarial estimate for organ-related events (GI, GU, vaginal, or fistula) was 18.4% (95% CI, 16.0%-21.2%). The 5-year actuarial estimate when aggregating all G≥3 endpoints (GI, GU, vaginal, fistulas, and non-GI/GU/vaginal) was 26.6% (95% CI, 23.8%-29.6%). Thirteen patients had a treatment-related death, 8 of which were associated with GI morbidity.
This report assesses severe morbidity from the largest prospective study on chemo-radiation therapy and image guided adaptive brachytherapy for locally advanced cervical cancer to date. Severe late morbidity was limited per endpoint and organ category, but considerable when aggregated across organs and all endpoints. The late morbidity results in the EMBRACE-I study compare favorably with published literature on standard radiograph based BT for GI morbidity, vaginal morbidity, and fistulas.
Pelvic insufficiency fractures after intensity modulated radiation therapy combined with chemotherapy for cervix carcinoma: Incidence and impact of bone mineral density
2023, Clinical and Translational Radiation Oncology
The aim of this study was to evaluate the incidence and predictive factors of Pelvic Insufficiency Fractures (PIFs) occurring after Intensity Modulated Radiation Therapy (IMRT) combined with chemotherapy for locally advanced cervical cancer (CC).
Medical records of patients receiving radio-chemotherapy with IMRT between 2010 and 2020 for advanced CC were reviewed. PIFs were detected during follow-up on pelvic Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). The cumulative incidence rate of PIFs and its confidence interval were calculated at 2 and 5 years of follow-up. Pre-therapeutic Bone Mineral Density (BMD) (g/cm³) was evaluated on CT simulation for sacrum and the fourth lumbar (L4) vertebrae. Sacrum dosimetric parameters (V30Gy, V40Gy, D50%, Dmean) were analyzed.
136 patients were included. The median follow-up was 4.4 years. Median dose of D50% and V40Gy sacrum were 35.2 Gy (20.6–46.4) and 32.2% (7.2–73.4) respectively. The 2-year and 5-year cumulative incidence rates were 15.7% (95% CI: 9.88–22.71) and 22% (95% CI: 14.58–30.45) respectively. Median time interval between RT completion and PIFs’ detection was 11.5 months (IQR: 7.4–22.3). Univariate analysis showed that older age (p < 0.01), postmenopausal status at baseline (p < 0.01), and lower sacral and spinal BMD at baseline (respectively p < 0.001 and p < 0.01) were significantly associated to all sites of PIFs, and lower sacral BMD with sacral fractures (p < 0.001).
Post-IMRT PIFs were detected in 18.4% of patients with locally advanced CC. Individual predisposing factors as older age, postmenopausal status, decreased bone density on the CT simulation were mainly predictive.
ESGO/ESTRO quality indicators for radiation therapy of cervical cancer
2023, Radiotherapy and Oncology
The European Society of Gynaecological Oncology (ESGO) has previously defined and established a list of quality indicators for the surgical treatment of cervical cancer. As a continuation of this effort to improve overall quality of care for cervical cancer patients across all aspects, ESGO and the European SocieTy for Radiotherapy and Oncology (ESTRO) initiated the development of quality indicators for radiation therapy of cervical cancer.
To develop a list of quality indicators for radiation therapy of cervical cancer that can be used to audit and improve clinical practice by giving to practitioners and administrators a quantitative basis to improve care and organizational processes, notably for recognition of the increased complexity of modern external radiotherapy and brachytherapy techniques.
Quality indicators were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for identification of potential quality indicators and documentation of scientific evidence, consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians (n = 99).
Using a structured format, each quality indicator has a description specifying what the indicator is measuring. Measurability specifications are detailed to define how the quality indicators will be measured in practice. Targets were also defined for specifying the level which each unit or center should be aiming to achieve. Nineteen structural, process, and outcome indicators were defined. Quality indicators 1–6 are general requirements related to pretreatment workup, time to treatment, upfront radiation therapy, and overall management, including active participation in clinical research and the decision making process within a structured multidisciplinary team. Quality indicators 7–17 are related to treatment indicators. Quality indicators 18 and 19 are related to patient outcomes.
This set of quality indicators is a major instrument to standardize the quality of radiation therapy in cervical cancer. A scoring system combining surgical and radiotherapeutic quality indicators will be developed within an envisaged future ESGO accreditation process for the overall management of cervical cancer, in an effort to support institutional and governmental quality assurance programs.
Association of persistent morbidity after radiotherapy with quality of life in locally advanced cervical cancer survivors
2023, Radiotherapy and Oncology
To quantify the association of persistent morbidity with different aspects of quality of life (QOL) in locally advanced cervical cancer (LACC) survivors.
Longitudinal outcome from the EMBRACE-I study was evaluated. Patient-reported symptoms and QOL were prospectively scored (EORTC-C30/CX24) at baseline and regular follow-ups. Physician-assessed symptoms were also reported (CTCAEv.3). Persistent symptoms were defined if present in at least half of the follow-ups. QOL items were linearly transformed into a continuous scale. Linear mixed-effects models (LMM) were applied to evaluate and quantify the association of persistent symptoms with QOL. Overall QOL deterioration was evaluated by calculating the integral difference in QOL over time obtained with LMM for patients without and with persistent symptoms.
Out of 1416 patients enrolled, 741 with baseline and ≥ 3 late follow-ups were analyzed (median 59 months). Proportions of persistent EORTC symptoms ranged from 21.8 % to 64.9 % (bowel control and tiredness). For CTCAE the range was 11.3–28.6 % (limb edema and fatigue). Presence of any persistent symptom was associated with QOL, although with varying magnitude. Role functioning and Global health/QOL were the most impaired aspects. Fatigue and pain showed large differences, with reductions of around 20 % for most of the QOL aspects. Among organ-related symptoms, abdominal cramps showed the largest effect.
Persistent symptoms are associated with QOL reductions in LACC survivors. Organ-related symptoms showed smaller differences than general symptoms such as fatigue and pain. In addition to optimizing treatment to minimize organ-related morbidity, effort should be directed towards a more comprehensive and targeted morbidity management.

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: This study was sponsored by the Medical University of Vienna. Uncommitted research funding was provided by Nucletron (Elekta) and Varian Medical Systems. Additional support was provided by the Austrian Federal Ministry of Science, Research, and Economy; the Austrian Foundation for Research, Technology, and Development; the Danish Cancer Society (grant R2-A180-09-S2); and the Lundbeck Foundation Center for Investigational Research in Radiation Oncology.

: Conflict of interest: none.

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Clinical InvestigationHealth-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study

Purpose

Methods and Materials

Results

Conclusions

Introduction

Section snippets

Patients

Treatment

Results

Discussion

Conclusions

Acknowledgments

Radiother Oncol

Radiother Oncol

Radiother Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Clin Ther

Radiother Oncol

Radiother Oncol

Eur J Cancer

Gynecol Oncol

Int J Radiat Oncol Biol Phys

Clinical Investigation
Health-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study