Why not de-intensification for uterine cervical cancer?
Introduction
It has been reported that about 70% of oropharyngeal cancers are related to human papillomavirus (HPV) infection and radiosensitive [1]. Therefore, recently de-escalation is attempted, and favorable preliminary clinical results has been demonstrated [2,3].
It is known that the proportion of HPV-related tumors is much higher in uterine cervical cancer than oropharyngeal cancer [4]. It is reported that the presence of HPV is seen in virtually all cervical cancer [5]. However, since the publication of the Gynaecological Groupe Europeen de Curietherapie-European Scoiety for Radiotherapy & Oncology (GEC-ESTRO) working group [6], dose-escalation is advocated, and a similar trend still dominates the community [7]. In contrast, the Japanese guideline has been adapted much less total dose [8]. It is evident that the latter group's local control rate is less than the higher dosage group [9,10]. Nevertheless, it cannot be ignored that the lower dosage can cure the majority of patients, which means that does de-escalation can safely be achieved in the majority of patients.
In oropharyngeal cancer, p16 and smoking status are used to categorize patients, and patients who are candidates for dose de-escalation are selected based on these clinical features. Recently, our group submitted an article in which histological type, reduction ratio based on initial tumor size, total treatment time, and tumor size before brachytherapy were adverse prognostic clinical factors for local control from a multi-center retrospective study including more than 450 patients. The authors hypothesized that using such clinical factors that has influence on local control, we can find a group of patients who can safely be treated by de-escalated strategy without risking their prognosis. The aim of this retrospective study was to identify a group of patients who can safely be treated by de-escalated treatment intensity using multi-institutional retrospective patients' data of locally advanced uterine cervical cancer patients treated with definitive chemoradiation therapy employing image-guided adaptive brachytherapy.
Section snippets
Materials and methods
Inclusion criteria for the study was described in detail in the previous report (under submission). In brief, locally advanced uterine cervical cancer patients with initial tumor size larger than 4 cm assessed by magnetic resonance imaging (MRI) who were treated by definitive concurrent chemoradiotherapy including image-guided adaptive brachytherapy (IGABT) with a follow-up period longer than 2 years were included. The following clinical information was collected in the retrospective study:
Results
While most institutions included in this study contoured CTVHR and organs at risk based on CT, three institutions (29 patients, 6.2%) contoured structures based on MRI. There was no statistical difference for LC between CT- and MRI-based brachytherapy (4-y LC 88.8% vs. 78.5%, p = 0.064). Therefore, whether CT- or MRI-based was not considered a factor for risk classifications in this study. Among 469 patients, 162 patients (34.5%) met the criteria of low-risk group: Scc, tumor reduction ratio
Discussion
It was shown in this study that low-risk patients with Scc, tumor reduction ratio ≥29%, tumor size before brachytherapy ≤4 cm, and TTT <9 weeks had over 90% of 4-y LC in every dose group over 50 Gy, suggesting that even patients initially having ≥4 cm, there exists a group of patients who respond well to the EBRT who achieve local control with lower total dose. On the other hand, in the other group, at least >60 Gy was needed to obtain favorable local control (Table 3). Statistical difference
Conclusion
Low-risk patients achieved favorable LC with <CTVHR D90 80 Gy. A personalized treatment strategy based on tumor response could also be adopted for uterine cervical carcinoma in the future.
Conflicts of interest statement
Dr. Itami reports personal fees from HekaBio, grants and personal fees from Itochu, grants from Elekta, personal fees from AlphaTAU, personal fees from ViewRay, personal fees from Palette Science, outside the submitted work.
Dr. Igaki reports personal fees from HekaBio, personal fees from AstraZeneca, personal fees from Itochu, outside the submitted work.
This study receives no financial support from any company, so there are no conflicts of interests to declare.
Acknowledgements
This study was partially supported by the Japan Agency for Medical Research and Development (AMED, 19ck0106305h0003) and the National Cancer Center Research and Development Fund (26-A-18 and 26-A-28). Part of the patients’ data was provided from institutions involved in the Working Group of the Gynecological Tumor Committee of the Japanese Radiation Oncology Study Group (JROSG). The authors are grateful for all doctors who were involved in data collection for this retrospective study.
References (21)
- et al.
Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study
Lancet Oncol.
(2017) - et al.
Human papillomavirus and cervical cancer
Lancet.
(2013) - et al.
Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology
Radiother. Oncol.
(2006) - et al.
The EMBRACE II study: the outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies
Clin Transl Radiat Oncol.
(2018) - et al.
Prospective multi-institutional study of definitive radiotherapy with high-dose-rate intracavitary brachytherapy in patients with nonbulky (<4-cm) stage I and II uterine cervical cancer (JAROG0401/JROSG04-2)
Int. J. Radiat. Oncol. Biol. Phys.
(2012) - et al.
Phase II study of concurrent chemoradiotherapy with high-dose-rate intracavitary brachytherapy in patients with locally advanced uterine cervical cancer: efficacy and toxicity of a low cumulative radiation dose schedule
Gynecol. Oncol.
(2012) - et al.
Breast conserving therapy versus mastectomy for stage I-II breast cancer: 20 year follow-up of the EORTC 10801 phase 3 randomised trial
Lancet Oncol.
(2012) - et al.
Involved site radiation therapy in adult lymphomas: an overview of international lymphoma radiation oncology group guidelines
Int. J. Radiat. Oncol. Biol. Phys.
(2020) - et al.
PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial
Lancet Oncol.
(2021) - et al.
American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: high-dose-rate brachytherapy
Brachytherapy.
(2012)
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2022, Advances in Radiation OncologyCitation Excerpt :Although the dose goal is lower than 85 Gy, several Japanese reports demonstrated favorable clinical outcomes.19,23,24 In our previous study, the LC rate was more than 90% even if the dose did not reach 85 Gy in the following low-risk cases: squamous cell carcinoma, reduction ratio before brachytherapy ≥29%, tumor size before brachytherapy ≤4 cm, and total treatment time <9 weeks.25 Risk stratification may be necessary to identify cases requiring more than 85 Gy for CTVHR (eg, large tumor size, adenocarcinoma), and should strive to increase the dose of CTVHR in such cases, in which HGI may be a helpful tool.
Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image-guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose-response analyses for local control in the low-dose range
2023, Japanese Journal of Clinical OncologyPhase I/II prospective clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer
2023, Journal of Gynecologic Oncology
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The all authors contributed equally to this work.