Elsevier

Gynecologic Oncology

Volume 163, Issue 1, October 2021, Pages 105-109
Gynecologic Oncology

Why not de-intensification for uterine cervical cancer?

https://doi.org/10.1016/j.ygyno.2021.07.021Get rights and content

Highlights

  • In HPV-related oropharyngeal cancer, treatment de-intensification has been tried.

  • Though most cervical cancer is HPV-related, no such attempt has been made.

  • It was hypothesized that low-risk patients could be treated by the reduced dose.

  • A subgroup analysis of a retrospective study indicated there exist such patients.

Abstract

Objective

The majority of uterine cervical cancer is known to be related to human papillomavirus (HPV), and HPV-related tumors are known to be radio-sensitive. In the management of HPV-related oropharyngeal cancer, de-intensification of treatment has been attempted; however, no such attempt is performed in the management of cervical cancer. The aim of this study was to identify a group of patients who can safely be treated by de-escalated treatment intensity.

Methods

From the Asian international multi-institutional retrospective study involving 13 Japanese, one Thailand, and one Korean institutions based on 469 patients, squamous cell carcinoma (Scc), tumor reduction ratio ≥29%, tumor size before brachytherapy ≤4 cm, and total treatment time (TTT) <9 weeks were identified as factors having an influence on local control. Based on these findings, low-risk patients having these four factors were extracted, and treatment outcomes categorized in 10 Gy increment of CTVHR D90 were compared.

Results

Among 469 patients, 162 patients (34.5%) met the criteria of low-risk group, and 63, 41, 43, and 15 patients were categorized in CTVHR D90 50–60 Gy, 60–70 Gy, 70–80 Gy, and >80 Gy, respectively. While 4-y progression-free survival ranged from 66 to 80%, 4-y local control was consistently over 90% in every dose group. Rectum and bladder D2cc and incidence of late adverse events decreased as CTVHR D90 decreased.

Conclusions

The low-risk patients achieved favorable local control with CTVHR D90 <80 Gy. A personalized treatment strategy based on tumor response could also be adopted for 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.

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