Early toxicity and treatment outcomes of extended field-intensity modulated radiotherapy for cervical cancer patients with para-aortic nodal metastasis.

Meetakshi Gupta

doi:10.3332/ecancer.2019.957

Abstract

ObjectiveExtended-field radiotherapy (EFRT) with concurrent chemotherapy represents standard treatment in cervical cancer patients with para-aortic lymph nodal (PALN) metastasis. While EFRT with Intensity Modulated RT (IMRT) has been demonstrated to reduce toxicities, the dose thresholds for minimizing acute toxicity is not clear. The present study was undertaken to report the early toxicity with extended-field intensity-modulated radiotherapy (EF-IMRT) for carcinoma of the cervix in our cohort of patients and determine dose-volume parameters that predict ≥grade II haematological toxicity and diarrhoea.MethodologyThis was a retrospective study of consecutive cervical cancer patients with PALN metastasis treated with EF-IMRT. Patients received rotational IMRT +/- neoadjuvant chemotherapy (NACT) and/or concurrent chemotherapy (45–50 Gy/25#/5 weeks) followed by high-dose rate brachytherapy. Acute haematological and gastrointestinal toxicity (diarrhoea and vomiting) was correlated with doses received by bowel and marrow. Receiver operator characteristics curves were used for deriving thresholds that predict for increased toxicity and tested on univariate and multivariate analysis. Finally, disease free and overall survival (DFS and OS) was calculated.ResultsA total of 43 patients were included. One-fourth of the patients (11/43) received NACT and 88% received concurrent chemotherapy. Within the upfront EF-IMRT cohort, 22.6% and 9.7% patients developed grade ≥III haematological (HT) and gastrointestinal (GI) toxicity respectively, with an increase in HT (≥ grade III HT =67%) in patients receiving NACT (p = 0.007). In the entire cohort bone marrow Volume receiving 10 Gy (V10>) 90% correlated with an increase in ≥ grade III HT (p = 0.05). No dose volume thresholds could be validated for GI toxicity. The OS and DFS at 2 years was 56% and 54%, respectively.ConclusionEF-IMRT is a feasible option for cervical cancer patients with PALN involvement and is associated with acceptable grade III toxicity. Future studies need to focus on minimizing HT toxicity.

Highlights

Cervical cancer is the second most common cancer in women in the developing world
EF-Intensity Modulated RT (IMRT) is a feasible option for cervical cancer patients with para-aortic lymph nodes (PALN) involvement and is associated with acceptable grade III toxicity
In recent years IMRT has been evaluated for reduction of acute toxicity during Extended-field radiotherapy (EFRT) by potentially reducing the doses delivered to the bowel and bone marrow

Summary

Introduction

Cervical cancer is the second most common cancer in women in the developing world. Standard of care includes pelvic radiotherapy with concurrent cisplatin. The pattern of spread in cervical cancer is orderly, initially involving the lower pelvic lymph nodes and progressing to higher pelvic lymph nodes and para-aortic lymph nodes (PALN) [1] The Gynecology Oncology Group reported PALN disease incidence to be 5% of stage I, 16% stage II and 25% stage III patients [1]. Extended-field radiotherapy (EFRT) with concurrent chemotherapy, currently represents standard recommendation in patients presenting with cervical cancer and with PALN metastasis [3]. Use of radiotherapy (hyper fractionated or standard) and concurrent chemotherapy was associated with 83% and 41% incidence of acute and late grade II or higher toxicity. The Radiation Therapy Oncology Group (RTOG) 9201 study reported a very high incidence of acute and late toxicities with the use of hyperfractionation while using conventional radiation portals [4, 5]

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Conclusion