Acute and long-term toxicity in patients undergoing induction chemotherapy followed by thermoradiotherapy for advanced cervical cancer

• Published in: International journal of hyperthermia 2022-12, Vol.39 (1), p.1440-1448
• Main Authors: Gao, X. S., Boere, I. A., van Beekhuizen, H. J., Franckena, M., Nout, R., Kruip, M. J. H. A., Kulawska, M. D., van Doorn, H. C.
• Format: Article
• Language: English
• Subjects: Cervical cancer; cisplatin; induction chemotherapy; radiotherapy; thermoradiotherapy; venous thrombo-embolism
• ISSN: 0265-6736; 1464-5157
• DOI: 10.1080/02656736.2022.2146213

To determine rates of vascular toxicity, acute kidney injury (AKI), chronic kidney disease (CKD) and survival in high-risk cervical cancer patients treated with platinum-based induction chemotherapy followed by thermoradiotherapy. Between January 1999 and April 2017, patients with large primary tumors (>6cm) and/or para-aortic lymph node (LN) metastases >1 cm and/or para-iliac LN >2 cm were included. Patient and tumor characteristics, Common Toxicity Criteria v4.03 scores, laboratory tests and treatment data were retrieved from patient records. CT scans were reviewed for the presence of thrombo-embolic events (TEE). The study protocol was approved by the Medical Ethics Review Committee of Erasmus MC, Rotterdam (MEC2017-133). The 105 included patients had a mean age of 47.9 years (range 22-79) and a median follow-up time of 43 months (IQR 14-72). Median tumor size was 6.0 cm (range 2.6-11.5), 30% had a clinical FIGO stage ≥ IIIB and 42% had enlarged para-aortic LN. Cisplatin-based therapy was started in 86 patients (82%), of whom 30 (35%) switched to carboplatin and 47% of patients completed six cycles of platinum-based chemotherapy. All patients received external beam radiotherapy as planned, 98 patients (93%) underwent brachytherapy as planned or received an external boost, and 95 patients (90%) completed all five planned hyperthermia treatments. During cisplatin chemotherapy, 34 patients experienced AKI (39%). At last follow-up, 35% of patients had chronic renal toxicity (GFR 59 − 15/min/1.73 m 2 ). At presentation, a TEE was present in 10 (10%) and another 23 (22%) patients experienced a TEE (18% venous, 4% arterial) during chemotherapy. Five-year overall survival was 58% (95% CI 47.8-68.6 SE 0.053). Achieving a five-year overall survival of 58%, platinum-based induction chemotherapy followed by thermoradiotherapy is an effective treatment for advanced-stage high-risk cervical cancer. However, treatment is accompanied by an unacceptably high prevalence of chemotherapy-associated TEE and acute kidney injury, as well as chronic kidney disease. Future studies should investigate the role of carboplatin in reducing toxicity and the effect of thromboprophylaxis in high-risk patients.