Radiotherapy induced ureteric stenosis in locally advanced cervical cancer: A review of current evidence.

BACKGROUND: Concurrent chemo-radiation followed by high dose rate brachytherapy is the standard of care for locally advanced cervical cancer. The proximity of the ureters to the tumor volume risks ureteric stenosis. Here we outline the current understanding of radiotherapy induced ureteric stenosis in patients treated for cervical cancer, focusing on the incidence, risk factors, clinical consequences, and management. METHODS: Searches on EMBASE, PubMed, Science Direct, and Google Scholar were performed for publications reporting on radiotherapy, cervix cancer and ureteric stenosis. Multi and single center, prospective/retrospective, cohort, and cross-sectional studies were included. RESULTS: This narrative review identified key issues relevant to radiation induced ureteric stenosis in cervical cancer in the literature. Thirteen studies were evaluated, identifying crude and actuarial rates of ureteric stenosis of 0.3-13.5% and 1.5-4.4% (at 5 years) respectively. The risk of ureteric stenosis is highest in the first 5 years after radiotherapy but continues to occur at a rate of 0.15% per year. Risk factors including advanced FIGO stage, tumor size >5 cm and baseline hydronephrosis increase the incidence of ureteric stenosis. EQD2 doses of ≥ 77Gy were significantly associated with ≥grade 3 ureteric morbidity. The majority of patients were managed with nephrostomy +/- ureteric stent insertion, with some requiring ureteral reimplantation, urinary diversion or nephrectomy. CONCLUSIONS: This review has identified multiple considerations, highlighting the need to identify patients highest at risk of ureteric stenosis. There is also a need to recognize ureters as organs at risk, record dose exposure, and apply dose constraints, all of which set the landscape for allowing dose optimization.

Ureter dose optimization during image guided brachytherapy for cervical cancer.

PURPOSE: In the era of image guided radiotherapy and interstitial needle use, radiation dose to ureters can cause toxicity. METHODS: A retrospective analysis of 106 patients with cervical cancer was performed to investigate ureter dose in brachytherapy patients. Re-optimization of brachytherapy treatment plans in 20 MRI planned patients was performed to reduce ureter dose whilst maintaining HRCTV D90 and OAR dose constraints. RESULTS: A total of 212 ureters were contoured and dose recorded. The crude incidence of ureteric stenosis was 6.6%. Ureter dose for all patients was 75.8 Gy and 74.4 Gy on the right and left respectively. A cohort of 20 MRI planned patients were reoptimized to reduce dose to ureters. Ureter dose was reduced from 91.1 Gy to 84.4 Gy and 73.9 Gy to 67.8 Gy on the right and left side respectively. A subgroup of patients with HRCTV D90 ≥84.3 Gy prior to reoptimisation saw a greater reduction in ureter dose of 13.3%. These were smaller tumours with better HRCTV coverage at the outset. Larger tumours with poorer HRCTV coverage (<84.3 Gy) saw a smaller reduction in ureter dose of 6.4%. Organ at risk dose to rectum, sigmoid and bladder were also significantly reduced. CONCLUSIONS: Patients treated with MRI guided brachytherapy and interstitial needles are at risk of ureteric stenosis. Contouring ureters and setting dose constraints should be considered to reduce ureteric dose while tracking HRCTV coverage.

Stratified follow-up for endometrial cancer: a move to more personalized cancer care.

OBJECTIVE: Hospital based follow-up has been the standard of care for endometrial cancer. Patient initiated follow-up is a useful adjunct for lower risk cancers. The purpose of this study was to evaluate outcomes of endometrial cancer patients after stratification into risk groupings, with particular attention to salvageable relapses. METHODS: All patients treated surgically for International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA endometrial cancer of all histological subtypes, from January 2009 until March 2019, were analyzed. Patient and tumor characteristics, treatment details, relapse, death, and last follow-up dates were collected. Site of relapse, presence of symptoms, and whether relapses were salvageable were also identified. The European Society of Medical Oncology-European Society of Gynecological Oncology 2020 risk stratification was assigned, and relapse free and overall survival were estimated. RESULTS: 900 patients met the eligibility criteria. Median age was 66 years (range 28-96) and follow-up duration was 35 months (interquartile range 19-57). In total, 16% (n=144) of patients relapsed, 1.3% (n=12) from the low risk group, 3.9% (n=35) from the intermediate risk group, 2.2% (n=20) from the high-intermediate risk group, and 8.7% (n=77) from the high risk group. Salvageable relapses were less frequent at 2% (n=18), of which 33% (n=6) were from the low risk group, 22% (n=4) from the intermediate risk group, 11% (n=2) from the high-intermediate risk group, and 33% (n=6) from the high risk group. There were only three asymptomatic relapses in the low risk patients, accounting for 0.33% of the entire cohort. CONCLUSIONS: Relapses were infrequent and most presented with symptoms; prognosis after relapse remains favorable. Overall salvageable relapses were infrequent and cannot justify intensive hospital based follow-up. Use of patient initiated follow-up is therefore appropriate, as per the British Gynaecological Cancer Society's guidelines, for all risk groupings.

Feasibility of ureter delineation and dose recording in the assessment of ureteric stenosis during brachytherapy for cervical cancer.

INTRODUCTION: Ureteric stenosis is the commonest complication to affect the ureter after radiotherapy for cervical cancer; despite this ureters are not contoured as organs at risk and limited dosimetric data exist for them. METHODS/MATERIALS: Bilateral ureters were retrospectively delineated on brachytherapy planning imaging for patients treated for cervical cancer between 2014 and 2019. Ureteric stenosis toxicity data and D2cc, D1cc, D0.1cc of the right and left ureter were collated. Ureter V80, V100, V120, and V150 were also analyzed. Univariate analysis was performed to identify predictors of high ureter dose and ureteric stenosis. RESULTS: 95 patients were identified and 190 ureters contoured on brachytherapy planning imaging, with a median follow-up duration of 24 months (IQR23.7). 4.2% (4) of patients had grade 3/4 ureteric stenosis. Mean ureter D0.1cc, D1.0cc and D2.0cc on the right were 80.4Gy (±28.9), 56.2Gy (±7.2) and 52.8Gy (±7.6), and on the left were 75.6Gy (±14.6), 54.3Gy (±5.5) and 52.7Gy (±5.5) respectively. Significantly higher ureter doses were present in patients with baseline hydronephrosis (p < 0.002) and interstitial needle use (p = 0.047). Ureters affected by ureteric stenosis received D0.1cc doses between 60-98Gy. 10-14% received point doses in excess of 150% of the prescribed dose (7Gy) with no resulting ureteric stenosis. No significant difference in D0.1cc was found in patients with or without ureteric stenosis. CONCLUSIONS: It is feasible to accurately contour ureters on brachytherapy planning imaging. Baseline hydronephrosis and interstitial needle use contribute to higher ureter doses. No association between dose and ureteric stenosis was found.