Lucas Gomes Sapienza

Outcomes and toxicity after salvage radiotherapy for vaginal relapse of endometrial cancer

Studies of salvage radiotherapy in locally recurrent endometrial cancer remain limited. The aim of this study was to evaluate the efficacy of salvage radiotherapy for vaginal relapse of endometrial cancer and to explore prognostic factors associated with outcomes. We evaluated 30 patients treated with salvage external-beam radiotherapy and/or vaginal brachytherapy for vaginal relapses of endometrial cancer between 2009 and 2018. The inclusion criteria were: pathologically-confirmed recurrence; loco-regional relapse (in absence of distant metastases); and salvage treatment including external-beam radiotherapy and/or vaginal brachytherapy. Outcomes were evaluated via Kaplan-Meier, with the log-rank test employed to compare differences among various groups and identify prognostic factors. 30 patients developed vaginal recurrence at a median time of 20.6 months (range 2-219) post-hysterectomy. The most common site of recurrence was the vaginal apex (60%), followed by the distal vagina (10%). Salvage radiotherapy entailed combination external-beam radiotherapy and vaginal brachytherapy (n=24) or single modality treatment (n=6), along with concurrent chemotherapy in 20 cases. At a median follow-up of 4.4 years (range 0.1-130) post-radiotherapy, the 5 year rates of local control, regional control, metastasis-free interval, disease-free interval, and overall survival were 89%, 91.5%, 75.5%, 69%, and 83%, respectively. Factors associated with improved disease-free interval included: endometrioid histology (p=0.03), isolated vaginal relapse (p=0.003), late recurrence (>9 months) (p=0.007), and combined modality radiotherapy (p=0.001). The only factor associated with overall survival was isolated vaginal relapse (in the absence of other recurrent disease) (p=0.02). Regarding toxicity, 18% of patients experienced acute grade ≥3 events (most commonly gastrointestinal). The 5 year rates of rectal bleeding, small bowel obstruction, and pelvic fracture were 31%, 18%, and 13%, respectively. Salvage radiotherapy imparts excellent loco-regional control for vaginal relapses of endometrial cancer and should entail combination external-beam radiotherapy and vaginal brachytherapy. Patients should be closely monitored for late gastrointestinal toxicity following salvage radiotherapy.

A Systematic Study on Local Failure Events Post Chemoradiation Therapy for Cervical Cancer: Understanding the Impact of Baseline Lateral Anatomic Compartment Involvement

To dissect the local failure (LF) events, including specific rates by anatomic compartments, after definitive chemoradiation therapy for locally advanced cervical cancer. Records of all consecutive women with locally advanced cervical cancer treated with definitive chemoradiation therapy and image guided adaptive brachytherapy were reviewed, focusing on the local disease status. No patient received external beam radiation therapy parametrial boost. Incidence estimations, timing analysis (true persistence [TP]) versus new recurrence [NR]), calculations of LF rates by anatomic compartments (at the time of LF detection), and test of association of compartment-specific LF with baseline (at diagnosis) involvement (adjusted odds ratio [aOR]), were performed. Among the 225 patients included (75% International Federation of Gynecology and Obstetrics [FIGO] III-IV; 32% intracavitary/interstitial brachytherapy use; median follow-up 46.2 months), 34 LFs occurred (24 TP; 10 NR), involving 92 anatomic compartments. Isolated LF was the first relapse in 55.9% (19/34), with no events after 3 years, resulting in 6.2% 3-year/5-year overall NR and 16.3% 3-year/5-year overall LF (NR + TP) rates. TP had worse survival compared to NR (2 year overall survival: 19.1% vs 72.9%, P = .04). The most involved compartments were the cervix (79.4%), parametrium (PMT) (61.8%), uterine corpus (33.3%), bladder (14.7%), vagina (11.8%), and mesorectum (2.9%). Recurrence followed the cardinal ligament (CL), uterosacral ligament, and pubocervical ligament directions in 58.8%, 35.3%, and 23.5% of cases, respectively. Only 2 intact PMT at diagnosis developed ipsilateral LF (1.1%, 2/181, CL only), whereas baseline ipsilateral PMT involvement with hydronephrosis was associated with ipsilateral LF (aOR 22.2, P 60%) after the cervix (80%). An intact baseline PMT has a low frequency (1%) and limited extension (CL only) of ipsilateral failure. In contrast, baseline hydronephrosis is strongly associated with extensive ipsilateral PMT relapse, requiring side-specific treatment intensification.

Understanding Hydronephrosis Occurrence by an Individual-Kidney Level Analysis of all Events Postchemoradiation Therapy for Locally Advanced Cervical Cancer

Hydronephrosis is a complex renal abnormality that requires assessment of individual-kidney status at different times for correct interpretation of the mechanism of damage. This study analyzes all hydronephrosis events in women with locally advanced cervical cancer. The status of 449 kidneys from 225 women treated with external beam radiation therapy (RT) with concurrent cisplatin and image guided adaptive brachytherapy were retrospectively reviewed. Hydronephrosis incidence, causes (including radiation-induced hydronephrosis [RIH]), associated factors, and resolution rates were analyzed. Univariable and multivariable analyses were performed at the individual-kidney level, clustered by individual patient. At baseline, 10.9% (49/449) of the kidneys were affected by hydronephrosis, which resolved in 38.8% (19/49) after RT. During follow-up, new hydronephrosis occurred in 15.8% (71/419) of the kidneys, caused more frequently by cancer recurrence than by RIH (2:1 ratio). The overall RIH incidence per kidney was 5.7% (95% CI, 3.2-8.1) and 7.2% (95% CI, 3.8-10.4) at 3 and 5 years, respectively. The rates of type A RIH (ureteral stenosis) at 3 and 5 years were 1.9% (95% CI, 0.5-3.3) and 3.5% (95% CI, 0.8-6.2). Both 3- and 5-year rates of type B RIH (damage to structures other than ureter) were 3.8% (95% CI, 1.7-5.9). Point A dose (P = .01; EQD2 Persistent hydronephrosis is not uncommon after definitive RT for locally advanced cervical cancer (20%), with RIH being a relevant etiology at 5 years (7%). In contrary to type B RIH (damage to other structures), type A (ureteral damage) is usually unilateral, associated with dose to the ipsilateral point A, and its incidence does not plateau over time.

US-guided versus US-assisted tandem insertion for cervical cancer: A nomenclature proposal