Radiotherapy for Postsurgical Vaginal Recurrences of Cervical Squamous Cell Carcinoma: Analysis of Dosing and Prognosis

Background: This study aimed to investigate the efficacy of salvage radiotherapy for vaginal recurrence of cervical squamous carcinoma in patients who previously underwent surgery and to explore prognostic factors (particularly dose-related) associated with survival post-recurrence.Methods: Ninety-seven patients with histologically proven squamous cell carcinoma-subtype cervical cancer who were treated for vaginal recurrence at Peking Union Medical College Hospital between July 2011 and November 2019 were identified. All patients had previously undergone surgery for the primary tumor and received salvage external beam radiotherapy, brachytherapy, or both. Factors predictive of overall survival (OS), progression-free survival (PFS), and local control (LC) were investigated, as were adverse effects.Results: The median follow-up time was 42.5 months. The estimated 5-year OS, PFS, and LC rates were 84%, 79%, and 91%, respectively. On multivariate analysis, a tumor size ≤4 cm and an endovaginal recurrence pattern were associated with longer PFS (both P < 0.05); however, only the latter was predictive of a longer LC (P < 0.05). In the 33 patients with recurrences that were paravaginal or invasive of surrounding organs, biologically equivalent doses in 2 Gy fractions of ≥70 Gy were independently predictive of longer LC (P < 0.05). Finally, 12.4% of the patients experienced grades ≥2 late complications; only 1 patient who received EBRT alone experienced grade 5 late complications.Conclusions: RT is an effective treatment for post-surgical vaginal recurrence in patients with cervical squamous cell carcinoma. For patients with extravaginal recurrence, a salvage dose of ≥70 Gy appears to be optimal.

Clinical results of image-guided interstitial brachytherapy with or without external beam radiotherapy for postsurgical vaginal recurrence of cervical and endometrial cancers

Purpose This study aimed to evaluate the clinical outcome and efficacy of image-guided interstitial brachytherapy (ISBT) for postsurgical vaginal recurrence of cervical and endometrial cancers. Materials and methods The study included 11 patients who received CT-based image-guided high-dose-rate ISBT with or without external beam radiotherapy (EBRT). Local control, progression-free survival, and treatment-related toxicities were evaluated retrospectively. Results Of the 11 patients, 4 underwent ISBT with EBRT and the other 7 ISBT alone; two of the latter patients received previous pelvic radiotherapy. After a median follow-up of 43.9 months (range 3.9–92.7 months), the 2-year local control rate was 100%. The median equivalent doses in 2 Gy fractions received by at least 90% of the clinical target volume for ISBT with versus without EBRT were 82.2 Gy (range 60.4–84.2 Gy) versus 69.0 Gy (range 50.8–98.2 Gy). The 2-year progression-free survival rates after ISBT with versus without EBRT were 75% versus 80%, and the difference was not significant (p = 0.74). Grade 3 late toxicities occurred in two patients. Conclusion Our radiotherapy strategy using image-guided ISBT, either with or without EBRT, for postsurgical vaginal recurrence showed effective treatment outcomes.

Ultrastaging of ‘negative’ pelvic lymph nodes in patients with low- and intermediate-risk endometrioid endometrial cancer who developed non-vaginal recurrences

ObjectiveEvidence on micrometastases and isolated tumor cells as factors associated with non-vaginal recurrence in low- and intermediate-risk endometrial cancer is limited. The goal of our study was to investigate risk factors for non-vaginal recurrence in low- and intermediate-risk endometrial cancer.MethodsRecords of all patients with endometrial cancer surgically managed at the Mayo Clinic before sentinel lymph node implementation (1999–2008) were reviewed. We identified all patients with endometrioid low-risk (International Federation of Gynecology and Obstetrics (FIGO) stage I, grade 1 or 2 with myometrial invasion <50% and negative peritoneal cytology) or intermediate-risk (FIGO stage I, grade 1 or 2 with myometrial invasion ≥50% or grade 3 with myometrial invasion <50% and negative peritoneal cytology) endometrial cancer at definitive pathology after pelvic and para-aortic lymph node assessment. All pelvic lymph nodes of patients with non-vaginal recurrence (any recurrence excluding isolated vaginal cuff recurrences) underwent ultrastaging.ResultsAmong 1303 women, we identified 321 patients with low-risk (n=236) or intermediate-risk (n=85) endometrial cancer (median age 65.4 years; 266 (82.9%) stage IA; 55 (17.1%) stage IB). Of the total of 321, 13 patients developed non-vaginal recurrence (Kaplan–Meier rate 4.7% by 60 months; 95% CI 2.1% to 7.2%): 11 hematogenous/peritoneal and two para-aortic and distant lymphatic. Myometrial invasion and lymphovascular space invasion were univariately associated with non-vaginal recurrence. In these patients, the original hematoxylin/eosin slides review confirmed all 646 pelvic and para-aortic removed lymph nodes as negative. The ultrastaging of 463 pelvic lymph nodes did not identify any occult metastases (prevalence 0%; 95% CI 0% to 22.8% considering 13 patients; 95% CI 0% to 0.8% considering 463 pelvic lymph nodes).ConclusionThere were no occult metastases in pelvic lymph nodes of patients with low- or intermediate-risk endometrial cancer with non-vaginal recurrence. Myometrial invasion and lymphovascular space invasion appear to be associated with non-vaginal recurrence.

Definitive radiotherapy for vaginal recurrence of early-stage endometrial cancer: survival outcomes and effect of mismatch repair status

ObjectiveTo evaluate clinical outcomes, prognostic factors, and toxicity in patients with vaginal recurrence of early-stage endometrial cancer treated with definitive radiotherapy.MethodsRetrospective review identified 62 patients with stage I–II endometrial cancer and vaginal recurrence treated with external beam radiotherapy and image-guided brachytherapy with definitive intent from November 2004 to July 2017. All patients had prior hysterectomy without adjuvant radiotherapy and >3 months follow-up. Mismatch repair (MMR) status was determined by immunohistochemical staining of the four mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6) when available in the pathology record. Rates of vaginal control, recurrence-free survival, and overall survival were calculated by Kaplan–Meier. Univariate and multivariate analyses were performed by Cox proportional hazards.ResultsMost patients had endometrioid histology (55, 89%), grade 1 or 2 tumor (53, 85%), and vaginal-only recurrence (55, 89%). With a median follow-up of 39 months (range, 3–167), 3- and 5-year rates of vaginal control, recurrence-free survival, and overall survival were 86% and 82%, 69% and 55%, and 80% and 61%, respectively. On multivariate analysis, non-endometrioid histology (HR 12.5, P<0.01) was associated with relapse when adjusted for chemotherapy use. Patients with non-endometrioid histology also had a 4.5-fold higher risk of death when adjusted for age (P=0.02). Twenty patients had known MMR status, all with grade 1–2 endometrioid tumors and 10 (50%) with MMR deficiency. The 3-year recurrence-free survival was 100% for MMR-proficient tumors and 52% for MMR-deficient (P=0.03). Late grade 2 and 3 gastrointestinal, genitourinary and vaginal toxicity was reported in 27% and 3%, 15% and 2%, and 16% and 2% of patients, respectively.ConclusionDefinitive radiotherapy with image-guided brachytherapy resulted in 5-year local control rates exceeding 80% and late severe toxicity rates were under 3%. Distant recurrence was common and highest for those with grade 3 or non-endometrioid tumors and MMR deficient grade 1–2 disease.

Vaginal metastasis in solid tumours: our four cases and review of the literature

Background Vaginal metastasis should be kept in mind when evaluating the staging tests of all cancers, especially endometrial cancer. Case presentation We present four patients with vaginal recurrence who recently applied to our clinic. Three cases were of endometrial cancer and one case of rectal cancer. All patients presented with vaginal bleeding. Conclusion Standard treatment for vaginal metastasis has not yet been established. Therapeutic options for vaginal metastasis—separately or in combination—are surgical resection, radiotherapy, and chemotherapy.

A prospective multicenter international single-arm observational study on the oncological safety of the sentinel lymph node algorithm in stage I intermediate-risk endometrial cancer (SELECT, SEntinel Lymph node Endometrial Cancer Trial)

BackgroundIn the primary treatment of apparent uterine-confined endometrial carcinoma, pelvic ± para-aortic lymphadenectomy has been considered the standard of care. Although some retrospective data suggest that the sentinel lymph node algorithm without complete lymphadenectomy can be used without jeopardizing oncologic outcome, prospective data are lacking.Primary ObjectivesTo assess the 36 month incidence of pelvic/non-vaginal recurrence in women with pathologically confirmed stage I intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes.Study HypothesisWe hypothesize that patients with stage I, intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes will demonstrate a pelvic/non-vaginal recurrence rate comparable to historical estimate of stage I, intermediate-risk endometrioid endometrial carcinoma patients (estimated 2.5%).Trial DesignThis prospective multicenter single-arm observational study will follow women with stage I, intermediate risk endometrioid endometrial adenocarcinoma who have undergone successful hysterectomy, bilateral salpingo-oophorectomy, and bilateral sentinel lymph node biopsies, for recurrence. All patients will undergo lymphatic mapping using indocynanine green and will either receive no adjuvant treatment or vaginal brachytherapy only. Patients will be followed for 36 months.Major Inclusion/Exclusion CriteriaPatients will be enrolled in the study cohort if all the following criteria are met: (i) at time of surgery: hysterectomy with bilateral adnexectomy, and successful bilateral pelvic sentinel lymph node mapping; (ii) on final pathology: pathologic stage I, intermediate-risk endometrioid endometrial carcinoma (grade 1 or grade 2 with ≥50% myometrial invasion, or grade 3 with <50% myometrial invasion), negative pelvic peritoneal cytology, and bilateral sentinel lymph nodes negative for malignancy; (iii) recommended adjuvant treatment: vaginal brachytherapy or no adjuvant treatment.Primary EndpointIncidence of pelvic/non-vaginal recurrence at 36 months.Sample Size182 patients for study cohortEstimated Dates for Completing Accrual and Presenting ResultsAccrual will be completed in 2023 with results reported in 2026.Trial RegistrationNCT04291612