Is Substantial Lymphovascular Space Invasion Prognostic for Clinical Outcomes in Type II Endometrial Cancer?

AIMS: Substantial lymphovascular space invasion (LVSI) compared with none or focal LVSI is predictive of lymph node involvement and worse clinical outcomes in endometrioid-type endometrial carcinoma. We aimed to quantify the incidence of substantial LVSI in type II (clear cell and serous) endometrial cancer and correlate the extent of LVSI with clinical outcomes. MATERIALS AND METHODS: A retrospective review was conducted on type II endometrial cancer patients who underwent surgical management from July 2017 to December 2019 using the three-tier LVSI scoring system. Binary logistic regression and Cox regression were used to analyse predictors of lymph node involvement or survival outcomes, respectively. The Kaplan-Meier method and Log-rank test were used to analyse differences in locoregional disease-free survival (LR-DFS), distant metastasis disease-free survival (DM-DFS) and overall survival between patients with substantial versus none/focal LVSI. RESULTS: In 79 patients with type II endometrial carcinoma, no LVSI, focal LVSI and substantial LVSI was present in 48.1%, 15.2% and 36.7% of patients, respectively. Lymph nodes were involved in 0.0% with no LVSI, 20.0% with focal LVSI and 60.0% with substantial LVSI (P < 0.001). The median follow-up was 22.2 months. In patients with none/focal versus substantial LVSI, the 2-year LR-DFS and DM-DFS rates were 91.5% versus 71.4% (P = 0.01) and 90.2% versus 63.8% (P = 0.005), respectively. On univariate analysis, myometrial invasion ≥50%, tumour size ≥3.6 cm, substantial versus none/focal LVSI, lymph node involvement and omission of adjuvant radiotherapy were significant predictors for worse LR-DFS and DM-DFS (P < 0.05). DISCUSSION: Substantial LVSI has a high incidence in type II pathology at our institution and predicts for lymph node involvement and worse clinical outcomes.

Regional Control and Chemoradiotherapy Dose Response for Clinically Involved Lymph Nodes in Patients with Locally Advanced Endometrial Cancers Who are Not Candidates for Upfront Surgical Staging Extrafascial Hysterectomy.

AIMS: There are limited data in endometrial cancer for nodal control and appropriate treatment volume for non-surgically resected nodes treated with chemoradiotherapy (CRT) for patients who are not candidates for upfront extrafascial hysterectomy. MATERIALS AND METHODS: Patients (n = 105) with clinical stage ≥ II endometrial cancer who were not candidates for upfront extrafascial hysterectomy treated with preoperative CRT were retrospectively reviewed. CRT included pelvic nodes to the common iliac for node-negative disease and para-aortic nodes to the renal vessel for any node-positive disease. Involved nodes most commonly received a boost of 55 Gy in 25 fractions ± additional 4-6 Gy sequential boost for nodes >2 cm. RESULTS: Of the included 95 patients, 55 patients were node positive, with a total of 300 positive nodes. At a median follow-up of 25 months (interquartile range 9-46), the 3-year regional control was 91%. The 3-year involved nodal control rate was 96%. Involved nodal control was significantly higher in type I histology, nodes <2 cm and by radiation dose (75% for <55 Gy, 98% for 55 Gy in 25 fractions and 89% for >55 Gy, P = 0.03). The 3-year para-aortic failure rate for node negative patients treated with pelvis-only CRT was significantly higher with positron emission tomography/computed tomography (PET/CT) versus computed tomography (CT)-based staging (0% versus 20%). CONCLUSION: This is the largest study examining regional control rates of involved lymph nodes with CRT for patients who were not candidates for upfront extrafascial hysterectomy. Nodal failure was low following CRT and dose ≥55 Gy in 25 fractions seems to be adequate for involved nodes.

Early outcomes after definitive chemoradiation therapy with Vienna/Venezia hybrid high-dose rate brachytherapy applicators for cervical cancer: A single-institution experience.

PURPOSE: The Vienna and Venezia (Elekta) are hybrid intracavitary/interstitial brachytherapy (BT) applicators for cervical cancers unsuitable for intracavitary BT alone to improve target coverage or reduce critical organ dose. There is limited outcome data with the use of these applicators outside published experience of the EMBRACE group. We report feasibility and early outcomes with the use of these hybrid applicators at our institution. METHODS AND MATERIALS: Hybrid applicators were used to treat 61 patients with cervical cancer from November 2011 to December 2019. Indications for hybrid applicator use were involvement of the vagina in 10 patients (16%), residual central or parametrial disease in 46 patients (75%), and a narrow introitus in 5 patients (9%). Toxicities were graded using the CTCAE v4.0. Outcomes were assessed with the Kaplan-Meier method. RESULTS: Median follow-up was 16 months (IQR 9-32 mos). Median HRCTV volume was 31.6 cm3 (IQR 25-48 cm3). Median HRCTV D90 was 86.1 Gy (IQR 84.3-88.0 Gy). In 54 patients with follow-up PET/CT at 3 months, complete initial imaging response locally was seen in 46 patients.Estimated 12-month Kaplan-Meier overall survival, locoregional control, distant control, and recurrence-free survival estimates were 86.9%, 80.6%, 73.8%, and 65.9%, respectively. The 12-month incidence of Grade 3+ GI/GU chronic toxicities was 5.7%, consisting of vesicovaginal fistula, rectovaginal fistula, and ureterovesical fistula. CONCLUSIONS: Our single-institution data support the use of the hybrid applicators, as an alternative to traditional BT applicators when clinically warranted. Use of hybrid applicators is feasible with adequate coverage of disease in the vagina and parametrium.

Is the risk of substantial LVSI in stage I endometrial cancer similar to PORTEC in the North American population? - A single-institution study.

OBJECTIVES: A pooled analysis of PORTEC-1 & 2 identified substantial lymphovascular space invasion (LVSI) in 4.8% of patients, which predicted for pelvic recurrence, distant metastasis, and overall survival. Our institution implemented the PORTEC three-tier system of LVSI reporting (absent, focal, or substantial). We aimed to quantify the incidence of substantial LVSI in a North American population and to correlate extent of LVSI with lymph node (LN) involvement. METHODS: A retrospective review was conducted on patients with clinically uterine-confined, endometrioid type endometrial cancer who underwent surgical staging and were found to have pT1a-b disease. Binary logistic regression was used to assess predictors of LN involvement (defined as ITC, micrometastases, or macrometastases). RESULTS: In total, 438 patients with pT1a-b disease were identified. In the overall cohort and in the subset meeting PORTEC-1 inclusion criteria (n = 195), no LVSI was present in 67.4% and 50.8%; focal LVSI was present in 16.7% and 24.1%; and substantial LVSI was present in 16.0% and 25.1%, respectively. Among patients who underwent surgical LN assessment (79.2%, n = 347), LNs were involved in 3.3% without LVSI, 7.5% with focal LVSI (OR 2.4), and 15.2% with substantial LVSI (OR 5.3) (p = .005), with a similar trend in the PORTEC-1 cohort. Extent of LVSI correlated with disease burden in LN metastases. CONCLUSION: Our incidence of substantial LVSI was three to five times higher than reported by PORTEC and correlated with LN involvement. This questions the reproducibility of the three-tier LVSI reporting system and emphasizes the need for multi-institutional data outside PORTEC for confirmation of our findings.

Stage II Testicular Seminoma: Patterns of Care and Survival by Treatment Strategy.

AIMS: Stage II testicular seminoma is highly curable with radiotherapy or multi-agent chemotherapy (MACT). These modalities have not been compared in a randomised manner. MATERIALS AND METHODS: Using the US National Cancer Data Base, we identified 2437 stage II seminoma patients (IIA = 960, IIB = 812, IIC = 665) treated with orchiectomy and either radiotherapy or MACT from 1998 to 2012. Factors affecting treatment modality (radiotherapy versus MACT) were studied using multivariable logistic regression. Propensity scores for treatment selection were incorporated into multivariable Cox regression analyses of overall survival. RESULTS: The median follow-up was 65 months (interquartile range 34-106). Rates of radiotherapy utilisation were: IIA = 78.1%, IIB = 54.4%, IIC = 4.2%. Rates of MACT utilisation were: IIA = 21.9%, IIB = 45.6%, IIC = 95.8%. For both IIA and IIB patients, later year of diagnosis, academic treatment facility and pathological confirmation of lymph node positivity were associated with increased utilisation of MACT. Also predictive for preferential utilisation of MACT were comorbidity score ≥ 1 and non-private insurance for IIA patients and T stage ≥ 2 for IIB patients. For IIA patients, survival was improved with radiotherapy compared with MACT with a 5 year survival of 99.0% (95% confidence interval 98.2-99.8) versus 93.0% (95% confidence interval 89.0-97.0). This advantage persisted on propensity-adjusted multivariate analysis (hazard ratio 0.28; 95% confidence interval 0.09-0.86; P = 0.027). For IIB patients, 5 year survival was 95.2% (95% confidence interval 92.8-97.6) for radiotherapy and 92.4% (95% confidence interval 89.2-95.6) for MACT (Log-rank P = 0.041), with no significant difference on multivariable analysis. CONCLUSIONS: Radiotherapy is associated with improved survival over MACT for IIA patients, with no significant survival difference for IIB patients.

Dural venous sinus thrombosis in anaplastic astrocytoma following concurrent temozolomide and focal brain radiotherapy plus bevacizumab.

Malignant gliomas have long been a therapeutic dilemma in neuro-oncology, with a poor overall prognosis. Standard treatment, consisting of primary resection, followed by radiation therapy and temozolomide, has improved prognosis. Recently, studies have looked at the addition of bevacizumab (Avastin), a humanized murine IgG1 monoclonal antibody against vascular endothelial growth factor-A, to conventional regiments. Bevacizumab gained US FDA approval for single agent use in recurrent glioblastoma in 2009. Known side effects of bevacizumab include increased risk of arterial and venous thromboembolism, as well as hemorrhage. With emerging data for the use of bevacizumab in malignant gliomas, the extent of risks such as bleeding and thrombosis in patients with primary brain tumors treated with bevacizumab remains unknown. Here, we present only the second reported case of dural venous sinus thrombosis during treatment with bevacizumab and the first reported case for a primary glioma treated with temozolomide, radiation, and bevacizumab.