Evaluation of Surgical Approaches and Use of Adjuvant Radiotherapy with Respect to Oncologic Outcomes in the Management of Clinically Early-Stage Cervical Carcinoma.

The standard of care for early-stage cervix cancer is radical hysterectomy with pelvic lymphadenectomy. Adjuvant radiotherapy (RT) or chemoradiotherapy may be administered to reduce the risk of recurrence in patients considered to be at elevated risk based on a combination of pathologic factors. We performed a retrospective review to determine oncologic outcomes in patients treated for early-stage cervix cancer and to determine if surgical approach impacted oncologic outcomes or the decision to use adjuvant therapy. In total, 174 women underwent radical hysterectomy and pelvic lymphadenectomy over the 15-year period. Most of these women (146) had open surgery and 28 had minimally invasive surgery (MIS). In total, 81 had adjuvant pelvic RT; 76 in the open surgery group (52%) and 5 in the MIS group (18%). Five-year PFS and OS, respectively, were 84% and 91%. Five-year PFS was significantly lower in patients who had MIS vs. open surgery, without a difference in 5-year OS, suggesting MIS should be avoided. Five-year PFS was the same with RT or with its omission, despite those treated with RT having higher risk disease. We have demonstrated excellent outcomes in patients with early-stage cervix cancer after primary surgery and selective use of RT, with few recurrences and excellent survival.

Treatment of Early Stage High-Risk Endometrioid-Type Endometrial Cancer and Patterns of Disease Relapse: A Retrospective Analysis.

PURPOSE: A recently published randomized controlled trial has demonstrated that in patients with endometrial cancer with high-risk features, the addition of chemotherapy to radiation therapy, compared with radiation therapy alone, resulted in a significant improvement in failure-free survival. However, in the study, the effect of chemotherapy was limited to stage III patients, and the benefit was less pronounced in stage I and II patients. Our study aims to investigate the current practice of treatment and clinical outcomes in stage I high-risk endometrioid-type endometrial cancer. METHODS AND MATERIALS: A single-center retrospective study was conducted on patients with stage I high-risk endometrioid-type endometrial cancer without serous or clear cell features who have undergone hysterectomy between 1998 and 2015. Data on patients, tumor, and treatments were collected and correlated with clinical outcomes. RESULTS: A total of 1,572 patients with stage I disease were identified and 46 patients who met the inclusion criteria were selected for final analysis. The median age at diagnosis was 63 years (range, 49-86 years) and median follow-up was 5.9 years. Among the entire cohort, 40 (87.0%) patients underwent adjuvant radiation therapy, of which 36 (78.2%) patients underwent external beam radiation therapy and 4 (8.7%) patients underwent vaginal brachytherapy. Two of the 40 patients who received adjuvant radiation therapy also received adjuvant chemotherapy. Six (13.0%) patients received no adjuvant treatment. Of the 46 patients, the cumulative risk of distant recurrence was 19.6%, and only 1 patient (2.2%) recurred within pelvis (perirectal lymph node). Five-year disease-free survival and overall survival rates were 73.1% and 80.1%, respectively. CONCLUSIONS: Adjuvant radiation therapy in stage I endometrioid-type endometrial cancer patients with high-risk features resulted in high rates of locoregional disease control, and most recurrences occurred at distant sites. Effective systemic therapy may be indicated in this patient population to further reduce the risk of distant relapses and improve survival.

A comparison of disease recurrence between robotic versus laparotomy approach in patients with intermediate-risk endometrial cancer.

OBJECTIVE: Advances in minimally invasive surgery, particularly with robotic surgery, have resulted in improved peri-operative outcomes in patients with endometrial cancer. In addition, randomized trials have shown that addition of adjuvant radiotherapy following surgery improves loco-regional disease control among stage I intermediate-risk endometrial cancer patients. We aimed to investigate the efficacy and safety of combined treatment of robotic surgery and adjuvant radiotherapy in this patient population. METHODS: A single-center retrospective study was conducted on stage I endometrioid-type endometrial cancer patients with intermediate-risk features (<50% myometrial involvement and grade 2-3 histopathology, or >50% myometrial involvement and grade 1-2 histopathology) treated with hysterectomy and adjuvant radiotherapy between January 2010 and December 2015. Data on surgery and radiotherapy were collected and correlated with clinical and surgical outcomes using log-rank. Oncologic outcomes were then compared between robotic surgery and laparotomy. RESULTS: A total of 179 intermediate-risk endometrial cancer patients were identified, of whom 135 (75.4%) received adjuvant radiotherapy and were included in the final analysis. Median age at diagnosis was 63 years (range 40-89) and median follow-up was 4.7 years (range 1.1-8.8). Seventy-seven patients (57%) underwent robotic surgery and 58 patients (43%) underwent laparotomy. Surgical staging with lymph node dissection was performed on 79.3% of the patients. The majority of patients (79.3%) received vaginal brachytherapy as part of adjuvant radiotherapy, while 20.7% received external-beam radiotherapy. Among the entire cohort, eight (5.9%) patients recurred and all eight recurrences occurred in the robotic surgery group; no recurrence was found in the laparotomy group. This translated into 5 year disease-free survival of 100% in the laparotomy group, compared with 91.8% in the robotic surgery group (p=0.005). No difference in overall survival was found between the two groups (p=0.51). CONCLUSION: Oncologic outcomes for stage I intermediate-risk endometrial cancer treated with hysterectomy and adjuvant radiotherapy at our institution are comparable to the previously published literature. The higher recurrence rate observed with robotic surgery at our institution has not been observed previously and requires further investigation.

Subsets of women with close or positive margins after breast-conserving surgery with high local recurrence risk despite breast plus boost radiotherapy.

PURPOSE: (1) To examine the effect of surgical margin status on local recurrence (LR) and survival following breast-conserving therapy; (2) To identify subsets with close or positive margins with high LR risk despite whole breast radiotherapy (RT) plus boost. METHODS AND MATERIALS: Subjects were 2,264 women with pT1-3, any N, M0 invasive breast cancer, treated with breast-conserving surgery and whole breast ± boost RT. Five-year Kaplan-Meier (KM) LR, breast cancer-specific and overall survival (BCSS and OS) were compared between cohorts with negative (n = 1,980), close (n = 222), and positive (n = 62) margins. LR rates were analyzed according to clinicopathologic characteristics. Multivariable Cox regression modeling and matched analysis of close/positive margin cases and negative margin controls were performed. RESULTS: Median follow-up was 5.2 years. Boost RT was used in 92% of patients with close or positive margins. Five-year KM LR rates in the negative, close and positive margin cohorts were 1.3%, 4.0%, and 5.2%, respectively (p = 0.001). BCSS and OS were similar in the three margin subgroups. In the close/positive margin cohort, LR rates were 10.2% with age <45 years, 11.8% with Grade III, 11.3% with lymphovascular invasion (LVI), and 26.3% with ≥4 positive nodes. Corresponding rates in the negative margin cohort were 2.3%, 2.4%, 1.0%, and 2.4%, respectively. On Cox regression analysis of the entire cohort, close or positive margin, Grade III histology, ≥4 positive nodes, and lack of systemic therapy were significantly associated with higher LR risk. When close/positive margin cases were matched to negative margin controls, the difference in 5-year LR remained significant (4.25% vs. 0.7%, p < 0.001). CONCLUSIONS: On univariable analysis, subsets with close or positive margins, in combination with age <45 years, Grade III, LVI, and ≥4 positive nodes, have 5-year LR >10% despite whole breast plus boost RT. These patients should be considered for more definitive surgery.

Ten-year locoregional recurrence risks in women with nodal micrometastatic breast cancer staged with axillary dissection.

PURPOSE: To compare the locoregional recurrence (LRR) rates in patients with nodal mirometastases (pNmic) with those in patients with node-negative (pN0) and macroscopic node-positive (pNmac) breast cancer; and to evaluate the LRR rates according to locoregional treatment of pNmic disease. METHODS AND MATERIALS: The subjects were 9,616 women diagnosed between 1989 and 1999 with Stage pT1-T2, pN0, pNmic, or pNmac, M0 breast cancer. All women had undergone axillary dissection. The Kaplan-Meier local recurrence, regional recurrence, and LRR rates were compared among those with pN0 (n=7,977), pNmic (n=490) and pNmac (n=1,149) and according to locoregional treatment. Multivariate analysis was performed to identify the significant factors associated with LRR. RESULTS: The median follow-up was 11 years. The 10-year Kaplan-Meier recurrence rate in the pN0, pNmic, and pNmac cohorts was 6.1%, 6.8%, and 8.7% for local recurrence; 3.1%, 6.2%, and 10.3% for regional recurrence; and 8.0%, 11.6%, and 15.2% for LRR, respectively (all p<.001). In the pNmic patients, the 10-year regional recurrence rate was 6.4% with breast-conserving surgery plus breast radiotherapy (RT), 5.4% with breast-conserving surgery plus locoregional RT, 4.6% with mastectomy alone, 11.1% with mastectomy plus chest wall RT, and 10.7% with mastectomy plus locoregional RT. In patients with pNmic disease and age<45 years, Grade 3 histologic features, lymphovascular invasion, nodal ratio>0.25, and estrogen receptor-negative disease, the 10-year LRR rates were 15-20%. On multivariate analysis of the entire cohort, pNmic was associated with greater LRR than Stage pN0 (hazard ratio [HR], 1.6; p=.002). On multivariate analysis of pNmic patients only, age<45 years was associated with significantly greater LRR (HR, 1.9; p=.03), and trends for greater LRR were observed with a nodal ratio>0.25 (HR, 2.0; p=.07) and lymphovascular invasion (HR, 1.7; p=.07). CONCLUSION: Women with pNmic had a greater risk of LRR than those with pN0 disease. Patients with pNmic in association with young age, Grade 3 histologic features, lymphovascular invasion, nodal ratio>0.25, and estrogen receptor-negative disease experienced 10-year LRR rates of ∼15-20%, warranting consideration of locoregional RT.

Adjuvant carboplatin and paclitaxel chemotherapy interposed with involved field radiation for advanced endometrial cancer.

OBJECTIVE: To evaluate recurrence and survival associated with adjuvant carboplatin and paclitaxel chemotherapy interposed with involved field radiation for advanced endometrial cancer. METHOD: This is a prospective cohort study of women with Stage III and IV endometrial cancer treated at a single institution between April 2002 and July 2006. Adjuvant therapy consisted of 4 cycles of intravenous paclitaxel (175 mg/m(2)) and carboplatin (350 mg/m(2)) every 3 weeks, followed by external beam radiotherapy (RT) to the pelvis (45 Gy), then another 2 cycles of chemotherapy. Para-aortic RT and/or HDR vault brachytherapy were added at the discretion of the treating physician. Toxicity of this protocol was previously reported. Primary endpoints for this study were disease-free and overall survival rates. RESULTS: Forty-three patients with a median age of 64 years (46-83 years) were evaluated. The majority had Stage IIIC disease (63%), and the most common histology was serous carcinoma (49%). Six cycles of combination chemotherapy were completed in 81%, and all patients completed pelvic RT. Median follow-up was 30 months (9-71 months). Twenty-one patients (49%) recurred at a median of 17 months (7-62 months). There were only 3 local recurrences, including 2 in the pelvis and 1 in the vagina/vulva. Median disease-free survival (DFS) was 50 months and median overall survival (OS) has not been reached. Three year DFS and OS rates were 53% and 68%, respectively. CONCLUSION: Adjuvant carboplatin and paclitaxel chemotherapy interposed with involved field radiation is associated with a low rate of local recurrence and favorable survival for advanced endometrial cancer.

Adjuvant paclitaxel and carboplatin chemotherapy with involved field radiation in advanced endometrial cancer: a sequential approach.

PURPOSE: To determine the feasibility of adjuvant paclitaxel and carboplatin chemotherapy interposed with involved field radiotherapy for women with advanced endometrial cancer. METHODS AND MATERIALS: This was a prospective cohort study of women with Stage III and IV endometrial cancer. Adjuvant therapy consisted of 4 cycles of paclitaxel (175 mg/m(2)) and carboplatin (350 mg/m(2)) every 3 weeks, followed sequentially by external beam radiotherapy (RT) to the pelvis (45 Gy), followed by an additional two cycles of chemotherapy. Para-aortic RT and/or HDR vault brachytherapy (BT) were added at the discretion of the treating physician. RESULTS: Thirty-three patients (median age, 63 years) received treatment between April 2002 and June 2005. Median follow-up was 21 months. Stage distribution was as follows: IIIA (21%), IIIC (70%), IVB (9%). Combination chemotherapy was successfully administered to 30 patients (91%) and 25 patients (76%), before and after RT respectively. Nine patients (27%) experienced acute Grade 3 or 4 chemotherapy toxicities. All patients completed pelvic RT; 19 (58%) received standard 4-field RT and 14 (42%) received intensity-modulated radiotherapy. Ten (30%) received extended field radiation. Four patients (12%) experienced acute Grade 3 or 4 RT toxicities. Six (18%) patients developed chronic RT toxicity. There were no treatment-related deaths. Two-year disease-free and overall survival rates were both 55%. There was only one pelvic relapse (3%). CONCLUSIONS: Adjuvant treatment with combination chemotherapy interposed with involved field radiation in advanced endometrial cancer was well tolerated. This protocol may be suitable for further evaluation in a clinical trial.