Surgical Outcomes of Patients Undergoing Extrafascial Hysterectomy After Neoadjuvant Radiotherapy With or Without Chemotherapy for Locally Advanced Endometrial Cancer Clinically Extending to the Cervix or Parametria.

Boisen MM ，Vargo JA ，Beriwal S ，Sukumvanich P ，Olawaiye AB ，Kelley JL ，Edwards RP ，Huang M ，Courtney-Brooks M ，Comerci JT ... -  《-》

Neoadjuvant radiotherapy and brachytherapy in endometrial cancer with gross cervical involvement: a CHIRENDO research group study.

Historically, radical hysterectomy followed by adjuvant radiotherapy has been offered to patients with endometrial cancer who have gross cervical involvement; however, this approach is known to carry considerable morbidity. Neoadjuvant radiotherapy followed by extra-fascial hysterectomy has been proposed as an alternative treatment but has been poorly studied to date. To evaluate the locoregional control rate associated with neoadjuvant radiotherapy followed by extra-fascial hysterectomy. A retrospective cohort study of 30 patients with endometrial cancer with gross cervical involvement treated between May 2006 and January 2016 was performed. Eligible patients were those aged >18 years with non-metastatic endometrial adenocarcinoma and gross cervical disease treated with curative intent at the Centre hospitalier de l'Université de Montréal. Treatment protocol consisted of pelvic neoadjuvant radiotherapy and high-dose rate brachytherapy followed by extra-fascial hysterectomy. Kaplan-Meier curves were used for survival analysis. The median age was 60 (range 37-82) and median body mass index was 32 kg/m2 (range 16-55). Twenty-four (80%) patients were diagnosed with a positive cervical/endocervical biopsy. Clinical staging confirmed 36.7% (n=11) as stage II, 20% (n=6) stage IIIB, 30% (n=9) stage IIIC1, and 13.3% (n=4) stage IIIC2. Seventy-seven per cent (n=23) of patients had an endometrioid histology. Locally advanced disease was identified by imaging alone in six patients. Rates of parametrial, adnexal, vaginal, and nodal invasion were 10% (n=3), 6.7% (n=2), 13.3% (n=4), and 43.3% (n=13) at diagnosis, respectively. All patients completed pelvic radiotherapy (13.3% extended field) and 90% received brachytherapy. Twenty per cent (n=6) of surgeries were performed using minimal invasive technique. On surgical specimen, 63.3% (n=19) had complete cervical response, 90% (n=27) had negative margins, and 10% (n=3) had residual nodal involvement. Median follow-up time was 62 months (range 1-120). Six recurrences were identified; all except one involved distant failure, and two with locoregional failure. Five-year locoregional control rate, disease-free, overall, and disease-specific survival were 90.5%, 78.5%, 92.6%, and 96.2%, respectively. Two patients (6.7%) had grade 3+ acute radiation-related complications (all grade 3). Grade 3+ post-operative morbidity was noted in 2 (6.7%) patients. Neoadjuvant radiotherapy followed by extra-fascial hysterectomy offers good locoregional control with low treatment-related morbidity in patients with endometrial cancer with overt cervical involvement.

Brodeur MN ，Samouëlian V ，Dabi Y ，Cormier B ，Beauchemin MC ，Barkati M ... -  《-》

Impact of different adjuvant radiotherapy modalities on women with early-stage intermediate- to high-risk endometrial cancer.

Vaginal brachytherapy was recommended for patients with intermediate-risk endometrial cancer, however, optimal radiotherapy modalities for intermediate-high- or high-risk patients remains controversial. Previous studies have mainly focused on survival outcomes and have seldom taken cost issues into consideration, especially for high-risk patients. The purpose of this study is to compare the survival outcomes and costs associated with two adjuvant radiotherapy modalities in the management of patients with early-stage, intermediate- to high-risk endometrial cancer. According to ESMO-ESCO-ESTRO criteria, 238 patients with stage I/II, intermediate- to high-risk endometrial cancer who underwent radiotherapy from January 2003 to December 2015 at our institution were reviewed. The vaginal brachytherapy group and external beam radiation therapy combined with the vaginal brachytherapy group were propensity score-matched at a 1:1 ratio. The Kaplan-Meier method and Cox proportional hazards regression model were used. A total of 361 patients met our inclusion criteria, the median age of the patients was 58 years (range, 28-85). All were diagnosed with stage I-II endometrial cancer (324 with stage I and 37 with stage II; 350 with endometrioid adenocarcinoma; and 10 with mucinous carcinoma). The median follow-up time was 60.5 months (range, 3-177). Among 119 matched pairs, no significant differences were found in overall (10.9% vs 8.4%, P=0.51), locoregional (4.2% vs 1.7%, P=0.45), or distant recurrence rates (6.7% vs 6.7%, P=1.0) between the two groups. There were also no differences in the 5-year overall (94.8% vs 93.9%, P=0.78) or progression-free survival (90.0% vs 84.4%, P=0.23) between the two groups. The rates of acute and late toxicity were significantly higher in the external beam radiation therapy combined with vaginal brachytherapy vs the vaginal brachytherapy group (all P<0.05), except for the acute hematological toxicity rate (17.6% vs 9.2%, P=0.06). External beam radiation therapy combined with vaginal brachytherapy had a higher median cost ($2759 vs $937, P<0.001) and longer median radiotherapy duration (41 days vs 17 days, P<0.001) than vaginal brachytherapy. Vaginal brachytherapy was associated with similar local control and long-term survival outcomes relative to the combination of external beam radiotherapy and vaginal brachytherapy and it also minimizes radiation-related complications, reduces medical costs, and shortens radiotherapy duration. Vaginal brachytherapy may be the optimal radiation modality for patients with early-stage endometrial cancer at intermediate to high risk.

Jin M ，Hou X ，Sun X ，Zhang Y ，Hu K ，Zhang F ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

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

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. 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. 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). 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.

Song J ，Le T ，Hopkins L ，Fung-Kee-Fung M ，Lupe K ，Gaudet M ，E C ，Samant R ... -  《-》