Dongsheng Tu

Trajectories of Cancer Antigen 125 (CA125) Within 3 and 6 Months After the Initiation of Chemotherapy Treatment for Advanced Ovarian Cancer and Clinical Outcomes: A Secondary Analysis of Data from a Phase III Clinical Trial

Background: A single measurement or a summary of a limited number of measurements of CA125 was considered in the prediction of clinical outcomes for patients with ovarian cancer. We aimed to identify the classes of patients with advanced ovarian cancer based on their CA125 trajectory and to investigate the heterogeneity of clinical outcomes among the patients in the different classes. Methods: CA125 trajectory classes were identified by latent-class mixed models based on values collected within 3 and 6 months post-treatment for 819 women with advanced ovarian cancer enrolled in a randomized trial. Results: Based on their CA125 values during the first 6 months of treatment, the patients with low CA125 levels at baseline that remained low during treatment had the best clinical outcome (a median survival of 83 months and a progression-free survival of 34 months). In contrast, the patients with high CA125 values at baseline with a modest decrease during treatment had the highest risk of death and progression (hazard ratio [95% confidence interval]: 4.83 [3.56, 6.54] for overall survival and 5.15 [3.87, 6.87] for progression-free survival). Conclusions: Longitudinal trajectories of CA125 may provide more direct information for the prognoses of patients with advanced ovarian cancer undergoing chemotherapy treatment.

Surgery versus no surgery in platinum-sensitive relapsed ovarian cancer: final overall survival analysis of the SOC-1 randomized phase 3 trial

Surgery for platinum-sensitive, relapsed ovarian cancer (PSROC) is widely practiced but had contradictory survival outcomes in previous studies. In this multicenter, open-label, phase 3 trial, women with PSROC, and having had one previous therapy and no platinum-based chemotherapy (platinum-free interval) of 6 months or more, were randomly assigned to either the surgery group (182 patients) or the no-surgery group (control) (175 patients). Patients with resectable diseases were eligible according to the international model (iMODEL), combined with a positron emission tomography-computed tomography imaging. Overall survival (OS) and progression-free survival were coprimary endpoints in hierarchical testing, and a significantly longer progression-free survival with surgery was previously reported. Final analysis of OS was planned at data maturity of 59%. Between 19 July 2012 and 3 June 2019, 357 patients were enrolled. Median follow-up was 82.5 months. Median OS was 58.1 months with surgery and 52.1 months for control (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.61-1.05, P = 0.11). The predefined threshold for statistical significance was not met, but prespecified sensitivity analysis was performed. Overall, 61 of 175 (35%) patients in control had crossed over to surgery following subsequent relapse, and adjusted HR for death in the surgery group compared with control was 0.76, 95% CI 0.58-0.99. In subgroup analysis of relapse sites by imaging, median survival was not estimable in the surgery group and was 69.5 months in control in patients with 60 months in the surgery group as compared with five of 175 (2.9%) patients in the control group. In patients with PSROC, surgery did not increase OS in the intention-to-treat population but resulted in a prolongation of survival following adjustment of crossover.ClinicalTrials.gov registration: NCT01611766 .

Minimally invasive compared to open surgery in patients with low-risk cervical cancer following simple hysterectomy: An exploratory analysis from the Gynegologic Cancer Intergroup/Canadian Cancer Trials Group CX.5/SHAPE trial

The Laparoscopic Approach to Cervical Cancer trial demonstrated that minimally invasive radical hysterectomy was associated with worse disease-free survival and overall survival among women with early-stage cervical cancer. It is unknown whether this applies to patients with low-risk disease following simple hysterectomy. Among patients who underwent simple hysterectomy in the Simple Hysterectomy And PElvic node assessment trial, univariate and multivariate Cox models were used to assess the association of minimally invasive versus open surgery with clinical outcomes, including pelvic and extra-pelvic recurrence-free survival, overall recurrence-free survival, and overall survival. Other variables included age, race, performance status, body mass index, stage, histologic type and grade, diagnostic procedure, lymphovascular space invasion before surgery and on final pathology, lymph node status, residual disease, and lesions >2 cm on final pathology. A total of 338 patients underwent simple hysterectomy. Of those, 281 (83%) were performed by minimally invasive surgery and 57 (17%) by open surgery. With a median follow-up of 4.5 years, a total of 12 (4.3%) recurrences were observed in 281 patients having simple hysterectomy by minimally invasive surgery versus 3 in 57 (5.3%) having open surgery (p = .73 from Fisher exact test). Although not randomized, the 2 groups were comparable except for histology and residual disease in the hysterectomy specimen. Patients with minimally invasive surgery had more adenocarcinoma and less adenosquamous compared to open surgery (35.9% versus 22.9% and 3.6% versus 14%, respectively; p = .005). Significantly fewer patients treated by minimally invasive surgery had residual disease in the hysterectomy specimen compared to open surgery (43.1 versus 57.9%; p = .04). No statistically significant difference between minimally invasive and open surgery in pelvic and extra-pelvic recurrence-free survival, overall recurrence-free survival, or overall survival was found. Our data indicate no statistical evidence that minimally invasive surgery is associated with poorer clinical outcomes for patients meeting the SHAPE criteria who underwent simple hysterectomy. Because the surgical approach was not a randomization factor, a large prospective trial is needed to confirm our results before a routine simple hysterectomy by minimally invasive surgery can be recommended.

Sexual Health and Quality of Life in Patients With Low-Risk Early-Stage Cervical Cancer: Results From GCIG/CCTG CX.5/SHAPE Trial Comparing Simple Versus Radical Hysterectomy

PURPOSE Simple hysterectomy and pelvic node assessment (SHAPE) is a phase III randomized trial (ClinicalTrials.gov identifier: NCT01658930 ) reporting noninferiority of simple compared with radical hysterectomy for oncologic outcomes in low-risk cervical cancer. This study presents secondary outcomes of sexual health and quality of life (QOL) of the SHAPE trial. METHODS Participants were randomly assigned to receive either radical or simple hysterectomy. Sexual health was assessed up to 36 months postoperatively using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised and QOL using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Cervical Cancer-Specific Module (QLQ-CX24) questionnaires. RESULTS Among participants with at least one QOL measure, clinical and pathologic characteristics were balanced and with no differences in preoperative baseline scores for sexual health or QOL between groups. FSFI total score met the cutoff for dysfunction up to 6 months ( P = .02) in the radical hysterectomy group. Group differences favored simple hysterectomy for FSFI subscales: desire and arousal at 3 months ( P ≤ .001) and pain and lubrication up to 12 months ( P ≤ .018). Both groups met the cutoff for sexual distress but was higher in radical hysterectomy at 3 months ( P = .018). For QLQ-CX24, symptom experience was significantly better up to 24 months ( P = .031) and body image better at 3, 24, and 36 months ( P ≤ .01) for simple hysterectomy. Sexual-vaginal functioning was significantly better up to 24 months ( P ≤ .022) and more sexual activity up to 36 months ( P = .024) in the simple hysterectomy arm. Global health status was significantly higher at 36 months for simple hysterectomy ( P = .025). CONCLUSION Simple hysterectomy was associated with lower rates of sexual dysfunction than radical hysterectomy, with a lower proportion of women having sustained sexual-vaginal dysfunction. These results further support the benefit of surgical de-escalation for low-risk cervical cancer.

Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening

Significance The optimal timing of surgery/chemotherapy and the benefits of earlier diagnosis of HGSC remain controversial. We developed a mathematical framework of tumor dynamics, populated the model with primary clinical data, and reliably recapitulated clinical observations. Our model predicts that 1) PDS is superior to NACT with relatively small tumor burden and when complete debulking is feasible, 2) timely adjuvant chemotherapy is critical for the outcome of PDS with <1-mm residual tumors, 3) earlier detection of relapse is unlikely beneficial with current therapies, and 4) earlier detection of primary HGSC could have substantial benefit. These results provide insights into the evolutionary dynamics of HGSC, argue for new clinical trials to optimize therapy, and are potentially applicable to other tumor types.

Radical Versus Simple Hysterectomy and Pelvic Node Dissection With Low-risk Early Stage Cervical Cancer

The reason this study is being done is to see if a simple hysterectomy is as good as a radical hysterectomy in preventing cancer of the cervix from returning, and whether, because less tissue surrounding the uterus is removed during surgery, there are fewer side-effects after the surgery and in the long-term.

Surgery or Chemotherapy in Recurrent Ovarian Cancer (SOC 1 Trial)?

The purpose of this study is to evaluate the role of secondary cytoreduction (SCR) and validate the risk model of patient selection criteria in platinum-sensitive recurrent ovarian cancer.