Prospective Clinical Correlation of the Histoculture Drug Response Assay for Ovarian Cancer.

The histoculture drug response assay (HDRA) has been correlated clinically to a number of cancer types (please see Chaps. 7 - 11 of the present volume). The present chapter reviews the clinical trials of the HDRA for ovarian cancer. A prospective clinical trial of the HDRA for advanced epithelial ovarian cancer (AEOC) was performed at Asan Medical Center, Seoul, Korea. The clinical trial compared the efficacy of first-line therapy paclitaxel and carboplatinum in the HDRA and the clinical response for the patients whose tumors were tested in the HDRA. A series of patients (104) were treated with adjuvant combination chemotherapy of paclitaxel and carboplatinum after primary cytoreductive surgery. Tumor fragments were cultured on Gelfoam® and tested with paclitaxel and carboplatinum and evaluated with the MTT endpoint. Patients were categorized into two groups as either sensitive to both drugs (SS) or not sensitive to one or both drugs (R) based on HDRA results. The recurrence rate was much lower in the SS group compared to the R group, 29.2% vs. 69.8%, respectively. The SS group had a significantly longer progression-free survival compared to the R group, 34.0 months vs. 16.0 months, respectively. In another clinical trial, the HDRA was performed on 85 cases of ovarian cancer and 97% were evaluable. HDRA results were correlated to clinical response of 15 patients who received cisplatinum-based therapy that included doxorubicin and cyclophosphamide (CAP therapy). The true-positive rate was 88%, the true-negative rate was 86%, the sensitivity was 88%, the specificity was 86%, and the accurate prediction rate was 87% when HDRA results were compared to the response of the treated patients.

Diagnostic value of integrated ¹8F-fluoro-2-deoxyglucose positron emission tomography/computed tomography in recurrent epithelial ovarian cancer: accuracy of patient selection for secondary cytoreduction in 134 patients.

OBJECTIVE: The aim of this study was to evaluate the diagnostic value of integrated ¹8F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography (¹8F-FDG-PET/CT) for suspected recurrence of epithelial ovarian cancer (EOC) with non-disseminated lesions. METHODS: We retrospectively reviewed the medical records of recurrent EOC patients who underwent secondary cytoreduction from January 2000 to December 2013. A total of 134 patients underwent secondary cytoreduction after imaging with either ¹8F-FDG-PET/CT or contrast-enhanced computed tomography (CECT). RESULTS: In a patient-based analysis of 134 patients, 124 (92.5%) were confirmed to be positive for malignancy. Among 72 patients with suspected non-disseminated recurrence on ¹8F-FDG-PET/CT, 65 (89.0%) were confirmed to have recurrence, giving 98.5% sensitivity, 87.7% accuracy, and 88.9% positive predictive value (PPV). In the 65 patients with recurrence, residual tumor remained in 14 patients, giving an accuracy of patient selection for secondary cytoreduction of 69.4% (50/72) and it is higher than that of CECT (64.0%). In 169 lesions removed from patients who underwent preoperative ¹8F-FDG-PET/CT, 135 (79.9%) were confirmed to be positive for malignancy and 124 were accurately detected by ¹8F-FDG-PET/CT, giving 91.9% sensitivity, 81.1% accuracy, and 85.5% PPV. Foreign body granuloma was found in 33.3% of 21 lesions with false-positive ¹8F-FDG-PET/CT findings (7/21). The mean preoperative cancer antigen 125 (CA-125) level in false-positive patients was 28.8 U/mL. CONCLUSION: Compared with CECT, ¹8F-FDG-PET/CT shows higher sensitivity in lesion-based analysis and better accuracy of patient selection for secondary cytoreduction. However, there is still a need for integration of the results of ¹8F-FDG-PET/CT, CECT, and CA-125 levels to aid treatment planning.

Impact of surgical staging on prognosis in patients with borderline ovarian tumours: A meta-analysis.

BACKGROUND: To quantify the effect of complete surgical staging (CSS) on prognosis in borderline ovarian tumour (BOT) patients through a meta-analysis. METHODS: We systematically reviewed published studies comparing CSS with incomplete surgical staging (ISS) in BOT patients through April 2015. End-points were recurrence and mortality rates. Study design features that possibly affected participant selection, recurrence/death detection, and manuscript publication were assessed. For pooled estimates of the effect of CSS on recurrence/death, random- or fixed-effects meta-analytical models were used after assessing cross-study heterogeneity. RESULTS: Eighteen observational studies (CSS, 1297 patients; ISS, 1473 patients) met our search criteria. Fixed-effects model-based meta-analysis indicated a reduced recurrence risk among CSS patients (odds ratio [OR]=0.64; 95% confidence interval [CI]: 0.47-0.87, P < 0.05, I(2) = 25.6). However, no significant between-group difference in mortality was observed (OR = 0.98; 95% CI: 0.42-2.29, P = 0.97, I(2) = 0). In subgroup analysis by histology, CSS was associated with a reduced recurrence risk in 16 studies of all histologic types (OR = 0.66; 95% CI: 0.48-0.91, P < 0.05, I(2) = 31.9) but not in two studies of only mucinous disease (OR = 0.41; 95% CI: 0.13-1.30, P = 0.13, I(2) = 0). In subgroup analyses with four studies with recurrence data according to fertility-sparing surgery, no significant association was found (OR = 0.51; 95% CI: 0.18-1.43, P = 0.20, I(2) = 0). There was no evidence of publication bias. CONCLUSIONS: In this meta-analysis based on observational studies, CSS appeared to significantly reduce recurrence among BOT patients. No survival impact was observed. Longer-term randomised controlled trials could verify this relationship but appear infeasible for this rare tumour.

Clinical Role of Adjuvant Chemotherapy after Radical Hysterectomy for FIGO Stage IB-IIA Cervical Cancer: Comparison with Adjuvant RT/CCRT Using Inverse-Probability-of-Treatment Weighting.

OBJECTIVE: To evaluate the clinical role of adjuvant chemotherapy (AC) in FIGO stage IB-IIA cervical cancer patients. STUDY DESIGN: A cohort of 262 patients with cervical cancer who received radical hysterectomy (RH) and adjuvant therapy at Asan Medical Center between 1992 and 2012 was enrolled. In this cohort, 85 patients received adjuvant chemotherapy (AC), and 177 received adjuvant radiotherapy or concurrent chemoradiation therapy (AR). Oncologic outcomes and adverse events in both treatment arms were compared using weighted Cox proportional hazards regression models with inverse-probability-of-treatment weighting (IPTW) to reduce the impact of treatment selection bias and potential confounding factors. RESULTS: During a 46.8-month median follow-up duration, 39 patients (14.9%) had recurrences, and 18 patients (6.9%) died of disease. In multivariate analysis, the hazard ratio (HR) for recurrence and death was not significantly different in patients in either treatment arm (p=0.62 and 0.12, respectively). Also, after IPTW matching, the HR for recurrence did not significantly differ between the arms (HR 1.57, 95% CI 0.68-3.62, p=0.29). Similarly, disease-free survival and overall survival were not significantly different between the arms (p=0.47 and 0.13, respectively). In addition, patients with AC had a much lower prevalence of long-term complications (lymphedema: n=8 (9.4%) vs. 46 (26.0%), p=0.03; ureteral stricture: n=0 vs. 9 (6.2%), p=0.05). CONCLUSION: Patients with FIGO stage IB-IIA cervical cancer can benefit from AC after RH with fewer long-term complications and non-inferior therapeutic effect to AR. Chemotherapy may therefore be an alternative adjuvant treatment option for cervical cancer, particularly in younger patients.

A case report of prenatally diagnosed tetrasomy 18p.

Tetrasomy 18p, one of the most commonly observed isochromosomes, consists of two copies of the p arms on chromosome 18[i(18p)]. It is known as a de novo occurrence of non-disjunction or centromeric mis-division during meiosis II in the vast majority of cases. It has a prevalence of 1/140,000-180,000 live births and affects both genders equally. A 28-year-old woman was referred at 33+2 weeks gestation to rule out fetal congenital heart disease. Her prenatal ultrasonography showed intrauterine growth retardation, cardiomegaly, and imperforate anus. Doppler ultrasonographic finding showed fetal anemia. Tetrasomy 18p was confirmed by conventional karyotyping and fluorescence in situ hybridization. Because of its very low prevalence rate, only several cases of tetrasomy 18p has been reported worldwide and it has not yet been reported in Korea before. Therefore, we report a case of prenatally diagnosed tetrasomy 18p.

Progression-free survival is accurately predicted in patients treated with chemotherapy for epithelial ovarian cancer by the histoculture drug response assay in a prospective correlative clinical trial at a single institution.

This study aimed to prospectively correlate clinical outcomes of advanced epithelial ovarian cancer (AEOC), with the results of in vitro chemosensitivity testing of taxol and carboplatin using the in vitro histoculture drug response assay (HDRA). A total of 104 patients with AEOC were treated with combination chemotherapy of taxol and carboplatin after primary cytoreductive surgery between 2007 and 2012 at the Asan Medical Center, Seoul, Korea. To compare chemosensitivity in the HDRA with clinical response, all patients were first categorized into two groups as either sensitive to both taxol and carboplatin (SS), or not sensitive to one or both drugs (R) based on HDRA results. The recurrence rate was much lower in the SS group compared to the R group; 29.2% vs 69.8%, respectively (p=0.02). The SS group had a significantly longer progression-free survival compared to the R group, 34.0 months vs 16.0 months, respectively (p=0.025). These results demonstrate that the HDRA prospectively correlates to clinical outcome from chemotherapy and that treatment regimens can be individualized based on the HDRA.