Prospective validation of the role of PET/CT in detecting disease after neoadjuvant chemotherapy in advanced ovarian cancer.

OBJECTIVES: The study aimed to compare the diagnostic accuracies of 2-[18F]FDG PET/CT and contrast-enhanced CT (ceCT) after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer (OC). MATERIALS AND METHODS: This study consisted historical observational cohort and prospective validation cohort. Patients with newly diagnosed stage III-IV OC scheduled for NACT were recruited, with imaging performed after three to six cycles of NACT before interval debulking surgery. Nineteen regions in the abdominopelvic cavity were scored for the presence and absence of disease, referenced to the intra-operative findings or histological specimens. Diagnostic metrics were compared using McNemar's test. RESULTS: In the historical cohort (23 patients, age 58 ± 13), 2-[18F]FDG PET had an overall accuracy (Acc) 82%, sensitivity (Sen) 38%, specificity (Spe) 97%, positive predictive value (PPV) 79% and negative predictive value (NPV) 82%; ceCT had an overall Acc 86%, Sen 64%, Spe 93%, PPV 75% and NPV 89%. In the prospective cohort (46 patients, age 59 ± 9), 2-[18F] FDG PET had an overall Acc 87%, Sen 48%, Spe 98%, PPV 84% and NPV 88%; ceCT had an overall Acc 89%, Sen 66%, Spe 95%, PPV 77% and NPV 91%. No significant difference was demonstrated between the two imaging modalities (p > 0.05). High false-negative rates were observed in the right subdiaphragmatic space, omentum, bowel mesentery and serosa. High omental metabolic uptake after NACT was associated with histological non-responders (p < 0.05). CONCLUSION: 2-[18F]FDG PET/CT had no additional value over ceCT with comparable diagnostic accuracy in detecting disease after NACT in advanced OC. CLINICAL RELEVANCE STATEMENT: 2-[18F]FDG PET/CT is not superior to contrast-enhanced CT in determining disease after neoadjuvant chemotherapy in advanced ovarian cancer; contrast-enhanced CT should be suffice for surgical planning before interval debulking surgery. KEY POINTS: • Additional value of 2-[18F]FDG PET/CT over contrast-enhanced CT is undefined in detecting disease after neoadjuvant chemotherapy. • 2-[18F]FDG PET/CT has comparable diagnostic accuracy compared to contrast-enhanced CT. • Contrast-enhanced CT will be suffice for surgical planning after neoadjuvant chemotherapy.

The Value of Four-Quadrant Cervical Biopsy in Women with Different Colposcopic Impressions.

The aim of this study was to compare the diagnostic efficacy of colposcopic-directed biopsy and four-quadrant biopsy in detecting high-grade cervical intra-epithelial neoplasia (CIN). Women attending three women's clinics for routine cervical screening were recruited. Colposcopy was arranged for women with any cytologic abnormalities greater than atypical squamous cells of undetermined significance (ASCUS), two consecutive ASCUS results or positive HPV testing. During colposcopy, a cervical biopsy was taken from the most suspicious area, but more than one biopsy was allowed. Four-quadrant biopsies at 3, 6, 9 and 12 o'clock and an endocervical curettage were also taken in all cases. A total of 1522 colposcopies were performed in 1311 subjects from June 2010 to August 2017, with 118 cases of high-grade CIN diagnosed. Colposcopic-directed biopsy detected 50.8% of the 118 high-grade CIN, while four-quadrant biopsy detected 86.4% (p < 0.0001). Twenty-seven cases (22.9%) of high-grade CIN were diagnosed in women with normal or unsatisfactory colposcopy. Among the 64 cases with low-grade colposcopic impression, four-quadrant biopsy detected significantly more high-grade CIN (53 cases, 82.8%) than colposcopic-directed biopsy (35 cases, 56.3%) (p = 0.0011). Four-quadrant cervical biopsies should be considered for all women with an abnormal smear or positive HPV testing, especially in patients with low-grade/normal/unsatisfactory colposcopy.

Tamoxifen use in recurrent ovarian cancer in a Chinese population: A 15 -year clinical experience in a tertiary referral center.

AIM: To review the clinical use and the effectiveness of tamoxifen in patients with advanced or recurrent ovarian cancer. METHODS: A retrospective review of clinical records was conducted in patients who received tamoxifen for the treatment of ovarian cancer between 2002 and 2016. We reviewed the clinical setting that it was given, duration of use, patients' tolerability, clinical benefit and progression-free survival. We also attempted to identify predictive markers for response. RESULTS: A total of 92 patients received tamoxifen during this 15-year period. The patients received a median of 2.5 lines of chemotherapy before switching to tamoxifen, and they remained on tamoxifen for a median of 5.6 months (range 0-85 months), with 24 patients receiving it for more than 12 months. Seventy-six patients continued on tamoxifen for more than 2 months. In this group, 75 patients had an evaluable response, either by CA 125 or clinically and clinical benefit rate (defined as complete, partial response and static disease) was seen in 42 patients (56%), with majority of patients having static disease. The median progression-free survival was 5.3 months (95% confidence interval, 2.6-8.1). Tamoxifen was well tolerated. Hormone receptor status was not demonstrated to predict response. CONCLUSION: Patients with advanced ovarian cancer who have failed previous lines of chemotherapy may achieve static disease with tamoxifen with minimal side effects. Tamoxifen may still have a role in the era of molecular target therapy.

Diffusion-weighted magnetic resonance imaging of primary cervical cancer in the detection of sub-centimetre metastatic lymph nodes.

BACKGROUND: Magnetic resonance imaging (MRI) has limited accuracy in detecting pelvic lymph node (PLN) metastasis. This study aimed to examine the use of intravoxel incoherent motion (IVIM) in classifying pelvic lymph node (PLN) involvement in cervical cancer patients. METHODS: Fifty cervical cancer patients with pre-treatment magnetic resonance imaging (MRI) were examined for PLN involvement by one subspecialist and one non-subspecialist radiologist. PLN status was confirmed by positron emission tomography or histology. The tumours were then segmented by both radiologists. Kruskal-Wallis tests were used to test for differences between diffusion tumour volume (DTV), apparent diffusion coefficient (ADC), pure diffusion coefficient (D), and perfusion fraction (f) in patients with no malignant PLN involvement, those with sub-centimetre and size-significant PLN metastases. These parameters were then considered as classifiers for PLN involvement, and were compared with the accuracies of radiologists. RESULTS: Twenty-one patients had PLN involvement of which 10 had sub-centimetre metastatic PLNs. DTV increased (p = 0.013) while ADC (p = 0.015), and f (p = 0.006) decreased as the nodal status progressed from no malignant involvement to sub-centimetre and then size-significant PLN metastases. In determining PLN involvement, a classification model (DTV + f) had similar accuracies (80%) as the non-subspecialist (76%; p = 0.73) and subspecialist (90%; p = 0.31). However, in identifying patients with sub-centimetre PLN metastasis, the model had higher accuracy (90%) than the non-subspecialist (30%; p = 0.01) but had similar accuracy with the subspecialist (90%, p = 1.00). Interobserver variability in tumour delineation did not significantly affect the performance of the classification model. CONCLUSION: IVIM is useful in determining PLN involvement but the added value decreases with reader experience.

A Case Series of Five Patients With Pure or Mixed Gestational Epithelioid Trophoblastic Tumors and a Literature Review on Mixed Tumors.

OBJECTIVES: To review the clinicopathologic features of five patients with epithelioid trophoblastic tumor (ETT). METHODS: Characteristics of patients diagnosed with ETT in 2000 to 2012 were reviewed. RESULTS: Among 190 patients with gestational trophoblastic neoplasia (GTN), two had pure ETT and three had mixed ETT and choriocarcinoma. The median age was 32.5 years. All the patients had localized disease in the uterus. One patient with pure ETT had a recurrence in the ureter 6 years after the initial treatment. Another patient with pure ETT had two full-term deliveries after fertility-sparing surgery. The three patients with mixed tumors had chemotherapy for GTN before their diseases were completely treated by hysterectomy. At a median follow-up of 102 months, all patients survived. CONCLUSIONS: ETT is indolent. Recurrence can happen, but the risk factors are not clear. When patients with GTN fail to respond to chemotherapy, the possibility of mixed GTN should be considered.

Placental Site Trophoblastic Tumor: A Distinct Entity of Gestational Trophoblastic Disease Experience from a Tertiary Referral Center in Hong Kong.

OBJECTIVE: To review the clinical and pathological characteristics of patients with placental site trophoblastic tumor (PS TT) managed in a tertiary referral center in Hong Kong. STUDY DESIGN: Patients with a diagnosis of PSTT from 1995 to 2012 were identified from a computer database. Clinical and patho- logical data were obtained from medical records and the electronic database. RESULTS: Ten patients with PSTT were identified. Only 4 patients (40%) had disease confined to the uterus at presentation (Stage I). The most common site of metastasis was the lung. Four patients had pretreatment serum hCG levels <1,000 IU/L, and all of them had disease 'confined to the uterus. Of the 4 patients with Stage I disease 3 had hysterectomy only and 1 had both hysterectomy and chemotherapy. All 4 patients achieved complete remission; although 1 of them had a recurrence successfully treated with che- motherapy. For patients with Stage III/IV disease most of them had both hysterectomy and chemotherapy. Only 1 patient (20%) was alive without evidence of disease. CONCLUSION: Patients with Stage I disease have excellent prognosis after hysterectomy, and adjuvant treatment is not recommended. A low pretreatment serum hCG level (<1,000 IU/L) was a good predictor of early stage disease. The prognosis for patients with metastatic disease was poor despite surgery and com- bination chemotherapy.

The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer.

The objective of this study was to identify the tumor characteristics associated with mismatch repair deficiency in young patients with endometrial carcinoma. Young patients (45 yr old or younger) with endometrial carcinoma treated by hysterectomy in our institution between July 2001 and June 2009 were identified. The clinical and pathologic data were obtained by review of clinical records. Among the 122 cases identified, paraffin sections were available in 67 cases for immunohistochemical staining and frozen tissue available in 62 cases for microsatellite instability (MSI) analysis. Both paraffin sections and frozen tissue were available in 36 cases. Among the 67 cases with immunohistochemical staining, 22 (32.8%) showed loss of expression of at least 1 mismatch repair protein. Defective MLH1 or MSH2 expression was associated with poor prognostic factors, including a higher incidence of pelvic lymph nodes metastasis (P=0.018) and higher stage (P=0.022) for MLH1, and an increased risk of lymphovascular permeation (P=0.015) for MSH2. On the contrary, defective MSH6 protein expression was associated with a lower incidence of high-grade tumors (P=0.04). Among the 62 cases with MSI analysis, 12 (19.4%) tumors were classified as microsatellite-high (MSI-H), whereas 2 (3.2%) were classified as microsatellite-low (MSI-L). There was no difference in the pathologic characteristics between MSI-stable and MSI-H tumor. We concluded that defective mismatch repair expression is important in young patients with endometrial carcinoma, with MSH6 protein being most commonly affected. The phenotype resulting from defective MSH6 expression was different from that caused by MLH1 or MSH2 loss.

Cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, and vincristine in the treatment of gestational trophoblastic neoplasia.

OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity profile of the cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, and vincristine (CHAMOC) regimen in the treatment of high-risk gestational trophoblastic neoplasia (GTN). METHODS: We conducted a retrospective study of all patients with GTN treated with the CHAMOC regimen between 1985 and 2012 in a tertiary referral center in Hong Kong. Medical records were reviewed, and data were analyzed. Response rate and toxicity profile were assessed. RESULTS: The CHAMOC regimen was given to 79 patients from 1985 to 2012, with a total of 388 cycles administered. Among the 79 patients, CHAMOC was given to 68 as the primary treatment of high-risk GTN, whereas it was used as the salvage chemotherapy in 11 patients for failure with other chemotherapy regimens or recurrent disease. Complete remission was achieved in 58 patients (85.3%) in the primary treatment group and 8 patients (72.7%) in the salvage treatment group. Grade 3 and grade 4 neutropenia were observed in 13.0% and 3.4% of the chemotherapy cycles, respectively. Grade 3 or 4 thrombocytopenia was rare (1.3% of all treatment cycles). No secondary malignancy was observed in our patients with a mean duration of follow-up of 9.7 to 13 years, except 1 patient with advanced colon cancer diagnosed shortly after chemotherapy, which was unlikely to represent a secondary malignancy from the chemotherapy. CONCLUSIONS: The CHAMOC regimen should be considered as an alternative to other chemotherapy regimens in the primary treatment of high-risk gestational trophoblastic disease, with comparable efficacy, similar short-term side-effects profile, and potentially fewer long-term complications.

Perfusion and diffusion characteristics of cervical cancer based on intraxovel incoherent motion MR imaging-a pilot study.

OBJECTIVES: To investigate the tissue characteristics of cervical cancer based on the intravoxel incoherent motion (IVIM) model and to assess the IVIM parameters in tissue differentiation in the female pelvis. METHODS: Sixteen treatment-naïve cervical cancer and 17 age-matched healthy subjects were prospectively recruited for diffusion-weighted (b = 0-1,000 s/mm(2)) and standard pelvic MRI. Bi-exponential analysis was performed to derive the perfusion parameters f (perfusion fraction) and D* (pseudodiffusion coefficient) as well as the diffusion parameter D (true molecular diffusion coefficient) in cervical cancer (n = 16), normal cervix (n = 17), myometrium (n = 33) and leiomyoma (n = 14). Apparent diffusion coefficient (ADC) was calculated. Kruskal-Wallis test and receiver operating characteristics (ROC) curves were used. RESULTS: Cervical cancer had the lowest f (14.9 ± 2.6%) and was significantly different from normal cervix and leiomyoma (p < 0.05). The D (0.86 ± 0.16 x 10(-3) mm2/s) was lowest in cervical cancer and was significantly different from normal cervix and myometrium (p < 0.05) but not leiomyoma. No difference was observed in D*. D was consistently lower than ADC in all tissues. ROC curves indicated that f < 16.38%, D < 1.04 × 10(-3) mm(2)/s and ADC < 1.13 × 10(-3) mm(2)/s could differentiate cervical cancer from non-malignant tissues (AUC 0.773-0.908). CONCLUSIONS: Cervical cancer has low perfusion and diffusion IVIM characteristics with promising potential for tissue differentiation. KEY POINTS: • Diffusion-weighted MRI is increasingly applied in evaluation of cervical cancer. • Cervical cancer has distinctive perfusion and diffusion characteristics. • Intravoxel incoherent motion characteristics can differentiate cervical cancer from non-malignant uterine tissues.

Differentiation of aggressive and indolent subtypes of uterine sarcoma using maximum standardized uptake value.

OBJECTIVE: The aim of the study was to elucidate the differential metabolic activities in aggressive and indolent subtypes of uterine sarcomas, which may aid in managing these heterogeneous tumours. METHODS: We retrospectively analysed the PET/computed tomography scans of consecutive patients (N=18) diagnosed with uterine sarcoma at our unit. The patients were divided into indolent (N=4) and aggressive (N=14) tumour groups, and the maximum standardized uptake values (SUV max) of all lesions (n=134) were measured. The SUV max of the lesions were compared between the two tumour groups using the Mann-Whitney U-test. We calculated the optimal cutoff value as determined by receiver operating characteristic analysis. A P-value less than 0.05 was considered statistically significant. RESULTS: The mean SUV max of aggressive (n=104) and indolent tumours (n=30) were significantly different (8.0 ± 7.3 vs. 1.9 ± 0.9 respectively; P<0.001). A cutoff of SUV max greater than 4.0 was able to exclude indolent tumours, with 100% specificity and positive predictive value (sensitivity 72%, negative predictive value 50% and accuracy 78%; area under the curve 97%). By applying this same cutoff value on the most metabolic active lesion in each patient, we were able to correctly classify all but one patient into either the aggressive or indolent tumour group with 100% specificity and positive predictive value (sensitivity 93%, negative predictive value 80% and accuracy 94%). CONCLUSION: Aggressive and indolent uterine sarcoma subtypes have differential metabolic activities that can be used to classify them and this can aid in patient management for preoperative surgical planning and treatment stratification.

Modified symbolic play test for Oriental children.

BACKGROUND: Symbolic play test (SPT) is a simple test for screening preverbal language in children. This test had been validated in English-speaking children. However, the toys may not be useful for other cultures such as Orientals like Chinese, Japanese, Koreans or Thais as they use chopsticks and bowls as eating utensils rather than spoon, fork or knife. The aim of this study was to find a set of miniature toys suitable for children of Oriental ethnic origin in order to get a reliable language test. METHODS: Altogether 140 children were recruited into this study. This included 62 control children and 78 with idiopathic developmental delay. The original SPT was applied together with an additional set of miniature toys appropriate for Oriental culture (i.e. modified version of SPT) by modifying play items in situations 3 and 4 to suit the Chinese culture. The authors replaced the knife, fork and plate with chopsticks and bowl in situation 3 and replaced the tractor and trailer with train carts in situation 4. For the ease of comparison, the authors segregated the age groups with the same age range as the original English-based SPT: less than 20 months (N= 11); 21-30 months (N= 45); 31-40 months (N= 43); 41-50 months (N= 21), and more than 50 months (N= 4). RESULTS: The mean scores of the cohort was higher (14.83) with the modified version of SPT than when the original SPT was used (13.64). A statistically significant increase in the mean score in situation 3 (3.67-3.24 = 0.43), situation 4 (3.76-3.36 = 0.40) and the overall score (14.83-13.64 = 1.19) was obtained when the modified SPT was used instead of the original SPT (all with P < 0.001). CONCLUSION: The authors recommend replacing play items like spoon, knife, fork and plate with Oriental culture-based items like chopsticks and bowl for the modified SPT (Oriental version). Users of the test should have a set of toy train carts available to supplement the tractor and trailer as these toys were not commonly seen in real life for Oriental children. The authors hope that the modified SPT can be used reliably to assess for preverbal ability of Oriental children, especially Chinese children.