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.

A questionnaire study on disparity of cervical cancer prevention programs in Asia-Oceania.

BACKGROUND: Despite the introduction of cervical cancer screening and human papillomavirus (HPV) vaccines, the utilization pattern was not standardized. The aim of this study was to elicit the current prevention care in Asia-Oceania. METHODS: An online questionnaire was circulated to different countries/cities in Asia-Oceania. The primary objective was to evaluate the coverage of HPV vaccination and cervical screening programs. The secondary objectives were to study the structures of these programs. Five case scenarios were set to understand how the respondents manage the abnormal screening results. RESULTS: Fourteen respondents from 10 countries/cities had participated. Cervical cancer ranked the first in Myanmar and Nepal. About 10%-15% did not have national vaccination or screening program. The estimated coverage rate for vaccination and screening varied from less than 1% to 70%, which the coverage ran in parallel with the incidence and mortality rates of cervical cancer. All regions approved HPV vaccines, although only four provided free or subsidized programs for nonavalent vaccine. Cervical cytology remained the most common screening tool, and 20%-30% relied heavily on visual inspection using acetic acid. The screening age groups varied in different regions. From the case scenarios, it was noted that some respondents tended to offer more frequent screening tests or colposcopy than recommended by international guidelines. CONCLUSION: This study revealed discrepancy in the practice of cervical cancer prevention in Asia-Oceania especially access to HPV vaccines. There is an urgent need for a global collaboration to eliminate cervical cancer by public education, reforming services, and medical training.

Cervical carcinomas with serous-like papillary and micropapillary components: illustrating the heterogeneity of primary cervical carcinomas.

Recent changes in the classification of cervical adenocarcinomas have re-categorized serous carcinoma as potentially nonexistent. However, clinical and pathological profiles of cervical adenocarcinomas with serous-like morphological features have not been systematically evaluated using the latest taxonomy and biomarkers. We studied 14 cases of primary cervical carcinomas with serous-like morphologies (papillary and micropapillary patterns). None of these cases exhibited evidence of serous carcinoma involving the upper tracts. Patient ages ranged between 34 and 86 years, most presented with abnormal uterine bleeding. Histologically, ten cases were classified as human papillomavirus (HPV)-associated carcinomas (eight usual-type endocervical adenocarcinomas and two adenosquamous carcinomas), of which six exhibited a papillary pattern and four had a micropapillary pattern. The four remaining cases were HPV-independent gastric-type adenocarcinomas, which displayed a papillary pattern in one case and a micropapillary pattern in three others. All ten HPV-associated carcinomas displayed block positive p16 and wild-type p53 by immunohistochemistry, with nine of them confirmed by HPV testing. Two of the four gastric-type adenocarcinomas had mutation-type p53, one of which also being p16 block positive. HER2 overexpression was demonstrated in 3/14 (21.4%) cases (2 HPV-associated and 1 HPV-independent). PD-L1 expression was identified in 4/10 (40%) cases, all HPV-associated. Targeted next-generation sequencing was performed in two cases with a micropapillary pattern, revealing a missense variant in ATM in an HPV-associated tumor and missense variants in TP53 and SMARCB1 in an HPV-independent tumor. The results demonstrated that primary endocervical adenocarcinomas can mimic the appearance of serous carcinoma, while not representing serous carcinoma. Serous-like papillary and micropapillary patterns may be present in both HPV-associated and HPV-independent cervical carcinomas, but none of the cases studied were unequivocally serous upon detailed analysis. Our findings support the exclusion of "cervical serous carcinoma" from existing classifications of cervical adenocarcinoma.

Association between IVIM parameters and treatment response in locally advanced squamous cell cervical cancer treated by chemoradiotherapy.

OBJECTIVE: To examine the associations of intravoxel incoherent motion (IVIM) parameters with treatment response in cervical cancer following concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: Forty-five patients, median age of 58 years (range: 28-82), with pre-CCRT and post-CCRT MRI, were retrospectively analysed. The IVIM parameters pure diffusion coefficient (D) and perfusion fraction (f) were estimated using the full b-value distribution (BVD) as well as an optimised subsample BVD. Dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC) were used to measure observer repeatability in tumour delineation at both time points. Treatment response was determined by the response evaluation criteria in solid tumour (RECIST) 1.1 between MRI examinations. Mann-Whitney U tests were used to test for significant differences in IVIM parameters between treatment response groups. RESULTS: Pre-CCRT tumour delineation repeatability was good (DSC = 0.81) while post-CCRT delineation repeatability was moderate (DSC = 0.67). Values of D and f had good repeatability at both time points (ICC > 0.80). Pre-CCRT f estimated using the full BVD and optimised subsample BVD were found to be significantly higher in patients with partial response compared to those with stable disease or disease progression (p = 0.01 and 95% CI = -0.02-0.00 for both cases). CONCLUSION: Pre-CCRT f was associated with treatment response in cervical cancer with good observer repeatability. Similar discriminative ability was also observed in estimated pre-CCRT f from an optimised subsample BVD. KEY POINTS: • Pre-treatment tumour delineation and IVIM parameters had good observer repeatability. • Post-treatment tumour delineation was worse than at pre-treatment, but IVIM parameters retained good ICC. • Pre-treatment perfusion fraction estimated from all b-values and an optimised subsample of b-values were associated with treatment response.

Association between MRI histogram features and treatment response in locally advanced cervical cancer treated by chemoradiotherapy.

OBJECTIVE: To examine the associations of histogram features of T2-weighted (T2W) images and apparent diffusion coefficient (ADC) with treatment response in locally advanced cervical cancer (LACC) following concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: Fifty-eight patients who underwent a 4-week CCRT regimen with MRI prior to treatment (pre-CCRT) and after treatment (post-CCRT) were retrospectively analysed. Histogram features were calculated from volumes of interest (VOIs) from one radiologist on T2W images and ADC maps. VOIs from two radiologists were used to assess observer repeatability in delineation and feature values at both time-points with the Dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC). Treatment response was defined as a 90% reduction in tumour volume. Paired Mann-Whitney U tests were used to determine if features changed significantly between examinations. Two-sample Mann-Whitney U tests were used to identify features that were significantly different between response groups. Receiver operating characteristic (ROC) analysis was done on significantly different MRI features between treatment response groups. RESULTS: Pre-CCRT delineation and feature repeatability were generally good (DSC > 0.700; ICC > 0.750). Post-CCRT repeatability was low (DSC < 0.700; ICC < 0.750), but ADC mean and percentiles retained good ICC scores. All features, except for T2WKurtosis, significantly changed between examinations. Post-CCRT ADC50 was the only feature that demonstrated both good observer variability and significant differences between treatment response groups (p = 0.036) and had an AUC of 0.701 with a cut-off of 1.357 × 10-6 mm2/s. CONCLUSION: ADC and T2W histogram features could be used to track changes in LACC tumours undergoing CCRT. Post-CCRT ADC50 was associated with treatment response with good observer repeatability. KEY POINTS: • Pre-treatment tumour delineation and histogram feature values had good observer repeatability, while these were less repeatable at post-treatment. • MRI histogram analysis could be used to track changes in the tumour as it undergoes concurrent chemoradiotherapy. • Post-treatment median ADC was associated with treatment response and had good repeatability.

Development of a surgical competency assessment tool for sentinel lymph node dissection by minimally invasive surgery for endometrial cancer.

INTRODUCTION: Sentinel lymph node dissection is widely used in the staging of endometrial cancer. Variation in surgical techniques potentially impacts diagnostic accuracy and oncologic outcomes, and poses barriers to the comparison of outcomes across institutions or clinical trial sites. Standardization of surgical technique and surgical quality assessment tools are critical to the conduct of clinical trials. By identifying mandatory and prohibited steps of sentinel lymph node (SLN) dissection in endometrial cancer, the purpose of this study was to develop and validate a competency assessment tool for use in surgical quality assurance. METHODS: A Delphi methodology was applied, included 35 expert gynecological oncology surgeons from 16 countries. Interviews identified key steps and tasks which were rated mandatory, optional, or prohibited using questionnaires. Using the surgical steps for which consensus was achieved, a competency assessment tool was developed and subjected to assessments of validity and reliability. RESULTS: Seventy percent consensus agreement standardized the specific mandatory, optional, and prohibited steps of SLN dissection for endometrial cancer and informed the development of a competency assessment tool. Consensus agreement identified 21 mandatory and three prohibited steps to complete a SLN dissection. The competency assessment tool was used to rate surgical quality in three preselected videos, demonstrating clear separation in the rating of the skill level displayed with mean skills summary scores differing significantly between the three videos (F score=89.4; P<0.001). Internal consistency of the items was high (Cronbach α=0.88). CONCLUSION: Specific mandatory and prohibited steps of SLN dissection in endometrial cancer have been identified and validated based on consensus among a large number of international experts. A competency assessment tool is now available and can be used for surgeon selection in clinical trials and for ongoing, prospective quality assurance in routine clinical care.

COVID-19 and gynecological cancers: Asia and Oceania Federation of Obstetrics and Gynecology oncology committee opinion.

Since the outbreak of COVID-19, there have already been over 26 million people being infected and it is expected that the pandemic will not end in near future. Not only the daily activities and lifestyles of individuals have been affected, the medical practice has also been modified to cope with this emergency catastrophe. In particular, the cancer services have faced an unprecedented challenge. While the services may have been cut by the national authorities or hospitals due to shortage of manpower and resources, the medical need of cancer patients has increased. Cancer patients who are receiving active treatment may develop various kinds of complications especially immunosuppression from chemotherapy, and they and their carers will need additional protection against COVID-19. Besides, there is also evidence that cancer patients are more prone to deteriorate from COVID-19 if they contract the viral infection. Therefore, it is crucial to establish guidelines so that healthcare providers can triage their resources to take care of the most needed patients, reduce less important hospitalization and visit, and to avoid potential complications from treatment. The Asia and Oceania Federation of Obstetrics and Gynecology (AOFOG) hereby issued this opinion statement on the management of gynecological cancer patients during the COVID-19.

Predictive biomarkers and tumor microenvironment in female genital melanomas: a multi-institutional study of 55 cases.

Female genital melanomas are rare. At diagnosis, most affected patients have advanced disease. Surgery remains the primary treatment, and adjuvant therapy is largely ineffective. Recently, immune checkpoints and the mitogen-activated protein kinase pathway have been explored as treatment targets. However, evaluation of these biomarkers in genital melanomas is limited. We evaluated the clinicopathological features of 20 vulvar, 32 vaginal, and three cervical melanomas and assessed programmed cell death ligand 1 (PD-L1) expression, CD8 tumor-infiltrating lymphocyte density, mismatch repair proteins, VE1 immunohistochemistry, and KIT and BRAF mutations. The median age of the patients was 66 years, and median tumor sizes were 25, 30, and 20 mm for vulvar, vaginal, and cervical tumors, respectively. Mean mitotic figures were 18, 19, and 30 per mm2. Thirty-seven patients (67%) had operable tumors. After a median follow-up of 15 months, only nine patients (16%) were alive. Eight of the nine survivors did not have lymph node metastasis. Using 5% as the threshold, PD-L1 expression was observed in 55%, 50%, and 33% of vulvar, vaginal, and cervical tumors, respectively, when the Roche SP263 antibody was used and 20%, 53%, and 0%, respectively, when the Dako 28-8 antibody was used. The median CD8 tumor-infiltrating lymphocyte density was significantly higher in vulvar/vaginal than cervical melanomas and correlated with PD-L1 expression. No cases exhibited loss of mismatch repair proteins. Five cases harbored KIT mutations, three of which were hotspots. BRAF V600E mutation was not detected. Univariable analysis showed that tumor size greater than or equal to 33 mm, mitotic figures of greater than or equal to 10 per mm2, lymph node metastasis, and low CD8+ tumor-infiltrating lymphocyte density were adverse prognostic factors. Thus, patients with genital melanomas have a poor prognosis, and evaluation of multiple biomarkers is necessary to identify patients who may benefit from immunotherapy or targeted therapy.

MRI texture features differentiate clinicopathological characteristics of cervical carcinoma.

OBJECTIVES: To evaluate MRI texture analysis in differentiating clinicopathological characteristics of cervical carcinoma (CC). METHODS: Patients with newly diagnosed CC who underwent pre-treatment MRI were retrospectively reviewed. Texture analysis was performed using commercial software (TexRAD). Largest single-slice ROIs were manually drawn around the tumour on T2-weighted (T2W) images, apparent diffusion coefficient (ADC) maps and contrast-enhanced T1-weighted (T1c) images. First-order texture features were calculated and compared among histological subtypes, tumour grades, FIGO stages and nodal status using the Mann-Whitney U test. Feature selection was achieved by elastic net. Selected features from different sequences were used to build the multivariable support vector machine (SVM) models and the performances were assessed by ROC curves and AUC. RESULTS: Ninety-five patients with FIGO stage IB~IVB were evaluated. A number of texture features from multiple sequences were significantly different among all the clinicopathological subgroups (p < 0.05). Texture features from different sequences were selected to build the SVM models. The AUCs of SVM models for discriminating histological subtypes, tumour grades, FIGO stages and nodal status were 0.841, 0.850, 0.898 and 0.879, respectively. CONCLUSIONS: Texture features derived from multiple sequences were helpful in differentiating the clinicopathological signatures of CC. The SVM models with selected features from different sequences offered excellent diagnostic discrimination of the tumour characteristics in CC. KEY POINTS: • First-order texture features are able to differentiate clinicopathological signatures of cervical carcinoma. • Combined texture features from different sequences can offer excellent diagnostic discrimination of the tumour characteristics in cervical carcinoma.

Molecular Imaging of Peritoneal Carcinomatosis in Ovarian Carcinoma.

OBJECTIVE. This article discusses the emerging roles of 18F-FDG PET/CT and DWI in the assessment of peritoneal carcinomatosis in ovarian carcinoma from diagnostic accuracy to disease prognostication with gross pathologic correlation. CONCLUSION. PET/CT and DWI have incremental clinical values over conventional modalities with high predictive values of incomplete cytoreduction in ovarian carcinoma. The respective quantitative metrics offer evaluation of tumor burden with prognostic value in ovarian carcinoma.

Nurse-led follow-up in survivorship care of gynaecological malignancies-A randomised controlled trial.

OBJECTIVE: To assess clinical and psychosocial outcomes of nurse-led follow-up in survivorship care of gynaecological malignancies. METHODS: Women with endometrial or ovarian cancer who were attending regular post-treatment follow-up at a tertiary referral centre were randomised into two groups-group-1: telephone follow-up by nurses and group-2: gynaecologists-led clinic follow-up. Women in group-1 were asked about their symptoms and quality of life (QoL) by nurses. Women in group-2 were followed up by gynaecologists and underwent symptom reviews and physical examinations. All ovarian cancer patients in both groups also had CA125 measured. All recruited women completed a QoL questionnaire (EORTC QLQ-C30), HADS-anxiety questionnaire and symptom checklist. RESULTS: 385 women (215 with endometrial and 170 with ovarian cancer) were randomised. There was no significant difference in the detection of recurrence according to the two follow-up protocols. However, women in the nurse-led arm scored higher on emotional (p = 0.023) and cognitive functioning (p = 0.012). Those in the gynaecologist-led arm scored higher on the HADS-anxiety scale (p = 0.001) and were more likely to report symptoms. CONCLUSIONS: Our results demonstrate a preliminary non-inferiority of nurse-led follow-up, with improved psychological morbidity and QoL. Thus, nurse-led follow-up can be considered an effective substitute for hospital-based care.

Impact of iASPP on chemoresistance through PLK1 and autophagy in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival. The growth of OCCC cell lines, OVTOKO and KK, were inhibited after iASPP silencing. Such effect was related to senescence triggering as evidenced by increased SA-ß-Gal staining and p21WAF1/Cip1 expression. Moreover, knockdown of iASPP induced PLK1 downregulation, whereas either genes' silencing sensitized the cells in response to cisplatin treatment. More prominent apoptosis was induced by cisplatin in OCCC cells after the knockdown of either iASPP or PLK1 as evidenced by the formation of more cleaved caspase 3. Heightened chemosensitivity to cisplatin after iASPP knockdown was further demonstrated in in vivo xenograft model. Additionally, both iASPP and PLK1 were shown to regulate autophagic flux as the induction of LC3B-II and LC3 puncta were much less in OCCC cells with either knockdown. Importantly, inhibition of autophagy also enhanced chemosensitivity to cisplatin in OCCC cells. These findings strongly imply that iASPP and PLK1 affect the chemoresistance of OCCC via the regulation of autophagy and apoptosis. Both iASPP and PLK1 can be potential therapeutic targets for treating OCCC in combination with conventional chemotherapy.

The mitosis-specific marker phosphohistone-H3 (PHH3) is an independent prognosticator in uterine smooth muscle tumours: an outcome-based study.

AIMS: Accurate mitosis counting, which is important in the diagnosis of uterine smooth muscle tumours (USMTs), is often difficult and subjective. The mitosis-specific immunohistochemical marker phosphohistone-H3 (PHH3) has been shown to be diagnostically useful, but its expression, in relation to outcome, has not been thoroughly investigated. The aim of this study is to evaluate PHH3 as a diagnostic and prognostic marker in USMTs. METHODS AND RESULTS: PHH3 expression was evaluated in 55 leiomyosarcomas (LMSs), 26 smooth muscle tumours of uncertain malignant potential (STUMPs), 18 leiomyomas with bizarre nuclei (LBN), and 12 leiomyomas (LMs). Scores were expressed as counts per 10 high-power fields (HPFs). Median follow-up durations of patients with LMS, STUMP, LBN and LM were, respectively, 39, 78, 65.5 and 49.5 months. Twenty-eight patients with LMSs (50.9%) died, and two (7.7%) patients with STUMPs experienced recurrence. The median PHH3 scores for LMSs were significantly higher than those for other categories of tumour. A score of ≥29/10 HPFs was also independently associated with a poor outcome. To test whether the PHH3 score could distinguish between benign USMTs with atypical histology and those that were clinically malignant, two biological groups were further delineated. Patients in group 1 (18 LBNs and 24 STUMPs) all had an uneventful outcome, whereas patients in group 2 (two recurrent STUMPs and 32 LMSs) all had a recurrence or tumour-related death. Median PHH3 scores for the two groups were, respectively, 2/10 HPFs and 27/10 HPFs. A PHH3 score of ≥7/10 HPFs was highly associated with malignancy. CONCLUSION: PHH3 is useful in evaluation of the biological behaviour of USMTs, and may serve as a prognostic indicator for LMSs.

Successful Treatment of a Pararenal Pregnancy Using High-Dose Methotrexate Regimen: A Case Report.

Background: Upper abdominal pregnancy is rare. Most patients present with hemoperitoneum, requiring emergency laparotomy. Case: A 32-year-old woman presented with acute abdominal pain and an elevated beta-human chorionic gonadotropin (ß-hCG) level. Ultrasound, computerized tomography (CT) scans, and laparoscopy failed to locate the source of elevated hCG. Subsequent positron emission tomography (PET)-CT demonstrated a cystic mass in the left pararenal region with no increased uptake. Repeated ultrasound scan revealed a live fetus implanted laterally to the abdominal aorta. After failing to respond to methotrexate at the usual dosage, a regimen used in gestational trophoblastic neoplasia was given. The pregnancy underwent miscarriage afterwards, and the hCG level gradually returned to normal. Conclusion: The site of an ectopic pregnancy should be sought thoroughly to avoid missing an abdominal pregnancy and hence disastrous hemoperitoneum. While medical therapy with high-dose methotrexate is not a standard treatment, it can be considered after failing the traditional therapy, provided that there is adequate treatment monitoring and expertise in handling the side effects of the medication.

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.

Relationship between intravoxel incoherent motion diffusion-weighted MRI and dynamic contrast-enhanced MRI in tissue perfusion of cervical cancers.

PURPOSE: To investigate the relationship between intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) and dynamic contrast-enhanced MRI (DCE-MRI) in cervical cancer perfusion. MATERIALS AND METHODS: Prospective newly diagnosed cervical cancer patients underwent diffusion-weighted MRI (13 b-values: 1-1000 s/mm(2) ) and DCE-MRI. The IVIM perfusion parameters, perfusion fraction (f), pseudodiffusion coefficient (D*), and flow-related parameter (fD*), were derived from a biexponential decay model. DCE-MRI was analyzed with a pharmacokinetic model and signal-time curve to derive the amplitude factor (A), estimated volume transfer constant between blood plasma, and the extravascular extracellular space (est K(trans) ), maximum relative enhancement (MaxRE), and area under the signal-time curve (AUC). Spearman's rank correlation coefficient (r) evaluated the correlative relationships. RESULTS: The f = 13.51% ± 1.76%, D* = 71.72 ± 7.55 × 10(-3) mm(2) /s, fD* = 9.64 ± 1.28 × 10(-3) mm(2) /s, A = 1.41 ± 0.43, est K(trans) = 0.19 ± 0.06 s(-1) , MaxRE of 120.02 ± 21.07%, and AUC 212,393 ± 54,423 was found in 25 cervical cancer patients. Statistically significant positive correlations were found between fD* and est K(trans) (r = 0.42, P = 0.038), fD* and A (r = 0.50, P = 0.011), fD* and MaxRE (r = 0.52, P = 0.008), f and AUC (r = 0.58, P = 0.003). CONCLUSION: The IVIM perfusion parameters showed moderate to good correlations with quantitative and semiquantitative perfusion parameters derived from DCE-MRI in cervical cancer.

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.

PET/Computed Tomography Transformation of Oncology: Ovarian Cancers.

Over the last quarter of a century, fluorine-18-fluorodeoxyglucose (FDG) PET/computed tomography (CT) has revolutionized the diagnostic algorithm of ovarian cancer, impacting on the initial disease evaluation including staging and surgical planning, treatment response assessment and prognostication, to the most important role in detection of recurrent disease. The role of FDG PET/CT is expanding with the adoption of new therapeutic agents. Other non-FDG tracers have been explored with fibroblast activation protein inhibitor being promising. Novel tracers may provide the basis for future theragnostic work. This article will review the evolution and impact of PET/CT in ovarian cancer management.

Comparison of the multiples of the median of serum anti-müllerian hormone and pregnancy outcomes in patients with gestational trophoblastic disease: A case-control study.

INTRODUCTION: Chemotherapy is crucial in treating gestational trophoblastic neoplasia (GTN), but its impact on gonadotoxicity is unclear. MATERIALS AND METHODS: This case-control study included 57 GTN patients and 19 age-matched patients with molar pregnancies (MP) in 2012-2018. Multiples of the median (MoM) of the serum AMH levels were compared between the two groups, and between patients using single-agent and combination chemotherapy, at baseline, 6, 12, and 24 months after treatment. Their pregnancy outcomes were also compared. RESULTS: There was no significant difference in the MoM of serum AMH between GTN and MP groups at all time points. Single-agent chemotherapy did not adversely affect the MoM. However, those receiving combination chemotherapy had lower MoM than those receiving single-agent chemotherapy at all time points. The trend of decline from the baseline was marginally significant in patients with combination chemotherapy, but the drop was only significant at 12 months (Z = -2.69, p = 0.007) but not at 24 months (Z = -1.90; p = 0.058). Multivariable analysis revealed that combination chemotherapy did not affect the MoM. There was no significant difference in the 4-year pregnancy rate and the livebirth rate between the single-agent and combination groups who attempting pregnancy, but it took 1 year longer to achieve the first pregnancy in the combination group compared to the single-agent group (2.88 vs. 1.88 years). CONCLUSION: This study showed combination chemotherapy led to a decreasing trend of MoM of serum AMH especially at 12 months after treatment, but the drop became static at 24 months. Although pregnancy is achievable, thorough counseling is still needed in this group especially those wish to achieve pregnancy 1-2 years after treatment or with other risk factors.

Inhibition of aberrantly overexpressed Polo-like kinase 4 is a potential effective treatment for DNA damage repair-deficient uterine leiomyosarcoma.

PURPOSE: Uterine leiomyosarcoma (LMS) is an aggressive sarcoma and a subset of which exhibit DNA repair defects. Polo-like kinase 4 (PLK4) precisely modulates mitosis, and its inhibition causes chromosome missegregation and increased DNA damage. We hypothesize that PLK4 inhibition is an effective LMS treatment. EXPERIMENTAL DESIGN: Genomic profiling of clinical uterine LMS samples was performed, and homologous recombination (HR) deficiency scores were calculated. PLK4 inhibitor (CFI-400945) with and without an ataxia telangiectasia mutated (ATM) inhibitor (AZD0156) were tested in vitro on gynecological sarcoma cell lines SK-UT-1, and SKN, and SK-LMS-1. Findings were validated in vivo using the SK-UT-1 xenograft model in Balb/c nude mouse model. The effects of CFI-400945 were also evaluated in a BRCA2 knockout SK-UT-1 cell line. The mechanisms of DNA repair were analyzed using a DNA damage reporter assay. RESULTS: Uterine LMS had a high HR deficiency score, overexpressed PLK4 mRNA, and displayed mutations in genes responsible for DNA repair. CFI-400945 demonstrated effective antitumor activity in vitro and in vivo. The addition of AZD0156 resulted in drug synergism, largely due to a preference for nonhomologous end-joining (NHEJ) DNA repair. Compared to wild-type cells, BRCA2 knockouts were more sensitive to PLK4 inhibition when both HR and NHEJ repairs were impaired. CONCLUSIONS: Uterine LMS with DNA repair defects is sensitive to PLK4 inhibition because of the effects of chromosome missegregation and increased DNA damage. Loss-of-function BRCA2 alterations or pharmacological inhibition of ATM enhanced the efficacy of PLK4 inhibitor. Genomic profiling of an advanced-stage or recurrent uterine LMS may guide therapy.