Significance of Pretreatment Hemoglobin-Albumin-Lymphocyte-Platelet Index for the Prediction of Suboptimal Surgery in Epithelial Ovarian Cancer.

Background: Epithelial ovarian cancer (EOC) is the leading cause of death in gynecological cancers in developed countries. In recent years, there has been a growing need for economical and accurate pretreatment laboratory investigations to assess the prognosis of patients with advanced EOC (AEOC). We aimed to investigate the role of the hemoglobin-albumin-lymphocyte-platelet (HALP) index in suboptimal cytoreduction and oncological outcomes. Methods: A prognostic prediction model for diagnosing suboptimal cytoreduction for patients with AEOC receiving neoadjuvant chemotherapy (NACT) was developed. Multivariate logistic regression analysis was performed to identify the independent predictors of suboptimal cytoreduction, with a P-value < 0.05, and then transformed into risk-scoring systems. Internal validation was performed using the bootstrapping procedure, and predictive cytoreduction (PSC) scores were compared using non-parametric receiver operating characteristic (ROC) regression. Survival analysis was performed using Kaplan-Meier estimation and Cox proportional regression. Results: In total, 473 patients were analyzed, and the rate of suboptimal surgery was 43%. A scoring system in predicting suboptimal cytoreduction included age, cancer antigen (CA)-125 level before surgery, performance status, cycles of chemotherapy, peritoneal cancer index, and HALP index ≤ 22.6. The model had good discriminative ability (area under the ROC (AUROC), 0.80; 95% confidence interval (CI), 0.76 - 0.84), outperforming the PSC score (AUROC, 0.75; 95% CI, 0.71 - 0.80). The score was divided into the low-risk (positive predictive value (PPV), 22.4; 95% CI, 17.8 - 27.7), moderate-risk (PPV, 65.9; 95% CI, 56.9 - 74.0), and high-risk (PPV, 90.6; 95% CI, 79.3 - 96.9) groups. The HALP index score of ≤ 22.6 was independently associated with progression-free survival (hazard ratio (HR), 2.92; 95% CI, 1.58 - 5.40) and overall survival (HR, 2.66; 95% CI, 1.57 - 4.49). Conclusion: The HALP index is a newly predicted factor for suboptimal cytoreduction and oncological outcomes in patients with AEOC after NACT.

Clinical Outcomes and Their Prognostic Factors among Cervical Cancer Patients with Bone Recurrence.

Background: Bone recurrence occurs in 0.75%-8% of cervical cancer patients after primary treatment. Only a few previous studies have reported on survival times associated with prognostic factors for bone recurrent cervical cancer. This study aimed to evaluate the oncological outcomes and their predictors among cervical cancer patients with bone recurrence. Methods: The medical records of cervical cancer patients with bone recurrence who received primary treatment at Songklanagarind Hospital from January 2002 to December 2017 were retrospectively reviewed. Prognostic factors were identified using a Cox regression model. Results: The study included 6,354 cervical cancer patients, of whom 98 (1.54%) had bone recurrence at a median time of 25 months after the primary treatment (range 4.9-136 months). The most frequent site of bone recurrence was the spine (81.00%); the two most common visceral coexisting recurrence sites were the lungs and the liver. The median recurrence-free interval (RFI) was 21 months. Of the patients with recurrence, 75 (76.50%) were treated with combined radiation therapy and chemotherapy. The one-year overall survival (OS) after recurrence was 22.70%. On multivariate analysis, age under 60 years at the time of recurrence diagnosis (hazard ratio [HR] = 2.48, 95% CI = 1.47-4.18, p=0.001) and an RFI less than 21 months (HR = 1.63, 95% CI = 1.04-2.55, p=0.03) were independent prognostic factors for OS after recurrence. Conclusion: Bone recurrence in cervical cancer patients is rare and is associated with poor survival. Our study found that age and RFI were significant prognostic factors for OS in cervical cancer patients with bone recurrence.

Microsatellite instability and oncological outcomes in Thai patients with endometrial cancer.

Here, we determined the frequency of microsatellite instability (MSI) and the impact of MSI-high (MSI-H) on clinical outcomes of Thai patients with endometrial cancer (EC). Tissue samples of 110 Thai patients with EC, who had undergone surgical staging, were tested for mismatch repair (MMR) gene deficiency, and the patients were grouped into MSI-H and MSI-stable (MSI-S) groups; 24.5% had MSI-H. Unlike MSI-S group patients, MSI-H group patients had synchronous and metachronous cancer. They showed better 3-year disease-free survival (DFS) than those in the MSI-S group (p=.182; 92.3% vs. 82.6%). The 3-year overall survival was 96.2% in MSI-H and 86.4% in MSI-S groups (p=.163). Multivariate analyses showed lower uterine involvement (p=.004), myometrial invasion ≥50% (p=.032), lymphovascular space invasion (p<.001) and MSI-S (p=.006) as prognostic factors for DFS. Our study showed that the prevalence of MMR gene deficiency in Thai patients with EC is common and associated with better outcomes.Impact StatementWhat is already known on this subject? Microsatellite instability (MSI) occurs in approximately 20-40% of endometrial cancer (EC) cases. MSI analysis in EC can identify patients at higher risk of hereditary nonpolyposis colorectal cancer and those having prognostic factors. Additionally, it is predictive of immune checkpoint inhibitor treatment. However, current evidence shows a correlation between clinicopathological characteristics and EC prognosis. Studies on EC and MSI status effect on survival outcome have yielded inconsistent results regarding the pathological significance of MSI in such malignancies.What do the results of this study add? The prevalence of mismatch repair (MMR) gene deficiency in Thai patients with EC is common (24.5%) and associated with better outcomes.What are the implications of these findings for clinical practice and/or further research? This study highlights the prevalence and impact of MSI on oncological outcomes in patients with EC in a low-incidence country. Future studies should focus on the detection of germline mutation to understand the accurate prevalence of Lynch syndrome in Thai patients with EC.

Salvage Treatment and Outcomes of Locally Advanced Cervical Cancer after Failed Concurrent Chemoradiation with or without Adjuvant Chemotherapy: Post Hoc Data Analysis from the ACTLACC Trial.

OBJECTIVES: To evaluate the type of salvage treatment and outcomes of patients with locally advanced cervical cancer who failed treatment with concurrent chemoradiation with or without adjuvant chemotherapy. METHODS: This was post hoc analyses of data from the randomized trial which included 259 patients who had FIGO stage IIB-IVA and had either pelvic radiation therapy concurrent with cisplatin followed by observation or paclitaxel plus carboplatin. Data of the patients who failed primary treatment were collected: type of salvage treatments, time to progress after salvage therapy, progression-free (PFS) and overall survivals (OS). RESULTS: After primary treatment, 85 patients had either persistence (36.5%), progression (18.8%), or recurrences (44.7%). The sites of failure were loco/regional in 52.9%, systemic failure in 30.6%, and loco-regional and systemic in 16.5%. Chemotherapy was given in 51.8%, being the sole therapy in 34.1%. Majority were combination agents (31.8%), with paclitaxel/carboplatin as the most common regimen. Radiation to the metastatic sites along with chemotherapy was used in 14.1% whereas palliative radiation therapy or supportive care was used in approximately 10% of each. The median time from the start of salvage treatment to progression was 9.2 months (range 0.2-64.0 months) with median PFS of 11.2 months (95% CI, 7.2-15.3 months). Median overall survival 27.3 months (95% CI, 4.4-69.6 months). CONCLUSIONS: Chemotherapy, either alone or with radiation therapy, was the most common salvage treatment in LACC after failure from primary treatment. The time to progress and PFS were less than 1 year with OS of approximately 2 years.

Intraoperative blood volume loss according to gestational age at delivery among pregnant women with placenta accreta spectrum (PAS): an 11-year experience in Songklanagarind Hospital.

A retrospective study was conducted to evaluate the intraoperative blood volume loss in pregnant women with PAS according to gestational age at delivery. A total of 116 women were enrolled, 39 (33.6%) had an intraoperative massive blood loss (>5000 ml). The massive haemorrhage group had statistically significantly higher percentages of increta and percreta type than the non-massive haemorrhage group (94.9 vs. 67.5%, p < .001). Multiple linear regression analysis showed a decreasing trend of intraoperative blood loss after 34 weeks' gestation with the nadir period between 35 and 36+6 weeks' gestation, especially from 36-36+6 weeks' gestation which was statistically significant, p <.05. The perinatal morbidities from 36-36+6 weeks were not statistically significantly different from 37 weeks' gestation. Therefore, we recommend that pregnant women with PAS and stable clinical symptoms should be scheduled for caesarean hysterectomy from 36-36+6 weeks' gestation.Impact statementWhat is already known on this subject? Massive obstetric haemorrhage from PAS disorders is the main concern for caesarean hysterectomy among these patients as it leads to secondary complications including coagulopathy, multisystem organ failure, and death.What do the results of this study add? The amount of intraoperative blood loss in pregnant women who underwent caesarean hysterectomy due to PAS, was lowest from 36-36+6 weeks' gestation.What are the implications of these findings for clinical practice and/or further research? We recommend that pregnant women with PAS and stable clinical symptoms should be scheduled for caesarean hysterectomy from 36-36+6 weeks' gestation.

Long-Term Outcomes and Sites of Failure in Locally Advanced, Cervical Cancer Patients Treated by Concurrent Chemoradiation with or without Adjuvant Chemotherapy: ACTLACC Trial.

OBJECTIVES: To evaluate sites of failure and long-term survival outcomes of locally advanced stage cervical cancer patients who had standard concurrent chemo-radiation (CCRT) versus those along with adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had FIGO stage IIB-IVA without para-aortic lymph node enlargement (excluding by International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC2r), The Eastern Cooperative Oncology Group (ECOG) scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: From 2015-2017, 259 patients were evaluated. The majority of patients were in stage II and had squamous cell carcinoma with a median tumor size of 5 cm. After the median follow-up of 40.87 months, 17.1% of the patients in arm A and 12.3% of the patients in arm B experienced recurrences (p=0.280). Adding all events of failure (persistence/progression/recurrence), treatment failures tended to be lower in arm A than in arm B: 13.2 versus 21.5 % for loco-regional failure (p = 0.076) and 3.9 versus 6.9% for loco-regional failure and systemic failure (p = 0.278). On the other hand, systemic failure tended to be higher in arm A than in arm B: 13.2% versus 6.9% (p =0.094). The 5-year progression-free survival and 5-year overall survival of patients in both arms were not significantly different. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response or survival of patients compared to CCRT alone. Although systemic failure tended to be lower in patients who had ACT after CCRT than those who had only CCRT, loco-regional failure with or without systemic failure tended to be higher. However, all of these differences were not statistically significant.

Validation of the Functional Assessment of Cancer Therapy with Cervical Cancer Subscale (FACT-CX) for Quality of Life in Thai Patients Prior to Chemoradiotherapy.

OBJECTIVE: Cervical cancer is the second most common cancer in Thailand. For cervical cancer, there is no cancer specific quality of life questionnaire. This study aims to develop and validate Thai FACT-CX. METHODS: The cross-sectional study included all women aged ≥18 years with stage IB2-IIIB who planned to undergo chemoradiotherapy. Those who did not understand Thai language, had other cancers (except for skin cancer), were diagnosed with impaired cognition and/or overt psychosis, and major depression were excluded. The FACT-CX comprises 42 items with 5 domains and a score range of 0-168. The WHOQOL-BREF comprises 26 items with 4 domains and a score range of 26-130. The participants were interviewed about demographic and clinical data. Both questionnaires were self-completed.  Factor analysis was used to compare our data with the previous structure. The reliability used Cronbach's alpha. Spearman's correlation determined relationship between the domains of the modified FACT-CX and WHOQOL-BREF. Both questionnaires were compared with socioeconomic and clinical variables using the Ranksum test and Kruskal-Wallis test. P-value > 0.05 considered significant. RESULTS: The 245 participants included. Expletory factor analysis revealed an accumulative variance of 0.42 with 4 factors. The internal consistency was 0.84, 0.81, 0.78, 0.77 and 0.90 for perception of self, suffering symptoms, family support, life resilience and total questions. There was correlation between the domains of the modified FACT-CX and WHOQOL-BREF.  Both the modified FACT-CX and WHOQOL-BREF could identify differences between the groups of patients. CONCLUSION: Finally, the Thai modified FACT-CX was found to be reliable and valid for measuring quality of life among untreated cervical cancer patients.
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A randomized controlled trial comparing concurrent chemoradiation versus concurrent chemoradiation followed by adjuvant chemotherapy in locally advanced cervical cancer patients: ACTLACC trial.

OBJECTIVE: To compare response rate and survivals of locally advanced stage cervical cancer patients who had standard concurrent chemoradiation therapy (CCRT) alone to those who had adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had International Federation of Gynecology and Obstetrics stage IIB-IVA without para-aortic lymph node enlargement, Eastern Cooperative Oncology Group scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or by ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: Data analysis of 259 patients showed no significant difference in complete responses at 4 months after treatment between arm A (n=129) and arm B (n=130): 94.1% vs. 87.0% (p=0.154) respectively. With the median follow-up of 27.4 months, 15.5% of patients in arm A and 10.8% in arm B experienced recurrences (p=0.123). There were no significant differences of overall or loco-regional failure. However, systemic recurrences were significantly lower in arm B than arm A: 5.4% vs. 10.1% (p=0.029). The 3-year progression-free survival (PFS) and 3-year overall survival (OS) of the patients in both arms were not significantly different. The hazard ratio of PFS and OS of arm B compared to arm A were 1.26 (95% CI=0.82-1.96; p=0.293) and 1.42 (95% CI=0.81-2.49; p=0.221) respectively. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response rate and survival compared to CCRT alone. Only significant decrease of systemic recurrences with ACT was observed, but not overall or loco-regional failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036164, Thai Clinical Trials Registry Identifier: TCTR 20140106001.

Complete hydatidiform mole with co-existing fetus: Predictors of live birth.

Multiple gestation consisting of complete hydatidiform mole with co-existing fetus (CHMCF) is unusual. From our institution, we reported two cases with unfavorable obstetric consequences. The recommendation for antenatal management is still not distinctly determined. Therefore, the aim of this article was to review the literature according to the predictors of infant survival and to develop a management guidance for pregnancy with CHMCF. Between January 1, 1993 and May 31, 2016, 12 case series and 89 case reports comprising of 204 pregnant women were identified. The pregnancies successfully delivered 78 live births (37.86%). For clinical symptoms, pregnant women with antenatal complications, including pregnancy-induced hypertension (PIH), hyperthyroidism (HTD) and hyperemesis gravidarum (HG), significantly developed adverse perinatal events. Low hCG blood level was the best predictor of fetal survival (P=0.006). We developed a model using logistic regression analysis which was enhanced by including an hCG cut-off level of 400,000mIU/mL. On the basis of our intensive review, we suggest that the patient with CHMCF without antenatal obstetric problems especially PIH, HTD and HG together with initial serum hCG level less than 400,000mIU/mL is a good candidate for pregnancy continuation and reaching fetal viability.

Prognostic value of ABO blood group in patients with early stage cervical cancer treated with radical hysterectomy with pelvic node dissection.

This study aimed to evaluate the prognostic value of ABO blood groups in early-stage cervical cancer patients. The cohort included 413 patients diagnosed with stages IA2-IB1 cervical cancer who received a radical hysterectomy between 2002 and 2014. The 5-year recurrence-free survival (RFS) and overall survival (OS) were 93.13 and 96.81 % for blood group O, 87.68 and 88.22 % for blood group A, 81.66 and 89.40 % for blood group B, and 83.12 and 94.12 % for blood group AB groups, respectively. Patients were stratified for analysis as either blood group O or non-O. The 5-year RFS and OS were 93.13 and 96.81 % for blood group O and 83.66 and 89.76 % for blood group non-O, respectively. In multivariate analysis, age (P = 0.025), histology (P = 0.020), and deep stromal invasion (P = 0.006) were independent adverse prognostic factors for RFS, while the statistically significant independent prognostic factors for OS were age (P = 0.007) and parametrial involvement (P < 0.001). The Cox model did not show any significant effects of non-O blood group on survival outcome. However, a time-varying-effect Cox model revealed that the non-O blood group was associated with a worse RFS (hazard ratio (HR) 2.69, 95 % confidence interval (95%CI) 1.12-6.46, P = 0.017) and OS (HR 3.13, 95%CI 0.88-11.16, P = 0.053) during the first 5 years. These findings suggest that early-stage cervical cancer patients with a non-O blood group have poorer RFS than the O blood group, which is evidence during the first 5 years.

Cytomorphologic and clinical factors of having high-grade cervical intraepithelial neoplasia/invasive carcinoma in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) smears.

OBJECTIVE: To determine the predictors for high-grade cervical intraepithelial neoplasia (CIN)/invasive carcinoma in women with atypical squamous cells, cannot exclude the high-grade squamous intraepithelial lesion (ASC-H) smears. MATERIAL AND METHOD: All women with ASC-H, who underwent colposcopy and had histolopathologic diagnosis between January 2004 and December 2011, were recruited. Clinical and cytomorphologic features were correlated with final histological diagnosis. Univariate and multivariate analysis were used to determine predicting factors for high-grade CIN/ invasive cancer RESULTS: Among 136,638 smears performed, 193 (0.14%) smears were reported as ASC-H and 121 smears were available for review. The underlying pathology were negative/reactive (N/R) 57 (47.1%), CIN 1 23 (19.0%), CIN 2-3 39 (32.0%), and invasive cancer 2 (1.6%). On univariate analysis, predicting factors of having high-grade CIN included a high N/C ratio, greater nuclear hyperchromasia, nuclear membrane irregularities, and the coarse chromatin. The multivariate analysis showed that a high nuclear-to-cytoplasmic (N/C) ratio (OR = 8.6, 95% CI = 1.1-70.1) and greater nuclear hyperchromasia (OR = 5.8, 95% CI = 1.6-20.8) were the independent predictors for high-grade CIN or invasive carcinoma. CONCLUSION: The presence of a high N/C ratio and greater nuclear hyperchromasia could be used to predict high-grade CIN or invasive carcinoma in ASC-H smears.