Vaginal Microbiota and Pregnancy Outcomes of Patients with Conization Histories.

Background: One of the major risks of preterm birth is a history of conization. However, the risk of infection due to this procedure is still not well known. Using next-generation sequencing, we aimed to reveal the influence of conization on vaginal microbiota in the following pregnancy, and their relationship between spontaneous preterm birth (sPTB). Methods: We conducted a prospective cohort study including 133 pregnant patients, of whom 25 had conization histories and 108 did not. Vaginal microbiome samples were collected using swabs by an obstetrician upon inclusion in the first trimester and during delivery. V1-V2 of the 16S rRNA gene were amplified and analyzed to identify the bacteria. Results: The conization group had a significantly lower delivery week (34 weeks vs. 36 weeks, p = 0.003) and higher sPTB rate (64% vs. 8.3%, p ≤ 0.001) than the control group. In the conization group, alpha (Chao 1, p = 0.02; phylogenetic diversity whole tree, p = 0.04) and beta diversity (permutational multivariate analysis of variance test, p = 0.04) of the vaginal microbiota was significantly higher during delivery in patients who delivered preterm than in those who delivered term. Community-state type IV in the first trimester was significantly associated with sPTB (overall odds ratio 3.80, 95% confidence interval 1.33-10.8, p = 0.01). Conclusions: Conization is a risk factor for sPTB. Increased risk of sPTB in patients after conization may belong to the vulnerable defense mechanism, due to the shortened cervix and decreased cervical mucus.

Risk Factors of Preterm Birth in Okinawa Prefecture, the Southernmost Island Prefecture of Japan.

OBJECTIVES: A high rate of preterm birth has been reported in Okinawa Prefecture, the southernmost island prefecture of Japan. Hence, this study aimed to identify the risk factors for preterm birth in this prefecture. METHODS: This retrospective study included data from January 2013 to December 2019 from three facilities in Okinawa Prefecture. Of 13,468 cases of preterm birth at ≥ 22 weeks of gestation, 11,868 were included in this study. Stillbirth and multiparity cases were excluded. First, we compared the overall preterm and full-term birth groups by categorizing the patient background, obstetric, and fetal risk factors. Further, we categorized preterm births into three groups (22-27, 28-33, and 34-36 weeks of gestation) and examined patient background factors to identify potential risk factors for the occurrence of preterm birth in each group. RESULTS: Preterm births accounted for 21.2% (2,521 cases) of all cases, with the rates of 2.6% (317 cases), 6.7% (800 cases), and 11.8% (1,404 cases) at 22-27, 28-33, and 34-36 weeks of gestation, respectively. To prevent preterm birth in Okinawa Prefecture, the present study specifically focused on patient background characteristics. In the multinomial logistic regression, the risk factors for preterm birth at 22-27 weeks of gestation were previous preterm birth (P < 0.0001) and lower age (P = 0.026); at 28-33 weeks of gestation, the risk factors were previous preterm birth (P < 0.0001) and history of cervical conization (P = 0.009); and at 34-36 weeks of gestation, only previous preterm birth (P < 0.0001) was a risk factor. CONCLUSIONS FOR PRACTICE: Previous preterm birth, younger age, and history of cervical conization were risk factors for Preterm birth in Okinawa. To reduce premature births in Okinawa Prefecture, it is important to pick up women with these risk factors and provide them with appropriate guidance and education on an ongoing basis.

Performance evaluation of a novel reticulocyte identification method that uses metachromatic nucleic acid staining based on a crossover analysis of emission DNA/RNA light (RNP Determination™) in hematology analyzer Celltac G.

INTRODUCTION: Assessing the percentage of reticulocytes (%Retic) is useful for diagnosing and treating blood diseases that present with anaemia. The Celltac G+™ hematology analyzer (HA) uses a novel reticulocyte identification method that involves metachromatic nucleic acid staining with acridine orange and crossover analysis of emission light of DNA/RNA (determination of red cells, nucleic acid-containing cells, and platelets, RNP Determination™). The red and green fluorescence generated by stained single-stranded RNA and double-stranded DNA express immaturity and morphological abnormality of erythrocytes by detecting erythrocyte RNA and DNA content. METHODS: The basic performance of the test automated analyzer (TAA) Celltac G+ was evaluated and compared with the flow cytometry reference method and the comparative automated analyzer (CAA) XN-1000/2000™. In addition, its precision, limit of quantity (LoQ), linearity, analytical measurement interval (AMI), accuracy, and comparability and the effects of interfering substances were evaluated. RESULTS: Evaluation of %Retic by the TAA demonstrated good precision and linearity. The AMI was confirmed from 0.02 to 8.23, and the LoQ in %Retic as the coefficient of variation within an 11% limit (SD, within a 0.01 limit) was 0.14. TAA correlated well with the reference method and routine HA (CAA). Some deviations were found between TAA and CAA in DNA measurements of erythrocytes from abnormal samples. CONCLUSION: Celltac G+ uses a novel measurement principle and can assess erythrocyte immaturity independent of DNA contents. It represents a new HA that provides novel, useful information on immaturity and morphological abnormality of erythrocytes.

2021 update of the 2012 ICSH Recommendations for identification, diagnostic value, and quantitation of schistocytes: Impact and revisions.

In 2012, the International Council for Standardization in Hematology (ICSH) published recommendations for the identification, quantitation, and diagnostic value of schistocytes. In the present review, the impact of these recommendations is evaluated. This work is based on citations in peer-reviewed papers published since 2012. The first 2012 ICSH Recommendations have also been revised to incorporate newly published data in the literature and current best laboratory practice. Recommended reference ranges have been proposed for healthy adults and full-term neonates of 1% or less schistocytes. More than 1% of morphologically identified schistocytes on the blood film are considered suspicious for thrombotic microangiopathy. For preterm infants, a normal level of 5% or less is recommended. The fragment red cell count (FRC) generated by some automated hematological analyzers provides a valuable screening tool for the presence of schistocytes. Specifically, the absence of FRCs can be used as a valuable parameter to exclude the presence of schistocytes on the blood film. The validity and usefulness of microscope schistocytes and automated FRCs, respectively, are discussed in the context of the laboratory diagnostic tests used for thrombotic microangiopathies.

Performance evaluation of leukocyte differential on the hematology analyzer Celltac G compared with two hematology analyzers, reference flow cytometry method, and two manual methods.

BACKGROUND: The automated hematology analyzer Celltac G (Nihon Kohden) was designed to improve leukocyte differential performance. Comparison with analyzers using different leukocyte detection principles and differential leukocyte count on wedge film (Wedge-Diff) shows its clinical utility, and comparison with immunophenotypic leukocyte differential reference method (FCM-Ref) shows its accuracy performance. METHODS: For method comparison, 598 clinical samples and 46 healthy volunteer samples were selected. The two comparative hematology analyzers (CAAs) used were XN-9000 (Sysmex) and CELL-DYN Sapphire (Abbott). The FCM-Ref provided by the Japanese Society for Laboratory Hematology was selected, and a flow cytometer Navios (Beckman-Coulter) was used. In manual differential, two kinds of automated slide makers were used: SP-10 (Sysmex) for wedge technique and SPINNER-2000 (Lion-Power) for spinner technique. The spinner technique avoids the issue of Wedge-Diff smudge cells by removing the risk of breaking cells and non-uniformity of blood cell distribution on films (Spinner-Diff). RESULTS: The Celltac G showed sufficient comparability (r = 0.67-1.00) with the CAAs for each leukocyte differential counting value at 0.00-40.87(109 /L), and sufficient comparability (r = 0.73-0.97) with FCM-Ref for each leukocyte differential percentage at 0.4-78.5. The identification ratio of the FCM-Ref in CD45-positive cells was 99.7% (99.4% to 99.8%). Differences were found between FCM-Ref/Celltac G/XN-9000/Spinner-Diff and Wedge-Diff for monocytes and neutrophils. The appearance ratio of smudge cells on wedge and spinner film was 12.5% and 0.5%. CONCLUSION: The Celltac G hematology analyzer's leukocyte differential showed adequate accuracy compared with the CAAs, FCM-Ref, and two manual methods and was considered suitable for clinical use.

Accuracy study of a novel alternate method measuring erythrocyte sedimentation rate for prototype hematology analyzer Celltac α.

INTRODUCTION: The erythrocyte sedimentation rate (ESR) is a nonspecific inflammation indicator. In laboratory testing, automated ESR analyzers may use the reference Westergren method (Reference WG), modified Westergren (Modified WG), or Alternate ESR method (Alternate ESR) based on photometric rheology. A prototype hematology analyzer Celltac α+ (Nihon Kohden Corporation) with built-in Novel ESR analysis technology (Novel ESR) was developed to improve the accuracy of Alternate ESR. Alternate ESR uses only the aggregation phase information of Reference WG. The Novel ESR adds sedimentation and packing phase information obtained by hematology analyzer measurands. High correlation with WG was ensured by predicting the ESR value using Hematocrit (Hct) and MCV values as correcting parameters. METHODS: Novel ESR was compared with Modified WG (MONITOR-40, Joko Corporation) and Reference WG, according to internationally recognized guidelines: Precision, carryover, limit of quantification, comparability, linearity, accuracy, and fibrinogen sensitivity. Samples from healthy volunteers and clinical patients were used. The correction performance of Novel ESR and Modified WG was compared with Reference WG by regression analysis in three range categories for ESR and measurands affecting ESR correction (Hct, MCV, and MCH). RESULTS: Novel ESR showed sufficient basic performance and comparability with Modified WG. In the accuracy study comparing with Reference WG, the regression equation was y = 1.026x + 0.5(r =  .945,P <  .001;n = 271). When evaluating the correction performance, the slopes were within 0.8-1.2, except for the high part of Hct. All intercepts were within 10 mm. CONCLUSION: This study validated the correction performance to the initial estimated ESR value by aggregation phase information using information reflecting sedimentation and packing phase obtained from automated hematology analyzer. The Celltac α+ Novel ESR provided results equivalent to Reference WG.

Platelet count evaluation compared with the immunoplatelet reference method and performance evaluation of the hematology analyzer Celltac G.

INTRODUCTION: The hematology analyzer, Celltac G (Nihon Kohden), designed to improve platelet count (Plt) accuracy, is equipped with new sheath flow control technology. Clinical evaluation of the Celltac G was assessed by comparability with XN-9000 (Sysmex Corporation) and CELL-DYN Sapphire (Abbott Diagnostics). The accuracy of all three analyzers, which use different measuring principles, was compared with the immunoplatelet reference method (FCM-Ref). METHODS: Repeatability and within-laboratory imprecision were assessed using 10 clinical fresh whole blood samples and three control materials with differing levels. Carryover was evaluated using 6 clinical fresh whole blood samples. For method comparison between the three analyzers, 388 samples were used. Plt accuracy among the three analyzers was evaluated using 54 blood samples, including 42 samples with a platelet count less than 50x109 /L. The International Council for Standardization in Haematology method for Plt was used as the FCM-Ref. RESULTS: The Celltac G showed sufficient performance with regard to imprecision, carryover, and comparability. The Analytical Measurement Interval (AMI) and linearity for all parameters of Plt were validated within 4.6 to 809.1 (×109 /L). All hematology analyzers showed some disagreement in Plt when compared with the immunoplatelet reference method. CONCLUSION: The Celltac G hematology analyzer is suitable for clinical use. Platelet count evaluation of the three analyzers suggests the need to determine a reportable measurement interval (RMI) in the clinical laboratory for adequate reporting of a Plt from multiple different values.

Definitive radiotherapy consisting of whole pelvic radiotherapy with no central shielding and CT-based intracavitary brachytherapy for cervical cancer: feasibility, toxicity, and oncologic outcomes in Japanese patients.

BACKGROUND: This prospective study investigated the feasibility, toxicity, and oncologic outcomes of definitive radiotherapy (RT) consisting of whole pelvic radiotherapy with no central shielding (noCS-WPRT) and CT-based intracavitary brachytherapy (ICBT) in Japanese patients with cervical cancer. METHODS: Patients with cervical cancer of FIGO stages IB1-IVA were eligible. The treatment protocol consisted of noCS-WPRT of 45 Gy in 25 fractions and CT-based high dose-rate ICBT of 15 or 20 Gy in 3 or 4 fractions prescribed at point A. The prescribed ICBT dose was decreased if the manual dwell time/position optimization failed to meet organs-at-risk constraints. Graphical optimization and additional interstitial needles were not applied. RESULTS: We enrolled 40 patients. FIGO stages were IB1: 11, IB2: 13, IIA2: 1, IIB: 11, IIIB: 3, and IVA: 1. Median (range) pretreatment tumor diameter was 47 (14-81) mm. Point A doses were decreased in 19 of 153 ICBT sessions (12%). The median follow-up duration was 33 months. The 2-year rates of pelvic control, local control (LC), and progression-free survival were 83%, 85%, and 75%, respectively. Pre-ICBT tumor diameter, high-risk clinical target volume (HR-CTV), total HR-CTV D90, and overall treatment time (OTT) significantly affected LC. Late adverse events (grade ≥ 3) were observed in 3 patients (2 in the bladder, 1 in the rectum). CONCLUSIONS: Definitive RT consisting of noCS-WPRT and CT-based ICBT was feasible for Japanese patients with cervical cancer. To further improve LC, additional interstitial needles for patients with a large HR-CTV and shorter OTT should be considered.

A Phase II Study of Neoadjuvant Chemotherapy Followed by Extended Field Concurrent Chemoradiotherapy for Para-aortic Lymph Node Positive Cervical Cancer.

BACKGROUND/AIM: We conducted a phase II study of neoadjuvant chemotherapy followed by extended field concurrent chemoradiotherapy in patients with cervical cancer with para-aortic node metastasis. PATIENTS AND METHODS: Thirty-seven women with stage IB1-IVA cervical cancer were enrolled. RESULTS: The median age was 52 years. Thirty-four patients other than 3 progressive disease, proceeded to extended field concurrent chemoradiotherapy. The 3-year overall survival and progression-free survival rates were 70.1% and 48.5%, respectively. The 3-year overall survival according to stages was significantly worse in stage IIIB. Twelve of the 17 patients with stage IIIB died of the disease. CONCLUSION: Neoadjuvant chemotherapy followed by extended field concurrent chemoradiotherapy may improve the prognosis of patients with stages IB and II cervical cancer with positive para-aortic node. However, new strategies should be investigated to improve a poor prognosis in stage IIIB disease with positive para-aortic node.

Flow cytometric analysis of Xenopus laevis and X. tropicalis blood cells using acridine orange.

Automated blood cell counters can distinguish cells based on their size and the presence or absence of a nucleus. However, most vertebrates have nucleated blood cells that cannot be counted automatically. We established an alternative automatic method for counting peripheral blood cells by staining cells with the fluorescent dye acridine orange (AO) and analysing cell populations using flow cytometry (FCM). As promising new animal models, we chose Xenopus laevis and three inbred strains of X. tropicalis. We compared the haematological phenotypes, including blood cell types, cell sizes, cellular structure, and erythrocyte lifespans/turnover rate among X. laevis and the three inbred strains of X. tropicalis. Each cell type from X. laevis was sorted according to six parameters: forward- and side-scattered light emission, AO red and green fluorescence intensity, and cellular red and green fluorescence. Remarkably, the erythrocyte count was the highest in the Golden line, suggesting that genetic factors were associated with the blood cells. Furthermore, immature erythrocytes in anaemic X. laevis could be separated from normal blood cells based on red fluorescence intensity. These results show that FCM with AO staining allows for an accurate analysis of peripheral blood cells from various species.

High-risk gestational choriocarcinoma with an unusual presentation and the treatment course of refractory or quiescent/minimally invasive disease.

•A patient with high-risk choriocarcinoma who had refractory or quiescent/minimally invasive disease.•She was treated with seven lines of chemotherapy and salvage surgeries.•The patient had persistently low hCG levels without evidence of disease for 4 years.•Then radiological evidence of pulmonary metastasis was finally achieved, and the patient was salvaged by surgery.•It is crucial to identify the site of active disease to facilitate surgical resection and cure.

Flow cytometric quantitation of EpCAM-positive extracellular vesicles by immunomagnetic separation and phospholipid staining method.

Extracellular vesicles (EV) have attracted attention as circulating biomarkers for many diseases, particularly cancer. Conventional immunofluorescence staining has been used for the detection of target antigens on EV by flow cytometry. However, the staining intensity depends on the amount of antigen expressed on the vesicles and is often only around the noise level. Instead of immunofluorescence, we combined immunomagnetic separation using nanosize MACS® MicroBeads with phospholipid staining of EV (IMS-PS method). EpCAM-positive EV were prepared from the culture supernatants of OVCAR3 (EpCAM-high), A431 (EpCAM-low) or Colon-26 (non-human control) cells as cancer models and were examined by the IMS-PS method using EpCAM mAb-coated MicroBeads. By employing Polaric-500c6F as the dye for staining EV phospholipids and using appropriate flow cytometry settings, autofluorescence was excluded, whereas pretreatment of the MicroBeads with conventional blocking agents reduced nonspecific binding to non-target vesicles. These modifications resulted in a linear relation between the number of EV detected and the sample volume, regardless of the level of EpCAM expression on the vesicles. A431 EV spiked into healthy volunteer plasma were enumerated with good accuracy. The IMS-PS method may be useful for clinical evaluation of EV with low levels of antigen expression that are difficult to detect by conventional immunofluorescence.

Computed tomography-based image-guided brachytherapy for cervical cancer: correlations between dose-volume parameters and clinical outcomes.

This study evaluated the oncologic outcomes and complications of cervical cancer patients in terms of CT-based image-guided brachytherapy (IGBT) parameters. Of 68 cervical cancer patients treated with definitive radiotherapy/concurrent chemoradiotherapy, most received whole-pelvis external beam RT (EBRT) of 40 Gy in 20 fractions, pelvic EBRT with central shield of 10 Gy in 5 fractions, and CT-based IGBT of 18 Gy in 3 fractions prescribed to point A. Cumulative EBRT and IGBT doses were calculated as the total equivalent dose in 2 Gy fractions (EQD2). The median follow-up was 31 (3-52) months. The 2-year overall survival, local control, pelvic control, and disease-free survival rates of the 68 patients were 92%, 83%, 82% and 73%, respectively. The HR-CTV D90, length from the tandem axis to left/right margin of the HR-CTV (T-LR), and HR-CTV volume were significant IGBT parameters for predicting local/pelvic control. Patients who received an HR-CTV D90 of >60 Gy, compared with ≤60 Gy, had significantly better local/pelvic control. Furthermore, 70 Gy was a marginally significant HR-CTV D90 cut-off affecting local control. T-LR was an independent IGBT parameter predicting local/pelvic control on multivariate analysis. Three patients developed Grade 3 or higher treatment-related complications. The D2cm3 of organs at risk were not significant predictors of complications. Future challenges for further improving outcomes include additional interstitial needles for irregularly shaped HR-CTVs, and moderate dose escalation, especially for patients with poor tumor responses.

The concept of platinum sensitivity could be applied to recurrent cervical cancer: a multi-institutional retrospective study from the Japanese Gynecologic Oncology Group.

PURPOSE: This study aimed at evaluating the applicability of the concept of platinum sensitivity to recurrent cervical cancer. METHODS: The clinical information of patients with recurrent cervical cancer, who were initially treated with platinum-based chemotherapy and received second-line platinum-based chemotherapy at the time of recurrence between January 2008 and December 2012, was retrospectively reviewed. RESULTS: A total of 677 patients from 71 medical centers were analyzed. The median overall survival (OS) for patients with platinum-free interval (PFI) of <6, 6-11, 12-17, and ≥18 months was 12.1 (95% CI 11.0-14.1) months, 17.4 (15.5-20.4) months, 20.2 (17.9-27.6) months, and 29.9 (26.7-36.0) months, respectively (P < 0.0001, log-rank). The best cut-off value of PFI that affected OS was 7 months, analyzed by the minimum P value method. The median progression-free survival (PFS) for patients with less than and more than PFI of 7 months was 6.2 months (95% CI 4.8-9.3) and 21.0 months (18.9-24.8) (P < 0.0001, log-rank), respectively, and the median OS for patients with less than and more than PFI of 7 months was 12.3 months (11.2-14.1) and 24.2 months (20.8-25.8) (P < 0.0001, log-rank). Multivariate analysis revealed that PFI (P < 0.0001, HR 0.449, 95% CI 0.369-0.548) alone had a statistically significant association with OS. CONCLUSIONS: This study showed that the concept of platinum sensitivity could be applied to recurrent cervical cancer and PFI could be one of the independent prognostic factors for patients with recurrent cervical cancer who have previously been treated with platinum-based chemotherapy.

Concurrent weekly cisplatin versus triweekly cisplatin with radiotherapy for locally advanced squamous-cell carcinoma of the cervix: a retrospective analysis from a single institution.

OBJECTIVE: To compare patients with cervical cancer who were primarily treated with concurrent chemoradiotherapy (CCRT) using 20 mg m-2 CDDP for 5 days every 3 weeks with weekly regimens of 40 mg m-2. METHODS: We retrospectively analyzed 185 patients with Stage IB-IVA squamous-cell carcinoma of the cervix who were treated with CCRT between 2005 and 2013 at our hospital. The CCRT regimen consisted of cisplatin (CDDP) at 20 mg m-2 for 5 days every 3 weeks or 40 mg m-2 weekly, administered concomitantly with RT. RESULTS: The median age was 50 years (range: 22-70 years) in the triweekly group and was 50.5 years (range: 28-70 years) in the weekly group. The 5-year overall survival rate in the triweekly and weekly groups were 82.0% and 83.3%, respectively (p = 0.851); their disease-free survival rate was 79.6% and 78.1%, respectively (p = 0.672). In the triweekly group, 56 patients (50.9%) had grade 3/4 leukopenia, which was significantly higher than that of 11 patients (15%) in the weekly group (p < 0.0001). CONCLUSION: The weekly CDDP regimen for CCRT seems better in patients with International Federation of Gynecology and Obstetrics Stages IB-IVA squamous-cell carcinoma of the cervix. Advances in knowledge: The weekly CDDP regimen for CCRT seems better in patients with International Federation of Gynecology and Obstetrics Stages IB-IVA squamous-cell carcinoma of the cervix.

Gestational choriocarcinoma complicated by infective endocarditis during chemotherapy.

•Little is known about the history of cancer patients complicated with IE.•It is very important to do the chemotherapy without delay for choriocarcinoma.•We report a case of choriocarcinoma complicated by IE during EMA-CO.•An accurate diagnosis/prompt treatment decisions are important for cancer with IE.

Prognostic Factors and Treatment Outcome for Patients with Stage IVB Cervical Cancer.

AIM: We report a retrospective evaluation for patients with stage IVB cervical cancer in order to identify survival rates and to improve our current practice. PATIENTS AND METHODS: We analyzed 85 patients with stage IVB cervical cancer. For patients appropriate for radical treatment, a combination of external-beam radiotherapy and intracavitary brachytherapy was delivered with/without chemotherapy. Patients with distant metastasis were treated using systemic chemotherapy or palliative radiotherapy. RESULTS: Forty-two patients were treated using radiotherapy alone, 31 using chemotherapy followed by radiotherapy, eight using chemotherapy alone, and four using best supportive care. The 5-year overall survival rate was 9.9%. Multivariate analysis revealed leukocytosis and a poor performance status were independent prognostic factors. Of the 43 patients without these prognostic factors, patients with only lymph node metastasis had a 5-year overall survival rate of 40.5%. CONCLUSION: Radical treatment should be considered in patients who have only lymph rode metastasis and are without leukocytosis and a poor performance status.

Prognostic factors in patients with vulvar cancer treated with primary surgery: a single-center experience.

Vulvar cancer is a relatively rare disease. The aim of this study was to investigate prognostic factors in vulvar squamous cell carcinoma patients treated with primary surgery. Forty cases of vulvar squamous cell carcinoma treated with primary surgery were retrospectively analyzed. Overall survival (OS) and disease-specific survival (DSS) were calculated using the Kaplan-Meier method and prognostic factors were analyzed by multivariate analyses. The median age was 68 years. The FIGO stage distribution was as follows: 18 cases (45.0 %) in stage I, four cases (10.0 %) in stage II, 15 cases (37.5 %) in stage III, and three cases (7.5 %) in stage IV. A radical local excision was performed in 15 patients, and radical vulvectomy in 25 patients, and seven of these patients were treated with postoperative RT. The 5-year DSS rate was 72.6 %, and the 5-year OS rate was 70.3 %. Age and surgical margin ≤5 mm were independent prognostic factors for OS, and positive inguinal LN metastasis and surgical margin ≤5 mm were identified as independent prognostic factors for DSS. Complete radical excision is important regardless of operation mode. Adjuvant treatment should be considered for inguinal LN positive patients.

Phase II study of concurrent chemoradiotherapy with weekly cisplatin and paclitaxel in patients with locally advanced uterine cervical cancer: The JACCRO GY-01 trial.

OBJECTIVE: A multicenter phase II trial was conducted to assess the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with weekly cisplatin (CDDP) and paclitaxel (PTX) in patients with locally advanced uterine cervical cancer. METHODS: Patients with FIGO stage III-IVA uterine cervical cancer without para-aortic lymphadenopathy were enrolled. Patients received definitive radiotherapy (RT) consisting of external beam whole-pelvic RT and high-dose-rate intracavitary brachytherapy. The cumulative linear quadratic equivalent dose was 62-65Gy prescribed at point A. weekly CDDP at 30mg/m(2) and PTX at 50mg/m(2) were administered concurrently with RT for ≥5 courses. RESULTS: Sixty-eight of the 70 registered patients were eligible. The complete response rate was 76.5% (95% confidence interval [CI], 66.4-86.6%). With a median follow-up of 27months (range, 7.9-33.5), the 2-year cumulative progression-free survival and the 2-year cumulative overall survival rates were 83.8% (95% CI, 75.1-92.6%) and 92.7% (95% CI, 86.4-98.9%), respectively. The pelvic cumulative disease progression-free and the 2-year cumulative distant metastasis rates were 89.6% (95% CI, 82.3-96.9%) and 13.2% (95% CI, 5.2-21.3%), respectively. The 2-year cumulative late complication rates were 25% for all grades, 13.2% for grade 1, 5.9% for grade 2, 2.9% for grade 3, and 2.9% for grade 4. CONCLUSIONS: For locally advanced cervical cancer, CCRT with weekly CDDP 30mg/m(2) and PTX at 50mg/m(2) demonstrated favorable antitumor activity, and was feasible and safe with respect to the protocol-specified serious adverse reactions and events. Evaluation of this regimen in phase III trials is warranted.