Clinical significance and predicting indicators of post-cancer-treatment survival in terminally ill patients with ovarian cancer.

AIM: Women with ovarian cancer (OC) often experience relapse and receive further repetitive chemotherapy. The objective of this study was to overview the remaining survival time after the final chemotherapy and to examine influential clinicopathologic indicators in those patients. METHODS: The medical charts of deceased OC patients who had died of the disease between 2003 and 2012 were retrospectively reviewed. We investigated post-cancer-treatment survival (PCS) defined as the interval between the date of the final chemotherapy and death. RESULTS: In all, 77 patients were enrolled. Three patients (3.9%) had received chemotherapy in the last 2 weeks. Eight (10.4%), 28 (36.4%), and 44 (57.2%) patients had received chemotherapy in the last 30, 60, and 90 days, respectively. There were no differences in either survival after recurrence or overall survival between the shorter (<75 days) and longer (≥75 days) PCS groups. On the other hand, patients in the shorter PCS group had significantly fewer chances of referral to a hospice or home-care than those in the latter group (P = 0.035). In multivariable analysis, a poorer performance status, an elevated white blood cell count, and a higher C-reactive protein value were significantly correlated with a shorter PCS (P = 0.004, 0.006 and 0.027, respectively). CONCLUSION: Half of the patients received chemotherapy within 75 days of death and we did not identify any survival benefit in patients who received chemotherapy near the end of life. We should provide information to patients about their prognosis and discuss the timing of withdrawal from chemotherapy from the early stage of their recurrence.

Oncologic and obstetric outcomes of early stage cervical cancer with abdominal radical trachelectomy: Single-institution experience.

AIM: Radical trachelectomy (RT) is a widely used fertility-sparing treatment for patients with early cervical cancer (CCA). RT, however, is an investigational treatment, and its gynecological and obstetric efficacy are being investigated. We retrospectively assessed the efficacy of abdominal RT (ART) as a fertility-sparing surgery. METHODS: From 2010 to 2014, patients with stage IA2-IB1 CCA (tumor ≤2 cm) who wished to preserve their fertility underwent ART. The major outcomes were mortality, recurrence, pregnancy complications, and obstetric outcome. RESULTS: Twenty-eight patients received ART. Adjuvant chemotherapy was performed in seven patients because of lymphovascular space invasion. During the median follow-up of 43 months, no recurrences occurred. Twelve women attempted to conceive, and eight of them became pregnant. A total of five children were born, and one baby was full term. Three cases of second trimester, and one case of third trimester preterm births were recorded. CONCLUSIONS: Fertility was preserved after ART in a moderate number of patients. The pregnancy and birth rates after ART have been improving, and increasing the full-term birth rate is the next goal. In addition, development of further types of minimally invasive surgery for CCA can be expected.

Opioid needs of terminally ill patients with gynecologic malignancies.

BACKGROUND: Little is known about patterns and predictive factors regarding opioid use for terminally ill patients with gynecologic malignancies. The aim of this study was to elucidate predictors affecting opioid requirements of end-of-life patients with gynecologic malignancies. METHODS: A retrospective study was carried out on patients with gynecological malignancies admitted to our institute and died during the years 2002 to 2012. The association between maximum opioid dose and factors affecting opioid requirements were examined. Data extracted from medical records included age, site of primary cancer, maximum total dose of opioids prescribed over 24 h, the site of recurrence and metastasis, procedures performed during the hospital stay, total number of chemotherapy courses and overall survival. RESULTS: The study identified 189 patients. Most patients had ovarian cancer (42.3 %) followed by cervical cancer (28.0 %) and then corpus malignancy (27.0 %). Opioid requirements decreased with increasing age, especially from the 50s onward. This was particularly marked in cervical cancer patients. In addition, pelvic metastasis was associated with the maximum dose of opioids and the average opioid use was highest in patients with cervical cancer. CONCLUSION: Young age and pelvic invasion were significant predictive factors regarding opioid requirements. Additionally, cervical cancer patients may require more opioids among those with gynecologic malignancies.

The prognostic impact of pulmonary metastasectomy in recurrent gynecologic cancers: a retrospective single-institution study.

The aim was to examine the impact of pulmonary metastasectomy in patients with recurrent gynecologic cancers. Thirty-seven patients with isolated lung metastases (< 3 nodules) in recurrent epithelial gynecologic cancers were treated at Nagoya University Hospital between 1985 and 2013. The clinicopathological data for the 23 patients who underwent surgical resection were retrospectively analyzed, and their survival was compared with patients who received chemotherapy only. The median age at the time of surgery was 56 years (range 28-77). The studied population comprised 7 patients with 2 or 3 nodules and 8 patients with chemoresistant tumors, including fourteen cervical, 4 endometrial, and 5 ovarian primary tumors, with 5-year overall survivals (OSs) after surgery of 61, 100, and 100%, respectively. The survival of recurrence-free interval after initial treatment (>2 years) was significantly favorable (5-year OS 100% vs. 41.7%, p=0.006). Among the 6 patients with re-recurrence of lung metastases, 5 patients underwent a second pulmonary metastasectomy, and all of the patients are currently alive without disease. None of the 29 operations yielded severe complications. Although the survival rate showed a tendency to be higher in the surgery group than in the chemotherapy-only group, no significant difference was observed (5-year OS 81.7% vs. 49.5%, p=0.072). Our results indicate that pulmonary metastasectomy contributed to long-term survival with a low-risk of complications. Surgery to remove isolated lung metastases might provide a favorable prognosis for patients with long recurrence-free intervals and for patients with chemoresistant or re-recurrent tumors.

PLAGL2 regulates actin cytoskeletal architecture and cell migration.

Pleomorphic adenoma gene like-2 (PLAGL2), a member of the PLAG gene family, is a C2H2 zinc finger transcriptional factor that is involved in cellular transformation and apoptosis. In this report, we show that PLAGL2 is associated with the organization of stress fibers and with small guanosine triphosphatase (GTPase) activity. Depletion of PLAGL2 in two different ovarian cancer cell lines, ES-2 and HEY, induced activation of RhoA, whereas activity of Rac1 was suppressed. Organization of actin stress fibers and focal adhesions was significantly promoted by PLAGL2 knockdown in a RhoA-dependent manner. Conversely, exogenous expression of PLAGL2 in MDA-MB-231 cells, a breast cancer cell line, resulted in the activation of Rac1 and the inactivation of RhoA. In addition, PLAGL2 expression induced lamellipodia formation and disruption of stress fiber formation. Finally, we show that CHN1 expression is essential for Rac1 inactivation in PLAGL2-depleted cells. Our results demonstrate a crucial role of PLAGL2 in actin dynamics and give further insight into the role of PLAGL2 in cellular transformation and apoptosis.

A recurrence-predicting prognostic factor for patients with ovarian clear-cell adenocarcinoma at reproductive age.

OBJECTIVES: We retrospectively analyzed the clinicopathological features and evaluated the prognostic indicators of recurrence in 132 patients with clear cell adenocarcinoma (CCC) of the ovary at reproductive age. PATIENTS AND METHODS: Between 1986 and 2011, as a regional population-based study, clinicopathological data on 132 young patients with CCC, collected under the central pathological review system, were subjected to uni- and multivariable analyses to evaluate recurrence-free survival (RFS). RESULTS: The median age was 40 (27-45) years. The median follow-up period for surviving patients was 46.4 months. During the observation period, there were 16 recurrences in 87 patients with stage I tumors (18.4 %), 8 in 17 with stage II (47.1 %), and 16 in 28 with III-IV (57.1 %). Subsequently, 35 patients died of the disease. Those with stage I or II did not reach the median RFS. The median RFS of stage III-IV was 21.6 months. When analysis was confined to stage I patients, there was no significant difference in the RFS of CCC patients between IA and IC(r) (intraoperative capsule rupture) (P = 0.7957). In contrast, CCC patients with IC excluding IC(r) [IC(non-r)] showed a poorer RFS than those with IC(r) (P < 0.0001). In multivariable analysis confined to stage I patients, the substage group was only an independent prognostic factor for RFS [IA vs. IC(non-r)] [hazard ratio (HR) = 9.394; 95 % CI, 1.445-61.070; P = 0.0190]. CONCLUSION: We should keep in mind the greater risk of recurrence in patients with stage IC disease or higher, other than those stage IC patients with intraoperative rupture.

Possible association between stem-like hallmark and radioresistance in human cervical carcinoma cells.

AIM: We aimed to investigate the possibility of an association between a stem-like hallmark and radiotherapeutic sensitivity in human cervical carcinoma cells. MATERIAL AND METHODS: Side-population (SP) cells and non-SP (NSP) cells in HeLa cells were isolated using flow cytometry and Hoechst 33342 efflux. We performed Western blot analysis to evaluate the expression of stem cell markers (CXCR4, Oct3/4, CD133, and SOX2) and apoptosis markers after irradiation. In addition, SP and NSP cells were injected into nude mice and we assessed subcutaneous tumor formation. To examine tolerance of irradiation, colony formation and apoptosis change were confirmed in the SP and NSP cells. RESULTS: SP cells showed a higher expression of CXCR4, Oct3/4, CD133, and SOX2 than NSP cells. The colony size of SP cells cultured on non-coated dishes was larger than that of NSP cells, and NSP cells were easily induced to undergo apoptosis. SP cells tended to form spheroids and showed a higher level of tumorigenicity compared with NSP cells. In addition, nude mice inoculated with SP cells showed greater tumor growth compared with NSP cells. SP cells showed a higher tumorigenicity and lower apoptotic potential, leading to enhanced radiotolerance. CONCLUSION: Tumor SP cells showed higher-level stem-cell-like characters and radioresistance than NSP cells. SP cells may be useful for new therapeutic approaches for radiation-resistant cervical cancer.

Secondary cytoreductive surgery potentially improves the oncological outcomes of patients with recurrent uterine sarcomas.

Uterine sarcomas are some of the most malignant and aggressive tumor types among the gynecologic malignancies, and they are associated with a high rate of recurrence and a poor prognosis. Due to their rarity and diversity, the optimal treatment for recurrent uterine sarcomas has not yet been elucidated. The aim of the present study was to investigate the potential of secondary cytoreductive surgery (SCS) for patients with recurrent uterine sarcomas. A total of 18 patients with recurrent uterine sarcomas were retrospectively identified at the Department of Obstetrics and Gynecology, Nagoya University (Nagoya, Japan) between January 2002 and December 2015. This included 8 patients with leiomyosarcoma, 6 with carcinosarcoma, 3 with endometrial stromal sarcoma and 1 with adenosarcoma. All patients underwent primary debulking surgery as the initial treatment. In summary, 9 patients were treated with SCS when they experienced their first recurrence, and the other 9 patients were treated with non-SCS methods, including chemotherapy or radiotherapy. In the SCS group, 5/9 patients had confined pelvic recurrences, 3 patients had extra-pelvic diseases, including pulmonary metastasis, and one patient had intra- and extra-pelvic recurrence. The 3-year overall survival (OS) rates were 77.8 and 11.1% in the SCS and non-SCS groups, respectively. The patients who underwent SCS experienced a significantly longer OS time compared with those in the non-SCS group (P=0.006). In addition, the disease-free survival after second-line therapy was significantly longer in the SCS group than in the non-SCS group (P=0.0496). These findings suggest that resection of recurrent uterine sarcomas may be beneficial for the improvement of patient survival. Prospective studies with sufficient statistical power are warranted for further evaluation of the effect of SCS.

Fertility-sparing surgery of malignant transformation arising from mature cystic teratoma of the ovary.

BACKGROUND: The purpose of this study was to evaluate the long-term clinical outcome of young women with malignant transformation arising from mature cystic teratoma of the ovary (MT-MCT) by comparing radical surgery and fertility-sparing surgery (FSS). PATIENTS AND METHODS: All patients treated with radical surgery or FSS for MT-MCT in multiple institutions were registered in this analysis. Univariate and multivariate analyses were performed to evaluate clinical outcome, including overall survival (OS) and disease-free survival (DFS). RESULTS: From 1986 to 2016, 62 patients with MT-MCT were treated in our group. The median follow-up period was 38.0 (2.0-227.9) months, and the median age was 54 (17-82) years old. Multivariate analysis revealed that only advanced stage was significantly correlated with poorer prognosis of patients [hazard ratio (HR) for death: 6.58, 95% confidence interval (CI): 1.82-24.78, P = 0.0048; HR for recurrence: 5.59, 95% CI: 1.52-21.83, P = 0.01]. Of a total of 13 women with stage I-II disease at less than 45 years old, 7 were treated with FSS, and there was no recurrence except for in one woman with stage II MT-MCT. There was no significant difference in long-term oncological outcome between radical surgery and FSS. CONCLUSION: FSS may be indicated for patients with stage I MT-MCT, who hope to preserve fertility, as no relapse was found after FSS.

KIF20A expression as a prognostic indicator and its possible involvement in the proliferation of ovarian clear­cell carcinoma cells.

Kinesin family member 20A (KIF20A), which is involved in cytokinesis and intracellular transportation, has been recently reported to be upregulated in several malignancies and may contribute to chemotherapeutic resistance. We examined the distribution and expression of KIF20A in clear­cell carcinoma (CCC) of the ovary to elucidate its clinical significance and molecular mechanism. Paraffin sections from ovarian CCC tissues (N=43) were immunostained with KIF20A antibody, and the staining intensities were semi­quantitatively evaluated. Furthermore, we investigated whether silencing of KIF20A contributes to the proliferation­inhibitory potential using CCC cells. During the observational period, 18 patients (41.9%) developed recurrence. The median time to recurrence was 11.5 months. Patients in the high KIF20A expression group showed poorer progression­free survival (PFS) and overall survival (OS) than those in the low expression group (P=0.0443 and P=0.0478, respectively). In multivariable analyses, KIF20A expression was also a significantly independent indicator of PFS and a marginally significant indicator of OS [PFS: HR (high vs. low), 5.488; 95% CI, 1.410­24.772 (P=0.0136); OS: HR, 2.835; 95% CI, 0.854­11.035, (P=0.0897)]. In in vitro studies, the ovarian CCC cell proliferation was significantly decreased by KIF20A silencing or in the presence of KIF20A inhibitor in CCC cells. Cell cycle G2/M arrest and a higher apoptosis­induced fraction were more frequently observed in si­KIF20A­transfected CCC cells than in the control cells. Although the present study was preliminary, these data indicate the possible involvement of KIF20A in the proliferation of CCC, suggesting that targeting this molecule may contribute to reversing the malignant potential consequently affecting the oncologic outcome of CCC patients.

Impact of positive ZEB1 expression in patients with epithelial ovarian carcinoma as an oncologic outcome-predicting indicator.

Several previous studies have revealed that the expression of zinc finger E-box binding homeobox 1 (ZEB1) in solid malignancies has an important significance on the clinical outcome of patients. However, the association between ZEB1 expression and survival in patients with epithelial ovarian carcinoma (EOC) remains unclear. The objective of the present study was to examine the extent of ZEB1 expression in EOC using immunohistochemical staining and investigate its association with patient outcome. A total of 40 patients with EOC initially treated with cytoreductive surgery and systematic chemotherapy were enrolled. ZEB1 expression was immunohistochemically categorized as negative, weak, moderate and strong according to the size of the staining area, and intensity. Subsequently, the associations between ZEB1 expression and recurrence/progression-free survival (RFS) rate were examined. The median age of patients in the current study was 54 years old (range, 22-72 years old). Among these patients, 15 (37.5%) exhibited International Federation of Gynecology and Obstetrics stage I disease, and 10 (25.0%), 13 (32.5%), and 2 (5%) had stage II, III, and IV disease, respectively. No patients with negative expression of ZEB1 experienced recurrence. In addition, ZEB1 expression was identified to be a significant predictor of a poorer RFS rate compared with negative expression (negative vs. weak, moderate and strong, P=0.0126). Furthermore, multivariate analyses revealed that moderate and strong ZEB1 expression levels were significant prognostic indicators of a poorer RFS rate in patients with EOC (hazard ratio, 2.265; 95% confidence interval, 1.072-8.021; P=0.0349). Confining analysis to patients with the clear-cell/mucinous histological type, those with moderate/strong ZEB1 expression demonstrated a significantly poorer RFS rate (P=0.0025). Positive ZEB1 expression may be an indicator to predict unfavorable RFS in patients with EOC.

Efficacy of glypican-3-derived peptide vaccine therapy on the survival of patients with refractory ovarian clear cell carcinoma.

Compared with other epithelial ovarian carcinoma subtypes, ovarian clear cell carcinoma (OCCC) has been recognized to show chemoresistance. Therefore, new treatment modalities are required for patients with OCCC that is refractory to chemotherapy. The carcinoembryonic antigen glypican-3 (GPC3) is expressed by approximately half of OCCC and is a promising immunotherapeutic target. The purpose of this study was to evaluate the effect of GPC3 peptide vaccine against refractory OCCC patients. We conducted a phase II trial with a GPC3-derived peptide vaccine in OCCC patients. Immunological responses were analyzed by ex vivo IFNγ ELISPOT assay. We also evaluated control subjects, who received best supportive care without vaccinations during the same period. Thirty-two patients with refractory OCCC were enrolled between July 2010 and September 2015, and underwent GPC3 peptide vaccination. Fifteen patients were vaccinated less than six times because their general condition progressively deteriorated, and 17 patients were vaccinated at least six times. Three patients showed a partial response as the best overall response. The GPC3 peptide vaccine induced a GPC3-specific CTL response in 15 out of 24 patients who had PBMCs collected three times or more. The prognosis of palliative care patients without GPC3 peptide vaccinations was significantly poorer than that of those with GPC3 peptide vaccinations (post cancer-treatment survival: p = 0.002). Although the disease control rate was not high, our results suggest that GPC3 peptide vaccinations may hold a significant impact to prolong survival of patients with refractory OCCC, allowing them to maintain quality of life with no serious toxicities.

Feasibility and benefit of concurrent chemoradiotherapy for elderly patients with uterine cervical cancer.

BACKGROUND: Elderly patients with uterine cervical cancer reportedly have a poorer prognosis than younger patients. Until now, the benefit of concurrent chemoradiotherapy (CCRT) for elderly patients has been considered limited. METHODS: We retrospectively analyzed 49 women with cervical cancer aged >70 years primarily treated with radiotherapy (RT) or CCRT in our institute between 2003 and 2014. Treatment compliance, toxicity, and survival benefit were analyzed. RESULTS: A total of 49 patients were identified in this retrospective analysis. Twenty patients with a median age of 75.4 years (range 70-77) were treated with CCRT and 29 patients with a median age of 77.9 years (range 70-89) underwent RT. In the CCRT group, 14 patients (70%) completed CCRT consisting of radiotherapy and 5 courses of cisplatin plus 5-fluorouracil including patients requiring a dose reduction of chemotherapy. The median overall survival (OS) in the CCRT and RT groups was 66.9 and 60.1 months, respectively (p = 0.156). The most common grade 3/4 acute toxicity was hyponatremia (35.0%), followed by neutropenia (15.0%) and diarrhea (10.0%) in the CCRT group, while this was anemia (17.2%) followed by radiation enteritis (10.3%) in the RT group. CONCLUSIONS: CCRT was well tolerated in elderly patients with cervical cancer. Careful attention should be paid to the different characteristics of treatment-related toxicities in this group compared with younger patients.

PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells.

There is an intensive need for the development of novel drugs for the treatment of epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy due to the high recurrence rate. TP53 mutation is a common event in EOC, particularly in high-grade serous ovarian cancer, where it occurs in more than 90% of cases. Recently, PRIMA-1 and PRIMA­1MET (p53 reactivation and induction of massive apoptosis and its methylated form) were shown to have an antitumor effect on several types of cancer. Despite that PRIMA-1MET is the first compound evaluated in clinical trials, the antitumor effects of PRIMA-1MET on EOC remain unclear. In this study, we investigated the therapeutic potential of PRIMA-1MET for the treatment of EOC cells. PRIMA-1MET treatment of EOC cell lines (n=13) resulted in rapid apoptosis at various concentrations (24 h IC50 2.6-20.1 µM). The apoptotic response was independent of the p53 status and chemo-sensitivity. PRIMA­1MET treatment increased intracellular reactive oxygen species (ROS), and PRIMA-1MET-induced apoptosis was rescued by an ROS scavenger. Furthermore, RNA expression analysis revealed that the mechanism of action of PRIMA­1MET may be due to inhibition of antioxidant enzymes, such as Prx3 and GPx-1. In conclusion, our results suggest that PRIMA-1MET represents a novel therapeutic strategy for the treatment of ovarian cancer irrespective of p53 status and chemo-sensitivity.

Oncologic outcome after recurrence in patients with stage I epithelial ovarian cancer: are clear-cell and mucinous histological types a different entities?

OBJECTIVES: This study was conducted to estimate the oncologic outcome of stage I epithelial ovarian carcinoma (EOC) patients after recurrence. STUDY DESIGN: After central pathological review and searching of the medical records of multi-institutions, a total of 103 relapsed patients with stage I EOC were analyzed. The major endpoint was postrecurrence survival (PRS). RESULTS: The median follow-up for surviving patients was 57.5 (5.7-242.0) months. The median age was 52 (14-89). Among the patients, 19 (18.4%) had FIGO IA disease, and 4 (3.9%) and 80 (77.7%) had IB and IC disease, respectively. Regarding the histological type, the clear-cell type was the most frequently observed (N=42: 40.8%). The 3/5-year overall and PRS rates of all patients were 63.7/47.9 and 38.2/24.0%, respectively. The 5-year PRS rates of patients with serous, endometrioid, clear-cell, and mucinous tumors were 44.9, 35.0, 19.8, and 0%, respectively. On stratifying by the histological type, the overall and postrecurrence survival rates of patients with the mucinous/clear-cell types were significantly poorer than in those with the non-mucinous/clear-cell types (OS: P=0.0253, PRS: P=0.0016). In multivariate analyses, the FIGO stage (IA/IB vs. IC) and histological type (clear-cell/mucinous vs. non- clear-cell/mucinous) retained their significance as prognostic factors of a poorer PRS {stage IC (vs. IA/B) HR: 2.176 (95% CI: 1.059-4.470), P=0.0343: clear-cell/mucinous (vs. non- clear-cell/mucinous): HR: 2.486(95% CI: 1.416-4.364), P=0.0015). CONCLUSIONS: Even if at stage I, once patients with a mucinous/clear-cell histology experience recurrence, subsequent survival is extremely poor.

Survival benefit of taxane plus platinum in recurrent ovarian cancer with non-clear cell, non-mucinous histology.

OBJECTIVE: This study was conducted to examine the effects of front-line chemotherapy on overall survival (OS) and postrecurrence survival (PRS) of patients with recurrent ovarian cancer, when stratifying the histologic type. METHODS: Five hundred and seventy-four patients with recurrent ovarian cancer with sufficient clinical information, including front-line chemotherapy, were analyzed. The pathologic slides were evaluated by central pathologic review. The patients were divided into two groups: group A (n=261), who underwent taxane plus platinum, and group B (n=313), who underwent conventional platinum-based chemotherapy without taxanes. RESULTS: The median age was 54 years (range, 14 to 89 years). Group A had significantly better median OS (45.0 months vs. 30.3 months, p<0.001) and PRS (23.0 months vs. 13.0 months, p<0.001) compared to group B. The OS and PRS were similar between the groups in patients with clear cell or mucinous histology. In contrast, among patients with non-clear cell, non-mucinous histologies, the OS and PRS of group A were significantly better than those of group B (OS, p<0.001; PRS, p<0.001). Multivariable analyses revealed that, among patients with non-clear cell, non-mucinous histologies, chemotherapy including taxane and platinum was an independent predictor of favorable survival outcomes. Conversely, in patients with clear cell or mucinous histology, taxane-including platinum-based combination chemotherapy did not improve the OS and PRS compared to a conventional platinum-based regimen which did not include taxanes. CONCLUSION: Since the emergence of taxane plus platinum, the prognosis of patients with recurrent ovarian cancer has improved. However, we here demonstrate that this improvement is limited to patients with non-clear cell, non-mucinous histologies.

Is there any association between where patients spend the end of life and survival after anticancer treatment for gynecologic malignancy?

BACKGROUND: It remains unknown whether the end-of-life (EOL) environment influences survival after anticancer treatment, particularly for gynecologic malignancy. OBJECTIVE: The study's objective was to clarify whether the survival time varied depending on where patients spend the EOL. METHODS: This retrospective study included patients who received initial oncologic treatment but died due to cancer recurrence and/or progression. The subjects were a cohort of 181 gynecologic malignant tumor cases in a single institution from 2002 to 2008. Measurement was of postcancer treatment survival (PCS), defined as the time interval between the last date of anticancer treatment after recurrence/progression and death from the disease, analyzed on stratification by type of supportive care or where patients spent the EOL. RESULTS: The median survival time was 26.1 (1.0-306.4) months. The distribution of the carcinoma type was as follows: 28.7% of patients with cervical (N=52), 27.6% with endometrial (N=50), and 43.1% with ovarian (N=79) cancer. The median PCS was 13.3 weeks. Patients in the hospice/home care group showed a significantly more favorable PCS than those in the hospital group (log rank: P=0.029). On multivariate analysis, the age (<60 versus ≥60) and site of supportive care (hospital versus hospice/home care) retained their significance as independent prognostic factors of poor PCS (age: HR=0.679, 95% CI, 0.496-0.928, P=0.0151; site of supportive care: HR=0.704, 95% CI, 0.511-0.970, P=0.0319). CONCLUSIONS: Our current data could be hypothesis generating; it is possible that the EOL environment is a crucial prognostic factor for survival after anticancer treatment.

Expression of CXCR4 indicates poor prognosis in patients with clear cell carcinoma of the ovary.

Recent reports have shown that CXCR4 is expressed in various solid tumors and is involved in tumor development and metastasis. We examined the distribution and expression of this molecule in clear cell carcinoma of the ovary to elucidate its clinical significance. Paraffin sections from clear cell carcinoma of the ovary tissues (n = 42) were immunostained with CXCR4 antibody, and the staining intensities were evaluated. The clinicopathologic factors examined were age, FIGO (International Federation of Gynecology and Obstetrics) staging, preoperative value of cancer antigen 125 test, and residual tumor after cytoreductive surgery. Overall survival and progression-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was completed using Cox proportional hazards analysis. Of the 42 carcinomas, lower level CXCR4 immunoexpression was observed in 21 cases (50.0%) (CXCR4(low) group); and higher level immunoexpression, in 21 cases (50.0%) (CXCR4(high) group). Five-year overall survival was significantly poorer in the CXCR4(high) group than in the CXCR4(low) group (overall survival, CXCR4(low) group [90.2%], CXCR4(high) group [50.3%]; P = .0002). In addition, CXCR4(high) immunoexpression significantly predicted a poorer progression-free survival when compared with lower expression (5-year progression-free survival, CXCR4(low) group [90.5%], CXCR4(high) group [36.2%]; P < .0001). Furthermore, multivariate analyses including the age, preoperative cancer antigen 125 test value, FIGO stage, and CXCR4 expressions revealed that CXCR4(high) expression was an independent prognostic factor for poorer overall survival and progression-free survival of patients with clear cell carcinoma of the ovary (overall survival, P = .0011; progression-free survival, P = .0008, respectively). Our current study suggested that the assessment of CXCR4 immunoreactivity may be a useful prognostic indicator and that CXCR4 may play a critical role in the progression of clear cell carcinoma of the ovary.