Effects of Pegylated Liposomal Doxorubicin and CA125 Level Variability Analysis in Platinum-refractory/resistant Recurrent Ovarian Cancer.

BACKGROUND/AIM: Ovarian cancer is a disease with significant impact, because more than half of cases exhibit recurrence despite platinum therapy. The choice of drug for cases of recurrence remains controversial, but the current option is pegylated liposomal doxorubicin (PLD). PATIENTS AND METHODS: We retrospectively reviewed the use of PLD in patients with ovarian cancer refractory or resistant to platinum-based therapy at our Department. We also examined efficacy, predictive indices of efficacy, and adverse events as well. RESULTS: In this study of PLD monotherapy for 60 platinum-refractory/resistant recurrent ovarian cancers, there was a median progression-free survival (PFS) of 4 months, median overall survival (OS) of 11 months, and the disease control rate (DCR) was 71.7%. The treatment effect can be predicted by the reduction of CA125 level after 2 courses. Patients with an increase and decrease in CA125 after 2 cycles of PLD, respectively, had a median OS of 14.5 (2-60) and 8 (2-51) months and a median PFS of 6 (2-38) months and 3 (0-47) months. CONCLUSION: PLD is clinically effective and useful because it provides a high DCR and is tolerable to adverse events. These findings can help support the use of PLD and guide physicians in their choice of treatment when encountering such cases.

Long-term Outcomes of Cervical Adenocarcinoma Treated With Concurrent Chemoradiotherapy Using Paclitaxel and Cisplatin.

BACKGROUND/AIM: We retrospectively analyzed the locally advanced adenocarcinoma (AC)/adenosquamous carcinoma (ASC) of the uterine cervix treated with concurrent chemoradiotherapy using cisplatin plus paclitaxel (TP-CCRT). PATIENTS AND METHODS: Thirty patients with stage IB-IVA AC/ASC were treated with whole pelvis external beam radiotherapy. A high-dose-rate intracavitary brachytherapy was delivered once per week at a fractional dose of 6 Gy. For TP-CCRT, the patients received cisplatin and paclitaxel. RESULTS: A complete response was achieved in 17 patients (77.3%) in the TP-CCRT group and 4 patients (50.0%) in the P-CCRT group. The 5-year OS rate in the TP-CCRT and P-CCRT groups was 74.2% and 25.0% (p=0.0094), the central DFS rate was 58.0% and 12.5% (p=0.0267), and the distant DFS rate was 63.6% and 12.5% (p=0.0042), respectively. CONCLUSION: TP-CCRT achieves a considerably better disease control for AC of the cervix, leading to a better OS.

Hysterectomy for Recurrent/Residual Cervical Cancer Following Definitive Radiotherapy.

BACKGROUND/AIM: Radical hysterectomy has been used for local recurrent or persistent (LR) cervical cancer after radiotherapy (RT), but the rate of serious complications is high and tolerance is low. This study determined the efficacy, safety, and prognostic factors of adjuvant simple hysterectomy in LR cervical cancer post-RT. PATIENTS AND METHODS: A total of 21 patients who underwent hysterectomy for LR cervical cancer post-RT in our Department between May 2007 and September 2018 were included in the study. Primary, definitive RT was performed. Histological response by definitive RT in the extirpated uterus was classified on the basis of histological response criteria: effect (Ef) 0-3. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 51.9% and 50.1%, respectively. Ef 1 was significantly associated with poorer prognosis compared to Ef 2 or Ef 3. CONCLUSION: Adjuvant hysterectomy could be a treatment of choice for LR cervical cancer post-RT.

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.

Lymphatic vessel involvement is predictive for lymph node metastasis and an important prognostic factor in endometrial cancer.

BACKGROUND: Lymphovascular space involvement is reported to be an important risk factor in endometrial cancer. This study was conducted to evaluate the separate prognostic effects of lymphatic invasion and venous invasion on the outcomes of patients with endometrial cancer. METHODS: From 2006 to 2013, 189 histologically confirmed endometrial cancer patients were examined. To study the venous invasion (v) of the endometrial cancer, Victoria blue-H&E staining-which positively stains the elastic fibers of vessels-was performed. Immunohistochemical staining with D2-40 was used to study the lymphatic invasion (ly) of the endometrial cancer. RESULTS: The median age of the patients was 57 (range 25-84) years. ly(+) and/or v(+) patients were significantly more likely to present an advanced cancer stage, G3 tumor, and deep myometrial invasion than ly(-)/v(-) patients. The incidence of lymph node metastasis was high in ly(+) patients, and that of ovarian metastasis was high in v(+) patients. Lymphatic vessel invasion was significantly correlated with regional lymph node metastasis. We found a significantly higher incidence of distant metastasis in ly(+) patients. Most recurrences in ly(+)/v(-) patients occurred in lymph nodes, while those in ly(+)/v(+) patients occurred mainly at distant organs. Finally, the prognosis was significantly poorer for ly(+) patients, in whom lymphatic invasion was an independent prognostic factor along with distant metastasis. CONCLUSIONS: Our study suggests that by separately evaluating lymphatic invasion and blood vessel invasion in endometrial cancer cases, useful information for predicting lymph node metastasis and recurrence sites as well as prognostic information can be obtained.

Therapy-free interval has prognostic value in patients with recurrent cervical cancer treated with chemotherapy following definitive concurrent chemoradiotherapy.

PURPOSE: Patients with cervical cancer recurrence after concurrent chemoradiotherapy (CCRT) who are not candidates for surgical resection or salvage radiotherapy have a dismal prognosis. The predictive factors for the effects of chemotherapy and prognostic factors in these patients were analyzed. METHODS: We collected data for patients with recurrent cervical cancer who were primarily treated with CCRT between 2000 and 2013. Among them, 57 patients treated with only systemic chemotherapy were analyzed for the overall survival (OS), the overall response rate (ORR), and prognostic factors. RESULTS: The median age was 47 years. Inside the irradiated field recurrence occurred in 24, outside in 20 and both in 13 patients. Time to recurrence after the CCRT (i.e., therapy-free interval; TFI) were <6 months in 11, 6-12 months in 15, ≥12 months in 23 patients, and persistent disease in 8 patients. The median OS was 18 months and ORR was 15.7%. Those with a longer TFI showed a tendency for better ORR (p = 0.051) and those receiving a taxane-containing regimen showed significantly higher ORR (p = 0.0232). Multivariate analysis revealed a significant correlation between the median OS and TFI (HR = 4.688, 95% CI = 2.178-11.10, p < 0.0001) and chemotherapy response (HR = 20.08, 95% CI = 3.936-368.4, p < 0.0001). Furthermore, even in patients with stable disease, the median OS increased corresponding to the length of the TFI (p < 0.0001). CONCLUSIONS: TFI has predictive value for response to chemotherapy and prognosis of patients with recurrent cervical cancer after definitive CCRT.

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.

Recurrent female adnexal tumor of probable Wolffian origin treated with debulking surgery, imatinib and paclitaxel/carboplatin combination chemotherapy: A case report.

In view of the small number of recurrent and metastatic cases of female adnexal tumors of probable Wolffian origin (FATWO), there is a distinct lack of evidence to support recommendations regarding treatment. In the present study, a 37-year-old female was diagnosed with a left adnexal tumor and underwent a left salpingo-oophorectomy (SO). The tumor was found to arise from the left tubal fimbria and extend to the posterior leaf of the broad ligament. Pathological examination identified a number of solid, tubular and cystic architectures, with areas of hyalinization, hemorrhage and necrosis. Immunohistochemistry detected that the tumor cells were positive for cytokeratin (CK)7, vimentin, inhibin and calretinin, and negative for CK20, epithelial membrane antigen, and the estrogen and progesterone receptors. Thus, the patient was diagnosed with FATWO. Following 15 months, the patient developed recurrent tumors and subsequently underwent a total abdominal hysterectomy, a right SO and extirpation of the disseminated tumors, but with incomplete debulking. The tumor cells were immunoreactive for KIT. As there are a limited number of treatment options and few reported cases, limiting the therapy recommendations, imatinib mesylate was administered for 6 months and the tumors were temporarily stabilized for 4 months until the disease progressed. The patient underwent a further debulking surgery that did not achieve complete debulking and was subsequently administered a combination chemotherapy of paclitaxel and carboplatin. This regimen resulted in an almost complete response after 10 cycles. The tumors continued to decrease in size, and the tumors in the left side of the Douglas pouch and the right para-colic gutter were no longer detectable. To the best of our knowledge, the current study is the first to report carboplatin and paclitaxel combination therapy demonstrating a response of this degree to recurrent FATWO following the failure of imatinib treatment. However, surgical debulking remains the most effective treatment for FATWO when is it is possible. The precise role of chemotherapy, radiotherapy and molecular-targeting therapy in the treatment of recurrent or metastatic FATWO remains to be elucidated, and therefore, novel strategies to overcome this disease must be prioritized.

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.

Ovarian preservation in young women with endometrial cancer of endometrioid histology.

OBJECTIVE: To clarify the frequency and risk factors of ovarian metastasis in women with endometrial cancer of endometrioid histology. DESIGN: Retrospective observational study. SETTING: University of the Ryukyus Japan 1990-2011. POPULATION: Eighty-eight women ≤ 45 years of age with endometrial cancer of only endometrioid histology. METHODS: Clinicopathological factors from the medical records were used. Fisher's exact test and logistic regression analysis were used to analyze predictive factors for ovarian metastasis. MAIN OUTCOME MEASURES: Risk factors of ovarian malignancy. RESULTS: All women underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and lymph node dissection. The median age was 39 years, and FIGO stage distributions were: stage I, 63 (71.6%) women; stage II, 14 (15.9%) women; and stage III, 11 (12.5%) women. Pathologically, ovarian metastasis was observed in four (4.5%) women. Only lymph node metastasis was a significant predictive factor for ovarian metastasis (p = 0.0038), and deep myometrial invasion was the only significant factor (p = 0.0085) for the prediction of lymph node metastasis. No ovarian malignancy was found in 72 women with invasion ≤ 50% myometrial depth and no enlargement of the ovaries. We observed ovarian metastasis in two (14.3%) of 14 women with deep myometrial invasion without ovarian tumor. CONCLUSION: Ovarian preservation surgery might be considered in endometrial cancer of endometrioid histology with ≤ 50% myometrial depth invasion with no ovarian mass after taking into account family history.

Radiotherapy- or radical surgery-induced female sexual morbidity in stages IB and II cervical cancer.

OBJECTIVE: The objective of this study was to evaluate the sexual function in cervical cancer survivors after radiotherapy (RT) or radical surgery (RS). METHODS: This was an observational and cross-sectional study. The Female Sexual Function Index (FSFI) self-reported questionnaires were distributed to 175 patients after RT (RT group) or RS (RS group) and 521 healthy women (control) between 2011 and 2012. Sexual functions were compared among these 3 groups. RESULTS: Eligible 92 patients (46 in RT group, 46 in RS group) and 148 control subjects were included for analysis. There was a significant difference in median (range) FSFI total score of 5.5 (3.6-34.7) in the RT group, 18.9 (3.4-31.2) in the RS group, and 22.1 (2-34.2) in the control group (P < 0.001). The median FSFI total score in the RT group was significantly lower than that in the control group (P < 0.001). Six sexual domains (desire, arousal, lubrication, orgasm, satisfaction, pain) were all significantly affected in the RT group, and no significant differences, except pain, were observed in the RS group as compared with the control group. CONCLUSIONS: Interventions involving counseling and rehabilitation for female sexual function should be provided in cervical cancer survivors, especially after RT.

Concurrent chemoradiotherapy for non-bulky stage IB/II cervical cancer without pelvic node enlargement.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) has not been extensively studied in patients with small cervical cancer tumors with no pelvic node enlargement. PATIENTS AND METHODS: We retrospectively analyzed 55 patients with stage IB1-IIB cervical cancer and tumors of ≤40 mm with no pelvic node enlargement treated with radiotherapy (RT)-alone. RESULTS: Cancer recurred in seven patients. Patient age (≤63 years) was identified as an independent factor for better disease-free survival (DFS) (p=0.027), and tumor size (≥25 mm) had a tendency to correlate with reduced locoregional DFS (p=0.089) by the Cox hazard model. Among patients aged 63 years or less, cancer recurred in five out of 18 patients with tumors of ≥25 mm, but in only one of 10 patients with tumors of ≤24 mm. CONCLUSION: In patients with stage IB1-IIB cervical cancer and small tumors with no node enlargement, CCRT may provide a better disease control for the group aged 63 years or less and with tumor size of 25 mm or more.

Long-term results and prognostic factors in patients with stage III-IVA squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy from a single institution study.

BACKGROUND: We evaluated the longer-term efficacy and safety of concurrent chemoradiotherapy (CCRT) incorporating high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a lower cumulative radiotherapy (RT) protocol and analyzed prognostic risk factors for survival among patients with FIGO stage III-IVA squamous cell carcinoma (SCC) of the cervix. PATIENTS AND METHODS: Ninety-nine patients with FIGO stage III-IVA SCC of the cervix between 1997 and 2008 were treated with CCRT using cisplatin 20 mg/m(2) for 5 days every 3 weeks or 40 mg/m(2) weekly. Acute and late toxicities were evaluated. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis. RESULTS: Median age was 53.5 years. Median follow-up period was 58 months (range 6-170 months). Pathologically complete response was achieved in 93 patients (96.9%). The 5-year OS and DFS were 72.0 and 69.3%, respectively. The 5-year local and distant DFS were 83.0 and 75.1%, respectively. Thirty-one patients (31.3%) experienced recurrence. Multivariate analysis showed that tumor size and pretreatment hemoglobin level remained an independent risk factor for OS and DFS. Acute toxicity was moderate. In terms of late adverse effects, 2 patients (2.0%) suffered from grade 4 late intestinal toxicity because of radiation enterocolitis, with both requiring intestinal surgery. CONCLUSIONS: Our study demonstrates that the CCRT schedule in patients with FIGO stage III-IVA SCC is efficacious and safe. In addition, the assessment of tumor size and pretreatment anemia can provide valuable prognostic information.

Concurrent chemoradiotherapy with paclitaxel and cisplatin for adenocarcinoma of the cervix.

BACKGROUND: It is unclear whether cisplatin-based concurrent chemoradiotherapy (CCRT) has the same effect on adenocarcinoma as on squamous cell carcinoma. PATIENTS AND METHODS: We retrospectively analyzed data for 32 patients with stage IIB-IVA cervical adenocarcinoma who were treated with radiotherapy (RT) or CCRT. Fourteen patients were treated with RT, 8 with CCRT using cisplatin alone (CCRT-P), and 10 with CCRT using cisplatin plus paclitaxel (CCRT-TP). RESULTS: Complete response was achieved in 7/14 patients in the RT group, 4/8 patients in the CCRT-P group, and 9/10 patients in the CCRT-TP group. Ten out of the 14 patients in the RT, 7/8 patients in the CCRT-P, and 2/10 patients in the CCRT-TP groups experienced locoregional recurrence. The 5-year overall survival rate in the RT, CCRT-P, and CCRT-TP groups was 7.1%, 25.0%, and 74.1%, respectively (p=0.0094). CONCLUSION: The present study demonstrated that CCRT-TP achieved much better local control for adenocarcinoma of the cervix, leading to a decrease in locoregional recurrence.