Tissue factor-induced fibrinogenesis mediates cancer cell clustering and multiclonal peritoneal metastasis.

Peritoneal metastasis is one of the most frequent causes of death in several types of advanced cancers; however, the underlying molecular mechanisms remain largely unknown. In this study, we exploited multicolor fluorescent lineage tracking to investigate the clonality of peritoneal metastasis in mouse xenograft models. When peritoneal metastasis was induced by intraperitoneal or orthotopic injection of multicolored cancer cells, each peritoneally metastasized tumor displayed multicolor fluorescence regardless of metastasis sites, indicating that it consists of multiclonal cancer cell populations. Multicolored cancer cell clusters form within the peritoneal cavity and collectively attach to the peritoneum. In vitro, peritoneal lavage fluid or cleared ascitic fluid derived from cancer patients induces cancer cell clustering, which is inhibited by anticoagulants. Cancer cell clusters formed in vitro and in vivo are associated with fibrin formation. Furthermore, tissue factor knockout in cancer cells abrogates cell clustering, peritoneal attachment, and peritoneal metastasis. Thus, we propose that cancer cells activate the coagulation cascade via tissue factor to form fibrin-mediated cell clusters and promote peritoneal attachment; these factors lead to the development of multiclonal peritoneal metastasis and may be therapeutic targets.

Clinical Study of Sentinel Lymph Node Detection Using Photodynamic Eye for Abdominal Radical Trachelectomy.

This study aimed to assess the accuracy of predicting pelvic lymph node status using sentinel lymph node (SLN) biopsy with indocyanine green (ICG) and to examine the outcomes of SLN biopsy-guided abdominal radical trachelectomy (ART). Patients with stage IA2-IB2 cervical cancer from January 2009 to January 2021 were included. ICG was injected before ART and SLNs were identified, excised, and assessed intraoperatively using fast-frozen sections. Systemic pelvic lymphadenectomy was subsequently performed. The SLN detection rate, sensitivity, and false-negative rate were determined. Thirty patients desiring fertility preservation were enrolled, of whom 26 successfully completed ART and four underwent radical hysterectomies because of metastatic primary SLNs. Bilateral SLNs were identified in all patients. The sensitivity, false-negative rate, and negative predictive value were 100%, 7.7%, and 92.3%, respectively. Three (12%) patients were lost to follow-up: two relapsed and one died of tumor progression. Of the nine patients who tried to conceive after surgery, four achieved pregnancy and three delivered healthy live infants. In women with early-stage cervical cancer who desired to conserve fertility, SLN mapping with ICG had a very high detection rate, sensitivity, and low false-negative rate. SLN biopsy-guided ART is a feasible and accurate method for assessing pelvic node status.

Review of Treatment and Prognosis of Stage IVB Cervical Carcinoma.

OBJECTIVES: In most patients, stage IVB cervical cancer is incurable, and the outcomes are poor. There is significant individual variation in patients with stage IVB cervical cancer, in whom standard treatment has not been well defined. This study aims to review the outcomes and discuss treatment strategies in patients with stage IVB cervical cancer. METHODS: From January 1, 1992, to December 31, 2011, we retrospectively reviewed the data of patients with stage IVB cervical cancer who were given a diagnosis at the Department of Gynecology of the Cancer Institute Hospital. RESULTS: A total of 111 patients were enrolled. At the time of analysis, the median overall survival (OS) was 16.6 months (range, 0.2-120.9 months), and the 5-year OS rate was 20.2%. The 5-year OS rate was 59.4% for those with only para-aortic lymph node metastases; 24.8% for those with lymphogenous metastases, excluding those with only para-aortic lymph node metastases; 6.1% for those with hematogenous metastases; and 0% for those with disseminated metastases. The OS in patients with lymphogenous metastases was better compared with that of those with either hematogenous or disseminated metastases (P < 0.0001). In multivariate analysis, the performance status, site of metastases (only lymph node or other metastases), and local stage were all independent prognostic factors. CONCLUSIONS: We determined performance status, site of metastases (only lymph node or other metastases), and local stage as independent prognostic factors in patients with stage IVB cervical cancer. Regarding treatment, we confirmed that the effectiveness of chemotherapy was also of significance.

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.

Vulvar Reconstruction Following Surgery for Vulvar Cancer Using a Stepladder V-Y Advancement Medial Thigh Flap.

OBJECTIVE: The aim of this study was to identify the risks and benefits of the stepladder V-Y advancement medial thigh flap for vulvovaginal reconstruction in comparison to direct skin closure. METHODS: Fifty-four patients with vulvar cancer treated in our hospital between 1992 and 2013 were enrolled in this study. The cohort group (group A) consisted of 25 patients who underwent surgery from August 2006 until April 2013. During this period, we changed our surgical paradigm to incorporate reconstructive plastic surgery immediately following surgery for vulvar cancer performed by gynecologic oncologists. The control group (group B) consisted of 29 patients treated between 1992 and August 2006. During this period, our surgical approach was limited to direct skin closure with no reconstructive plastic surgery. Perioperative findings and clinical outcomes were compared retrospectively. RESULTS: Patient characteristics and surgical procedures, other than the reconstructive surgery, were the same for the 2 groups. The mean blood loss and operative times were similar, and there were no major complications in either group; however, the average length of hospital stay was significantly shorter in group A (P = 0.04). CONCLUSIONS: Stepladder V-Y advancement medial thigh flap lowers posttreatment morbidity and improves quality of life for patients with vulvar cancer. Rapid recovery from surgery is reflected in the short hospital stay, and it enables immediate induction of adjuvant therapy. It may possibly contribute to improved treatment outcome.

Resection of the vaginal vault for vaginal recurrence of cervical cancer after hysterectomy and brachytherapy.

BACKGROUND: We describe our experiences with vaginal vault resection for vaginal recurrence of cervical cancer after hysterectomy and radiotherapy. After operative treatment, the rate of vaginal vault recurrence of uterine cervical cancer is reported to be about 5%. There is no consensus regarding the treatment for these cases. METHODS: Between 2004 and 2012, eight patients with vaginal vault recurrence underwent removal of the vaginal wall via laparotomy after hysterectomy and radiotherapy. RESULTS: The median patient age was 45 years (range 35 to 70 years). The median operation time was 244.5 min (range 172 to 590 min), the median estimated blood loss was 362.5 mL (range 49 to 1,890 mL), and the median duration of hospitalization was 24.5 days (range 11 to 50 days). Two patients had intraoperative complications: a grade 1 bowel injury and a grade 1 bladder injury. The following postoperative complications were observed: one patient had vaginal vault bleeding, three patients developed vesicovaginal fistulae, and one patient had repeated ileus. Two patients needed clean intermittent catheterization. Local control was achieved in five of the eight cases. CONCLUSIONS: Vaginal vault resection is an effective treatment for vaginal recurrence of cervical cancer after hysterectomy and radiotherapy. However, complications of this procedure can be expected to reduce quality of life. Therefore, this operation should be selected with great care.

Clinical characteristics of non-squamous cell carcinoma of the vagina.

OBJECTIVE: The prognosis and vaginal disease control rate after treatment with radiotherapy or concurrent chemoradiotherapy (CCRT) are reported to be worse for primary non-squamous cell carcinoma (non-SCC) of the vagina than for squamous cell carcinoma (SCC) of the vagina. Our objective was to examine the clinicopathological characteristics of primary non-SCC of the vagina and suggest an appropriate treatment strategy. MATERIALS AND METHODS: In a retrospective chart review, we identified patients with primary vaginal cancer who were treated in our hospital between 1990 and 2013. Twelve patients with histologically diagnosed non-SCC were identified. None of these cases was associated with in utero diethylstilbestrol exposure. Clinical data, including patient characteristics, stage, treatment outcome, and the site of recurrence, were recorded. RESULTS: The 12 identified cases included 5 of clear cell carcinoma, 3 of adenocarcinoma, 2 of adenosquamous carcinoma, 1 of carcinosarcoma, and 1 of mucinous adenocarcinoma. The most common location of the tumor was the upper one third of the vagina (56%). Initial treatment involved surgery in 8 patients. Among them, 4 received adjuvant chemotherapy, 3 received adjuvant radiotherapy, and 1 received neither. The initial treatment among the remaining 4 patients was CCRT in 1, neoadjuvant chemotherapy in 2 (followed by CCRT or surgery), and best supportive care in 1. The last 3 patients had lung metastasis. Six patients experienced recurrence, including vaginal recurrence in 2 patients and lymphatic spread in 4 patients. Five of these 6 patients experienced hematogenous metastasis. CONCLUSIONS: Despite the absence of in utero diethylstilbestrol exposure in our cases, clear cell adenocarcinoma accounted for 41.7% (5/12) cases. A favorable local control rate was achieved in all 12 cases, but the incidence of distant metastasis, especially to the lung, was high. Prevention of distant metastasis may be the key to treating patients with non-SCC of the vagina.

Radiation-induced osteosarcoma might mimic metastatic bone lesions: a case with bone scan and FDG PET/CT imaging.

We report on a 53-year-old woman with osteosarcoma of the skull who underwent radiation therapy for metastatic brain tumor. She had a history of uterine endometrial cancer treated with chemotherapy and surgery 9 years previously. FDG PET/CT for surveillance showed nodular accumulation at the right suprainguinal region and very avid accumulation at the left side of the occipital bone. Bone scan showed increased accumulation at the same portion of the occipital bone. The occipital tumor was surgically removed and diagnosed as radiation-induced osteosarcoma.

Prognosis for endometrial cancer patients treated with systematic pelvic and para-aortic lymphadenectomy followed by platinum-based chemotherapy.

OBJECTIVE: The purpose of this study was to analyze the prognosis for endometrial cancer patients treated with systematic pelvic and para-aortic lymphadenectomy (PLA and PALA) followed by platinum-based chemotherapy. MATERIALS AND METHODS: From 1994 to 2004, in the Cancer Institute Hospital, 502 patients who were surgically treated with systematic PLA and PALA were enrolled in this study. Their prognosis and clinicopathological features were retrospectively reviewed. RESULTS: One hundred ninety-one (38.0%) patients received adjuvant platinum-based chemotherapy. Lymph node (LN) metastasis was observed in 80 (15.9%) patients, pelvic-only LN metastasis in 27 (5.4%), para-aortic-only LN metastasis in 15 (3.0%), and both pelvic and para-aortic LN metastasis in 38 (7.6%). The median number of metastatic LNs was 2 (range, 1-57), 1 (range, 1-4), and 6 (range, 2-50) in patients with pelvic-only, para-aortic-only, and both pelvic and para-aortic LN metastasis, respectively (P < 0.001). Only 2.6% (2/76) of patients with no myometrial invasion had LN metastasis, and no less than 8.9% (22/247) of patients with myometrial invasion (limited to the inner half) had LN metastasis. Five-year overall survival (OS) for LN metastasis-negative and -positive patients was 96.7% and 76% (P < 0.001), respectively. Five-year OS for patients with metastasis in 1 or 2 LNs was 84.8% and was significantly higher than that for patients with metastasis in 3 or more LNs (57.8%; P = 0.011). In patients with LN metastasis, 5-year OS of endometrioid adenocarcinoma and non-endometrioid adenocarcinoma cell types was 90.2% and 56.7% (P = 0.0016), respectively. CONCLUSIONS: Under the settings of thorough PLA and PALA followed by intensive platinum-based chemotherapy for endometrial cancer, metastasis in 1 or 2 LNs seems to have little effect on survival, although para-aortic LNs are involved. This therapeutic strategy could not improve the prognosis of patients with metastasis in 3 or more LNs or patients with non-endometrioid adenocarcinoma cell types along with LN involvement.

Platinum-free interval in second-line chemotherapy for recurrent cervical cancer.

OBJECTIVE: The purpose of this study was to determine whether the platinum-free interval (PFI) was a predictive indicator in second-line treatment of cervical cancer in patients who had undergone prior platinum-based chemotherapy. The role of the PFI in selecting the second-line regimen in other gynecologic malignancies is also discussed. METHODS: In this retrospective study, we examined the clinical records of patients with recurrent or metastatic cervical cancer who had received platinum-containing combination regimens as second-line chemotherapy. All patients had received prior platinum-containing chemotherapy or concurrent chemoradiotherapy. RESULTS: The overall response rate to second-line chemotherapy was 25.8%; 7 patients achieved a complete response and 17 a partial response. The median progression-free survival (PFS) was 5.1 months and median overall survival (OS) was 13.5 months. The response rate was 12.5%, 14.2%, 20.0%, 22.2%, and 55.0%; median PFS was 4.0, 5.1, 4.4, 5.8, and 7.4 months; and median OS was 10.2, 14.4, 11.9, 16.3, and 19.7 months when PFI was within 3, 3 to 5, 6 to 11, 12 to 23, and more than 24 months, respectively. Age (>50 years), size (>3 cm), prior radiotherapy, and PFI (>24 months) were identified as prognostic factors in the multivariate analysis for PFS and OS. CONCLUSIONS: The results indicate that a PFI of more than 24 months is the discriminating point between platinum-sensitive and platinum-resistance cervical cancer. This indicates that PFI offers a useful tool in selecting agents for second-line chemotherapy in a wide range of gynecologic malignancies.

Feasibility and acute toxicity of Concurrent Chemoradiotherapy (CCRT) with high-dose rate intracavitary brachytherapy (HDR-ICBT) and 40-mg/m2 weekly cisplatin for Japanese patients with cervical cancer: results of a Multi-Institutional Phase 2 Study (JGOG1066).

OBJECTIVE: To assess the feasibility and acute toxicity of concurrent chemoradiotherapy (CCRT) with high-dose rate intracavitary brachytherapy (HDR-ICBT) and standard dose delivery of cisplatin for Japanese patients with cervical cancer. MATERIALS AND METHODS: The phase 2 study included Japanese patients with International Federation of Gynecology and Obstetrics stage III to IVA uterine cervical cancer who had no para-aortic lymphadenopathy (>10 mm) assessed by computed tomography. Patients were 20 to 70 years of age and had Eastern Cooperative Oncology Group performance status of 0 to 1. The radiotherapy protocol consisted of whole-pelvis external beam radiotherapy and HDR-ICBT. The cumulative linear quadratic equivalent dose (EQD2) was 62 to 65 Gy prescribed at point A. Cisplatin was administered weekly at a dose of 40 mg/m(2) for 5 courses. RESULTS: Between March 2008 and January 2009, 72 patients from 25 institutions were enrolled, and 71 patients were eligible and evaluable for compliance and severe toxicity. The median age of the patients was 57 years (range, 32-70 years). Sixty-five patients (92%) received the planned 5 courses of chemotherapy. Four patients had cisplatin dose reduction according to the protocol. Radiotherapy was completed per protocol in 68 patients (96%). Median overall treatment time was 50 days (range, 37-66 days). The following grade 3 or 4 acute adverse events were observed: neutropenia in 31 patients (44%), anemia in 10 patients (14%), diarrhea in 4 patients (6%), and anorexia in 3 patients (4%). CONCLUSIONS: Concurrent chemoradiotherapy with HDR-ICBT and standard weekly delivery of cisplatin was feasible with acceptable toxicity in Japanese patients with cervical cancer.

Phase II study of concurrent chemoradiotherapy with high-dose-rate intracavitary brachytherapy in patients with locally advanced uterine cervical cancer: efficacy and toxicity of a low cumulative radiation dose schedule.

OBJECTIVE: A multicenter phase II trial was conducted to assess the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with high-dose-rate intracavitary brachytherapy (HDR-ICBT) using a low cumulative prescribed dose schedule in patients with locally advanced uterine cervical cancer. METHODS: The Japanese Gynecologic Oncology Group (JGOG) study JGOG1066 enrolled patients with FIGO stages III-IVA uterine cervical cancer who had no para-aortic lymphadenopathy (>10 mm) assessed by CT. Patients received definitive radiotherapy (RT) consisting of external beam whole pelvic RT and HDR-ICBT. The cumulative linear quadratic equivalent dose (EQD2) was 62-65 Gy prescribed at point A. Cisplatin 40 mg/m(2) weekly was administered concurrently with RT for 5 courses. RESULTS: Of the 72 patients registered, 71 were eligible. With a median follow-up of 28 months, the 2-year progression-free survival rate and pelvic disease progression-free rate were 66% (95% CI, 54% to 76%) and 73% (95% CI, 61% to 82%), respectively. Progression-free survival decreased significantly with increased central tumor size (P=0.036). The 2-year cumulative late complication rates were 24% for all grades, 9% for grade 1, 12% for grade 2, 3% for grade 3, and 0 for grades 4/5. CONCLUSIONS: The JGOG1066 demonstrated that CCRT using HDR-ICBT with a low cumulative RT dose schedule achieved comparable outcome as those achieved with global dose schedules (EQD2=85 Gy) with a lower incidence of late toxicity for locally advanced uterine cervical cancer in a Japanese population.

Unexpected tumor progression after conization for carcinoma in situ of the uterine cervix.

AIM: To determine the safety and usefulness of conization with an electrosurgical loop (the loop electrosurgical excision procedure [LEEP]) in young women with carcinoma in situ (CIS) of the uterine cervix. METHODS: A retrospective medical chart review of five patients with CIS initially treated with LEEP conization between 2002 and 2010 and who later experienced recurrence in the form of invasive or advanced disease was conducted. RESULTS: The median patient age at initial LEEP conization was 41years (33-56years). The margin status in conization specimens was positive in three of the five patients. The median time to detection of tumor progression was 50months (17-58months). Magnetic resonance imaging was effective in detecting tumor recurrence in all cases. In four patients, hysterectomy was performed to treat the recurrence; these four patients are currently alive and disease-free. One patient with cervical lymph nodes and bone metastases was treated with chemotherapy alone; however, the patient died. In surgical specimens, tumor progression was observed extending toward the endometrium in all five patients and toward the vagina in two patients. CONCLUSION: This study indicates that patients with CIS occasionally show unexpected tumor progression after conization and the progression could be life-threatening. Recurrent disease often shows tumor progression toward the endometrium or vagina, leading to difficulties in its detection at periodic pelvic examinations.

Parametrial involvement in FIGO stage IB1 cervical carcinoma diagnostic impact of tumor diameter in preoperative magnetic resonance imaging.

BACKGROUND: In the surgical treatment for early-stage cervical carcinoma, it is important to identify preoperatively a low-risk group of patients as candidates for less radical surgery to avoid the morbidity associated with radical hysterectomy. The aim of this study was to evaluate the correlation between tumor diameter measured preoperatively using magnetic resonance imaging (MRI) and pathological prognostic factors in International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical carcinoma. METHODS: A total of 125 patients with FIGO stage IB1 cervical cancer were included in this study. Clinical records, pathology reports, and MRI findings were retrospectively reviewed. RESULTS: Histological diagnosis was squamous cell carcinoma in 57 patients and non squamous cell carcinoma in 68 patients. All patients underwent preoperative evaluation by MRI within a median period of 13.5 days before surgery. The tumor diameter measured by MRI ranged from zero (no tumor detected) to 42 mm, with a median of 23 mm.Pathological prognostic factors included parametrial involvement, lymph node metastasis,deep stromal invasion, and lymphovascular space invasion. All these factors were found less frequently in patients with a smaller tumor diameter. Most notably, parametrial involvement was seen in none of the patients with tumors 20 mm or less and was detected only in patients with tumors greater than 20 mm (P = 0.01). CONCLUSIONS: In the FIGO stage IB1 cervical carcinoma, the tumor diameter measured preoperatively by MRI correlates well with other pathological prognostic factors, especially with parametrial involvement. This finding suggests that the tumor diameter measured in preoperative MRI may serve as a strong predictor of parametrial involvement in FIGO stage IB1 cervical carcinoma, which can be used to select a candidate population for less radical surgery without the need for a cone biopsy before hysterectomy.

Radiotherapy quality assurance of the Japanese Gynecologic Oncology Group study (JGOG1066): a cooperative phase II study of concurrent chemoradiotherapy for uterine cervical cancer.

BACKGROUND: To assess radiotherapy protocol compliance in a multi-institutional phase II study of concurrent chemoradiotherapy for patients with locally advanced cancer of the uterine cervix (JGOG1066). METHODS: For study protocol development, various radiotherapy parameters were examined and consensus was reached by Japanese radiation oncologists with cervical cancer treatment expertise. Quality assurance (QA) was also discussed and included in the protocol. A credentialing process was used to select institutions for participation in the study. Individual case reviews referring to 18 QA items were undertaken for each patient. Radiotherapy data were submitted to the Japanese Gynecologic Oncology Group (JGOG) data center and reviewed by the members of the radiotherapy committee. The QA evaluation was classed as per protocol, deviation, and violation. RESULTS: Individual case reviews were performed on 69 of 72 patients entered in the study. In 24 patients (35%), there were no deviations for any QA items. There were also no deviations seen for 5 of the 18 items in 69 patients evaluated. Deviations of 64 QA items were seen in 45 cases, and violations were seen in 4 cases (4 items). The most common deviation concerned appropriate application for the external beam radiotherapy (EBRT) boost to involved nodes or parametrium (32 cases). The 4 violations were identified in the QA items regarding high-dose rate intracavitary brachytherapy. CONCLUSIONS: Radiotherapy protocol compliance was favorable except for the EBRT boost indications. The results of this study validate the quality of radiotherapy in JGOG1066, and indicate that the final analysis will provide meaningful results.

Neoadjuvant chemotherapy followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for Stage IB2-IIB cervical cancer--irinotecan and platinum chemotherapy.

OBJECTIVE: To evaluate the effectiveness of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for stage IB2-IIB cervical cancer. METHODS: Forty-six consecutive patients with stage IB2-IIB cervical cancer were treated with NAC followed by radical hysterectomy plus postoperative chemotherapy. Median (range) body mass index (BMI) of the patients was 20.2 (16.2-26.4). Regimens for NAC and postoperative chemotherapy were irinotecan and cisplatin (CPT-11/CDDP) or CPT-11 and nedaplatin (CPT-11/NDP). A total of six cycles of NAC and postoperative chemotherapy were prescribed. No use of radiotherapy was scheduled, except in the case of a recurrence. RESULTS: With a median follow-up period for survivors of 38.8 months (range 24-54 months), the 2- and 3-year progression-free survival rates were 91.2% and 86.1%, respectively. Overall response rate of NAC was 80.4%. Recurrence was observed in seven patients. In the absence of radiotherapy, pelvic recurrence was observed in only three patients; another two had para-aortic lymph nodes and the remaining two distant metastases. Toxicities due to chemotherapy were generally tolerable. Postoperative complications included urinary fistula (four patients, 8.7%) and bowel obstruction (two patients, 4.3%), all of which required surgical intervention. CONCLUSION: The results indicate that NAC followed by surgery plus postoperative chemotherapy but no radiotherapy offers a viable option in the treatment of stage IB2-IIB cervical cancer. Although a relatively large incidence of postsurgical complications was observed among low-BMI patients, this treatment offers the advantage of minimizing radiation-induced morbidity, allowing radiotherapy to be reserved for the possible event of pelvic recurrence.

Phase I study of concurrent chemoradiotherapy with weekly cisplatin and paclitaxel chemotherapy for locally advanced cervical carcinoma in Japanese women.

The purpose of this study was to evaluate the use of concurrent chemoradiotherapy involving weekly administration of cisplatin and paclitaxel for the treatment of locally advanced cervical carcinoma in Japanese women. Twenty Japanese patients were registered for this phase I study. Radiation therapy was performed using external irradiation and high-dose rate intracavitary irradiation of the pelvis. Chemotherapy was performed once a week until termination of the radiation therapy. The dose of cisplatin was decided as 30 mg/m2, and the initial dose of paclitaxel was set as 30 mg/m2, with a planned incremental increase of 10 mg/m2 up to 70 mg/m2. When 3 to 6 patients were registered at each dose level and dose-limiting toxicity (DLT) was noted in more than 3 patients, the dose level was assumed to be the maximum tolerated dose. Among the 20 patients, 1 patient experienced DLT during 2 courses because of dehydration and arrhythmia. In another patient, chemotherapy was discontinued after 4 courses because of a hypersensitivity reaction to paclitaxel at dose level 3. No patient experienced DLT resulting from hematologic toxicities. All patients underwent radiation therapy according to schedule without any discontinuations. A complete response was obtained in 16 patients. Based on the results obtained from this study, weekly administration of 30 mg/m2 cisplatin and 50 mg/m2 paclitaxel with concurrent chemoradiotherapy can be considered a tolerable and safe dose for the treatment of locally advanced cervical carcinoma in Japanese women.

Treatment results of adjuvant chemotherapy after radical hysterectomy for intermediate- and high-risk stage IB-IIA cervical cancer.

OBJECTIVE: To determine the effectiveness of chemotherapy alone as postoperative adjuvant therapy for intermediate- and high-risk cervical cancer. METHODS: The study group comprised of 65 consecutive patients with stage IB or IIA squamous cell or adenosquamous cervical cancer who were initially treated with radical hysterectomy and pelvic lymphadenectomy between 1993 and 2002. Tumors were of intermediate-risk (stromal invasion > 50%, n = 30) or high-risk (positive surgical margin, parametrial invasion, and/or lymph node involvement, n = 35). In all cases, chemotherapy was administered adjuvantly: three courses of bleomycin, vincristine, mitomycin, and cisplatin for intermediate-risk cases and five courses for high-risk cases. Disease-free survival and complications of the combined therapy were investigated. RESULTS: Estimated 5-year disease-free survival was 93.3% for the 30 patients with intermediate-risk tumors (100% for those with squamous cell carcinoma and 71.4% for those with adenosquamous carcinoma) and 85.7% for the 35 patients with high-risk tumors (89.3% for those with squamous cell carcinoma and 71.4% for those with adenosquamous carcinoma). The incidence of locoregional recurrence was 3.3% in the intermediate-risk group and 8.6% in the high-risk group. Side effects of chemotherapy and complications of the combined therapy were within acceptable limits. No patient had severe bleomycin-related pulmonary toxicity. Only 1.5% of patients developed small bowel obstruction, which was cured by conservative therapy. CONCLUSIONS: The treatment results suggest the potential role of adjuvant chemotherapy alone for patients with cervical cancer.

Effectiveness of postoperative chemotherapy for para-aortic lymph node metastasis of endometrial cancer.

OBJECTIVE: To examine the effectiveness of postoperative chemotherapy for para-aortic lymph node (PAN) metastasis in patients with endometrial cancer. METHODS: Among 350 clinical stage I-II endometrial cancer patients who underwent systemic pelvic and para-aortic lymphadenectomy during the period 1995 through 2002, 26 patients were identified with PAN metastasis. Of these patients, nine had only one positive PAN and 17 had two or more positive PANs (mean 4.9, range 1-22). All patients were treated postoperatively with a single chemotherapy regimen consisting of ifosfamide, epiadriamycin, and cisplatin scheduled for 5 cycles. Median (range) follow-up for surviving patients was 85 (38-119) months. Treatment outcome, including disease-free survival relative to the number of positive PANs, was investigated. RESULTS: Among the 26 patients with PAN involvement, four developed recurrence. Three of the four patients had 10 or more positive PANs. Estimated 5-year disease-free survival rates were 89% for patients with one positive PAN, 82% for those with two or more positive PANs, and 85% for all patients. No significant difference was identified between the first two groups (P = 0.6543). CONCLUSIONS: Postoperative chemotherapy can yield a favorable outcome in endometrial cancer patients with PAN metastasis, even those with multiple positive nodes.