Concurrent definitive chemoradiation incorporating intensity-modulated radiotherapy followed by adjuvant chemotherapy in high risk locally advanced cervical squamous cancer: a phase II study.

BACKGROUND: Although the prognosis of locally advanced cervical cancer has improved dramatically, survival for those with stage IIIB-IVA disease or lymph nodes metastasis remains poor. It is believed that the incorporation of intensity-modulated radiotherapy into the treatment of cervical cancer might yield an improved loco-regional control, whereas more cycles of more potent chemotherapy after the completion of concurrent chemotherapy was associated with a diminished distant metastasis. We therefore initiated a non-randomized prospective phaseII study to evaluate the feasibility of incorporating both these two treatment modality into the treatment of high risk locally advanced cervical cancer. OBJECTIVES: To determine whether the incorporation of intensity-modulated radiotherapy and the addition of adjuvant paclitaxel plus cisplatin regimen into the treatment policy for patients with high risk locally advanced cervical cancer might improve their oncologic outcomes. STUDY DESIGN: Patients were enrolled if they had biopsy proven stage IIIA-IVA squamous cervical cancer or stage IIB disease with metastatic regional nodes. Intensity-modulated radiotherapy was delivered with dynamic multi-leaf collimators using 6MV photon beams. Prescription for PTV ranged from 45.0 ~ 50.0 Gy at 1.8 Gy ~ 2.0 Gy/fraction in 25 fractions. Enlarged nodes were contoured separately and PTV-nodes were boosted simultaneously to a total dose of 50.0-65 Gy at 2.0- 2.6 Gy/fraction in 25 fractions. A total dose of 28 ~ 35 Gy high-dose- rate brachytherapy was prescribed to point A in 4 ~ 5 weekly fractions using an iridium- 192 source. Concurrent weekly intravenous cisplatin at 30 mg/m2 was initiated on the first day of radiotherapy for over 1-h during external-beam radiotherapy. Adjuvant chemotherapy was scheduled within 4 weeks after the completion of concurrent chemo-radiotherapy and repeated 3 weeks later. Paclitaxel 150 mg/m2 was given as a 3-h infusion on day1, followed by cisplatin 35 mg/m2 with 1-h infusion on day1-2 (70 mg/m2 in total). RESULTS: Fifty patients achieved complete response 4 weeks after the completion of the treatment protocol, whereas 2 patients had persistent disease. After a median follow-up period of 66 months, loco-regional (including 2 persistent disease), distant, and synchronous treatment failure occurred in 4,5, and 1, respectively. The 5-year disease-free survival, loco-regional recurrence-free survival, distant-metastasis recurrence-free survival was 80.5%, 90.3%, and 88.0%, respectively. Four of the patients died of the disease, and the 5-year overall survival was 92.1%. Most of the toxicities reported during concurrent chemo-radiotherapy were mild and transient. The occurrence of hematological toxicities elevated mildly during adjuvant chemotherapy, as 32% (16/50) and 4% (2/50) patients experienced grade 3-4 leukopenia and thrombocytopenia, respectively. Grade 3-4 late toxicities were reported in 3 patients. CONCLUSIONS: The incorporation of intensity-modulated radiotherapy and adjuvant paclitaxel plus cisplatin chemotherapy were highly effective and well-tolerated in the treatment of high-risk locally advanced cervical cancer. The former yields an improved loco-regional control, whereas distant metastases could be effectively eradicated with mild toxicities when adjuvant regimen was prescribed.

Comparison Study of Laparoscopic Sentinel Lymph Node Mapping in Endometrial Carcinoma Using Carbon Nanoparticles and Lymphatic Pathway Verification.

STUDY OBJECTIVE: To evaluate the detection rate and accuracy of sentinel lymph node (SLN) mapping using cervical and fundal injections of carbon nanoparticles (CNPs) in laparoscopic surgery of endometrioid endometrial cancer (EC) and to identify uterine lymphatic drainage pathways validated by mapping. DESIGN: A prospective consecutive study (Canadian Task Force classification II-2). SETTING: An academic research center. PATIENTS: Consecutive patients with a pathologic diagnosis of early-stage EC scheduled for primary laparoscopic-assisted staging surgery (laparoscopic hysterectomy, bilateral salpingo-oophorectomy, or comprehensive lymphadenectomy). INTERVENTIONS: Enrolled patients underwent laparoscopic SLN mapping with a 50-mg CNP tracer injection. Fifty patients received fundal subserosal injections at 4 sites (the fundal group), whereas 65 patients received cervical submucosal injections at 2 sites (the cervical group). After SLN mapping, all patients underwent laparoscopic staging surgery. MEASUREMENTS AND MAIN RESULTS: No allergic reactions to CNPs were observed in either group. The overall SLN detection rates were 100% and 92% in the cervical and fundal groups, and the bilateral SLN detection rates were 97% and 68% (p < .001), respectively. A total of 12 metastatic SLNs were accurately detected in 5 patients. The sensitivity of metastatic lymph node detection was 100% in the cervical group, which is higher than that in the fundal group (80%). The false-negative rates were 0% and 20%, respectively, in the cervical and fundal groups. Furthermore, we verified 3 uterine lymphatic pathways using the 2 injection methods. The upper paracervical pathway was the most common drainage pathway in both groups (91.4% in the cervical group vs 80.24% in the fundal group), whereas the infundibulopelvic pathway was observed only in the fundal group (15.11%). CONCLUSION: SLN mapping by CNPs in laparoscopic surgery for EC is a safe and effective alternative, with a higher detection rate and better accuracy with cervical injections than fundal injections. The upper paracervical pathway was the most common lymphatic pathway, whereas the infundibulopelvic pathway was only displayed in fundal injections.

Neoadjuvant Bleomycin, Etoposide, and Cisplatin (BEP) Chemotherapy in the Treatment of Extensively Advanced Yolk Sac Tumors: A Single Center Experience.

OBJECTIVE: This study aimed to investigate the role of neoadjuvant bleomycin, etoposide, and cisplatin (BEP) regimen in patients with extensively advanced yolk sac tumors (YSTs). METHODS: Between July 1982 and December 2015, a total of 58 patients with YST were initially treated at our institution, among which 18 were evaluated to be inoperable and received neoadjuvant BEP regimen. They were either too debilitated by the disease [Eastern Cooperative Oncology Group Performance Status Scale (ECOG ps) ≥2] to undergo a major surgery or were with too extensively disseminated lesions to be optimally debulked. This cohort of patients was retrospectively reviewed. RESULTS: One or 2 cycles of BEP regimen were prescribed to the majority of patients preoperatively. At the completion of neoadjuvant chemotherapy, 17 of them had ECOG ps of 1 or less. Seventeen (94.4%) exhibited clinical partial tumor regression, and 1 (5.6%) had clinical stable disease. Pathological complete tumor regression was observed in 2 (11.1%) patients, whereas the remaining 16 (88.9%) had nearly complete pathological regression. Seventeen patients were cytoreduced to no macroscopic residual disease; the remaining 1 was cytoreduced to macroscopic residual disease of 2 cm or less. No major surgical complications occurred. After a median follow-up of 83.5 months, 17 patients were free of recurrence. Five-year disease-free survival and overall survival were both 94.4%. Fertility-sparing surgery was carried out in all the 17 patients with the desire to preserve their fertility, and 5 infants were delivered in 6 patients who attempted conception. CONCLUSIONS: One or 2 cycles of neoadjuvant BEP regimen followed by cytoreductive surgery offer a chance for cure in extensively advanced patients with YSTs and help pave the way for fertility-sparing surgery.

Retrospective analysis of prognostic variables and clinical outcomes in surgically staged intermediate risk endometrial carcinoma.

OBJECTIVE: To identify independent prognostic variables for surgically staged intermediate risk endometrial carcinoma as defined by the Gynecologic Oncology Group 99 (GOG99) criteria. STUDY DESIGN: Retrospective study of 239 patients with FIGO stage IB-occult IIB endometrioid type endometrial cancer, who were primarily treated with comprehensive staging surgery. Data were collected on clinicopathological variables, extent of primary surgery, postoperative adjuvant treatment, and patterns of recurrences. Kaplan-Meier survival curves were used to estimate disease free survival (DFS) and overall survival (OS), and multivariate Cox regression models were used to identify independent prognostic variables. The median follow-up time was 67 months (range, 12-183 months). RESULTS: The 5-year DFS and OS were 91.0% and 93.0%, respectively. On univariate Kaplan-Meier analysis, age>60 years, deep myometrial invasion (MI), presence of lymph vascular invasion (LVSI), and negative progesterone receptor (PR) status were significantly associated with diminished 5-year DFS and OS. The univariate analysis on patterns of failures demonstrated that patients with older age or positive LVSI were more inclined to develop locoregional recurrence, while PR status and the depth of MI had a statistically significant impact on distant failure. On multivariate analysis, PR status, age, and the depth of MI were independent prognostic variables for 5-year DFS, and age was the only independent prognostic variable for 5-year OS. LVSI and age were independent prognostic variables for locoregional recurrence, while PR status and depth of MI were independent prognostic variables for distant recurrence. CONCLUSIONS: Age, depth of MI, PR status and presence of LVSI are of independent prognostic value for intermediate risk endometrial cancer. The presence of these variables warrants consideration when deciding upon treatment strategies.

Nerve plane-sparing radical hysterectomy: a simplified technique of nerve-sparing radical hysterectomy for invasive cervical cancer.

BACKGROUND: In order to simplify the complicated procedure of nerve-sparing radical hysterectomy, a novel technique characterized by integral preservation of the autonomic nerve plane has been employed for invasive cervical cancer. The objective of this study was to introduce the nerve plane-sparing radical hysterectomy technique and compare its efficacy and safety with that of nerve-sparing radical hysterectomy. METHODS: From September 2006 to August 2010, 73 consecutive patients with International Federation of Gynecology and Obstetrics stage IB to IIA cervical cancer underwent radical hysterectomy with two different nerve-sparing approaches. Nerve-sparing radical hysterectomy was performed for the first 16 patients (nerve-sparing radical hysterectomy group). The detailed autonomic nerve structures were identified and separated by meticulous dissection during this procedure. After January 2008, the nerve plane-sparing radical hysterectomy procedure was developed and performed for the next 57 patients (nerve plane-sparing radical hysterectomy group). During this modified procedure, the nerve plane (meso-ureter and its extension) containing most of the autonomic nerve structures was integrally preserved. The patients' clinicopathologic characteristics, surgical parameters, and outcomes of postoperative bladder function were compared between the two groups. RESULTS: There were no significant differences between the nerve plane-sparing radical hysterectomy and nerve-sparing radical hysterectomy groups regarding age, International Federation of Gynecology and Obstetrics stage, pathological type, preoperative treatment, or need for intraoperative blood transfusion. The nerve plane-sparing radical hysterectomy group had a higher body mass index than that of the nerve-sparing radical hysterectomy group (P = 0.028). The mean surgical duration in the nerve plane-sparing radical hysterectomy and nerve-sparing radical hysterectomy groups were (262 ± 46) minutes and (341 ± 36) minutes (P < 0.01). On the 8th postoperative day, 41 (71.9%) patients in the nerve plane-sparing radical hysterectomy group and nine (56.3%) patients in the nerve-sparing radical hysterectomy group had a postvoid residual urine volume of < 100 ml (P = 0.233). The median duration of catheterization was eight days (range 8 - 23 days) for the nerve plane-sparing radical hysterectomy group and eight days (range 8 - 22 days) for the nerve-sparing radical hysterectomy group (P = 0.509). Neither surgery-related injury nor pathologically positive margins were reported in either group. CONCLUSION: Nerve plane-sparing radical hysterectomy is a reproducible and simplified modification of nerve-sparing radical hysterectomy, and may be preferable to nerve-sparing radical hysterectomy for treatment of early-stage invasive cervical cancer.

[Clinical analysis of 35 cases of vulvar intraepithelial neoplasia grade III].

OBJECTIVE: To evaluate the etiology, clinicopathological characteristics, treatment and prognosis of VINIII. METHODS: Thirty-five patients with VINIII admitted in Cancer Hospital of Chinese Academy of Medical Sciences between 1993 and 2008 were analyzed retrospectively. RESULTS: All 35 patients attended to hospital with the symptoms of pruritus vulvae and lumps. Among of them, there were 28 (80%) cases whose lesions presented as multiple plaques, while 7 (20%) cases lesion were monofocal. Fifteen out of 35 cases had coexistent with human papillomavirus (HPV) related lesions, and there were the evidence of HPV in 22 patients whose pathologic sections revealed koilocytes. 34 cases (97%) except one received different types of surgical resections, including wide local resection (14/34), simple vulvectomy (16/34) and simple vulvectomy plus perianal skin resection (4/34), while there two cases shown positive cut-edges and one of them received radiotherapy postoperatively. Four out of the 34 cases recurred locally in 2, 4, 6 and 22 months and received surgical treatment again or laser therapy, respectively. The median follow-up period was 66 months (range 1-166), and none of them were died of the disease itself except one case died of the concurrent cervical cancer. Among 26 cases received the investigation of the quality of life, there were nine cases (35%) suffered from sexual dysfunction after the operation, and one of them received vulvoplasty. CONCLUSIONS: VINIII has good prognosis. The development of VINIII may be related to the infection of HPV, because most of them concurrent with HPV diseases. Its primary treatment is surgical resection, while affecting on the quality of life.

[An initial experience of the use of sentinel lymph node biopsy in squamous cell cancer of the vulva].

OBJECTIVE: To evaluate the feasibility of sentinel lymph node biopsy (SLNB) in patients with vulvar cancer. METHODS: Twenty-one patients with vulvar squamous cancer undergoing radical surgery admitted in Cancer Hospital of Chinese Academy of Medical Sciences from Oct. 2004 to Apr. 2008, were enrolled in the study. SLNB procedure was performed with blue dye alone in the first eleven patients, while the later ten patients, a combination procedure with radioactive tracer and blue dye was used to detect sentinel lymph node (SLN). All resected nodes were submitted to the pathological examination, which was considered as the gold standard to determine the efficacy of SLNB. The complications related to SLNB were also observed during the study. RESULTS: The sentinel node was identified in 20 patients (95%), included 8 cases with unilateral SLNs and 12 cases with bilateral SLN. A total of 83 SLN were identified with a mean number of 4.2 per patient (range, 1 - 9) or 2.6 per groin (range, 1 - 6). Difference between the mean number of SLN (4.4 per patient, 2.5 per groin) identified by blue dye or by combined procedure (3.9 per patient, 2.7 per groin) was not statistically significant (t = 0.459, P = 0.652;t = -0.421, P = 0.717). Twenty patients were detected to positively superficial inguinal SLN and one of them also positively bilateral deep femoral SLN, 8 (10 groins) of them were detected positively nodal metastases. Among of eight patients, 7 (9 groins) of them were detected more than one SLN involved, while 1 of them were detected false-negative node involved. The false negative rate of was 10% (1/10), negative predictive value was 96% (22/23). No complications were attributed to the study. CONCLUSIONS: SLNB procedure in vulvar cancer is feasible and safe. SLN identification appears to be highly accurate for detecting metastases in the ipsilateral inguinal lymphatic basins.

[A prospective study on nerve-sparing radical hysterectomy in patients with cervical cancer].

OBJECTIVE: To assess the nerve-sparing radical hysterectomy (NSRH) technique and its impact on postoperative voiding function. METHODS: Forty-four patients with International Federation of Gynecology and Obstetrics (FIGO) stage I b1-IIa cervical cancer were enrolled and randomized into NSRH group (study group, n = 22) and conventional radical hysterectomy (CRH) group (control group, n = 22). The pelvic autonomic nerve pathway (including hypogastric nerve, pelvic splanchnic nerve, inferior hypogastric plexus and bladder branch) was completely preserved in the NSRH group. Related parameters were compared between the two groups. RESULTS: The estimated blood loss in NSRH group and CRH group were (550 +/- 241) ml and (475 +/- 284) ml, respectively, with no significant difference (P > 0.05). The mean operation time in NSRH group and CRH group were (329 +/- 43) min and (272 +/- 56) min, respectively, with a significant difference (P < 0.01). More patients in NSRH group had post-void residual urine volume (PVR) < 100 ml than that in CRH group on day 8 after surgery (68% vs. 18%, P < 0.01). The median duration of postoperative catheterization was significantly shorter in NRSH group (8 - 23 days, median 8 days) than that in CRH group (8 - 32 days, median 20 days; P < 0.01). Neither surgery-related injury nor pathologically positive margin was reported in either of the groups. CONCLUSIONS: NSRH is a feasible and safe technique for preserving bladder function. Larger prospective studies are needed to confirm the efficacy of this technique.