Extended cytoreduction of tumor at the porta hepatis by an interdisciplinary team approach in patients with epithelial ovarian cancer

Objective

The objective of this study was to describe the development and experience in resection of tumor at the porta hepatis in patients with ovarian cancer by an interdisciplinary team approach.

Methods

From August 2007 to June 2009, 11 women (2 primary and 9 recurrent ovarian cancers) underwent extended cytoreductive surgery including resection of tumor at the porta hepatis by hepatobiliary surgeons.

Results

Tumor resection at the porta hepatis was required in 7.1% of the patients (11/155) during the study period. The median tumor size of the porta hepatis was 2.0 cm (range, 0.7-4 cm). All visible tumors at the porta hepatis were completely resected with co-operation of hepatobiliary surgeons. Optimal cytoreduction was achieved in all patients. There was no significant morbidity related to tumor resection of the porta hepatis and mortality associated with surgery. Five of 11 patients had recurrent disease at median 8 months (range, 1-13) after the surgery with a median follow-up of 8 months (range, 3-21 months).

Conclusion

Tumor resection at the porta hepatis is feasible with acceptable morbidities in patients with ovarian cancer by an interdisciplinary team approach with hepatobiliary surgeons. Long term follow up is needed to know the impact on survival.     

CA125 surveillance increases optimal resectability at secondary cytoreductive surgery for recurrent epithelial ovarian cancer

Objective

Recent data suggest that serial CA125 surveillance following remission in asymptomatic patients with epithelial ovarian cancer (EOC) does not impact overall survival. However, earlier detection of recurrence may influence resectability at secondary cytoreductive surgery (SCS). We hypothesized that a shorter time interval between CA125 elevation and SCS correlates with a higher likelihood of optimal resection among eligible patients.

Methods

We identified patients with recurrent epithelial ovarian cancer who underwent SCS from 1995 to 2009 at our institution. All patients initially underwent primary cytoreductive surgery followed by platinum-based chemotherapy. CA125 elevation was considered the first value two-times the patient's nadir level. Our “study interval” was the time between CA125 elevation and SCS. Optimal SCS was defined as microscopic residual disease (≤ 0.5 cm). Our analysis compared patients who underwent optimal vs. suboptimal SCS.

Results

Seventy-four patients who underwent SCS for recurrent EOC met inclusion criteria. Median disease-free interval prior to SCS was 19 vs. 12 months for the optimal and suboptimal SCS groups. More patients undergoing suboptimal SCS had ascites (21% vs. 2%, p = 0.01) and carcinomatosis (42% vs. 5%, p < 0.0001). Patients who underwent optimal SCS went to the operating room 5.3 vs. 16.4 weeks (HR 1.03, 95% CI 1.01-1.06, p = 0.04) from the time of their CA125 elevation. Optimal SCS was associated with a longer overall survival (47 vs. 23 months, p < 0.0001).

Conclusions

Each week delay after first CA125 elevation correlated with a 3% increased chance of suboptimal resection at SCS. Serial CA125 surveillance for early detection of recurrence may increase rates of optimal SCS and potentially influence overall survival.     

Robotic-assisted resection of liver and diaphragm recurrent ovarian carcinoma: description of technique

Goals

To describe port placement and operative technique for resection of right hepatic and full-thickness diaphragm metastatic ovarian carcinoma in a patient with recurrent disease using the da Vinci® Surgical System.

Case

A 60-year-old female with recurrent platinum sensitive ovarian cancer presented with disease confined to the liver by PET-CT scan. The lesion measured 3.4 cm on the dome of the right hepatic lobe. After two attempts at intra-hepatic arterial chemo-embolization the lesion remained stable. She subsequently agreed to robotic-assisted resection of the right lobe liver mass after refusing laparotomy for 9 months.

Procedure

Pnuemoperitoneum was established in the left upper quadrant by directly inserting a 5-mm laparoscope. There were no midline adhesions. The 12-mm camera port was placed in the midclavicular line on the right 10 cm off the costal margin with the right and left operative arms 10 cm from the camera near the costal margin, and the third arm in the right flank. The robot was docked from the right shoulder. Resection was accomplished with a monopolar spatula in the right, fenestrated bipolar grasper in the left, and double fenestrated grasper in the third operative arm. Adhesions between diaphragm and liver were separated, the liver lesion was excised, the diaphragm lesion was resected full thickness, and diaphragm was closed with running prolene. Surgicel® was placed on the liver for hemostasis. Console time was 82 min and the patient discharged on day-5 after drainage of a cytology negative pleural effusion day-4.

Conclusions

Robotic resection of liver and full-thickness diaphragm lesions is possible. The port placement used in this patient was efficient and without operative arm collisions. Patients with isolated upper-abdominal recurrence are candidates for robotic secondary cytoreduction.     

Nuclear P27 expression in benign, borderline (LMP) and invasive tumors of the ovary and its association with prognosis: a gynecologic oncology group study

Objective

Nuclear p27 expression was examined in non-invasive and invasive ovarian tumors from a cross-sectional study, and clinical relevance of p27 was evaluated in the primary tumors from women participating in two randomized phase III treatment trials.

Methods

An immunohistochemistry assay was used to detect p27 in formalin-fixed paraffin-embedded ovarian tumors from 3 distinct sources.

Results

Among the initial 91 ovarian tumors tested, low p27 expression (< 50% positive cells) was observed in 5.4% of non-invasive tumors versus 42.6% of invasive tumors (p < 0.001). In 145 ovarian cancers with high-risk early stage disease, 16.5% exhibited low p27 expression, and categorized p27 was not associated with age, race, or performance status. Low expression of p27 was common in poorly differentiated tumors (35.7%) compared to moderately (15.0%) and well (9.5%) differentiated tumors (p = 0.024) and rare in clear cell carcinomas (2.4%) compared to other histologies (p = 0.014). In the 139 cancers with advanced disease, 60% displayed low p27 expression, and categorized p27 expression was not associated with age, race, performance status, tumor grade, histologic subtype, measurable disease status or survival. Exploratory analyses revealed an association of cyclin E to p27 ratio > 1.0 with an increased risk of death (hazard ratio = 1.53; p = 0.017).

Conclusions

Low p27 expression could be associated with malignant transformation of the ovarian epithelium and FIGO stage. A cyclin E to p27 ratio > 1.0 may be associated with shorter survival in these patients. Further study is required to confirm the trend for increased recurrences with low p27 expression in early stage disease.     

The impact of ultra-radical surgery in the management of patients with stage IIIC and IV epithelial ovarian,fallopian tube,and peritoneal cancer

Objective

The aim of this study is to estimate the percentage of patients with metastatic ovarian, fallopian tube, and primary peritoneal cancer requiring ultra-radical surgery to achieve cytoreduction to less than 1 cm (optimal) or no macroscopic residual disease (complete).

Methods

Perioperative data were collected prospectively on consecutive patients undergoing elective cytoreductive surgery for metastatic epithelial ovarian, fallopian tube, or primary peritoneal cancer at the Norfolk and Norwich University Hospital, a tertiary referral cancer centre in the United Kingdom from November 2012 to June 2016.

Results

Over a 42-month period, 135 consecutive patients underwent cytoreductive surgery for stage IIIC and IV ovarian, fallopian tube, or primary peritoneal cancer. The median age of the patients was 69 years. 47.4% of the patients underwent diaphragmatic peritonectomy and/or resection, 20% underwent splenectomy, 14.1% had excision of disease from porta hepatis and celiac axis, and 5.2% of the patients had gastrectomy. Cytoreduction to no macroscopic visible disease (complete) and to disease with greater tumour diameter of less than 1 cm (optimal) was achieved in 54.1 and 34.1% of the cases, respectively. Without incorporating surgical procedures in the upper abdomen (‘ultra-radical’), the combined rate of complete and optimal cytoreduction would be only 33.3%.

Conclusions

Up to 50.4% of the patients in this study required at least one surgical procedure classified as ultra-radical, emphasizing the importance of cytoreductive surgery in the upper abdomen in management of women with stage IIIC and IV ovarian, fallopian tube, and primary peritoneal cancer.

     

Rectosigmoid resection at the time of primary cytoreduction for advanced ovarian cancer. A multi-center analysis of surgical and oncological outcomes

Objective

The aim of the study was to determine the impact of rectosigmoid resection, at the time of primary cytoreductive surgery, on morbidity and survival of patients with advanced ovarian cancer.

Methods

We performed a retrospective medical chart review of patients who underwent rectosigmoid resection for ovarian, tubal and peritoneal cancers between 1998 and 2008 at the IEO in Milan and JHMI in Baltimore. Perioperative and follow-up data were collected.

Results

A total of 238 patients were identified; 180 (75%) had stages IIC-IIIC and 58 (25%) had stage IV. Complete cytoreduction was achieved in 41% of the cases. Stapled coloproctostomy was performed in 98% while hand sewn in only 2%; a protective ileostomy and colostomy were necessary (constructed) in 2 (0.8%) and 5 (2%) cases respectively. The complications associated to rectosigmoid resection were anastomotic leakage in 7 (3%) patients and pelvic abscess in 9 (3.7%). Fifty percent of patients recurred during the study period, but only 5% of them showed a relapse at the level of the pelvis whereas 8% presented with abdominal recurrence associated with pelvic disease as well. The median overall survival time among patients with complete cytoreduction was 72 months compared with 42 months among the rest of patients (p = 0.002).

Conclusions

Rectosigmoid colectomy may significantly contribute to achieve a complete primary cytoreduction for advanced stage ovarian, tubal and peritoneal cancers. Pelvic complete debulking accomplished by rectosigmoid resection could be associated with a lower rate of pelvic recurrence as well.     

Risk factors for recurrence of ovarian borderline tumors

Objective

The objective of this study was to identify clinicopathologic features that are associated with an increased risk of recurrence for borderline ovarian tumors (BOT).

Methods

We performed a retrospective review of all patients treated for BOT at our institution from 1979 to 2008. Progression-free survival (PFS) was defined as the time of diagnosis to time of recurrence/death or last follow-up. The Kaplan-Meier method was used to calculate the PFS rate and the Wilcoxon-Gehan test was performed to identify prognostic factors.

Results

A total of 266 patients were identified. The median age was 43 years (range, 15-94 years). The majority of patients (68.4%) had FIGO stage I disease and serous histology (73.7%). Only 23 (8.6%) patients developed recurrent disease. The median PFS was 19 years and the median follow-up was 4 years. Abnormal baseline CA-125 (> 35 U/ml), advanced stage, age at diagnosis, and invasive implants were associated with decreased PFS. Of the 196 patients with serous BOT, those with a micropapillary pattern had a 3-year PFS of 75.9% (95%CI, 55.6-87.8) compared with 94.3% (95% CI, 88.4-97.3) for patients without micropapillary pattern (P < 0.001).

Conclusion

Age at diagnosis, an elevated preoperative CA-125, invasive implants, and micropapillary histology were clinical factors associated with increased risk of recurrence in women with BOT. Including these clinicopathologic features will likely identify patients at higher risk for recurrence, for whom development of new treatment strategies would be appropriate.     

A comparative detail analysis of the learning curve and surgical outcome for robotic hysterectomy with lymphadenectomy versus laparoscopic hysterectomy with lymphadenectomy in treatment of endometrial cancer: a case-matched controlled study of the first one hundred twenty two patients

Goal

To determine the learning curve and surgical outcome for the first one hundred twenty-two robotic hysterectomy with lymphadenectomy patients in comparison to the first one hundred twenty-two patients who underwent the same procedure laparoscopically.

Materials and methods

An analysis of the first 122 patients who underwent a robotic assisted hysterectomy with lymphadenectomy (RHBPPALND) was compared to the first 122 patients who underwent a total laparoscopic hysterectomy with lymphadenectomy (LHBPPALND). The learning curve of the surgical procedure was determined by measuring operative time with respect to chronological order of each patient who had undergone their respective procedure. Number of lymph nodes, estimated blood loss, days of hospitalization, and complications of all patients were also analyzed and compared.

Results

The learning curve of the surgical procedure was determined by measuring operative time with respect to chronological order of each patient who had undergone their respective procedure. Data were analyzed for mean age, body mass index, operative time, estimated blood loss, lymph node retrieval and complications for both surgical procedures. The mean operative time was 147.2 ± 48.2 and 186.8 ± 59.8 for RHBPPALND and LHBPPALND respectively. The mean EBL was statistically significant at 81.1 ± 45.9 and 207.4 ± 109.4 for RHBPPALND and LHBPPALND respectively. The total number of pelvic and aortic lymph nodes was 25.1 ± 12.7 for RHBPPALND and 43.1 ± 17.8 for LHBPPALND. The number of pelvic lymph node was 19.2 ± 9.0 and 24.7 ± 11.9 for RHBPPALND and LHBPPALND. The days of hospitalization of RHBPPALND and LHBPPALND were 1.5 ± 0.9 and 3.2 ± 2.3. The number of intraoperative complications for RHBPPALND, and LHBPPALND was 1 and 7, respectively.

Conclusion

Robotic hysterectomy with lymphadenectomy has a faster learning curve in comparison to laparoscopic hysterectomy with lymphadenectomy. The adequacy of surgical staging was comparable between the two surgical methods. RHBPPALND is associated with shorter hospitalization, less blood loss and less intraoperative and major complications, and lower rate of conversion to open procedure.     

Secondary cytoreductive surgery for recurrent platinum-sensitive ovarian cancer

Objective

To determine the risks and benefits of secondary cytoreductive surgery for recurrent platinum-sensitive ovarian cancer.

Methods

Data were obtained retrospectively for all women with recurrent platinum-sensitive epithelial ovarian cancer who underwent a second debulking operation between 1998 and 2008 at the University of Texas Southwestern Medical Center. Survival analysis and comparisons were performed using the Kaplan-Meier method, log-rank test, and Cox multivariate proportional hazards model.

Results

Optimal secondary cytoreductive surgery (< 5 mm of residual disease) was achieved in 32 of 40 patients (80%). Nine women (23%) developed major complications. Two variables, residual disease of less than 5 mm vs 5 mm or greater (median 63 months vs 11 months; P = 0.003); and less than 5 vs 5 or more sites of disease relapse (median 63 months vs 22 months; P = 0.009), were independently associated with survival and retained prognostic significance on multivariate analysis.

Conclusions

Optimal secondary cytoreductive surgery was associated with a survival advantage and acceptable risks.     

Laparoscopic pelvic exenteration for gynaecological malignancy: is there any advantage?

Introduction

Pelvic exenteration (PE) remains one of the most mutilating surgical procedures with important postoperative morbidity. Laparoscopic approach has emerged in an attempt to reduce postoperative complications. The aim of the present study was to compare outcomes between laparoscopic pelvic exenteration combined with a vaginal or perineal approach, versus classical approach.

Methods

A cohort study was performed by identifying patients who underwent laparoscopic pelvic exenteration, and retrospectively comparing data with open cases from the same period of time, from 2000 to 2008.

Results

Fourteen patients underwent laparoscopic PE and 29 patients underwent an open exenterative procedure. All patients except one (97.6%) had received prior radiotherapy. Eighteen patients (41.9%) underwent total PE, 17 anterior PE (39.5%), and 8 posterior PE (18.6%). Urinary diversion (UD) technique consisted of 24 Miami pouch (68.6%), 9 Bricker diversion (25.7%), 1 Kock pouch (2.9%), and 1 ureterostomy (2.9%). Most frequent postoperative complications were related to the urinary diversion (45%) and bowel reconstruction (27.9%). Median estimated blood loss for the laparoscopy and laparotomy group was 400 ml (range 200-700 ml) and 875 ml (range 200-1600 ml), respectively. Transfusion rate was also significantly higher in the laparotomy group. Operative time, margin status, length of hospital stay, operative and postoperative morbidity, and disease and overall survival were not significantly different between both groups.

Conclusions

Laparoscopic PE is feasible with curative intent to selected patients. Potential postoperative advantages of laparoscopic approach when compared to classical approach, oncological safety of the procedure, and QOL considerations need to be further investigated.     

A randomized, controlled trial to compare ketorolac tromethamine versus placebo after cesarean section to reduce pain and narcotic usage

Objective

The purpose of this study was to determine whether postcesarean section administration of ketorolac tromethamine reduces pain and narcotic usage.

Study design

A double-blinded randomized, placebo-controlled trial of ketorolac tromethamine was performed. Patients were randomly assigned to receive either ketorolac tromethamine or placebo. Patient-controlled analgesia (PCA) was used for pain control. Visual analog scales (VAS) were administered postoperatively to assess pain levels. Morphine equivalents and attempts were recorded.

Results

There were 22 patients in each arm of the study. There was no significant difference between patient demographics, blood loss, and type of anesthesia. Pain scores were significantly different at 2, 3, 4, 6, 12, and 24 hours by analysis of variance (ANOVA) (P = .033). There was a significant decrease in pain medication usage (P = .008) in the study group.

Conclusion

Ketorolac tromethamine is efficacious in reducing postoperative pain and narcotics usage after cesarean section.     

Large cell neuroendocrine carcinoma of the cervix: prognostic factors and survival advantage with platinum chemotherapy

Objective

Large cell neuroendocrine carcinoma of the cervix (LCNEC) is a rare cervical neoplasm associated with poor survival. Our objective was to identify treatments associated with improved survival.

Methods

Relevant data were abstracted from an English literature MEDLINE search, SEER database, and a patient treated at our institution. Multivariate analysis was performed by generating Cox proportional hazard ratios.

Results

We identified 62 patients with LCNEC: 49 cases from the English literature, 12 patients in the SEER database and our patient. Out of the 62 women, median age was 37 (range, 21-75). FIGO stage was as follows: 58% had stage I disease, 16% had stage II, 2% had stage III, 8% had stage IV disease and 16% had no stage documented. Of all patients, 73% underwent primary surgery, 4.7% underwent primary radiation, 4.7% underwent chemotherapy, 8% had chemoradiation, and 9.6% had no primary treatment. Of all patients, 58% died of disease, 26% had no evidence of disease, 3% were alive with disease, and 13% had no survival data. The overall median survival was 16.5 months (0.5-151 months). Median overall survival for stage I, II, III, and IV cancers was 19, 17, 3, and 1.5 months, respectively. In a multivariate analysis, earlier stage (p < 0.00001) and the addition of chemotherapy (p = 0.04) were associated with improved survival. Both platinum agents (p = 0.034) and platinum and etoposide together (p = 0.027) were associated with improved survival.

Conclusions

Perioperative chemotherapy, in particular platinum with or without etoposide, improves survival in the rare LCNEC.     

Carcinosarcoma of the ovary: a review of the literature

Objective

Carcinosarcoma of the ovary is a rare tumor with a grim prognosis. This article critically reviews the literature pertinent to the pathology, pathogenesis, diagnosis, management, and outcome of patients with ovarian carcinosarcoma (OCS).

Methods

MEDLINE was searched for all research articles published in English between January 1, 1981 and August 30, 2011 which reported on patients diagnosed with carcinosarcoma of the ovary. Given the rarity of this tumor, studies were not limited by design or number of reported patients.

Results

Patients with OCS generally present with advanced stage disease, and symptoms similar to those of patients with epithelial ovarian cancer (EOC). Retrospective studies have shown that cytoreductive surgery improves outcomes in patients with OCS. Similarly, platinum-based chemotherapy appears to be active in the treatment of OCS.

Conclusions

Ovarian carcinosarcomas are rare and aggressive tumors, associated with a poor prognosis. The mainstay of treatment remains cytoreductive surgical effort for metastatic disease followed by platinum-based chemotherapy. The role of targeted therapies may be promising in the treatment of OCS.     

Racial disparities in ovarian cancer surgical care: a population-based analysis

Objective

To investigate differences according to racial classification in the frequency of ovarian cancer-related surgical procedures and in access to high-volume surgical providers among women undergoing initial surgery for ovarian cancer.

Methods

The Maryland Health Services Cost Review Commission database was accessed for women age > 18 years undergoing a surgical procedure that included oophorectomy for a malignant ovarian neoplasm between 7/1/01 and 6/30/09. Multivariate logistic regression analyses were used to evaluate for differences in the likelihood of selected surgical procedures and access to high-volume surgical providers (surgeons ≥ 10 cases/year; hospitals ≥ 20 case/year) according racial classification.

Results

A total of 2487 patients were identified who underwent a primary surgical procedure that included oophorectomy for a malignant ovarian neoplasm: White = 1884 (75.4%), African-American = 400 (16.1%), and other/unknown = 203 (8.2%). Compared to White patients, African-American patients were significantly younger (mean age 55.4 years vs 59.9 years, P < 0.0001) and less likely to have commercial insurance (28.5% vs 39.5%, p < 0.0001). Compared to White patients, African-American racial classification was associated with a statistically significant and independent lower likelihood of hysterectomy (OR = 0.53, 95%CI = 0.42-0.66, p < 0.0001), colon resection (OR = 0.65, 95%CI = 0.48-0.87, p = 0.004), lymphadenectomy (OR = 0.67, 95%CI = 0.50-0.91, p = 0.01), and surgery by a high-volume surgeon (OR = 0.55, 95%CI = 0.44-0.69, p < 0.0001).

Conclusions

Among women undergoing initial surgery for ovarian cancer, African-American patients are significantly less likely to be operated on by a high-volume surgeon and to undergo important ovarian cancer-specific surgical procedures compared to White patients.     

Increased circulating hepatocyte growth factor (HGF): a marker of epithelial ovarian cancer and an indicator of poor prognosis

Objective

Hepatocyte growth factor (HGF) has been described to be increased in different cancers. In the present study we wanted to investigate whether HGF in serum can distinguish between benign and malignant ovarian tumors, and whether serum HGF levels can predict the outcome in patients with ovarian carcinomas.

Methods

We included 123 consecutive patients appointed for laparotomy due to a pelvic mass. Preoperative levels of serum cancer antigen 125 (CA 125), HGF and HGF activator (HGFA) were quantified with immunological methods. We performed immunohistochemical analyses of HGFα, HGFβ and the receptor c-Met. Five-year survival of patients with advanced disease (stage III and stage IV) was analyzed with the Kaplan-Meier method.

Results

Sixty patients had ovarian carcinomas, 23 borderline tumors, and 40 benign ovarian tumors. Patients with ovarian carcinomas had significantly higher preoperative HGF and CA 125 serum levels than patients with benign ovarian tumors, and borderline tumors. Patients with borderline tumors had significantly higher CA 125 values than benign cases. A combination of CA 125 and HGF increased the specificity in predicting carcinoma. We observed abundant HGFα, HGFβ and c-Met expressions in all ovarian tumors. Patients with advanced disease and preoperative serum HGF values ≥ 2 SD above reference value had a shorter disease-free survival than patients with advanced disease and serum HGF < 2 SD above reference value.

Conclusions

HGF in serum is an indicator of ovarian carcinoma in women with a pelvic mass, and of a poor prognosis in advanced ovarian cancer.     

Recurrence patterns and prognosis of endometrial stromal sarcoma and the potential of tyrosine kinase-inhibiting therapy

Objective

Endometrial stromal sarcoma (ESS) is a rare uterine malignancy. The current treatment approaches yield unsatisfactory results, and potential therapeutic targets need exploration.

Methods

We reviewed the electronic medical records of 74 patients with low-grade ESS who had been evaluated at the University of Texas MD Anderson Cancer Center between 1995 and 2006. Using immunohistochemistry, we tested the expression of targets in paraffin-embedded tissue samples taken from 13 of the patients.

Results

Forty-seven patients (64%) had a recurrence, and 16 (22%) had died of their disease at last follow-up. The 10-year progression-free survival (PFS) rate was 43% (median PFS duration, 108 months), and the overall survival (OS) rate was 85% (median OS, 288 months). Patients who received hormonal therapy had an overall response rate of 27%; another 53% had stable disease, with a median time to progression of 24 months. No complete response or partial response was observed among patients who received radiotherapy or chemotherapy. In the paraffin-embedded specimens we tested, c-abl was expressed universally. Expression of PDGF-α, PDGF-β, VEGF, and c-Kit was detected in 33%, 36%, 54%, and 8%, of specimens, respectively. EGFR and HER-2 were not detectable in any specimens.

Conclusions

Our study suggests that ESS is a hormone-dependent malignancy, with hormonal therapy having activity in recurrent disease. Targeted therapy, specifically targeting c-abl may be a potential treatment for this disease.     

Feasibility and safety of type C2 total extraperitoneal abdominal radical hysterectomy (TEARH) for locally advanced cervical cancer

Introduction

Radical hysterectomy represents the gold standard treatment in patients with early-stage cervical cancer and a valid choice of treatment, after neoadjuvant chemotherapy (NACT), in locally advanced tumors. Laparotomy is still considered the standard approach for radical hysterectomy; however, the extraperitoneal route has been described as a valid alternative for pelvic lymphadenectomy, with shorter operative time, shorter ileus and reduced postoperative pain and hospitalization. We designed the first prospective study to evaluate the technique of total extraperitoneal radical hysterectomy for surgical treatment of locally advanced cervical cancer after platinum-based NACT, in terms of feasibility and safety.

Methods

Consecutive patients affected by locally advanced cervical carcinoma were considered for eligibility in this observational study. After a primary complete evaluation, all patients were submitted to platinum-based NACT. Inclusion criteria were: stage IB2-IIIB cervical carcinoma already submitted to neoadjuvant chemotherapy with a complete or partial response after three cycles of chemotherapy, WHO performance status ≤ 1, adequate renal, hepatic and cardiac function, BMI < 40, age ≤ 75 years, no concurrent or previous malignant disease, no previous radiation therapy, and signed informed consent. Patients included in the study were submitted to type C2 extraperitoneal radical hysterectomy.

Results

From January 2006 to October 2008, 46 patients were enrolled and compared with a control group selected from the historical database. The mean operative time in the extraperitoneal radical hysterectomy group was 195 min (range: 120-240) versus 235 min (range: 215-310) in the intraperitoneal radical hysterectomy group (P < 0.05). Median postoperative ileus was 32 h (range: 24-36) versus 67 h (range: 42-78) (P < 0.05). VAS (Visual Analogue Scale) score at 24 and 48 h was 8 (range: 6-8) versus 8 (range: 6-9) (P = NS) and 3.5 (range: 2-7) versus six (range: 5-9) (P < 0.05) respectively. No differences in terms of intraoperative and postoperative complications were recorded.

Conclusions

Total extraperitoneal radical hysterectomy in locally advanced cervical cancer is feasible and safe. If compared with intraperitoneal abdominal radical hysterectomy, no significant differences in terms of surgical data or complications were found. Extraperitoneal radical hysterectomy seems to compare favorably to the intraperitoneal approach in terms of operative time, postoperative ileus, and VAS score at 48 h.     

A phase II, single-arm study of the anti-α5β1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer

Objective

This phase II, multicenter, single-arm, two-stage study in platinum-resistant, advanced epithelial ovarian or primary peritoneal cancer evaluated the efficacy, safety, and tolerability of weekly single-agent volociximab. Pharmacokinetic/pharmacodynamic (PK/PD) studies were also performed.

Methods

Sixteen patients were enrolled in Stage 1. Volociximab was administered at 15 mg/kg IV qwk until progression of disease or drug intolerability. Tumor response was assessed every 8 weeks. Serum samples for PK or whole blood for the evaluation of circulating tumor cells, endothelial cells, and endothelial progenitor cells were obtained on Days 1, 8, 15, 29, and 50. Ascites from one patient was collected for volociximab concentration analysis. Archived tumor tissue was analyzed by immunohistochemistry (IHC) for α5 integrin expression.

Results

Safety data are available on all 16 patients; 14 were evaluable for efficacy. One patient had stable disease at 8 weeks. The remaining 13 progressed on treatment. Twelve patients (75%) experienced study-related adverse events (AEs); the most common (≥ 20%) were headache and fatigue. Three patients experienced possible study-related serious AEs (SAEs): reversible posterior leukoencephalopathy syndrome, pulmonary embolism, and hyponatremia. Peak serum concentrations of volociximab increased 2-3 fold from Day 1 to Day 50. Clinically relevant trough levels were achieved (> 150 μg/mL). IHC analysis of archived tumor sections showed low-to-moderate expression of α5 integrin on all ovarian cancer tissue evaluated.

Conclusion

Despite insufficient clinical activity in this refractory patient population to continue the study, weekly volociximab was well tolerated, and the gained understanding of the mechanism of action of volociximab will inform future development efforts.     

Docetaxel plus trabectedin appears active in recurrent or persistent ovarian and primary peritoneal cancer after up to three prior regimens: a phase II study of the Gynecologic Oncology Group

Objective

This study aims to estimate the activity of docetaxel 60 mg/m² IV over 1 h followed by trabectedin 1.1 mg/m² over 3 h with filgrastim, pegfilgrastim, or sargramostim every 3 weeks (one cycle).

Methods

Patients with recurrent and measurable disease, acceptable organ function, PS ≤ 2, and ≤ 3 prior regimens were eligible. A two-stage design was utilized with a target sample size of 35 subjects per stage. Another Gynecologic Oncology Group study within the same protocol queue involving a single agent taxane showed a response rate (RR) of (16%) (90% CI 8.6-28.5%) and served as a historical control for direct comparison. The present study was designed to determine if the current regimen had an RR of ≥ 36% with 90% power.

Results

Seventy-one patients were eligible and evaluable (prior regimens: 1 = 28%, 2 = 52%, 3 = 20%). The median number of cycles was 6 (438 total cycles, range 1-22). The number of patients responding was 21 (30%; 90% CI 21-40%). The odds ratio for responding was 2.2 (90% 1-sided CI 1.07—Infinity). The median progression-free survival and overall survival were 4.5 months and 16.9 months, respectively. The median response duration was 6.2 months. Numbers of subjects with grade 3/4 toxicity included neutropenia 7/14; constitutional 8/0; GI (excluding nausea/vomiting) 11/0; metabolic 9/1; pain 6/0. There were no treatment-related deaths nor cases of liver failure.

Conclusions

This combination was well tolerated and appears more active than the historical control of single agent taxane therapy in those with recurrent ovarian and peritoneal cancer after failing multiple lines of chemotherapy. Further study is warranted.     

Initial failure site according to primary treatment with or without para-aortic lymphadenectomy in endometrial cancer

Objective

The objective of this study was to compare the initial failure sites in patients with endometrial cancer who underwent surgical treatment including pelvic lymphadenectomy with or without para-aortic lymphadenectomy.

Methods

A retrospective chart review was carried out for 657 endometrial cancer patients with no residual disease after initial treatments including lymphadenectomy at two tertiary centers between 1987 and 2004. Surgical treatment at one institute included pelvic lymphadenectomy (PLX) without para-aortic lymphadenectomy (PALX), while surgical treatment including PLX + PALX was routinely performed at the other institute. We identified patients with recurrence and evaluated initial failure sites. Rates of recurrence in the respective sites were compared according to the type of lymphadenectomy.

Results

Of the 657 patients, 103 (15.7%) suffered recurrence. There was no significant difference between the rate of intrapelvic recurrence in the PLX alone group and that in the PLX + PALX group (4.7% vs. 2.9%, p = 0.22). The rate of extrapelvic recurrence in the PLX alone group was significantly higher than that in the PLX + PALX group (16.1% vs. 6.2%, p < 0.0001), and the rate of para-aortic node (PAN) recurrence in the PLX alone group was also significantly higher than that in the PLX + PALX group (5.1% vs. 0.6%, p = 0.0004). In the analysis of patients who received adjuvant chemotherapy, the rate of PAN recurrence in the PLX alone group was significantly higher than that in the PLX + PALX group (9.5% vs. 1.3%, p = 0.0036).

Conclusion

PAN recurrence was a failure pattern peculiar to the PLX alone group. Adjuvant chemotherapy might not be able to replace surgical removal as a treatment for metastatic lymph nodes.