Cediranib in Combination with Olaparib in Patients without a Germline BRCA1/2 Mutation and with Recurrent Platinum-Resistant Ovarian Cancer: Phase IIb CONCERTO Trial.

PURPOSE: The efficacy, safety, and tolerability of cediranib plus olaparib (cedi/ola) were investigated in patients with nongermline-BRCA-mutated (non-gBRCAm) platinum-resistant recurrent ovarian cancer. PATIENTS AND METHODS: PARP inhibitor-naïve women aged ≥18 years with platinum-resistant non-gBRCAm ovarian cancer, ECOG performance status of 0-2, and ≥3 prior lines of therapy received cediranib 30 mg once daily plus olaparib 200 mg twice daily in this single-arm, multicenter, phase IIb trial. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using RECIST 1.1. Progression-free survival (PFS), overall survival (OS), and safety and tolerability were also examined. RESULTS: Sixty patients received cedi/ola, all of whom had confirmed non-gBRCAm status. Patients had received a median of four lines of chemotherapy; most (88.3%) had received prior bevacizumab. ORR by ICR was 15.3%, median PFS was 5.1 months, and median OS was 13.2 months. Forty-four (73.3%) patients reported a grade ≥3 adverse event (AE), with one patient experiencing a grade 5 AE (sepsis), considered unrelated to the study treatment. Dose interruptions, reductions, and discontinuations due to AEs occurred in 55.0%, 18.3%, and 18.3% of patients, respectively. Patients with high global loss of heterozygosity (gLOH) had ORR of 26.7% [4/15; 95% confidence interval (CI), 7.8-55.1], while ORR was 12.5% (4/32; 95% CI, 3.5-29.0) in the low gLOH group. CONCLUSIONS: Clinical activity was shown for the cedi/ola combination in heavily pretreated, non-gBRCAm, platinum-resistant patients with ovarian cancer despite failing to meet the target ORR of 20%, highlighting a need for further biomarker studies.

Pembrolizumab activity in patients with Fanconi anemia repair pathway competent and deficient tumors.

BACKGROUND: Given the observed antitumor activity of immune-checkpoint-inhibitors in patients with mismatch-repair deficient (MSI-H) tumors, we hypothesized that deficiency in homologous-recombination-repair (HRR) can also influence susceptibility. METHODS: Patients with disease progression on standard of care and for whom pembrolizumab had no FDA approved indication received pembrolizumab. Patients with MSI-H tumors were excluded. Objectives included immune-related objective response rate (iORR), progression-free survival (PFS) and 20-weeks-PFS. Pembrolizumab was given every 3 weeks and scans performed every six. We evaluated a triple-stain (FANCD2foci/DAPI/Ki67) functional assay of the Fanconi Anemia (FA) pathway: FATSI, in treated patients' archived tumors. The two-stage sample size of 20/39 patients evaluated an expected iORR≥20% in the whole population vs. the null hypothesis of an iORR≤5%, based on an assumed iORR≥40% in patients with functional FA deficiency, and < 10% in patients with intact HRR. An expansion cohort of MSI stable endometrial cancer (MS-EC) followed. Exploratory stool microbiome analyses in selected patients were performed. RESULTS: Fifty-two patients (45F,7M;50-evaluable) were enrolled. For the 39 in the two-stage cohort, response evaluation showed 2CR,5PR,11SD,21PD (iORR-18%). FATSI tumor analyses showed 29 competent (+) and 10 deficient (-). 2PR,9SD,17PD,1NE occurred among the FATSI+ (iORR-7%) and 2CR,3PR,2SD,3PD among the FATSI(-) patients (iORR-50%). mPFS and 20w-PFS were 43 days and 21% in FATSI+, versus 202 days and 70% in FATSI(-) patients. One PR occurred in the MS-EC expansion cohort. CONCLUSIONS: Pembrolizumab has meaningful antitumor activity in malignancies with no current FDA approved indications and FA functional deficiency. The results support further evaluation of FATSI as a discriminatory biomarker for population-selected studies.

Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study.

PURPOSE: The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery. MATERIALS AND METHODS: Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m2 for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery. Secondary objectives included postoperative toxicity and HIPEC pharmacokinetics. RESULTS: Of 98 patients, 49 (50%) received HIPEC. Complete gross resection was achieved in 82% of the HIPEC patients and 94% of the standard-arm patients. Bowel resection was performed in 37% of patients in the HIPEC arm compared with 65% in the standard (P = .008). There was no perioperative mortality and no difference in use of ostomies, length of stay, or postoperative toxicity. At 24 months, eight patients (16.3%; 1-sided 90% CI, 9.7 to 100) were without progression or death in the HIPEC arm and 12 (24.5%; 1-sided 90% CI, 16.5 to 100) in the standard arm. With a medium follow-up of 39.5 months, 82 patients progressed and 37 died. The median progression-free survival in the HIPEC and standard arms were 12.3 and 15.7 months, respectively (hazard ratio, 1.54; 95% CI, 1 to 2.37; P = .05). There was no significant difference in median overall survival (52.5 v 59.7 months, respectively; hazard ratio, 1.39; 95% CI, 0.73 to 2.67; P = .31). These analyses were exploratory. CONCLUSION: HIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with carboplatin during secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer.

Prophylactic Negative Pressure Wound Therapy After Laparotomy for Gynecologic Surgery: A Randomized Controlled Trial.

OBJECTIVE: To estimate the effectiveness of prophylactic negative pressure wound therapy in patients undergoing laparotomy for gynecologic surgery. METHODS: We conducted a randomized controlled trial. Eligible, consenting patients, regardless of body mass index (BMI), who were undergoing laparotomy for presumed gynecologic malignancy were randomly allocated to standard gauze or negative pressure wound therapy. Patients with BMIs of 40 or greater and benign disease also were eligible. Randomization, stratified by BMI, occurred after skin closure. The primary outcome was wound complication within 30 (±5) days of surgery. A sample size of 343 per group (N=686) was planned. RESULTS: From March 1, 2016, to August 20, 2019, we identified 663 potential patients; 289 were randomized to negative pressure wound therapy (254 evaluable participants) and 294 to standard gauze (251 evaluable participants), for a total of 505 evaluable patients. The median age of the entire cohort was 61 years (range 20-87). Four hundred ninety-five patients (98%) underwent laparotomy for malignancy. The trial was eventually stopped for futility after an interim analysis of 444 patients. The rate of wound complications was 17.3% in the negative pressure wound therapy (NPWT) group and 16.3% in the gauze group, absolute risk difference 1% (90% CI -4.5 to 6.5%; P=.77). Adjusted odds ratio controlling for estimated blood loss and diabetes was 0.99 (90% CI 0.62-1.60). Skin blistering occurred in 33 patients (13%) in the NPWT group and in three patients (1.2%) in the gauze group (P<.001). CONCLUSION: Negative pressure wound therapy after laparotomy for gynecologic surgery did not lower the wound complication rate but did increase skin blistering. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02682316. FUNDING SOURCE: The protocol was supported in part by KCI/Acelity.

Multi-disciplinary summit on genetics services for women with gynecologic cancers: A Society of Gynecologic Oncology White Paper.

OBJECTIVE: To assess current practice, advise minimum standards, and identify educational gaps relevant to genetic screening, counseling, and testing of women affected by gynecologic cancers. METHODS: The Society of Gynecologic Oncology (SGO) organized a multidisciplinary summit that included representatives from the American College of Obstetricians and Gynecologists (ACOG), the American Society Clinical Oncology (ASCO), the National Society of Genetic Counselors (NSGC), and patient advocacy groups, BrightPink and Facing our Risk of Cancer Empowered (FORCE). Three subject areas were discussed: care delivery models for genetic testing, barriers to genetic testing, and educational opportunities for providers of genetic testing. RESULTS: The group endorsed current SGO, National Comprehensive Cancer Network (NCCN), and NSGC genetic testing guidelines for women affected with ovarian, tubal, peritoneal cancers, or DNA mismatch repair deficient endometrial cancer. Three main areas of unmet need were identified: timely and universal genetic testing for women with ovarian, fallopian tube, and peritoneal cancers; education regarding minimum standards for genetic counseling and testing; and barriers to implementation of testing of both affected individuals as well as cascade testing of family members. Consensus building among all stakeholders resulted in an action plan to address gaps in education of gynecologic oncology providers and delivery of cancer genetics care.

Clinical implications of pleural effusions in ovarian cancer.

The pleural cavity constitutes the most frequent extra-abdominal metastatic site in ovarian carcinoma (OC). In patients with OC and pleural effusions, a positive fluid cytology is required for a stage IV diagnosis. Unfortunately, about 30% of malignant pleural effusions exhibit false-negative cytological pleural fluid results. In those circumstances, exploratory video-assisted thoracoscopic surgery (VATS) serves as a diagnostic, staging and even therapeutic modality. Maximal (no visible disease) or, at least, optimal (no residual implant greater than 1 cm) cytoreduction should be the primary surgical goal in stage IV OC patients. This is due to residual tumour after cytoreductive surgery being one of the most important factors impacting on survival. Although malignant pleural effusions do not preclude abdominal surgical debulking, excision of gross pleural nodules may be necessary to achieve optimal cytoreduction. VATS quantifies pleural tumour burden and allows for intrathoracic cytoreduction or, if the latter is not feasible, ensures that abdominal surgery is not unnecessarily performed on women in whom gross tumour would still remain in the pleural space afterwards. Taxane-platinum neoadjuvant chemotherapy should be offered to this group. Patients with tumour extension into the pleural space have a median overall survival of 2 years.

Establishing a sentinel lymph node mapping algorithm for the treatment of early cervical cancer.

OBJECTIVE: To establish an algorithm that incorporates sentinel lymph node (SLN) mapping to the surgical treatment of early cervical cancer, ensuring that lymph node (LN) metastases are accurately detected but minimizing the need for complete lymphadenectomy (LND). METHODS: A prospectively maintained database of all patients who underwent SLN procedure followed by a complete bilateral pelvic LND for cervical cancer (FIGO stages IA1 with LVI to IIA) from 03/2003 to 09/2010 was analyzed. The surgical algorithm we evaluated included the following: 1. SLNs are removed and submitted to ultrastaging; 2. any suspicious LN is removed regardless of mapping; 3. if only unilateral mapping is noted, a contralateral side-specific pelvic LND is performed (including inter-iliac nodes); and 4. parametrectomy en bloc with primary tumor resection is done in all cases. We retrospectively applied the algorithm to determine how it would have performed. RESULTS: One hundred twenty-two patients were included. Median SLN count was 3 and median total LN count was 20. At least one SLN was identified in 93% of cases (114/122), while optimal (bilateral) mapping was achieved in 75% of cases (91/122). SLN correctly diagnosed 21 of 25 patients with nodal spread. When the algorithm was applied, all patients with LN metastasis were detected; with optimal mapping, bilateral pelvic LND could have been avoided in 75% of cases. CONCLUSIONS: In the surgical treatment of early cervical cancer, the algorithm we propose allows for comprehensive detection of all patients with nodal disease and spares complete LND in the majority of cases.

Incidence of lymph node and adnexal metastasis in endometrial stromal sarcoma.

OBJECTIVE: To determine the incidence of adnexal and lymph node (LN) metastasis in newly diagnosed endometrial stromal sarcoma (ESS). METHODS: We identified all cases with a diagnosis of ESS evaluated at our institution from January 1, 1980 to October 31, 2009. All uterine pathology was reviewed at our center. High-grade or undifferentiated tumors and ESS arising in extrauterine sites were excluded. Pertinent clinical data were abstracted from electronic medical records. Appropriate statistical tests were performed using SPSS16.0. RESULTS: We identified 94 cases of ESS. LN metastasis was identified in 7 (19%) of 36 patients who underwent LN evaluation. Six of the 7 cases with LN metastasis had lymphovascular invasion (LVI). LVI status was not reported in the other case. Five of the 7 patients with LN metastasis had grossly positive LNs with or without other gross extrauterine disease. Of 20 patients with disease grossly limited to the uterus and grossly normal LNs, 2 (10%) had LN metastasis. Both of these cases had LVI and extensive myoinvasion. Eighty-seven cases (93%) underwent salpingo-oophorectomy. Adnexal metastasis was identified in 11 (13%) of 87 cases, all manifested by gross adnexal tumor and occurring in patients with other gross pelvic extrauterine disease. CONCLUSION: The incidence of LN metastasis in ESS is commonly associated with gross extrauterine disease, extensive myoinvasion, and LVI. Since myoinvasion and LVI status often are not assessable at the time of hysterectomy, LN dissection remains a reasonable option at primary surgery. The rate of adnexal metastasis appears to be negligible in the absence of gross adnexal and extrauterine tumor.

Sentinel lymph node biopsy in the management of early-stage cervical carcinoma.

OBJECTIVES: We aimed to determine the sentinel lymph node detection rates, accuracy in predicting the status of lymph node metastasis, and if pathologic ultrastaging improves the detection of micrometastases and isolated tumor cells at the time of primary surgery for cervical cancer. METHODS: A prospective, non-randomized study of women with early-stage (FIGO stage IA1 with lymphovascular space involvement--IIA) cervical carcinoma was conducted from June 2003 to August 2009. All patients underwent an intraoperative intracervical blue dye injection. Patients who underwent a preoperative lymphoscintigraphy received a 99m Tc sulfur colloid injection in addition. All patients underwent sentinel lymph node (SLN) identification followed by a complete pelvic node and parametrial dissection. SLN were evaluated using our institutional protocol that included pathologic ultrastaging. RESULTS: SLN mapping was successful in 77 (95%) of 81 patients. A total of 316 SLN were identified, with a median of 3 SLN per patient (range, 0-10 SLN). The majority (85%) of SLN were located at three main sites: the external iliac (35%); internal iliac (30%); and obturator (20%). Positive lymph nodes (LN) were identified in 26 (32%) patients, including 21 patients with positive SLN. Fifteen of 21 patients (71%) had SLN metastasis detected on routine processing. SLN ultrastaging detected metastasis in an additional 6/21 patients (29%). Two patients had grossly positive LN at exploration, and mapping was abandoned. Three of 26 (12%) patients had successful SLN mapping; however, the SLN failed to identify the metastatic LN. Of these 3 false negative cases, 2 patients had a metastatic parametrial node as the only positive LN with multiple negative pelvic nodes including negative SLN. One patient with stage IA1 disease and lymphovascular invasion had unilateral SLN mapping and a metastatic common iliac LN identified on completion lymphadenectomy of the contralateral side that did not map. The 4 (5%) patients with unsuccessful mapping included 1 who had grossly positive nodes identified at the time of laparotomy; the remaining 3 occurred during each surgeon's initial SLN mapping learning phase. CONCLUSION: SLN mapping in early-stage cervical carcinoma yields high detection rates. Ultrastaging improves micrometastasis detection. Parametrectomy and side-specific lymphadenectomy (in cases of failed mapping) remain important components of the surgical management of selected cases.

Ventral hernia following primary laparotomy for ovarian, fallopian tube, and primary peritoneal cancers.

OBJECTIVES: To evaluate the incidence and risk factors for ventral hernia development following primary laparotomy for ovarian, fallopian tube, and peritoneal cancers. METHODS: All patients who underwent primary laparotomy for ovarian, tubal, or peritoneal cancer from 3/05 to 12/07 were identified. Hernias were identified radiographically or during physical exam. One-year and 2-year hernia rates were calculated. Clinicopathologic factors were evaluated for an association with the development of hernia using univariate and multivariate analysis. RESULTS: We identified 239 cases with 12 months of follow-up. Median age was 60 years (17-89 years), and median body mass index (BMI) was 25.0 kg/m(2) (16.9-58.5 kg/m(2)). Advanced stage disease (FIGO stage III/IV) was diagnosed in 182/239 (76%). The 1-year hernia rate was 8.8% (21/239): 13/21 (61.9%) were symptomatic, and 8/21 (38.1%) underwent hernia repair operations. On multivariate analysis, only BMI (p=0.004) and intraperitoneal (IP) chemotherapy (p=0.016) retained their independent association with hernia development by 12 months. Of the 239 patients, 167 had 24 months of follow-up. The 2-year hernia rate was 23.4% (39/167): 25/39 (64.1%) were symptomatic, and 17/39 (43.6%) underwent hernia repair operations. Multivariate analysis in this group demonstrated that advanced stage (p=0.033), wound complications (p=0.029), and BMI (p=0.012) were independently associated with hernia development by 24 months. CONCLUSIONS: The development of ventral hernia is a significant postoperative morbidity in patients undergoing primary surgery for ovarian, tubal, or peritoneal cancer. Independent associations with hernia development include: BMI and IP chemotherapy by Year 1, and BMI, wound complications and advanced stage by Year 2.

Surgical resection of recurrent upper abdominal cervical cancer: A case report and review of the literature.

► An isolated cervical cancer recurrence to the liver was resected after a partial response was achieve with chemotherapy. ► The patient had a 10 month disease free interval after surgery. ► Liver resection in case of isolated cervical cancer recurrence may be beneficial in selected cases.

Video-assisted thoracic surgery (VATS) evaluation of pleural effusions in patients with newly diagnosed advanced ovarian carcinoma can influence the primary management choice for these patients.

OBJECTIVES: To assess the utility of thoracoscopy in defining the extent of intrathoracic disease and survival outcomes in patients with moderate to large pleural effusions at the time of diagnosis of advanced ovarian carcinoma. METHODS: We reviewed the records of all patients with untreated advanced ovarian carcinoma and moderate to large pleural effusions who underwent video-assisted thoracoscopic surgery (VATS) our institution between 6/01 and 10/08. Demographic, clinicopathologic and outcome data were collected for all patients with a final diagnosis of ovarian carcinoma. RESULTS: Forty-two patients met eligibility criteria, with a median age of 58 years; median CA-125 level of 1747 U/mL; and medium serum albumin of 3.9 g/dl. VATS was performed for right-sided effusions in 30 patients (71%). Macroscopic pleural disease was found in 29 patients (69%). Of the 11 patients with negative cytology, macroscopic pleural disease was found in 4 (36%). Intrathoracic cytoreductive surgery was performed in 6 (33%) of the 18 patients with intrathoracic disease >1 cm. After VATS, 29/42 (69%) patients underwent attempted primary abdominal surgical debulking. Thirteen patients (31%) received neoadjuvant chemotherapy. Twelve (92%) of these patients underwent interval cytoreductive surgery. Patients who were directed after VATS to neoadjuvant chemotherapy instead of primary surgical cytoreduction had a 2-year PFS rate of 22% compared to 42% for the primary cytoreductive group (P=0.36). CONCLUSIONS: Overall, management was altered based on VATS findings in 43% of cases. Further investigation is needed to define the prognostic significance of VATS evaluation of the burden of pleural disease.

Incidence and management of bevacizumab-associated gastrointestinal perforations in patients with recurrent ovarian carcinoma.

OBJECTIVE: The objective of this study was to examine the incidence and management of bevacizumab-associated gastrointestinal (GI) perforations in patients with recurrent ovarian carcinoma. METHODS: We identified all patients who received bevacizumab off protocol from August 2004-August 2008. We examined their medical records for reports of confirmed GI perforation, associated clinicopathological factors, treatment, and outcomes. RESULTS: Six (4%) of 160 patients with ovarian carcinoma who had been treated with bevacizumab developed GI perforations, with a median of 4 (range, 2-8) previous cytotoxic regimens. The median serum CA-125 at the start of treatment was 228 U/mL (range, 50-3106 U/mL). The median number of bevacizumab cycles prior to perforation was 10.5 (range, 2-20). The median time from the last bevacizumab dose to diagnosis of GI perforation was 13 days (range, 1-28 days). Four (67%) patients underwent an exploratory surgery. At laparotomy, one had a gastric perforation and one had an appendiceal perforation; the site of perforation could not be identified in the other 2 Two patients (33%) were managed conservatively-one with a PEG tube and the other with supportive care. The median time of death from the date of diagnosis of GI perforation was 27 days (range, 4-326 days). Only two patients-one with a gastric and the other with an appendiceal perforation-survived >65 days. The 30-day mortality rate following a bevacizumab-associated GI perforation was 50%. CONCLUSION: Bevacizumab-associated GI perforations in patients with recurrent ovarian carcinoma occurred in 4% of our patients. The prognosis of patients diagnosed with bevacizumab-associated GI perforations in this study was poor, and treatment should be individualized.

A prospective outcomes analysis of palliative procedures performed for malignant intestinal obstruction due to recurrent ovarian cancer.

OBJECTIVE: To obtain prospective outcomes data on patients (pts) undergoing palliative operative or endoscopic procedures for malignant bowel obstruction due to recurrent ovarian cancer. METHODS: An institutional study was conducted from July 2002 to July 2003 to prospectively identify pts who underwent an operative or endoscopic procedure to palliate the symptoms of advanced cancer. This report focuses on pts with malignant bowel obstruction due to recurrent ovarian cancer. Procedures performed with an upper or lower gastrointestinal (GI) endoscope were considered "endoscopic." All other cases were classified as "operative." Following the procedure, the presence or absence of symptoms was determined and followed over time. All pts were followed until death. RESULTS: Palliative interventions were performed on 74 gynecologic oncology pts during the study period, of which 26 (35%) were for malignant GI obstruction due to recurrent ovarian cancer. The site of obstruction was small bowel in 14 (54%) cases and large bowel in 12 (46%) cases. Palliative procedures were operative in 14 (54%) pts and endoscopic in the other 12 (46%). Overall, symptomatic improvement or resolution within 30 days was achieved in 23 (88%) of 26 patients, with 1 (4%) postprocedure mortality. At 60 days, 10 (71%) of 14 pts who underwent operative procedures and 6 (50%) of 12 pts who had endoscopic procedures had symptom control. Median survival from the time of the palliative procedure was 191 days (range, 33-902) for those undergoing an operative procedure and 78 days (range, 18-284) for those undergoing an endoscopic procedure. CONCLUSION: Patients with malignant bowel obstructions due to recurrent ovarian cancer have a high likelihood of experiencing relief of symptoms with palliative procedures. Although recurrence of symptoms is common, durable palliation and extended survival are possible, especially in those patients selected for operative intervention.

The rate of port-site metastases after 2251 laparoscopic procedures in women with underlying malignant disease.

BACKGROUND: The aim was to describe the rate of laparoscopic trocar-related subcutaneous tumor implants in women with underlying malignant disease. METHODS: An analysis of a prospective database of all patients undergoing transperitoneal laparoscopic procedures for malignant conditions performed by the gynecologic oncology service. RESULTS: Between July 1991 and April 2007, laparoscopic procedures were performed in 1694 patients with a malignant intraabdominal condition and in 505 breast cancer patients undergoing risk-reducing, diagnostic or therapeutic laparoscopic procedures without intraabdominal disease. Port-site metastases were documented in 20 of 1694 patients (1.18%) who underwent laparoscopic procedures for a malignant intraabdominal condition. Of these, 15 patients had a diagnosis of epithelial ovarian or fallopian tube carcinoma, 2 had breast cancer, 2 had cervical cancer, and 1 had uterine cancer. Nineteen of 20 patients (95%) had simultaneous carcinomatosis or metastases to other sites at the time of port-site metastasis. Patients who developed port-site metastases within 7 months from the laparoscopic procedure had a median survival of 12 months whereas patients who developed port-site metastasis >7 months had a median survival of 37 months (P=0.004). No port-site recurrence was documented in patients undergoing risk-reducing, diagnostic or therapeutic laparoscopic procedures for breast cancer without intraabdominal disease. CONCLUSION: The rate of port-site tumor implantation after laparoscopic procedures in women with malignant disease is low and almost always occurs in the setting of synchronous, advanced intraabdominal or distant metastatic disease. The presence of port-site implantation is a surrogate for advanced disease and should not be used as an argument against laparoscopic surgery in gynecologic malignancies.

Treatment patterns of FIGO Stage IB2 cervical cancer: a single-institution experience of radical hysterectomy with individualized postoperative therapy and definitive radiation therapy.

OBJECTIVE: The treatment of FIGO stage IB2 cervical cancer is controversial. Our aim was to assess treatment patterns, outcomes, and complications in patients with stage IB2 cervical cancer. METHODS: A retrospective study of patients with stage IB2 cervical carcinoma at a single institution between January 1982 and September 2006 was performed. To adequately control treatment variables, we only included patients who underwent their entire treatment at our institution. Toxicity was assessed using NCI Common Toxicity Criteria (CTC). RESULTS: We identified 82 patients, of whom 47 met the strict inclusion criteria. Of these, 27 patients (57%) underwent primary radical hysterectomy (RH) and 20 (43%) were treated with definitive radiation/chemoradiation therapy (RT/CRT). Patients selected for RT/CRT had a higher American Society of Anesthesiologist (ASA) score than those selected for surgery (P=0.037). The 3-year progression free survival rate was 52% for the RH group and 55% for the RT/CRT group (P=0.977). The 3-year overall survival rates were 72% and 55%, respectively (P=0.161). Overall, 52% of patients in the RH group received postoperative radiation therapy as part of their adjuvant treatment. CTC grade 3, 4, and 5 complications affected 5 patients (19%) in the RH group and 3 (15%) in the RT/CRT group. CONCLUSION: Both RH and definitive RT/CRT are adequate management strategies for patients with FIGO stage IB2 cervical cancer. However, there was a subset of patients in whom RH as monotherapy was appropriate. Further studies are needed to evaluate the role of new preoperative models that will accurately identify these patients.

Oncologic outcome of fertility-sparing radical trachelectomy versus radical hysterectomy for stage IB1 cervical carcinoma.

OBJECTIVE: To compare the oncologic outcomes of women who underwent a fertility-sparing radical trachelectomy (RT) to those who underwent a radical hysterectomy (RH) for stage IB1 cervical carcinoma. METHODS: We performed a case-control study of all patients with stage IB1 cervical carcinoma who underwent a vaginal or abdominal RT between 11/01 and 6/07. The control group consisted of patients with stage IB1 disease who underwent an RH between 11/91 and 6/07 and who would be considered candidates for fertility-sparing surgery. Information was extracted from a prospectively acquired database. Recurrence-free and disease-specific survival (RFS and DSS) were estimated using Kaplan-Meier estimates and compared with the log-rank test where indicated. Multivariate analysis was performed using the Cox regression method. RESULTS: Forty stage IB1 patients underwent an RT and 110 patients underwent an RH. There were no statistical differences between the two groups for the following prognostic variables: histology, median number of lymph nodes removed, node positive rate, lymph-vascular space involvement (LVSI), or deep stromal invasion (DSI). The median follow-up for the entire group was 44 months. The 5-year RFS rate was 96% (for the RT group compared to 86% for the RH group (P=NS). On multivariate analysis in this group of stage IB1 lesions, tumor size <2 cm was not an independent predictor of outcome, but both LVSI and DSI retained independent predictive value (P=0.033 and 0.005, respectively). CONCLUSION: For selected patients with stage IB1 cervical cancer, fertility-sparing radical trachelectomy appears to have a similar oncologic outcome to radical hysterectomy. LVSI and DSI appear to be more valuable predictors of outcome than tumor diameter in this subgroup of patients.