Recurrence patterns after extended treatment with bevacizumab for ovarian, fallopian tube, and primary peritoneal cancers.

OBJECTIVE: To evaluate patterns of recurrence for ovarian, fallopian tube, and primary peritoneal cancer patients undergoing extended treatment with bevacizumab (BEV). METHODS: A retrospective review of patients with primary ovarian, fallopian tube, or peritoneal cancer treated with BEV alone or in combination with other chemotherapy from 2001 to 2011 was performed. Qualified patients were identified by chemotherapy records. Electronic medical records, labs, and imaging reports were reviewed and abstracted. RESULTS: Of 108 patients identified, 89 patients met study criteria by having disease progression either during treatment with BEV or after discontinuing BEV without initiating any other treatment. Patients on extended BEV therapy (>12 cycles) were more likely to recur in extra-visceral sites (p=0.04), especially in lymph nodes (p=0.0002), and presented with fewer symptoms at time of recurrence (p=0.02), compared to patients who had received ≤ 12 cycles. CA-125 becomes less reliable for the detection of recurrent disease with extended BEV therapy (p=0.03 for ≤12 cycles vs. p=0.08 for >12 cycles). Radiology was superior to CA-125, symptom, and physical exam, in detecting recurrence with extended BEV therapy (all p<0.0001). CONCLUSIONS: Extended treatment with BEV in ovarian, fallopian tube, and peritoneal cancers results in alterations in the patterns of recurrence. Radiologic imaging is more reliable than CA-125, symptoms, or physical exam, in identifying recurrent disease in patients undergoing BEV treatment. As novel targeted therapies continue to be employed, guidelines for gynecologic cancer surveillance must continue to be reexamined.

FOXP3+ regulatory T-cells are abundant in vulvar Paget's disease and are associated with recurrence.

OBJECTIVE: To characterize clinical features of vulvar Paget's disease, and examine the quantity of immunosuppressive regulatory T-cells in vulvar Paget's tissue. METHODS: Vulvar Paget's cases from 1992 to 2007 from two institutions were identified by pathology database search. Regulatory T-cells were identified with FOXP3 immunohistochemistry and quantified at the dermal-epidermal junction using image analysis software. Thirteen non-neoplastic inflammatory cases were stained for comparison. RESULTS: Cases included 33 women treated for primary vulvar Paget's, and 7 referred at recurrence. Of the 24 primary cases with greater than 5 months follow-up, recurrence was documented in 12/24(50%). Eight women (20%) recurred multiple times, but no recurrences were invasive. Significantly more patients with positive margins developed recurrent disease (82% vs 23%, p=0.01). Secondary neoplasms occurred in 10/40(25%). FOXP3+ cells at the dermal-epidermal junction were quantified in 29 primary and 13 recurrent tissue samples. FOXP3+ cells were absent in surrounding normal vulvar skin. FOXP3+ cells averaged 66/HPF in primary vulvar Paget's and 66/HPF in recurrent Paget's, compared to 22/HPF in non-neoplastic inflammatory cases (p=0.0003, p=0.001). Primary cases with positive surgical margins had more FOXP3+ cells than those with negative margins (85 vs 49, p=0.01). Recurrent cases with positive margins had more FOXP3+ cells than negative cases (84 vs 33, p=0.06). FOXP3 levels in primary specimens were higher in cases which recurred (78 vs 35, p=0.02). CONCLUSIONS: Increased regulatory T-cells may be associated with more extensive cases of vulvar Paget's disease that result in positive surgical margins and are associated with recurrence of disease, suggesting immunosuppression as a key factor.

Alternative intraperitoneal chemotherapy regimens for optimally debulked ovarian cancer.

OBJECTIVE: GOG 172 showed a survival benefit with intraperitoneal (IP) cisplatin for advanced ovarian cancer, but patients tolerated the regimen poorly. We hypothesized that women treated with alternative IP chemotherapy strategies may have less toxicity and improved compliance. METHODS: We reviewed the records of women with ovarian cancer and optimal surgical debulking who underwent IP chemotherapy at our institution. Primary outcomes analyzed were completion rates and toxicities of IP chemotherapy. Secondary outcomes were progression-free and overall survival. Statistical analysis was performed using STATA 10.0. RESULTS: Thirty-nine patients with primary ovarian or peritoneal cancer who underwent IP chemotherapy were identified over a 2 year period. Patients were treated with IV paclitaxel followed by IP cisplatin (64%) or IP carboplatin (36%). Median two cycles of intravenous (IV) taxane and carboplatin were given prior to initiating IP therapy in 77% of patients. Median number of IP chemotherapy cycles was 5 and median total number of cycles was 8. Seventy-four percent (74%) of patients received four or greater cycles of IP chemotherapy. There was a higher rate of completion of intended number of IP cycles in the carboplatin group (92%) versus 60% in the IP cisplatin group (p=0.05). Grade 3 non-hematologic toxicities were more common in the IP cisplatin group than in the IP carboplatin group (24% and 0%, p=0.046). At median follow-up of 24 months, the median progression-free interval and overall survival have not yet been reached for either group. CONCLUSION: Intraperitoneal chemotherapy regimens using carboplatin or cisplatin and dropping day 8 IP paclitaxel have less toxicity and less discontinuation of therapy.

Glassy cell carcinoma of the cervix revisited.

OBJECTIVE: Glassy cell carcinoma (GCC) of the cervix has traditionally been characterized as an aggressive histologic subtype with poor outcomes. An earlier series from our institution supported a grim prognostic outlook, demonstrating a survival rate of only 55% in women with stage I disease. We present a comparison of a contemporary series of patients with GCC. METHODS: All cases of GCC treated from 1993 to 1999 identified by our tumor registry were reviewed for a variety of clinicopathologic features, treatment strategies, and outcome. RESULTS: A total of 403 cases of invasive cancer of the cervix were identified. There were 22 patients with histologically confirmed GCC, representing only 5.4% of all cervical cancer diagnoses. Patients with GCC had an overall survival of 73% (16/22) and a disease-free survival of 64% (14/22). The incidence of stage I lesions was 64% (14/22). Overall survival of patients with stage I disease was 86% (12/14), with a disease-free survival of 71% (10/14) at a median follow-up of 28.5 months. Seven stage IB lesions were treated with surgery alone, whereas six received adjuvant radiation or chemoradiation following surgery. Two patients in each treatment group recurred, yielding an overall recurrence rate of 29% (4/14). However, of those who recurred with stage I disease, all 4 patients had two or more intermediate risk factors (lymph-vascular space invasion [LVSI], deep tumor invasion, or tumor size greater than 3 cm). CONCLUSIONS: Glassy cell carcinoma of the cervix appears to have a better prognosis than previously reported. We observed that intermediate risk histopathologic features identified in squamous cell cohorts are also predictive of a poorer outcome in patients with GCC. Thus, patients with LVSI, deep stromal invasion, and large tumor size are at the highest risk for pelvic relapse and should be candidates for adjuvant treatment.