Outcomes following percutaneous upper gastrointestinal decompressive tube placement for malignant bowel obstruction in ovarian cancer.

OBJECTIVE: The objective of this study was to evaluate peri-operative and survival outcomes of ovarian cancer patients undergoing percutaneous upper gastrointestinal decompression for malignant bowel obstruction (MBO). METHODS: Retrospective chart review was used to identify patients with ovarian, peritoneal, or fallopian tube cancer who underwent palliative decompressive treatment for MBO from 1/2002 to 12/2010. Kaplan-Meier methods were used to estimate the median survival (MS) and multivariate analysis used to determine if any variables were associated with the hazard of death. RESULTS: Fifty-three patients met inclusion criteria. Median length of diagnosis prior to intervention was 21 months. Fifteen (28.3%) patients experienced complications and 9 required revision. Forty-nine (92.5%) experienced relief of symptoms after placement, and 91% tolerated some form of oral intake. Following placement, 19 (36%) patients received additional chemotherapy and 21(41%) patients received total parental nutrition (TPN). Thirty-five patients were discharged home/outpatient facility, 16 to hospice care, and 2 died prior to discharge. MS for all patients was 46 days. Patients who received chemotherapy had a MS of 169 days compared to 33 days (p<0.001). We failed to find an association between survival and TPN or performance status. CONCLUSIONS: Malignant bowel obstruction is a common complication of ovarian cancer. Management is palliative; risks and benefits of any therapy must be considered. Percutaneous decompressive therapy provides relief from associated symptoms, and allows patients to be discharged home. Median survival in this group is limited, and decisions regarding aggressive therapy should be individualized.

Effect of chemotherapy delays and dose reductions on progression free and overall survival in the treatment of epithelial ovarian cancer.

INTRODUCTION: Hematologic, gastrointestinal, and neurologic complications are common side effects of the platinum and taxane-based chemotherapy used in the primary treatment of epithelial ovarian cancer (EOC). These side effects and the impact of the resultant chemotherapy dose modification on disease free interval have not been extensively studied. The goal of this study was to determine the effect of chemotherapy delays and dose reductions on progression free survival (PFS) and overall survival (OS). METHODS: A review of patients with primary epithelial ovarian, peritoneal, and fallopian tube carcinoma treated between 1/2000 and 12/2007 was performed. Inclusion criteria were advanced stage disease and first line chemotherapy with a platinum and taxane regimen. Cox proportional hazard models were used to determine the effect of chemotherapy reductions and delays on PFS and OS. RESULTS: One hundred and fifty seven patients met the inclusion criteria. Patients were divided into four groups: no delays or reductions (48%), delay only (27%), reduction only (8%), and both delay and reduction (18%). The mean number of delays/reductions per patient was 1.1 (range=0-5) and therapy was delayed a mean of 8 days. The most common reasons for delays/reductions were neutropenia (n=51), thrombocytopenia (n=45), and neuropathy (n=18). There were no differences detected in PFS or OS between groups. CONCLUSIONS: There were no differences detected in survival between patients who required dose adjustments and treatment delays and those who did not. The lack of association between survival and chemotherapy alterations suggests that in specific circumstances patients with advanced ovarian cancer should have individualized treatment plans.

Which factors predict bowel complications in patients with recurrent epithelial ovarian cancer being treated with bevacizumab?

BACKGROUND: Increased rates of bowel perforation in patients with recurrent epithelial ovarian cancer (EOC) treated with bevacizumab have been reported, but the risk factors for this association are uncertain. We sought to identify factors associated with bowel perforation and fistula formation in recurrent EOC patients treated with bevacizumab. METHODS: A chart review of all patients treated with bevacizumab for recurrent EOC at a single institution was performed. Pertinent patient characteristics and treatment information were collected. Univariate logistic regression was performed to analyze multiple variables. RESULTS: One hundred twelve patients who were treated with 160 different bevacizumab regimens were identified. The median age was 60 years (range, 29-78 years). Patients had received a median of 4 prior chemotherapy regimens (range, 1-10). The median number of cycles was 4 (range, 0.5-31). Ten patients (9%) were diagnosed with bowel perforations, and another 2 patients (1.8%) were diagnosed with fistulas. The 30-day mortality following perforation was 50%, with 30% of patients dying within 1 week. Patients with rectovaginal nodularity were more likely to develop a bowel perforation or fistula than those who did not have this finding, OR=3.64 (95% CI=1.1 to 12.1, p=0.04). None of the other variables were significantly associated with bowel perforations or fistula formation. CONCLUSIONS: Rectovaginal nodularity is associated with an increased risk of bowel perforation or fistula formation for patients with recurrent EOC treated with bevacizumab. Careful consideration should be given prior to initiating bevacizumab treatment in EOC patients with rectovaginal nodularity since the mortality rate with bevacizumab associated bowel perforations is 50%.

Sustained progression-free survival with weekly paclitaxel and bevacizumab in recurrent ovarian cancer.

OBJECTIVE: To determine efficacy, toxicity, and survival in patients with recurrent epithelial ovarian cancer (EOC) receiving combination of weekly paclitaxel and biweekly bevacizumab (PB). METHODS: We reviewed chemotherapy logs identifying all patients receiving combination PB. Toxicities were graded using CTCAEv3.0 criteria. Response rates (RR) were measured using RECIST criteria or by CA-125 levels per modified Rustin criteria. RR and progression-free survival (PFS) were determined and plotted using Kaplan-Meier survival analysis. RESULTS: Fifty-one patients receiving at least two cycles of chemotherapy were evaluable for survival and 55 patients receiving one cycle of PB were evaluable in toxicity analysis. The mean number of previous regimens was four. The overall median PFS was 7 months and median OS was 12 months. The overall response rate (ORR) was 60% (CR 25% and PR 35%). Median PFS for complete and partial responders were 14 and 5 months respectively. Stable disease was seen in 26% with median PFS of 6 months. Thirteen experienced treatment delays for a variety of factors. The most G3/4 toxicities were fatigue (16%), hematologic (9%) and neurotoxicity (7%). Three patients (5%) experienced bowel perforations. CONCLUSIONS: Combination of paclitaxel and bevacizumab is feasible and demonstrates an acceptable toxicity profile and a high response rate. These observations should be useful in planning future clinical trials with this combination therapy.

Correlation between patient weight and defects in DNA mismatch repair: is this the link between an increased risk of previous cancer in thinner women with endometrial cancer?

The objective is to determine the relationship between obesity and defects in DNA mismatch repair (MMR) in women with endometrial cancer and to establish whether our previous finding of a higher rate of previous malignancy in thinner women with endometrial cancer is related to these factors. Specimens from 109 patients with primary uterine cancer were used to create a tissue microarray, which was stained with antibodies against MMR genes MLH1, MSH2, MSH6, and PMS2. Genotyping of normal and tumor tissues for microsatellite instability (MSI) was performed. Patients were stratified by body mass index (BMI) and correlated with a history of previous malignancy and defects in MMR. The average BMI of the overall population was 33 kg/m(2). Defective MMR was seen in 22% of tumors. The mean BMI in patients with tumors with MSI was 30.5, compared with 33.8 in microsatellite stable (MSS) tumors (P= 0.06); MSS tumors were more commonly seen in patients with a BMI more than 40 (25% vs 5% in patients with tumors with MSI, P= 0.07). Prior to their diagnosis of endometrial cancer, 16/109 (15%) patients reported having a prior malignancy, 11 (69%) had breast cancer, and 1 had colorectal cancer. Patients with tumors with MSI had previous cancer in 17% of cases, compared with 14% of patients with MSS tumors (P= 0.75). Our previous finding of an increased rate of prior malignancy in thinner patients with endometrial cancer does not appear to be due to alterations in MMR, and hereditary nonpolyposis colorectal cancer-associated cancers are rarely the prior malignancy.

Cisplatin therapy for disseminated mixed mesodermal sarcoma of the uterus.

Eighteen patients with metastatic mixed mesodermal sarcoma of the uterus received cisplatin therapy at the University of Texas (UT) M.D. Anderson Hospital and Tumor Institute at Houston. The dose of cisplatin varied from 75 mg/m2 to 100 mg/m2. Previous therapy included surgery in 11 patients, radiotherapy in two patients, and surgery plus radiotherapy in four patients. One patient had no prior therapy. Seven patients had also received prior chemotherapy with doxorubicin. Of 12 patients with measurable disease, one (8%) had a complete response and four (33%) had a partial response for an overall response rate of 42%. The median progression-free survival of patients treated with cisplatin as first- and second-line therapy was 4.5 and 5.5 months, respectively. Cisplatin demonstrated moderate activity with mild toxicity in this group of patients with metastatic mixed mesodermal uterine sarcomas. Further studies including cisplatin-containing combination regimens seem to be warranted.

Phase I trial of escalating doses of paclitaxel combined with fixed doses of cisplatin and doxorubicin in advanced endometrial cancer and other gynecologic malignancies: a Gynecologic Oncology Group study.

PURPOSE: The primary objective of this phase I trial was to determine the feasibility of administering a combination of paclitaxel, cisplatin, and doxorubicin with or without granulocyte colony-stimulating factor (G-CSF) in patients with advanced endometrial and other gynecologic cancers. PATIENTS AND METHODS: Patients were chemotherapy-naive. Doxorubicin was administered as a brief infusion, paclitaxel for 3 hours, and cisplatin for 60 minutes. Treatments were repeated every 3 weeks. For most dose levels, the cisplatin and doxorubicin were fixed at 60 mg/m(2) and 45 mg/m(2), whereas the paclitaxel was escalated in successive cohorts from 90 to 250 mg/m(2). Patients who had received previous radiotherapy to the whole pelvis were escalated separately from those who had not. RESULTS: Eighty patients received 320 cycles of therapy. When G-CSF was not used, myelosuppression prevented escalation beyond the starting dose for patients with or without previous pelvic radiotherapy. When G-CSF was added, neurotoxicity became dose-limiting for both groups. Ten patients were removed from the study for asymptomatic declines in ejection fraction, but no symptomatic congestive heart failure was observed. Major antitumor responses occurred in 46% of patients (six of 13) with measurable endometrial carcinoma and 50% of patients (eight of 16) with measurable cervical carcinoma. CONCLUSION: The combination of paclitaxel, doxorubicin, and cisplatin at relevant single-agent doses is active and feasible with the addition of G-CSF. A regimen of cisplatin 60 mg/m(2), doxorubicin 45 mg/m(2), and paclitaxel 160 mg/m(2) with G-CSF support is recommended for further testing.

Hyperfractionated split-course whole abdominal radiotherapy for ovarian carcinoma: tolerance and toxicity.

Whole abdominal irradiation after chemotherapy and second look laparotomy for advanced ovarian carcinoma is poorly tolerated because of hematologic toxicity that frequently necessitates interruption or abandonment of treatment. A new treatment strategy using a hyperfractionated split course schedule to deliver a total of 30 Gy in 30 fractions over 6 weeks was designed in an attempt to overcome this problem, while not compromising the tolerance of late reacting normal tissues. Of 23 patients treated between August 1984 and June 1986, only one failed to complete therapy as scheduled. Six patients with gross residual disease also received a limited field boost of 15 Gy in 15 fractions after completion of treatment to the whole abdomen. None of these six patients achieved disease control, and five required surgery for intestinal obstruction with pathologic evidence of radiation bowel injury. Of the 17 patients who received no boost, five developed gut obstructions associated with tumor recurrence and not attributable to irradiation. We conclude that whole abdominal irradiation using the hyperfractionated split course schedule without a boost is safe and feasible but its therapeutic efficacy appears confined to subsets of patients with no visible residual disease at the time of second look laparotomy, or in whom all visible residual tumor can be resected.

Ovarian cancer recurrences in patients with no macroscopic tumor at second-look laparotomy.

Second-look laparotomy has been relied upon extensively to guide the treatment of ovarian cancer. Among patients with other than well-differentiated primary tumors, the recurrence rate approximates 50% for patients with either negative or microscopically positive findings at second-look laparotomy. Although patients with persistent microscopic disease have received additional therapy, the patients with negative findings have not. The risk of recurrence seems high enough to consider adjuvant therapy for patients with negative findings at second-look laparotomy. However, since half of the patients remain disease free for an extended interval, and in view of the potential toxicity, any adjuvant treatment should be carried out by strict investigational protocol.

Bilateral ovarian hemangiomas associated with diffuse abdominopelvic hemangiomatosis.

A case of bilateral ovarian hemangiomas and abdominopelvic hemangiomatosis associated with thrombocytopenia is reported. After total abdominal hysterectomy and excision of a hemangioma adhered to the colon, the platelet count returned to normal, and the patient has remained asymptomatic for five years. A review of three previous cases of bilateral hemangiomas associated with abdominopelvic hemangiomatosis reveals only one patient living two years after diagnosis. The etiology of the hemangiomas is unknown. The thrombocytopenia appears to be secondary to the hemangiomas. The recommended treatment is removal of all resectable hemangioma masses.

Hexamethylmelamine chemotherapy for disseminated endometrial cancer.

To evaluate the role of hexamethylmelamine (HMM) in the treatment of endometrial cancer, 20 women with metastatic or recurrent endometrial carcinoma received HMM orally at a dose of 8 mg/kg/day. Six patients (30%) showed a partial response, with a median duration of response of 3.5 months and a range of 1 to 7 months. Two patients responded to HMM as a second-line agent following previous treatment with nonhormonal chemotherapy. There were no complete responses. The major toxicities noted with HMM therapy were nausea, vomiting, and neurotoxicity. In 6 patients (30%), therapy with HMM was discontinued because of toxicity. Although HMM is active against endometrial cancer when given at a dose of 8 mg/kg/day, it appears to have limited usefulness because toxicity precludes its prolonged administration.

Doxorubicin and cyclophosphamide chemotherapy for disseminated endometrial cancer.

Twenty-six cases of metastatic adenocarcinoma of the endometrium treated with doxorubicin hydrochloride (Adriamycin) and cyclophosphamide at M. D. Anderson Hospital and Tumor Institute were retrospectively analyzed. Thirteen patients were treated initially for disseminated disease and 13 for a recurrence. Eight of 26 patients, or 31%, showed a partial response. There were no complete responses. The median duration of remission was 4 months, with a range of 2 to 12 months. Previous exposure to progestins did not significantly affect subsequent response to doxorubicin and cyclophosphamide. Toxicity from chemotherapy was moderate. Four patients (15%) developed serious myelosuppression, 2 developed cardiac arrhythmia, and 1 developed a doxorubicin extravasation. No deaths were attributable to chemotherapy. The combination of doxorubicin and cyclophosphamide has demonstrable, albeit limited, activity against metastatic endometrial cancer.

Mixed germ cell tumors of the ovary.

Forty-two patients with mixed germ cell tumors of the ovary who were treated at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston from 1944 through 1983 are retrospectively reviewed. The median age of these patients was 16 years. The most common symptom was abdominal pain, occurring in 38 patients (90%). Detailed analysis of clinical and pathologic features is presented. Twenty of 42 patients are alive and well. Current management of mixed germ cell tumors, including the roles of second-look laparotomy and monitoring of tumor markers, is discussed. Optimal treatment consists of surgery followed by combination chemotherapy.

Quality assurance of second opinion pathology in gynecologic oncology.

OBJECTIVE: To determine the effect of routine second review of pathologic material that was sent to Ohio State University before initiation of therapy. METHODS: All the gynecologic-oncologic histopathology review diagnoses made during a 1-year period were compared with original pathologic diagnoses. When there was a discrepant diagnosis with the second interpretation, the case was reviewed by at least two pathologists. Discrepancies were coded as no diagnostic disagreement, no diagnostic disagreement but pertinent information not included, diagnostic disagreement without clinical consequences, diagnostic disagreement with minor clinical significance, or diagnostic disagreement with major clinical significance. Proportions and confidence intervals were calculated. RESULTS: Pathology reports from 295 referred patients were reviewed. Two hundred forty-five (83.1%) showed no discrepancy. Discrepancies were found in 50 cases (16.9%). There was significant information missing in four cases (1.4%), diagnostic disagreement with no clinical significance in 22 cases (7.5%), and diagnostic disagreement with minor clinical significance in 10 cases (3.4%). In 14 cases (4.7%, 95% confidence interval 2.28, 7.12) the changes in diagnoses had major therapeutic or prognostic implications that included changes from malignant or low malignant potential to benign (seven cases), malignant to low malignant potential (three cases), change in tumor type (two cases), and assessment of invasion (two cases). The cost of reviewing 295 specimens was approximately $39,235. The cost of identifying each major discrepancy was about $2802. CONCLUSION: Routine pathology review of gynecologic-oncologic cases before definite treatment revealed notable discrepancies in diagnoses. In 4.7% of cases, the change in diagnosis had a major effect on proper treatment planning or a significant prognostic implication.

Ureteral assessment after radical hysterectomy.

Postoperative intravenous pyelography was performed in 233 patients with stage IB cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy between January 1962 and December 1985. Four patients developed symptoms of ureteral injury, two (0.8%) ureteral fistulae, and one (0.4%) stricture and obstruction due to recurrent carcinoma. No ureteral injuries were observed in 229 asymptomatic patients. A 5.2% incidence of transient severe ureteral dilatation occurred in asymptomatic patients, but resolved within a median of 94 days. A significant urinary tract anomaly was observed in 3.4% of preoperative pyelograms. All of these anomalies were apparent at surgery and presented no intraoperative difficulties. Three patients (1.3%) sustained intraoperative ureteral transections, which were diagnosed and repaired without sequelae. In patients with early cervical carcinoma having primary operative treatment, the role of routine preoperative and postoperative intravenous pyelography is questionable.

The significance of müllerian inclusions found at second-look laparotomy in patients with epithelial ovarian neoplasms.

When no visible tumor is identified at second-look laparotomy, selected biopsy specimens or cytologic washings may reveal microscopic tumor or benign pathologic atypia. The pathology material from 311 patients with epithelial ovarian carcinoma who had no macroscopic tumor at second-look laparotomy was evaluated for psammoma bodies, müllerian inclusions (benign glandular inclusions), microscopic tumor, and either inflammation or fibrosis. Progression-free intervals and survival rates were influenced by the presence of müllerian inclusions (favorably), tumor or positive cytology (unfavorably), and inflammation or fibrosis (unfavorably). Multivariate analysis (proportional hazards model) demonstrated that both the progression-free interval and survival rates were influenced significantly by the presence of microscopic tumor and tumor grade. Of 51 patients with müllerian inclusions and no microscopic tumor, 23 received additional treatment after second-look laparotomy. No differences were noted in the progression-free interval or survival rates when these patients were compared with the 28 nontreated patients. Of the treated patients, three died from chemotherapy toxicity, whereas there were no chemotherapy-related deaths in the nontreated group. These findings indicate that the presence of müllerian inclusions at second-look laparotomy does not justify treatment, and that further treatment after misinterpretation of these benign pathologic entities may lead to harmful results.

Diagnosis of recurrent cervical carcinoma after radical hysterectomy.

A standard surveillance program for cervical carcinoma patients treated with radical hysterectomy is reviewed. Between 1962-1984, 249 patients with stage IB cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy were entered in the surveillance program. Of the 27 patients (11%) diagnosed with recurrent carcinoma, 17 (63%) were identified by clinical history, 22 (81%) by physical examination, five (18%) by vaginal cytology, six (22%) by chest radiography, and eight (30%) by renal contrast imaging. Combined clinical history and physical examination identified 24 patients (89%) with recurrent carcinoma. Disease recurrence was detected by vaginal cytology in one asymptomatic patient with a normal examination. The recommended surveillance procedures for patients with cervical carcinoma after radical hysterectomy include clinical history, physical examination, and vaginal cytology. Chest radiography and renal contrast imaging should be reserved for symptomatic patients.

Fallopian tube carcinoma.

Seventy-one cases of primary adenocarcinoma of the fallopian tube treated at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston were reviewed. The most common presenting symptoms were abdominal pain, abnormal uterine bleeding, and vaginal discharge. The most common physical finding was a palpable abdominal or pelvic mass. The preoperative diagnosis was correct for two patients. Initial therapy consisted of surgery alone, surgery plus radiation therapy, surgery plus chemotherapy, and a combination of surgery, chemotherapy, and radiation therapy in 10, 32, 21, and eight cases, respectively. The median survival for patients in these treatment groups was 33, 22, 27, and 22 months, respectively; the median survival for all patients was 23 months. No statistically significant differences emerged among the survival curves of patients treated with each of the above regimens.

High-risk metastatic gestational trophoblastic disease.

The clinical course of 61 patients with high-risk metastatic gestational trophoblastic disease was reviewed. Currently, 34 patients (56%) are alive and in complete remission. The survival rate after full-term pregnancy was significantly worse than after any other type of antecedent pregnancy. Analyzing survival by individual high-risk criteria revealed significantly improved survival for those patients with elevated beta-human chorionic gonadotropin titer alone when compared with all other high-risk criteria. Fifty-eight percent of patients (14 of 24) primarily treated with alternating-sequential therapy consisting of methotrexate and actinomycin-D experienced a complete remission. Of those patients primarily treated with methotrexate, actinomycin-D, and cyclophosphamide, 63% (20 of 32) achieved a complete remission. Treatment with second-line chemotherapy was largely unsuccessful. Aggressive early treatment is warranted in this group of patients, using multiagent chemotherapy. A search for newer more effective regimens should continue.