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Nasser S, Arsenic R, Lohneis P, et al.
A case of primary peritoneal carcinoma: evidence for a precursor in the fallopian tube.
Anticancer Res. 2014; 34(1):407-12 [PubMed] Related Publications

BACKGROUND: Primary high-grade serous peritoneal carcinoma (PPSC) is a rare malignancy with an ambiguous pathogenesis.
CASE REPORT: We report on a 51-year-old woman presenting with a routine smear test cytology suspicious of adenocarcinoma. She underwent hysteroscopy, laparsocopy with multiple biopsies and bilateral salpingoophorectomy. She was diagnosed with a serous tubal intraepithelial carcinoma in situ (STIC) in the right fallopian tube. Subsequently, she underwent radical surgery and was diagnosed with peritoneal high-grade serous carcinoma. Interestingly, both ovaries remained histologically tumour-free.
DISCUSSION: High-grade serous carcinomas that arise on the peritoneum with tumour-free ovaries are rare. The findings in this case, coupled with current evidence, strongly suggest a precursor lesion in the fallopian tube (STIC lesions). The clinical implications of this theory reside in the potential for improving early detection strategies. Nonetheless, more data on precursor lesions in the fallopian tubes and their transformation to serous carcinoma are required to plan for future screening methods.

Hagemann AR, Novetsky AP, Zighelboim I, et al.
Phase II study of bevacizumab and pemetrexed for recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer.
Gynecol Oncol. 2013; 131(3):535-40 [PubMed] Article available free on PMC after 01/12/2014 Related Publications

OBJECTIVE: We aimed to evaluate the efficacy and safety of combination bevacizumab/pemetrexed for the treatment of recurrent epithelial ovarian cancer (EOC).
METHODS: Platinum-sensitive or -resistant patients with recurrent or persistent EOC were eligible if they had received up to 2 prior chemotherapy regimens, including a platinum/taxane regimen without prior bevacizumab. Pemetrexed 500 mg/m(2) IV and bevacizumab 15 mg/kg IV were administered every 3 weeks. The primary endpoint was 6-month progression-free survival (PFS); other endpoints included toxicities, PFS and overall survival (OS).
RESULTS: Thirty-four patients received a median of 7 treatment cycles (range, 2-26). Median follow-up was 25.7 months (range, 3.0-47.2). Six month progression-free survival (PFS) was 56% (95% CI: 38-71). The following response rates were documented (%; 95% CI): 0 complete response, 14 partial responses (41%; 25-59), 18 stable disease (53%; 35-70) and 2 progressive disease (6%; 1-20). Median PFS was 7.9 months (95% CI, 4.6-10.9), with a median OS of 25.7 months (95% CI, 15.4-29.8). Twenty-two patients (64.7%) had a platinum-free interval (PFI) of >6 months prior to enrollment. Grade 3-4 hematologic toxicities included neutropenia (50%), leukopenia (26%), thrombocytopenia (12%) and anemia (9%). Non-hematologic grade 3-4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). Two patients developed hematologic malignancies within one year of treatment.
CONCLUSIONS: Combination bevacizumab/pemetrexed is an active option for both platinum-sensitive and -resistant recurrent EOC. Further investigation of cost and novel toxicities associated with this regimen may be warranted.

Related: Ovarian Cancer Pemetrexed Bevacizumab (Avastin)

Patrao L, Sa J, Fonseca-Moutinho JA, et al.
Left fallopian tube primitive serous adenocarcinoma presenting as a cardiac tamponade - a case report and review of literature.
Eur J Gynaecol Oncol. 2013; 34(3):261-2 [PubMed] Related Publications

A 61-year-old woman presented to the emergency room complaining of anterior left thoracic pain and shortness of breath even after minor efforts. Her previous medical history was unremarkable. Pulmonary angiographic tomography showed a moderate bilateral pleural effusion that had collapsed inferior lung lobes, a large pericardial effusion, and several enlarged lymph nodes in the anterior mediastinum. Echocardiogram (ECG) showed a considerable pericardial effusion with some degree of heart function impairment. Pericardiocentesis and thoracocentesis revealed neoplastic cells in both pericardial and pleural fluids. Abdominal and pelvic ultrasound showed a complex cystic mass with a 13-cm diameter located at left adnexal region and another complex cystic tumor with five-cm diameter at right adnexal region, with small amount of peritoneal effusion. Surgical staging was performed. Pathologic diagnosis was primitive left fallopian tube serous adenocarcinoma with peritubal involvement and multiple peritoneal and lymphatic metastases (FIGO Stage IV; TNM pT3c M1). Chemotherapy was initiated. Death occurred 25 months after diagnosis, with secondary dissemination (breast and lung). No recurrence of pericardial effusion was registered after chemotherapy, suggesting a high susceptibility of pericardial metastasis.

Katsumata N, Yasuda M, Isonishi S, et al.
Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial.
Lancet Oncol. 2013; 14(10):1020-6 [PubMed] Related Publications

BACKGROUND: The primary analysis of the JGOG 3016 trial showed that a dose-dense paclitaxel and carboplatin regimen significantly improves progression-free and overall survival compared with the conventional regimen as first-line chemotherapy for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. We report the long-term follow-up results for survival.
METHODS: This randomised controlled trial was done at 85 centres in Japan. Patients with stage II-IV ovarian cancer were randomly assigned to receive conventional treatment (carboplatin area under the curve [AUC] 6 mg/mL per min and paclitaxel 180 mg/m(2) on day 1) or dose-dense treatment (carboplatin AUC 6 mg/mL per min on day 1 and paclitaxel 80 mg/m(2) on days 1, 8, and 15). The treatments were repeated every 3 weeks for six cycles; responding patients had three additional cycles. The randomisation was done centrally by telephone or fax, stratified by residual disease, stage, and histological type. The primary endpoint was progression-free survival; overall survival was a secondary endpoint. Long-term information on adverse events was not collected. Efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00226915.
FINDINGS: 637 patients were enrolled, of whom 631 were analysed (312 assigned to the dose-dense regimen, 319 to the conventional regimen). Median follow-up was 76·8 months (IQR 68·9-85·6). Median progression-free survival was significantly longer in the dose-dense treatment group than in the conventional treatment group (28·2 months [95% CI 22·3-33·8] vs 17·5 months [15·7-21·7]; hazard ratio [HR] 0·76, 95% CI 0·62-0·91; p=0·0037). Median overall survival was 100·5 months (95% CI 65·2-∞) in the dose-dense treatment group and 62·2 months (52·1-82·6) in the conventional treatment group (HR 0·79, 95% CI 0·63-0·99; p=0·039).
INTERPRETATION: Dose-dense treatment offers better survival than conventional treatment and is a potential new standard of care for first-line chemotherapy for patients with advanced epithelial ovarian cancer.

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Jain M, Puri V
Synchronous carcinosarcoma uterus and primary serous carcinoma of bilateral fallopian tubes: a case report.
J Reprod Med. 2013 Jul-Aug; 58(7-8):361-4 [PubMed] Related Publications

BACKGROUND: The coexistence of multiple primary tumors in the female genital tract is very rare. Carcinosarcoma of the uterus is very rarely encountered among multiple genital malignancies.
CASE: A 63-year-old woman presented with synchronous carcinosarcoma of the uterus and primary serous carcinoma of bilateral fallopian tubes. The diagnosis was confirmed histopathologically and immunohistochemically.
CONCLUSION: This case is presented for its rarity and unique presentation. To the best of our knowledge, ours is the first reported case of this unique combination of synchronous genital malignancies.

Burger RA, Brady MF, Rhee J, et al.
Independent radiologic review of the Gynecologic Oncology Group Study 0218, a phase III trial of bevacizumab in the primary treatment of advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer.
Gynecol Oncol. 2013; 131(1):21-6 [PubMed] Article available free on PMC after 01/10/2014 Related Publications

OBJECTIVES: Gynecologic Oncology Group Study 0218 (GOG-0218), a phase III, placebo-controlled trial in newly diagnosed stage III/IV ovarian cancer (OC), demonstrated a benefit in investigator (INV)-assessed progression-free survival (PFS) with bevacizumab (BEV) administered with and following carboplatin/paclitaxel (CP) for up to 15 months vs. CP alone. To determine the reliability of Response Evaluation Criteria in Solid Tumors (RECIST) in assessing disease progression (PD) in GOG-0218, an independent review of radiologic and clinical data (IRC) was conducted.
METHODS: Blinded reviews followed RECIST 1.0 in accordance with the study protocol; PFS was analyzed in the intent-to-treat population.
RESULTS: CP+BEV→BEV achieved a significant PFS improvement in both assessments. Hazard ratios for PFS (IRC: 0.623; 95% confidence interval [CI]: 0.503-0.772; p<0.0001 vs. INV: 0.624; 95% CI: 0.520-0.749; p<0.0001) and the improvement in median PFS (IRC: 19.1 and 13.1 months vs. INV: 18.2 and 12 months) were similar between IRC and INV assessments. There was high concordance between IRC- and INV-determined PD status (77%) and date (73%). Subgroup analyses were consistent with the primary IRC findings. Early and late discontinuation discordance measures showed no evidence of INV bias.
CONCLUSION: IRC analysis confirmed a significant PFS improvement with CP+BEV→BEV vs. CP alone. Concordance was not influenced by extent of residual disease after cytoreductive surgery or initial stage. The IRC size, high participation rate, and strong concordance between IRC and INV assessments suggest that RECIST can be applied objectively in OC studies.

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Otsuka I, Kameda S, Hoshi K
Early detection of ovarian and fallopian tube cancer by examination of cytological samples from the endometrial cavity.
Br J Cancer. 2013; 109(3):603-9 [PubMed] Article available free on PMC after 01/10/2014 Related Publications

BACKGROUND: Accumulating evidence suggests that many ovarian high-grade serous carcinomas (HGSCs) originate in the fallopian tube. Malignant cells shed by tubal lesions can be detected by examination of cytological samples from the endometrial cavity (endometrial cytological testing). To evaluate the use of this method for detecting HGSC, we examined epithelial ovarian, fallopian tube, and primary peritoneal cancer patients.
METHODS: Endometrial cytological testing was performed for endometrial cancer screening in asymptomatic women and for pre-treatment evaluation in symptomatic suspected ovarian, tubal, and peritoneal cancer patients.
RESULTS: Of the 122 ovarian, tubal, and peritoneal cancer patients, malignant cells were identified in 5 patients who did not show detectable abnormalities on imaging studies. Cervicovaginal cytology was positive in only one of these five patients. Four patients were asymptomatic and one was symptomatic. Three asymptomatic patients had early-stage HGSCs, and the other asymptomatic patient had positive peritoneal cytology findings but no detectable tumour. HGSC patients were significantly more likely to have positive findings on endometrial cytology than patients with other histological types (23% vs 6%, P=0.02).
CONCLUSION: Endometrial cytological testing can detect early-stage ovarian, tubal, and peritoneal HGSCs without detectable pelvic masses and may be useful for ovarian cancer screening.

Related: Cancer Screening and Early Detection Ovarian Cancer

Novetsky AP, Smith K, Babb SA, et al.
Timing of referral for genetic counseling and genetic testing in patients with ovarian, fallopian tube, or primary peritoneal carcinoma.
Int J Gynecol Cancer. 2013; 23(6):1016-21 [PubMed] Article available free on PMC after 01/10/2014 Related Publications

OBJECTIVE: The objective of this study was to assess patients' preferences of the timing of referral for genetic counseling and testing in relation to the diagnosis, treatment, and recurrence of ovarian, tubal, or primary peritoneal cancers.
METHODS: Ninety-two patients who underwent counseling and testing by 1 certified genetic counselor were identified. An introductory letter, consent form, and questionnaire were mailed to gather information regarding factors influencing the decision to undergo genetic counseling and testing and opinions regarding optimal timing. Medical records were reviewed for demographic and clinical data.
RESULTS: Of 47 consenting women, 45 underwent testing. Eight (18%) were found to have a genetic mutation. Women lacked consensus about the optimal time for referral for and to undergo genetic testing, although women with stage I disease preferred testing after completion of chemotherapy. Most women were comfortable receiving the results by phone, but one third preferred an office visit.
CONCLUSIONS: Patients' views regarding the best time to be referred for and undergo counseling and testing varied greatly. Because of the high mortality of this disease, clinicians should discuss referral early and personalize the timing to each patient. The subset of patients who prefer results disclosure during an office visit should be identified at the time of their initial counseling.

Related: Endometrial (Uterus) Cancer Endometrial Cancer Ovarian Cancer

Dhillon S
Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer.
BioDrugs. 2013; 27(4):375-92 [PubMed] Related Publications

Bevacizumab (Avastin®) is a recombinant, humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody that neutralizes the biological activity of VEGF and inhibits tumor angiogenesis. In the EU, in adult patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, bevacizumab (in combination with carboplatin and paclitaxel) is approved for the first-line treatment of advanced disease and (in combination with carboplatin and gemcitabine) is approved for the treatment of patients with first recurrence of platinum-sensitive disease who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. This article summarizes the pharmacology of bevacizumab and reviews the efficacy and tolerability of bevacizumab combination therapy in well-designed clinical studies in these indications. The addition of bevacizumab to first-line carboplatin plus paclitaxel, followed by bevacizumab maintenance therapy significantly prolonged progression-free survival in women with newly-diagnosed advanced disease (GOG-0218 and ICON7 studies). Progression-free survival was also significantly prolonged after second-line treatment with bevacizumab in combination with carboplatin and gemcitabine, followed by maintenance treatment with bevacizumab alone in women with recurrence (≥ 6 months after front-line platinum-based therapy) of platinum-sensitive disease (OCEANS study). Bevacizumab combination therapy had a generally acceptable tolerability profile in these studies, with the nature of adverse events generally similar to that observed in previous clinical trials in patients with other solid tumors. Although several unanswered questions remain, such as the optimal dosage and duration of treatment, current evidence suggests that bevacizumab combination therapy extends the treatment options available for patients with ovarian cancer.

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Brockbank EC, Harry V, Kolomainen D, et al.
Laparoscopic staging for apparent early stage ovarian or fallopian tube cancer. First case series from a UK cancer centre and systematic literature review.
Eur J Surg Oncol. 2013; 39(8):912-7 [PubMed] Related Publications

OBJECTIVE: To describe the experience of laparoscopic staging of apparent early stage adnexal cancers.
METHODS: Prospectively collected data on women who had laparoscopic staging for apparent early stage adnexal cancers from May 2008 to September 2012 was reviewed. All women had had a prior surgical procedure at which the diagnosis was made, without comprehensive staging. A systematic MEDLINE search from 1980 to 2012 for publications on laparoscopic staging was performed.
RESULTS: Thirty-five women had laparoscopic staging. Median age was 45 years (range 21-73). Median operative time was 210 min (range 90-210). Four intra-operative and one post-operative complication occurred; overall complication rate 5/35 (14%). One vena cava and one transverse colon injury underwent laparotomies for repair. Laparotomy conversion rate 2/35 (6%). Following laparoscopic staging, the cancer was upstaged for eight (23%) women; microscopic omental involvement (four women), pelvic lymph node involvement (two women), para-aortic lymph node involvement (one woman) and contra-lateral ovarian involvement (one woman). After follow up for a median of 18 months (range 3-59) the disease free survival was 94% and overall survival was 100%. Nine studies were identified on laparoscopic staging of adnexal cancer, of which this is the largest single institution series.
CONCLUSIONS: This study adds to the evidence that laparoscopic staging is at least as safe as staging by laparotomy with appropriate and similar oncological outcomes, but with the advantages of minimal access surgery. We therefore advocate the use of laparoscopy to achieve surgical staging for women with presumed early stage adnexal cancer.

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Abaid LN, Micha JP, Rettenmaier MA, et al.
A phase II study of modified dose-dense paclitaxel and every 4-week carboplatin for the treatment of advanced-stage primary epithelial ovarian, fallopian tube, or peritoneal carcinoma.
Cancer Chemother Pharmacol. 2013; 72(1):101-7 [PubMed] Related Publications

PURPOSE: Traditional dose-dense chemotherapy regimens for advanced stage ovarian cancer incorporate weekly paclitaxel on a 21-day cycle and are associated with favorable efficacy but high rates of neutropenia, thrombocytopenia, and anemia. The purpose of this phase II study was to assess the response rate and toxicity of modified dose-dense paclitaxel and every 4-week carboplatin for the treatment of advanced-stage ovarian, fallopian tube, and primary peritoneal carcinoma.
METHODS: All eligible patients were treated with 6 cycles of intravenous dose-dense paclitaxel (80 mg/m²) days 1, 8, and 15 and carboplatin (AUC 5 or 6) Day 1 during a 28-day cycle in accordance with an IRB-approved protocol. Patients who had clinically defined stable disease or better with a CA-125 ≤ 35 U/ml following the completion of primary induction therapy were subsequently administered a planned 12 cycles of paclitaxel (135 mg/m²; every 21 days) consolidation therapy.
RESULTS: Eighty-eight patients received at least 3 cycles of induction dose-dense chemotherapy, of whom 76 completed 6 cycles of chemotherapy; the overall response rate was 84.2 % (56.6 % complete response). Fifty-three patients received an aggregate 473 cycles (median = 9; range 1-12) of consolidation chemotherapy. Grade 3-4 hematological toxicity included neutropenia (22.7 %), thrombocytopenia (7.9 %), and anemia (1.1 %). Further, grade 3 neuropathy developed in one (1.1 %) patient. The patients' median disease-free survival and overall survival were 22.5 and 31.5 months, respectively.
CONCLUSIONS: This phase II study suggests that first-line treatment comprising modified dose-dense paclitaxel and monthly carboplatin chemotherapy with paclitaxel consolidation therapy preserves the efficacy of traditional dose-dense chemotherapy, while minimizing hematologic toxicity.

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Bijron JG, Seldenrijk CA, Zweemer RP, et al.
Fallopian tube intraluminal tumor spread from noninvasive precursor lesions: a novel metastatic route in early pelvic carcinogenesis.
Am J Surg Pathol. 2013; 37(8):1123-30 [PubMed] Related Publications

Pelvic serous carcinoma is usually advanced stage at diagnosis, indicating that abdominal spread occurs early in carcinogenesis. Recent discovery of a precursor sequence in the fallopian tube, culminating in serous tubal intraepithelial carcinoma (STIC), provides an opportunity to study early disease events. This study aims to explore novel metastatic routes in STICs. A BRCA1 mutation carrier (patient A) who presented with a STIC and tubal intraluminal shedding of tumor cells upon prophylactic bilateral salpingo-oophorectomy (PBSO) instigated scrutiny of an additional 23 women who underwent a PBSO and 40 patients with pelvic serous carcinoma involving the tubes. Complete serial sectioning of tubes and ovaries of patient A did not reveal invasive carcinoma, but subsequent staging surgery showed disseminated abdominal disease. STIC, intraluminal tumor cells, and abdominal metastases displayed an identical immunohistochemical profile (p53/WT1/PAX8/PAX2) and TP53 mutation. In 16 serous carcinoma patients (40%) tubal intraluminal tumor cells were found, compared with none in the PBSO group. This is the first description of a STIC, which plausibly metastasized without the presence of invasion through intraluminal shedding of malignant surface epithelial cells in the tube and subsequently spread throughout the peritoneal cavity. These findings warrant a reconsideration of the malignant potential of STICs and indicate that intraluminal shedding could be a risk factor for early intraperitoneal metastasis. Although rare in the absence of invasive cancer, we show that intraluminal shedding of tumor cells in the fallopian tubes from serous carcinoma cases are common and a likely route of abdominal spread.

Related: TP53 WT1 PAX8 gene

Liu F, Wei J, Shen D, Liu J
Mucinous borderline tumor involving fallopian tube: case report and review of the literature.
Int J Clin Exp Pathol. 2013; 6(5):962-5 [PubMed] Article available free on PMC after 01/10/2014 Related Publications

We report the case of a 74-year-old woman with a primary mucinous borderline tumor of the fallopian tube coexisting with an ovarian mucinous borderline tumor. Data were obtained through histopathologic study of the excised surgical specimen. p53, estrogen receptor (ER) and PAX8 expression were evaluated by immunohistochemistry on the available right fallopian tube and ovary. Both the ovarian and fallopian tube borderline ovarian tumors were negative for p53, ER and PAX8. However, the staining pattern highlighted the transition from a normal ciliated cell to neoplastic epithelia in the fallopian tube fimbria. This is the first report to indicate that mucinous borderline tumors may arise from the ciliated cells at the fallopian tube fimbrial epithelia. ER and PAX8 are useful markers in identifying the transition and origination of these tumors.

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Yokoyama Y, Futagami M, Fujimoto T, et al.
Investigation of the clinicopathological features of fallopian tube malignancy.
Oncol Rep. 2013; 30(1):79-84 [PubMed] Related Publications

The present study investigated the clinico-pathological features of fallopian tube malignancy (FTM) and elucidated the biological behavior of this disorder. Data were compiled concerning FTM from 68 patients from 7 institutes. The patients included 60 cases with fallopian tube carcinoma and 8 cases with fallopian tube carcinosarcoma. The clinical stage was stage III or higher in 72% of the cases. A complete response or partial response was achieved in 56 and 10 of the 68 patients with FTM, respectively, indicating a response rate of 97.1%. The median observation period for FTM was 41 months (3 to 126 months). Three of the 19 patients with stage I/II disease (16%) and 31 of the 49 patients with stage III/IV disease (63%) experienced recurrence, with a median progression-free survival of 17.5 months, and a 3-year overall survival of 77.2%. Regarding the site of recurrence, local intraperitoneal recurrence (26.2%) and solitary recurrences in lymph nodes (19.0%) and in the liver (16.7%) were relatively frequent. Secondary debulking surgery (SDS) was performed in 15 patients (44%) out of the 34 recurrent FTMs. Conversely, recurrence was associated with ascites (carcinomatous peritonitis) in 4 of the 34 recurrent patients, but all 4 patients died. The median survival period after recurrence was 28 months: 7.5 and 30 months with and without ascites, respectively (P<0.001). A univariate analysis showed that prognosis was significantly correlated only with whether SDS could be performed. These results suggest that since FTM frequently results in solitary recurrence, aggressive recurrence treatment including SDS could improve prognosis.

Dao MD, Alwan LM, Gray HJ, et al.
Recurrence patterns after extended treatment with bevacizumab for ovarian, fallopian tube, and primary peritoneal cancers.
Gynecol Oncol. 2013; 130(2):295-9 [PubMed] Related Publications

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.

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Kalampokas E, Kalampokas T, Tourountous I
Primary fallopian tube carcinoma.
Eur J Obstet Gynecol Reprod Biol. 2013; 169(2):155-61 [PubMed] Related Publications

Primary fallopian tube carcinoma (PFTC) is a rare gynaecological tumour that accounts for 0.14-1.8% of genital malignancies. The most common age of occurrence is between 40 and 65 years, and the mean age is 55 years. The factors that contribute to its appearance are not well known. Population studies show that the mean incidence of PFTC is 3.6 per million women per annum. Overall survival percentages for patients with PFTC are generally low, in the range of 22-57%. Pre-operative diagnosis is rare and PFTC is usually confirmed by a pathologist, but earlier diagnosis with early clinical manifestation and prompt investigation improves the prognosis. Both PFTC and epithelial ovarian cancer (EOC) are treated with similar surgical and chemotherapy methods. Studies have shown that the prognosis for PFTC is worse than that for EOC or other primary gynaecological tumours. This article reviews and presents the current updates of this rare gynaecological malignancy.

Erickson BK, Conner MG, Landen CN
The role of the fallopian tube in the origin of ovarian cancer.
Am J Obstet Gynecol. 2013; 209(5):409-14 [PubMed] Article available free on PMC after 01/10/2014 Related Publications

Advanced cases of epithelial ovarian, primary peritoneal, and primary tubal malignancies have a relatively poor prognosis and collectively remain the most deadly of all gynecologic malignancies. Although traditionally thought of as one disease process, ongoing research suggests that there is not 1 single site or cell type from which these cancers arise. A majority of the serous tumors appear to originate from dysplastic lesions in the distal fallopian tube. Therefore, what we have traditionally considered "ovarian" cancer may in fact be tubal in origin. In this article, we will review epithelial ovarian cancer classification and genetics, theories regarding cells of origin with a focus on tubal intraepithelial carcinoma, and implications for prevention and screening.

Related: BRCA1 BRCA2 Ovarian Cancer

Aich RK, Dasgupta S, Chakraborty B, et al.
Primary fallopian tube carcinoma with metastasis in the contralateral ovary.
J Indian Med Assoc. 2012; 110(7):494-5, 498 [PubMed] Related Publications

Primary malignant neoplasm of the fallopian tube is one of the rarest gynaecological malignancies and a pre-operative diagnosis is often missed due to its diagnostic confusion with the tubo-ovarian mass, hydrosalpinx, ectopic pregnancy and ovarian malignancy. Transcoelomic, lymphatic, transluminal and haematogenous spread may occur to the other abdominal and pelvic organs as well as to the distant sites. Though the body of the uterus, ovaries and the contralateral fallopian tube are frequently involved, in the present case the contralateral ovary was the only site of involvement which is very unusual.

Nezhat FR, Denoble SM, Cho JE, et al.
Safety and efficacy of video laparoscopic surgical debulking of recurrent ovarian, fallopian tube, and primary peritoneal cancers.
JSLS. 2012 Oct-Dec; 16(4):511-8 [PubMed] Article available free on PMC after 01/10/2014 Related Publications

BACKGROUND AND OBJECTIVE: Studies on the role of laparoscopy in secondary or tertiary cytoreduction for recurrent ovarian cancer are limited. Our objective is to describe our preliminary experience with laparoscopic secondary/tertiary cytoreduction in patients with recurrent ovarian, fallopian, and primary peritoneal cancers.
METHODS: This is a retrospective analysis of a prospective case series. Women with recurrent ovarian, fallopian tube, or primary peritoneal cancers deemed appropriate candidates for laparoscopic debulking by the primary surgeon(s) were recruited. The patients underwent exploratory video laparoscopy, biopsy, and laparoscopic secondary/tertiary cytoreduction between June 1999 and October 2009. Variables analyzed include stage, site of disease, extent of cytoreduction, operative time, blood loss, length of hospital stay, complications, and survival time.
RESULTS: Twenty-three patients were recruited. Only one surgery involved conversion to laparotomy. Seventeen (77.3%) of the patients had stage IIIC disease at the time of their initial diagnosis, and 20 (90.9%) had laparotomy for primary debulking. Median blood loss was 75 mL, median operative time 200 min, and median hospital stay 2 d. No intraoperative complications occurred. One patient (4.5%) had postoperative ileus. Eighteen (81.8%) of the patients with recurrent disease were optimally cytoreduced to 1cm. Overall, 12 patients have no evidence of disease (NED), 6 are alive with disease (AWD), and 4 have died of disease (DOD), over a median follow-up of 14 mo. Median disease-free survival was 71.9 mo.
CONCLUSIONS: In a well-selected population, laparoscopy is technically feasible and can be utilized to optimally cytoreduce patients with recurrent ovarian, fallopian, or primary peritoneal cancers.

Related: Ovarian Cancer USA

Safra T, Berman T, Yachnin A, et al.
Weekly topotecan for recurrent ovarian, fallopian tube and primary peritoneal carcinoma: tolerability and efficacy study--the Israeli experience.
Int J Gynecol Cancer. 2013; 23(3):475-80 [PubMed] Related Publications

OBJECTIVES: The purpose of this study was to assess the clinical activity and toxicity of weekly topotecan in a large cohort of epithelial ovarian (EOC), primary peritoneal (PPC), and tubal cancer patients.
METHODS: Records of patients with recurrent EOC, PPC, and tubal cancer who were treated with weekly topotecan (4.0 mg/m on days 1, 8, and 15 on a 28-day cycle) after failure of more than 1 prior regimen were retrospectively reviewed in 8 centers in Israel.
RESULTS: Two hundred four patients were evaluated for efficacy and toxicity. Median age was 62 years (range, 27-89 years); 121 (59.3%) were platinum sensitive. Patients were exposed to a median of 2 previous lines (range, 1-9), and 48.5% received only 1 prior chemotherapy regimen. Median follow-up was 15.5 months (range, 2.5-112 months). Overall response rate was 26.5%, of which 11 patients (5.4%) had complete response, and 43 patients (21.1%) had partial response. Clinical benefit rate (complete response + partial response + stable disease) was 65.7%. Median progression-free survival was 4.0 months (95% confidence interval [CI], 3.5-4.5 months). There was no significant difference between platinum-sensitive and platinum-resistant patients regarding response rate or progression-free survival. Median overall survival from disease diagnosis was 45.0 months (95% CI, 40.04-49.6 months) and 16.0 months (95% CI, 12.3-19.7 months) from initiation of topotecan therapy. Overall survival was significantly different between patients with platinum-sensitive and platinum-resistant disease (19.9 vs. 10.8 months, respectively, P = 0.003; 95% CI, 8.1-16.3 months). Multivariate analysis showed that only platinum sensitivity and topotecan line were associated with overall survival. Weekly topotecan was well tolerated-with only 16.7% of patients experiencing grade 3 to 4 hematologic toxicities. There were no other grade 4 toxicities, and only 6.9% grade 3 toxicities.
CONCLUSIONS: In this large cohort of recurrent EOC, PPC, and tubal cancer, weekly topotecan was well tolerated with good clinical benefit rate, comparable to previous studies.

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Mendivil AA, Micha JP, Brown JV, et al.
Increased incidence of severe gastrointestinal events with first-line paclitaxel, carboplatin, and vorinostat chemotherapy for advanced-stage epithelial ovarian, primary peritoneal, and fallopian tube cancer.
Int J Gynecol Cancer. 2013; 23(3):533-9 [PubMed] Related Publications

OBJECTIVES: We sought to assess the response rate and toxicity of paclitaxel, carboplatin, andvorinostat primary induction therapy for the treatment of advanced-stage ovarian carcinoma.
METHODS: Patients were treated with 6 cycles of weekly paclitaxel (80 mg/m), carboplatin (6 times area under the curve), and vorinostat (200 mg) every 28 days according to an institutional review board-approved protocol. The subjects were eligible for response evaluation; in patients who achieved stable disease or better following the conclusion of primary induction chemotherapy, they were subsequently treated with a planned 12 cycles of paclitaxel (135 mg/m) and vorinostat (400 mg) maintenance chemotherapy every 28 days.
RESULTS: Eighteen patients received a combined 90 cycles (median, 6 cycles; range, 1-6 cycles) of primary induction chemotherapy. Of the 18 subjects, 7 demonstrated a complete response, and 2 subjects exhibited a partial response (a total response rate of 50.0%). Eight patients also received a combined total of 50 cycles (median, 5 cycles; range, 1-12 cycles) of consolidation therapy. Grade 3/4 neutropenia and thrombocytopenia were observed in 9 (56.3%) and 2 (12.5%) patients. One patient (6.3%) developed grade 3 anemia, and another (6.3%) manifested a grade 3 neuropathy. Remarkably, we observed a significant gastrointestinal event (eg, bowel anastomotic perforation) in 3 patients, which effectuated the study's closure.
CONCLUSIONS: Because the current study was prematurely terminated, we cannot derive a conclusive assessment regarding the efficacy of this treatment. Nevertheless, the high incidence of severe gastrointestinal toxicity warrants further consideration when using vorinostat in the adjuvant setting for patients who have undergone a bowel resection as part of their initial tumor debulking.

Related: Carboplatin Endometrial (Uterus) Cancer Endometrial Cancer Ovarian Cancer Paclitaxel

Schilder RJ, Sill MW, Lankes HA, et al.
A phase II evaluation of motesanib (AMG 706) in the treatment of persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas: a Gynecologic Oncology Group study.
Gynecol Oncol. 2013; 129(1):86-91 [PubMed] Article available free on PMC after 01/10/2014 Related Publications

OBJECTIVES: Vascular endothelial growth factors (VEGF) and their receptors have a critical role in stimulating the growth of ovarian cancer cells. Motesanib is a small molecule inhibitor of multiple receptor tyrosine kinases including VEGF receptors 1-3, as well as c-KIT and platelet-derived growth factor which are related to the VEGF family.
PATIENTS AND METHODS: Twenty-two eligible patients with recurrent ovarian, fallopian tube or primary peritoneal carcinoma were treated with an oral daily dose of 125 mg of motesanib. Peripheral blood was analyzed for circulating tumor cells (CTC) and circulating endothelial cells/circulating endothelial progenitors (CEC/CEP), VEGF levels and cell-free circulating DNA (cfDNA).
RESULTS: The study was abruptly halted after four patients developed posterior reversible encephalopathy syndrome. One patient had a partial response and seven patients had stable disease at the time they were removed from study treatment. Twelve of the 22 patients (50%) had indeterminate responses at trial closure. Early closure without clinical efficacy data precludes meaningful correlative studies.
CONCLUSIONS: The serious central nervous system toxicity observed in patients with recurrent ovarian cancer precluded full examination of this agent in this population. There were no clear cut explanations for the high incidence of this known class effect in the study population compared with patients with other cancers.

Related: Angiogenesis Inhibitors Ovarian Cancer VEGFA

Bamias A, Bamia C, Zagouri F, et al.
Improved survival trends in platinum-resistant patients with advanced ovarian, fallopian or peritoneal cancer treated with first-line paclitaxel/platinum chemotherapy: the impact of novel agents.
Oncology. 2013; 84(3):158-65 [PubMed] Related Publications

OBJECTIVE: The prognosis for patients with platinum-resistant advanced ovarian cancer remains poor. The impact of approved agents on survival has not been clarified during the last decade. We studied survival trends during the last 15 years in platinum-resistant patients treated with cytoreductive surgery followed by paclitaxel/platinum chemotherapy.
METHODS: Patients with epithelial ovarian, fallopian or peritoneal cancer, stages III/IV and platinum-resistant disease after first-line chemotherapy with paclitaxel/platinum were included. They were grouped according to the period of chemotherapy: group A 31/3/1995-31/12/2001 (n = 56) and Group B 1/1/2002-24/12/2008 (n = 57). In order to compensate for the difference in follow-up between the 2 groups, we performed minimum follow-up (MFU) analyses by considering as cases only women who had an event within 3 years of follow-up. Patients with no events for up to 3 years were censored at that time.
RESULTS: MFU analyses showed that median overall survival (OS) was significantly longer in group B: 12.3 vs. 17.5 months (p = 0.012). This was due to a doubling of the median OS after relapse: 5.7 vs. 10.9 months (p = 0.0180). Multivariate Cox regression indicated group and histology as factors statistically significantly associated with OS. Following relapse, patients in group B were predominantly treated with liposomal doxorubicin and gemcitabine, and patients in group A were treated with platinum compounds, docetaxel and oral etoposide (p < 0.001).
CONCLUSIONS: The introduction of novel agents without cross-resistance to platinum or taxanes has improved the prognosis of platinum-resistant patients.

Related: Carboplatin Cisplatin Endometrial (Uterus) Cancer Endometrial Cancer Ovarian Cancer Paclitaxel

Kaur H, Levinsky E, Colgan TJ
Papillary syncytial metaplasia of fallopian tube endometriosis: a potential pitfall in the diagnosis of serous tubal intraepithelial carcinoma.
Arch Pathol Lab Med. 2013; 137(1):126-9 [PubMed] Related Publications

Histopathologic diagnosis of tubal intraepithelial carcinoma (TIC) has emerged as a significant challenge in the last few years. The avoidance of pitfalls in the diagnosis of TIC is crucial if a better understanding of its natural history and outcome is to be achieved. Herein, we present a case of a 52-year-old woman who underwent a risk-reducing salpingo-oophorectomy procedure. Histologic examination of a fallopian tube demonstrated a focus of atypical epithelial proliferation, which was initially considered to be a TIC. Complete study of the case indicated that the focus was, in fact, papillary syncytial metaplasia of tubal mucosal endometriosis. Papillary syncytial metaplasia may resemble TIC and should be considered in cases of proliferative lesions of the tubal epithelium.

Vang R, Shih IeM, Kurman RJ
Fallopian tube precursors of ovarian low- and high-grade serous neoplasms.
Histopathology. 2013; 62(1):44-58 [PubMed] Related Publications

Traditionally, it was thought that ovarian high-grade serous carcinoma arises from the ovarian surface epithelium and epithelial inclusion glands and that the pathogenesis is de novo; nonetheless, a convincing precursor in the ovary or peritoneum has not been identified to date. During the last few years, however, there has been a dramatic shift in thinking, and a candidate precursor is now recognized in the fallopian tube, especially within the fimbriated end - serous tubal intra-epithelial carcinoma (STIC). Accordingly, STIC is probably the earliest histologically recognizable lesion in the pathogenesis of high-grade serous carcinoma, but steps in this pathway which precede STIC have also been proposed. With subsequent progression, STIC implants onto the ovary and then develops into an invasive high-grade serous carcinoma with rapid tumour growth. For invasive low-grade serous carcinoma, it is well-established that its pathogenesis begins with serous cystadenoma/adenofibroma, which develops sequentially into atypical proliferative serous tumour (typical serous borderline tumour), non-invasive micropapillary (low-grade) serous carcinoma (micropapillary serous borderline tumour) and then invasive low-grade serous carcinoma in a relatively slow stepwise process. It is presumed that cystadenoma/adenofibroma arises from epithelial inclusion glands in the ovary, but recent evidence suggests that epithelial inclusion glands originate in the fallopian tube. Alternatively, it has been proposed that the other early precursors in the low-grade pathway, including serous borderline tumours, non-invasive implants and endosalpingiosis, may also arise directly from tubal mucosa. Therefore, the precursor of most ovarian high-grade serous carcinomas originates in the fallopian tube, and that for low-grade serous tumours may also be derived from the tube. This review paper provides an overview of the fallopian tube's potential role in the pathogenesis of both types of serous neoplasms of the ovary.

Related: Ovarian Cancer

Lengyel E, Fleming S, McEwen KA, et al.
Serial sectioning of the fallopian tube allows for improved identification of primary fallopian tube carcinoma.
Gynecol Oncol. 2013; 129(1):120-3 [PubMed] Article available free on PMC after 01/10/2014 Related Publications

OBJECTIVE: Serial sectioning of the fallopian tube in women undergoing risk reducing surgery has been shown to increase the detection rate of occult malignancy in BRCA mutation carriers. We undertook this study to determine whether this protocol at the time of surgery for ovarian cancer (OV) or primary peritoneal malignancies (PP) changes the detection rate of fallopian tube carcinoma (FT). We secondarily investigated where this difference affects patient outcomes.
METHODS: A retrospective review of 130 patients treated at the University of Chicago Medical Center for ovarian, peritoneal or fallopian tube carcinoma was conducted. Sixty five patients diagnosed with OV, PP or FT who had serial sectioning of the fallopian tubes at the time of diagnoses (SS) were compared to 65 patients whose fallopian tubes were sectioned in a standard fashion (PSS).
RESULTS: Serial sectioning of the fallopian tube at the time of pathologic examination in women with presumed OV or PP led to an increase in the number of women diagnosed with FT as the primary site of origin (p<0.001). Clinical or pathologic risk factors leading to an increased risk of FT were not identified. Survival between the two groups was similar.
CONCLUSION: In women with presumed OV or PP, serial sectioning identifies women with FT. FT may be more common than previously noted; however distinct biologic or clinical behavior to differentiate it from OV or PP could not be identified. Clinical management of FT should continue to be the same as that of OV or PP.

Related: Ovarian Cancer

Alvarado-Cabrero I, Stolnicu S, Kiyokawa T, et al.
Carcinoma of the fallopian tube: Results of a multi-institutional retrospective analysis of 127 patients with evaluation of staging and prognostic factors.
Ann Diagn Pathol. 2013; 17(2):159-64 [PubMed] Related Publications

The aim of this study was to determine the impact of prognostic factors in primary fallopian tube carcinoma (PFTC). All cases of PFTC diagnosed between 1990 and 2010 were retrieved from the files of 6 academic centers. The cases were staged according to a modification of the International Federation of Obstetrics and Gynecology staging system proposed by Alvarado-Cabrero et al (Gynecol Oncol 1999; 72: 367-379). One hundred twenty-seven PFTC cases were identified. The mean age of the patients was 64.2 years. Stage distribution was as follows: 72 (57%), stage I; 19 (15%), stage II; 28 (22%), stage III; and 8 (6.2%), stage IV. Depth of infiltration of the tubal wall was an independent prognostic factor in stage I cases (P < .001). Carcinomas located in the fimbriated end even without invasion had a worse prognosis than did carcinomas involving the tubal portion of the organ. The presence of vascular space invasion correlated with the depth of tubal wall invasion (P = .001) and the presence of lymph node metastases (P = .003). Tumor grade significantly correlated with survival (P < .0001), but histologic type was of marginal significance and only if it was grouped as nonserous/non-clear cell vs serous/clear cell (P = .04). The depth of invasion of the tubal wall and the presence of carcinoma in the fimbriated end even without invasion are important prognostic indicators. The modified International Federation of Obstetrics and Gynecology staging system should be used on a routine basis in all carcinomas of the fallopian tube.

Halon A, Materna V, Donizy P, et al.
MRP2 (ABCC2, cMOAT) expression in nuclear envelope of primary fallopian tube cancer cells is a new unfavorable prognostic factor.
Arch Gynecol Obstet. 2013; 287(3):563-70 [PubMed] Article available free on PMC after 01/10/2014 Related Publications

OBJECTIVE: To determine the prognostic value of the immunohistochemical evaluation of the multidrug resistance-associated protein 2 (MRP2) expression, together with its subcellular localization in primary fallopian tube carcinomas (PFTCs).
METHODS: The immunohistochemical analysis was performed using samples originating from 70 patients with PFTCs.
RESULTS: (1) We documented that MRP2 can be localized in the plasma membrane (MRP2c), as well as in the nuclear envelope (MRP2n) of the PFTC cells. (2) Patients with more advanced stage, with progression of the disease and patients who died, showed significantly higher expression of the MRP2n. (3) Univariate and multivariate analyses showed that MRP2n is an unfavorable prognostic factor in PFTCs. (4) The analysis of the classic clinicopathological data revealed that only the FIGO stage had prognostic value, both in the univariate, as well as in multivariate analysis.
CONCLUSIONS: (1) This study suggests that MRP2n is a new disadvantageous prognostic factor in PFTCs and (2) that expression in nuclear envelope can be associated with lower differentiation of cancer cells and their resistance to the cisplatin. (3) We have also confirmed independent prognostic value of FIGO stage in PFTCs.

Related: Transitional Cell Cancer of the Renal Pelvis and Ureter

Nezhat CH, Dun EC, Wieser F, Zapata M
A rare case of primary extranodal marginal zone B-cell lymphoma of the ovary, fallopian tube, and appendix in the setting of endometriosis.
Am J Obstet Gynecol. 2013; 208(1):e12-4 [PubMed] Related Publications

Extranodal marginal zone B-cell lymphomas are uncommon. Most occur in the gastrointestinal tract. Marginal zone B-cell lymphomas of the female genital tract are rare, and few cases exist of marginal zone B-cell lymphomas of the uterus, cervix, and fallopian tubes. We report the first marginal zone B-cell lymphoma of the ovary, fallopian tube, and appendix arising in endometriosis.

Related: Appendix Cancers MALT Lymphoma Ovarian Cancer

Tanner EJ, Long KC, Feffer JB, et al.
Parenchymal splenic metastasis is an independent negative predictor of overall survival in advanced ovarian, fallopian tube, and primary peritoneal cancer.
Gynecol Oncol. 2013; 128(1):28-33 [PubMed] Related Publications

OBJECTIVE: The purpose of this study was to evaluate the significance of parenchymal splenic metastasis (PSM) in ovarian (OC), fallopian tube (FTC), and primary peritoneal cancer (PPC).
METHODS: All patients with stage IIIB-IV OC, FTC, and PPC undergoing primary cytoreduction from 2001 to 2010 at our institution were identified. In patients undergoing splenectomy, pathology was reviewed for the presence of PSM. Multivariate Cox regression and Kaplan-Meier survival analysis were used to evaluate factors associated with overall survival (OS).
RESULTS: Of 576 patients identified, stage was: IIIB - 23 (4%), IIIC - 468 (81.2%), and IV - 85 (14.8%). Optimal cytoreduction was achieved in 430 patients (74.7%), including 85 of 97 patients (87.6%) undergoing splenectomy. PSM was identified in 20 patients (20.6%) undergoing splenectomy, including 3 of 5 patients (60%) with radiographically identified parenchymal liver metastases and 17 of 92 patients (18.5%) without such radiographic findings (P=0.059). Age, preoperative albumin, residual disease, stage, bulky upper abdominal disease, IP chemotherapy, and PSM were associated with OS on univariate analysis. Splenectomy was not associated with survival. Age, preoperative albumin, residual disease, stage, and PSM (HR=0.46; 95% CI, 0.27-0.77) were associated with OS on multivariate analysis. In the subset of patients undergoing splenectomy, OS was lower for patients with PSM versus those without PSM (28.5 v 51.2months, P=0.004).
CONCLUSIONS: PSM is independently associated with decreased OS in patients with advanced OC, FTC, and PPC. PSM occurs in the setting of other evidence of hematogenously disseminated disease, but also occurs outside this setting. PSM should be considered a criterion for stage IV disease.

Related: Ovarian Cancer

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