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Fallopian Tube Cancer

Primary fallopian tube cancer (tubal cancer) is rare and accounts for just 1 to 2 percent of all gynecologic cancers. It is more common for cancer to spread (metastasize) from other parts of the body than for cancer to originate in the fallopian tubes.

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  • PubMed search for publications about Fallopian tube cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Fallopian tube cancer
    MeSH term: Fallopian Tube Neoplasms
    International US National Library of Medicine
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Sørensen RD, Schnack TH, Karlsen MA, Høgdall CK
Serous ovarian, fallopian tube and primary peritoneal cancers: a common disease or separate entities - a systematic review.
Gynecol Oncol. 2015; 136(3):571-81 [PubMed] Related Publications
OBJECTIVE: The aim of this systematic review is to analyze data on risk factors, epidemiology, clinicopathology and molecular biology from studies comparing primary peritoneal cancer, fallopian tube cancer and ovarian cancer of serous histology, in order to achieve a greater understanding of whether or not these disorders should be considered as separate entities.
METHODS: A systematic literature search was conducted in PubMed and MEDLINE. Case-control studies comparing primary serous peritoneal or fallopian tube carcinomas with primary serous ovarian carcinomas or a control group were included.
RESULTS: Twenty-eight studies were found eligible. Primary peritoneal cancer patients were older, had higher parity, were more often obese and had poorer survival compared to ovarian cancer patients. Differences in protein expression patterns of Her2/neu, estrogen and progestin receptors and frequency of loss of heterozygosity differed between primary peritoneal cancer and primary ovarian cancer patients. No major differences were found between primary fallopian tube cancer and primary ovarian cancer. The proportion of serous tubal intraepithelial carcinomas (STIC) was lower in primary peritoneal cancer and primary ovarian cancer compared to primary fallopian tube cancer.
CONCLUSION: Except from differences in the proportion of STIC only few differences between primary fallopian tube cancer and primary ovarian cancer have been found. In contrast, observed differences in risk factor profile, clinicopathologic and prognostic factors, as well as in the molecular patterns, indicate that peritoneal cancer and ovarian cancer may be linked to different carcinogenic pathways.

Gilks CB, Irving J, Köbel M, et al.
Incidental nonuterine high-grade serous carcinomas arise in the fallopian tube in most cases: further evidence for the tubal origin of high-grade serous carcinomas.
Am J Surg Pathol. 2015; 39(3):357-64 [PubMed] Related Publications
Most nonuterine high-grade serous carcinomas (HGSCs) in women with hereditary breast and ovarian cancer syndrome, due to germline BRCA1/2 mutation, arise in the fimbria of the fallopian tube. However, the site of origin of sporadic HGSC, which is usually widely disseminated at presentation, is not well established. We sought to characterize cases of HGSC discovered incidentally in patients not known to be at high risk, in order to determine the site distribution and possible origin of sporadic HGSC. Incidental microscopic, non-mass-forming cases of serous tubal intraepithelial carcinoma or HGSC in salpingo-oophorectomy specimens in which the tubes and ovaries had been extensively examined were identified. No patients were known or suspected BRCA1/2 mutation carriers. Twenty-one cases were identified (mean age: 57 y). Surgery was for benign disease (n=15), uterine endometrioid adenocarcinoma or atypical hyperplasia (n=3), bladder carcinoma (n=1), or ovarian serous borderline tumor (n=2). In 16 of 21 cases, the lesion was confined to the fallopian tube (unilateral in 14 cases, bilateral in 2). There was serous tubal intraepithelial carcinoma in all cases and invasive HGSC into the underlying lamina propria in 8 of these 16 cases; the invasive focus measured 1.3 cm or less in every case. In the remaining 5 cases, there was fallopian tube mucosal and ovarian involvement; in 2 of these cases, there was also microscopic peritoneal involvement. Sporadic cases of nonuterine HGSC arise in the fallopian tube fimbria in a large majority of cases, providing further evidence for the tubal origin of these neoplasms.

Wan J, Li XM, Gu J
Primary choriocarcinoma of the fallopian tube: a case report and literature review.
Eur J Gynaecol Oncol. 2014; 35(5):604-7 [PubMed] Related Publications
Choriocarcinoma is a highly malignant tumor of trophoblastic origin. Primary fallopian tube choriocarcinoma is an extremely rare occurrence, especially in women over 50 years of age. This article concerns a case of tubal choriocarcinoma developing in a 54-year-old woman, which the authors present together with a brief review of the literature. The woman presented with irregular vaginal bleeding for two months, following three months of amenorrhea. Transvaginal dopolar and pelvic computed tomography (CT) scan showed an adnexal cystomic-solid mass. Her serum human chorionic gonadotropin (hCG) levels were 29,1116 mIU/ml. The patient underwent hysterectomy and bisalpingo-oophorectomy. Histology was suggestive of tubal choriocarcinoma. Immunohistochemistry tests were positive for the hCG, Ki 67, CK, PLAP, and negative for CD30, supporting the diagnosis of choriocarcinoma. A combination of 5-Fu and KSM was administrated postoperatively. After four cycles of chemotherapy, her serum hCG level fell to the normal range. The patient remains disease-free 14 months after disease diagnosis.

Kalampokas E, Sofoudis C, Boutas I, et al.
Primary fallopian tube carcinoma: a case report and mini-review of the literature.
Eur J Gynaecol Oncol. 2014; 35(5):595-6 [PubMed] Related Publications
Primary fallopian tube carcinoma (PFTC) is an uncommon gynecologic tumor, responsible for 0.14% to 1.8% of genital malignancies, with a mean incidence of 3.6 per million women per annum. The factors that contribute to its appearance are not well-known. Overall survival percentages for patients with PFTC are generally low. Although the preoperative diagnosis rarely occurs and it is usually first confirmed by the pathologist, an earlier diagnosis occurs with early clinical manifestation and prompt investigation leading to better prognosis. Both PFTC and epithelial ovarian cancer (EOC) are treated with similar surgical and chemotherapy methods. The authors report a case of a patient with bilateral high grade serous carcinoma of the fallopian tube, whose initial presentation was bilateral cystic adnexal masses and serosanguinous discharge, with no other pelvic involvement. This article also reviews in brief and presents updates of this rare gynecological malignancy.

Arko D, Žegura B, Virag M, et al.
Preoperative diagnosis of fallopian tube malignancy with transvaginal color doppler ultrasonography and magnetic resonance imaging after negative hysteroscopy for postmenopausal bleeding.
Coll Antropol. 2014; 38(3):1047-50 [PubMed] Related Publications
Primary fallopian tube carcinoma is a rare malignancy and is not often diagnosed preoperatively. We present a case of a 67-year-old woman who complained of postmenopausal vaginal bleeding. After a negative hysteroscopy, transvaginal ultrasound showed a well vascularized solid-cystic tumor in the adnexal region separate from the ovary. The presence of an adnexal mass was confirmed by MR imaging. Total abdominal hysterectomy with bilateral salpingoophorectomy, omentectomy and appendectomy, as well as pelvic and paraaortic lymphadenectomy was performed. The pathohistological diagnosis was poorly differentiated serous adenocarcinoma of the fallopian tube, FIGO stage IA. The patient was subsequently treated with platinum based adjuvant chemotherapy.

Cai SQ, Ma FH, Qiang JW, et al.
Primary fallopian tube carcinoma: correlation between magnetic resonance and diffuse weighted imaging characteristics and histopathologic findings.
J Comput Assist Tomogr. 2015 Mar-Apr; 39(2):270-5 [PubMed] Related Publications
OBJECTIVE: The aim of this study was to investigate the magnetic resonance (MR) and diffusion-weighted (DW) imaging characteristics of primary fallopian tube carcinoma (PFTC).
METHODS: The clinical, MR, and DW imaging characteristics and pathologic findings of 23 patients with 27 tumors were studied retrospectively. The MR and DW imaging appearance of tumors including laterality, size and shape, architecture, signal intensity, apparent diffusion coefficient (ADC) value, enhancement pattern, hydrosalpinx, and intrauterine fluid collection were evaluated and correlated with pathologic findings.
RESULTS: Histopathologically, all 27 tumors were serous carcinoma with a unilateral tumor in 19 patients and bilateral tumors in 4 patients. Thirteen patients (57%) with PFTC were misdiagnosed preoperatively, 10 of which as epithelial ovarian carcinoma. The mean (SD) largest diameter was 61 (7) mm. The tumor shape was fusiform, sausagelike, or serpentine in 19 patients (70%) and nodular or irregular in 8 patients (30%). Twenty (74%) of the 27 tumors were solid, and 7 (26%) were cystic-solid. The solid components showed hypointensity to isointensity on T1-weighted imaging, and isointensity to slight hyperintensity on T2-weighted imaging. There were obvious hyperintensity on DW imaging; obvious hypointensity on ADC maps with a mean (SD) ADC value of 0.79 (0.22) × 10 mm; and mild (8/27, 30%), moderate (13/27, 48%), and marked (6/27, 22%) enhancement on contrast-enhanced imaging. Ipsilateral hydrosalpinx, intrauterine fluid collection, and ascites were found in 14 tumors (52%) and 7 (30%) and 5 (22%) patients, respectively.
CONCLUSIONS: The PFTC has some characteristic MR imaging features. The DW imaging, ADC maps, and ADC values are helpful for the detection and differentiation of PFTC from other pelvic masses.

Ma Y, Duan W
Clinical and survival analysis of 36 cases of primary fallopian tube carcinoma.
World J Surg Oncol. 2014; 12:311 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Primary fallopian tube carcinoma (PFTC) is rarely seen clinically. Herein, we investigate the clinical and pathological characteristics and appropriate therapies for PFTC.
METHODS: A total of 36 patients for whom PFTC was pathologically confirmed from January 2001 to July 2011 in Beijing Hospital of Gynecology and Obstetrics, an affiliate of Capital Medical University, were retrospectively analyzed.
RESULTS: A total of 36 cases underwent surgical staging in our hospital: 47.2% were early stage cases , and 52.8% were advanced stage cases. Of the 36 cases, 24 cases were pure adenocarcinoma, 10 cases were mixed, and there was 1 case of undifferentiated carcinoma, 1 case of undifferentiated carcinoma combined with transitional cell carcinoma, 5 cases of moderately differentiated carcinoma, and 29 cases of moderately to poorly differentiated carcinoma. There were no cases of highly differentiated carcinoma. Among the cases examined, 38.9% (14/36) had omentum metastasis, and 19 cases had an elevated CA125 during a preoperative biochemical laboratory test. Approximately 35 cases received postoperative adjuvant chemotherapy. The 3-year and 5-year overall survival rates for the 36 cases were 80.7% and 65.4%, respectively. Single-factor analysis showed that the pathological conditions of residual tumor diameter >1 cm (P < 0.001), omentum metastasis (P = 0.003), ovary metastasis (P = 0.004) and elevated preoperative CA125 (P = 0.044) were associated with prognosis, whereas pathological surgical staging (P = 0.069), retroperitoneal lymph node metastasis (P = 0.499), and pathological classification (P = 0.183) were not associated with prognosis. Multifactor analysis showed that a residual tumor diameter >1 cm (P = 0.019) and omentum metastasis (P = 0.015) were associated with prognosis, and were, therefore, the independent risk factors of prognosis.
CONCLUSIONS: PFTC is a rare female genital tract malignancy. Most patients are in an advanced stage at diagnosis, which results in a poor prognosis. Complete surgical staging and maximal resection should be recommended.

Horng HC, Teng SW, Huang BS, et al.
Primary fallopian tube cancer: domestic data and up-to-date review.
Taiwan J Obstet Gynecol. 2014; 53(3):287-92 [PubMed] Related Publications
Primary fallopian tube carcinoma (PFTC) is a rare gynecological malignancy with the following characteristics: its preoperative diagnosis is easy to miss or delay because of a lack of specific symptoms and signs; it is difficult to distinguish from serous epithelial ovarian cancer or primary peritoneal serous carcinoma during or even after operation because they have the same histopathological features; and there is uncertainty regarding the optimal management because of the lack of available standard guidelines. All of these factors contribute to the major challenge of undertaking a comprehensive study of this disease. To improve our understanding of this rare disease, the domestic data were summarized first. We searched PubMed on this topic, using the term "primary fallopian tube tumor and Taiwan" (from January 1, 1990 to November 3, 2013) and identified 15 published articles, but only 11 studies focused on the outcome of patients with PFTC in Taiwan. These limited data were not enough to increase our knowledge in dealing with this disease; therefore, the addition of large series or published review articles addressing this topic was needed. According to these reports, we concluded: (1) the main type of PFTC was serous type, often poorly differentiated; (2) the diagnosis of PFTC is frequently missed or delayed; (3) PFTC is often of an earlier International Federation of Gynecology and Obstetrics (FIGO) stage than is epithelial ovarian cancer (EOC), because of the appearance of earlier but nonspecific symptoms or signs, such as abdominal pain, vaginal bleeding, and watery discharge or mass; (4) the most important clinicopathological prognostic factor was FIGO stage; (5) the therapeutic strategy is still uncertain, but is often based on the guidelines for treating EOC. An intensive surgical effort such as a complete surgical resection or optimal cytoreduction surgery with a minimal residual tumor followed by a platinum-paclitaxel combination chemotherapy with/without targeted therapy (for example, antiangiogenesis agents) may provide the best possibility of disease-free or overall survival.

Topolovec Z, Mrcela M, Sijanović S, et al.
Primary serous papillary adenocarcinoma of the fallopian tube.
Acta Clin Croat. 2014; 53(2):242-5 [PubMed] Related Publications
Fallopian tube cancer is least common of all gynecologic tumors, with the mean age at onset between 54 and 63 years. This case report presents a 67-year-old female, gravida 1, para 1, with primary adenocarcinoma of the fallopian tube, detected and diagnosed preoperatively in clinical stage IIIc. The patient was asymptomatic, with only mild vaginal discharge of amber color and normal measured value of CA 125. The diagnosis was based on routine clinical and ultrasound examination, followed by surgery, surgical-pathological staging of the disease, and finally paclitaxel and platinum based chemotherapy. The patient has been in remission for nine years now.

Colón E, Carlson JW
Evaluation of the fallopian tubes after neoadjuvant chemotherapy: persistence of serous tubal intraepithelial carcinoma.
Int J Gynecol Pathol. 2014; 33(5):463-9 [PubMed] Related Publications
The origin of pelvic serous carcinoma continues to be controversial. Recent studies of patients undergoing primary surgery for ovarian, primary peritoneal, and uterine serous carcinomas have indicated the value of complete fimbrial sampling for detecting occult serous tubal intraepithelial carcinoma (STIC). Evidence suggests that a significant proportion of pelvic serous carcinomas may arise from in situ lesions on the distal fallopian tube. In this study, 14 consecutive cases of interval debulking surgery after neoadjuvant chemotherapy were reviewed, using both hematoxylin and eosin staining and, as needed, immunohistochemistry for p53 and MIB-1. The degree of fimbrial sampling was evaluated, and cases were examined for tumor involvement in the endosalpinx and the presence of STIC. Tumor treatment response was classified using a semiquantitative 4-tier scale. The results indicate that STIC can persist despite chemotherapy and can be readily identified during microscopic examination. These results are expected to improve the quality of the pathology evaluation by providing data-driven recommendations for sampling in interval surgery cases and showing the value of a systematic approach to evaluating the fallopian tube (sectioning and extensively examining the fimbria protocol). These results demonstrate that a tubal primary can still be assigned in these situations. Finally, this study raises interesting biologic questions about the sensitivity of cells originating from serous cancer tumor to chemotherapy. The presence or absence of STIC in specimens from interval surgery after neoadjuvant treatment has not previously, to our knowledge, been addressed.

Zeppernick F, Meinhold-Heerlein I
The new FIGO staging system for ovarian, fallopian tube, and primary peritoneal cancer.
Arch Gynecol Obstet. 2014; 290(5):839-42 [PubMed] Related Publications
INTRODUCTION: Recent molecular research has revolutionized the understanding of ovarian cancer. It is now non-controversial that the term ovarian cancer summarizes a heterogenous group of malignant epithelial tumors. Findings of large clinical trials investigating surgical and systemic therapeutic approaches have defined the most important prognostic parameters. Therefore, the oncology committee of FIGO, headed by the South African gynecologic oncologist Lynette Denny, took the effort to revise the FIGO classification of ovarian cancer that was implemented in 1988.
MATERIAL AND METHODS: The recent publication of Jaime Prat describing the new FIGO classification is summarized. The major changes compared to the hitherto existing classification from 1988 are presented.
RESULTS: The primary anatomy is now documented (ov for ovarian, ft for fallopian tube, p for peritoneal, X for not assessed). The histological subtype is also documented (HGSC for high-grade serous carcinoma, LGSC for low-grade serous carcinoma, MC for mucinous carcinoma, CCC for clear cell carcinoma, and EC for endometrioid carcinoma). There is no stage I peritoneal cancer. Stage IC is subdivided into intraoperative rupture (IC1), pre-operative rupture (IC2), and malignant ascites or peritoneal washings (IC3). Due to its anatomic position within the pelvis, metastasis to the sigmoid colon is considered stage II. Former stage IIC has been erased. Stage IIIA1 and IIIA2 have been defined for intra-pelvic tumor with metastasis to retro-peritoneal lymph nodes up to 1 cm (IIIA1) or larger than 1 cm (IIIA2). With this, some of the former stage IIIC cases become IIIA and some IIIB, respectively. Involvement of retroperitoneal lymph nodes must be proven cytologically or histologically. Stage IV has been subdivided into IVA (malignant pleural effusions) and IVB (parenchymal metastases and/or extra-abdominal metastases including tumors in inguinal lymph nodes or lymph nodes outside of the abdominal cavity, umbilical tumor deposit, and transmural bowel infiltration (with mucosal involvement).
CONCLUSION: The new FIGO classification takes into account the recent findings on the origin, pathogenesis, and prognosis of different ovarian cancer subtypes, summarizes groups of tumors pragmatically, and implies a reproducible and stage-dependent therapeutical approach.

McNeish IA, Ledermann JA, Webber L, et al.
A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†.
Ann Oncol. 2014; 25(10):1988-95 [PubMed] Related Publications
BACKGROUND: We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer.
PATIENTS AND METHODS: Patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer were randomised 2 : 1 to receive 8-week cycles of weekly paclitaxel (wPxl; 80 mg/m(2)/week ×6 with 2-week break) plus saracatinib (S; 175 mg o.d.) or placebo (P) continuously, starting 1 week before wPxl, until disease progression. Patients were stratified by taxane-free interval (<6 versus ≥6 months/no prior taxane). The primary end point was progression-free survival (PFS) rate at 6 months. Secondary end points included overall survival (OS) and response rate (RR).
RESULTS: A total of 107 patients, median age 63 years, were randomised. Forty-three (40%) had received >2 lines of prior chemotherapy. The 6-month PFS rate was 29% (wPxl + S) versus 34% (wPxl + P) (P = 0.582). Median PFS was 4.7 versus 5.3 months (hazard ratio 1.00, 95% confidence interval 0.65-1.54; P = 0.99). RR (complete + partial) was 29% (wPxl + S) versus 43% (wPxl + P), P value = 0.158. Grade 3/4 adverse events were 36% versus 31% (P = 0.624); the most frequent G3/4 toxicities were vomiting (5.8% saracatinib versus 8.6% placebo), abdominal pain (5.8% versus 0%) and diarrhoea (4.3% versus 5.7%). Febrile neutropenia was more common in the saracatinib arm (4.3%) than placebo (0%). Response, PFS and OS were all significantly (P < 0.05) better in patients with taxane interval ≥6 months/no prior taxane (n = 85) than those <6 months (n = 22), regardless of randomisation.
CONCLUSIONS: Saracatinib does not improve activity of weekly paclitaxel in platinum-resistant ovarian cancer. Taxane-free interval of ≥6 months/no prior taxane was associated with better outcome in both groups.
TRIALS REGISTRATION: Clinicaltrials.gov NCT01196741; ISRCTN 32163062.

Cass I, Walts AE, Barbuto D, et al.
A cautious view of putative precursors of serous carcinomas in the fallopian tubes of BRCA mutation carriers.
Gynecol Oncol. 2014; 134(3):492-7 [PubMed] Related Publications
OBJECTIVE: To compare the frequency and distribution of candidate precursors of serous carcinoma in the fallopian tubes of BRCA mutation carriers to BRCA non-mutation carriers (controls) at risk-reducing bilateral salpingo-oophorectomy (RRSO).
METHODS: 78 BRCA carriers (52 BRCA1, 26 BRCA2) and 23 controls underwent RRSO. Fallopian tubes were serially cross-sectioned, and adnexa were entirely submitted and examined by two gynecologic pathologists blinded to BRCA mutation status. The presence and location of serous tubal intraepithelial carcinoma (STIC), p53 overexpression (≥ 6 consecutively stained nuclei), Ki67 overexpression, atypia/low grade dysplasia and epithelial hyperplasia were compared between BRCA carriers and controls. Patient age was dichotomized: ≤ 50 and >50 years.
RESULTS: 9 (12%) BRCA carriers had occult carcinoma: 8 STIC and 1 stage IC tubal carcinoma with STIC. No occult carcinomas or STIC was seen in controls. STIC involved the distal tube in all cases and was multifocal in three cases. STIC was more common in women >50 (p=0.06). P53 overexpression was common in BRCA carriers (30%) and controls (43%) (p=0.5) and did not correlate with age. Only 5/9 (55%) of STIC exhibited p53 overexpression. 2 patients had Ki67 overexpression: both BRCA1 carriers with STIC. No difference in the frequency of atypia/low grade dysplasia or hyperplasia was observed between BRCA carriers and controls.
CONCLUSIONS: STIC is the dominant precursor of serous fallopian tube carcinoma in BRCA carriers. There is insufficient evidence to support p53 overexpression alone as a putative precursor. Atypia/low grade dysplasia and epithelial hyperplasia are not pre-neoplastic lesions of serous fallopian tube carcinoma.

Rabban JT, Vohra P, Zaloudek CJ
Nongynecologic metastases to fallopian tube mucosa: a potential mimic of tubal high-grade serous carcinoma and benign tubal mucinous metaplasia or nonmucinous hyperplasia.
Am J Surg Pathol. 2015; 39(1):35-51 [PubMed] Related Publications
Mucosal alterations of the fallopian tube are generally thought to represent alterations of the native tubal mucosal epithelium, whether benign or malignant. The current paradigm implicating the fallopian tube fimbriae as the origin of most pelvic high-grade serous carcinomas (HGSCs) is based on the premise that HGSC growing within the tubal mucosa originated there. This has fueled proposals to redefine classification rules for assigning the primary site of origin on the basis of the presence or absence of HGSC in the tubal mucosa. The corollary is that it is unlikely for metastatic carcinoma to grow within fallopian tube mucosa. Evidence to support or refute this corollary is minimal, in part because the fallopian tubes historically have been ignored. This study reports the pattern and topography of 100 nongynecologic cancers that metastasized to the fallopian tubes. Most tumors were adenocarcinoma (87%), and the remainder included lymphomas, neuroendocrine tumors, and mesotheliomas. The most common primary origins of tumor were the colon (35%) and breast (15%). Gross evidence of a tubal nodule or mass was only seen in 35% of cases. Ovarian metastases were present in 95% of cases, although 23% did not exhibit gross evidence of metastasis. Tumor involved the fimbriae in 49% of cases, including 10% of cases in which the tumor was restricted to the fimbriae without involving the nonfimbriated portion of the tube. The anatomic distribution of metastases included the tubal mucosa (29%), submucosa (43%), muscularis (54%), serosa (76%), lymphovascular spaces (38%), intraluminal space (16%), and mesonephric remnants (39%). The most common architectural pattern of mucosal growth was a flat layer (22/29 cases), followed by varying degrees of stratification, tufting, and papillary growth. High-grade atypia was present in 18/29 cases of mucosal growth, resulting in patterns that resembled primary tubal HGSC. Accompanying growth in the tubal submucosa frequently produced a pseudoinvasive pattern mimicking invasive tubal HGSC. Immunohistochemical expression of p53 by 8/18 high-grade mucosal metastases further contributed to the resemblance to primary tubal HGSC. Bland cytology was present in 11/29 cases of mucosal growth, some of which also exhibited mucinous features, resulting in patterns that resembled either tubal mucinous metaplasia or nonmucinous tubal hyperplasia. Although uncommon, it is possible for metastases of nongynecologic cancers to grow within the mucosa of the fallopian tube and create a potential diagnostic pitfall. Intramucosal growth of a tumor in the fallopian tube is not pathognomonic of a primary tubal origin of the tumor. These findings may carry implications for proposed criteria using the status of the fallopian tube mucosa to assign primary origin of a gynecologic cancer.

Deb P, Singh V, Dutta V, Kapoor K
An unusual case of cavernous haemangioma of the Fallopian tube.
J Cancer Res Ther. 2014 Apr-Jun; 10(2):363-4 [PubMed] Related Publications
Fallopian tubes are one of the uncommon sites for neoplastic lesions in the female genital tract. Haemangiomas of the fallopian tubes are rare benign neoplasms that are documented as isolated case reports only. We present a rare case of incidentally detected cavernous haemangioma of the fallopian tube in a post menopausal female who underwent hysterectomy and bilateral salphingoopherectomy for dysfunctional uterine bleeding.

Suidan RS, Ramirez PT, Sarasohn DM, et al.
A multicenter prospective trial evaluating the ability of preoperative computed tomography scan and serum CA-125 to predict suboptimal cytoreduction at primary debulking surgery for advanced ovarian, fallopian tube, and peritoneal cancer.
Gynecol Oncol. 2014; 134(3):455-61 [PubMed] Article available free on PMC after 01/09/2015 Related Publications
OBJECTIVE: To assess the ability of preoperative computed tomography (CT) scan of the abdomen/pelvis and serum CA-125 to predict suboptimal (>1cm residual disease) primary cytoreduction in advanced ovarian, fallopian tube, and peritoneal cancer.
METHODS: This was a prospective, non-randomized, multicenter trial of patients who underwent primary cytoreduction for stage III-IV ovarian, fallopian tube, and peritoneal cancer. A CT scan of the abdomen/pelvis and serum CA-125 were obtained within 35 and 14 days before surgery, respectively. Four clinical and 20 radiologic criteria were assessed.
RESULTS: From 7/2001 to 12/2012, 669 patients were enrolled; 350 met eligibility criteria. The optimal debulking rate was 75%. On multivariate analysis, three clinical and six radiologic criteria were significantly associated with suboptimal debulking: age ≥ 60 years (p=0.01); CA-125 ≥ 500 U/mL (p<0.001); ASA 3-4 (p<0.001); suprarenal retroperitoneal lymph nodes >1cm (p<0.001); diffuse small bowel adhesions/thickening (p<0.001); and lesions >1cm in the small bowel mesentery (p=0.03), root of the superior mesenteric artery (p=0.003), perisplenic area (p<0.001), and lesser sac (p<0.001). A 'predictive value score' was assigned for each criterion, and the suboptimal debulking rates of patients who had a total score of 0, 1-2, 3-4, 5-6, 7-8, and ≥ 9 were 5%, 10%, 17%, 34%, 52%, and 74%, respectively. A prognostic model combining these nine factors had a predictive accuracy of 0.758.
CONCLUSIONS: We identified nine criteria associated with suboptimal cytoreduction, and developed a predictive model in which the suboptimal rate was directly proportional to a predictive value score. These results may be helpful in pretreatment patient assessment.

Penson RT, Moore KM, Fleming GF, et al.
A phase II study of ramucirumab (IMC-1121B) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.
Gynecol Oncol. 2014; 134(3):478-85 [PubMed] Related Publications
OBJECTIVE: Vascular endothelial growth factor (VEGF) receptor-mediated signaling contributes to ovarian cancer pathogenesis. Elevated VEGF expression is associated with poor clinical outcomes. We investigated ramucirumab, a fully human anti-VEGFR-2 antibody, in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Primary endpoints were progression-free survival at 6 months (PFS-6) and confirmed objective response rate (ORR).
METHODS: Women who received ≥ 1 platinum-based chemotherapeutic regimen and had a platinum-free interval of <12 months with measurable disease were eligible. Patients received 8 mg/kg ramucirumab intravenously every 2 weeks.
RESULTS: Sixty patients were treated; one patient remained on study as of September 2013. The median age was 62 years (range: 27-80), and median number of prior regimens was 3. Forty-five (75%) patients had platinum refractory/resistant disease. Thirty-nine patients (65.0%) had serous tumors. PFS-6 was 25.0% (n=15/60, 95% CI: 14.7-37.9%). Best overall response was: partial response 5.0% (n=3/60), stable disease 56.7% (n=34/60), and progressive disease 33.3% (n=20/60). The most common treatment-emergent adverse events possibly related to study drug were headache (65.0%; 10.0% Grade ≥ 3), fatigue (56.7%; 3.3% Grade ≥ 3), diarrhea (28.3%; 1.7% Grade ≥ 3), hypertension (25.0%; 3.3% Grade ≥ 3), and nausea (20.0%; no Grade ≥ 3). Two patients experienced intestinal perforations (3.3% Grade ≥ 3). Pharmacodynamic analyses revealed changes in several circulating VEGF proteins following initial ramucirumab infusion, including increased VEGF-A, PlGF and decreased sVEGFR-2.
CONCLUSIONS: Although antitumor activity was observed, the predetermined efficacy endpoints were not met.

Horng HC, Teng SW, Lai CR, et al.
Prognostic factors of primary fallopian tube cancer in a single institute in Taiwan.
Int J Gynaecol Obstet. 2014; 127(1):77-81 [PubMed] Related Publications
OBJECTIVE: To improve the understanding of primary fallopian tube carcinoma (PFTC) through an analysis of possible clinical and pathologic determinants of prognosis.
METHODS: A retrospective review of the database of a tertiary hospital in Taiwan for 1978-2007 was conducted to identify patients with a diagnosis of PFTC and to evaluate the clinicopathologic features associated with PFTC outcome.
RESULTS: Fifty-eight patients (mean age 62.5 years) had a diagnosis of PFTC. Stage III/IV disease (55%) and poorly differentiated tumors (52%) were most common. The median follow-up was 93 months (range, 11-333 months). The 5-year disease-free survival rate was 59%, and the overall survival rate was 64%. Factors important in disease-free and overall survival in univariate analysis included the presence of pelvic and/or para-aortic lymph node metastases, International Federation of Gynecology and Obstetrics stage, high preoperative carbohydrate antigen 125 serum level, completion of optimal debulking surgery, and the use of paclitaxel-based chemotherapy; however, only patients with optimal cytoreduction had a decreased hazard of recurrence (hazard ratio [HR] 0.06; 95% confidence interval [CI] 0.01-0.23) and mortality (HR 0.08; 95% CI, 0.02-0.31) in multivariate analysis.
CONCLUSION: Advanced tumor stage, in particular the presence of lymph node metastases, worsened the prognosis of patients with PFTC. However, optimal debulking surgery significantly improved the prognosis, emphasizing the importance of the treatment strategy.

Usami T, Kato K, Taniguchi T, et al.
Recurrence patterns of advanced ovarian, fallopian tube, and peritoneal cancers after complete cytoreduction during interval debulking surgery.
Int J Gynecol Cancer. 2014; 24(6):991-6 [PubMed] Related Publications
OBJECTIVES: Similar to primary debulking surgery, complete resection of all macroscopic diseases during interval debulking surgery (IDS) is the primary objective while using neoadjuvant chemotherapy followed by IDS for advanced ovarian, fallopian tube, and peritoneal cancers. However, most patients develop recurrent disease even after complete cytoreduction during IDS. This study aims to identify recurrence patterns of the ovarian, fallopian tube, and peritoneal cancers in patients who underwent complete cytoreduction during IDS.
METHODS: We retrospectively reviewed data of patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers who were treated at our hospital from January 1, 2005, to December 31, 2011.
RESULTS: In this study, 105 patients underwent neoadjuvant chemotherapy followed by IDS and achieved complete cytoreduction. The median follow-up period was 42.1 months. Recurrence was documented in 70 patients (66.7%), and 35 (33.3%) showed no evidence of disease. Peritoneal dissemination was the most common recurrence (60.0%) observed. In multivariate analysis, positive peritoneal cytology (P = 0.0003) and elevated pre-IDS serum CA125 levels (P = 0.046) were independent risk factors for recurrence.
CONCLUSIONS: After complete cytoreduction during IDS in patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers, positive peritoneal cytology at IDS and elevated pre-IDS CA125 levels are associated with an increased risk of cancer recurrence. Positive peritoneal cytology during IDS is a particularly strong predictive factor for poor outcomes in these patients.

Kos Z, Broaddus RR, Djordjevic B
Fallopian tube high-grade serous carcinoma with intramucosal spread and presenting as a malignancy on pap smear.
Int J Gynecol Pathol. 2014; 33(4):443-8 [PubMed] Related Publications
For the first time, we report a case of a primary high-grade serous carcinoma of the fallopian tube in a 69-yr-old woman with intraepithelial involvement of endocervical glands. The patient had a remote history of tubal ligation and no known personal or family history of breast or gynecologic cancer. She initially presented with an abnormal Pap smear, and, on a subsequent endometrial curettage, detached fragments of high-grade adenocarcinoma were identified. Upon hysterectomy and bilateral salpingoophorectomy, invasive high-grade serous carcinoma was found in the proximal stump of a ligated fallopian tube. Morphologically identical tumor extensively involved the endocervical glands. A single focus of malignant cells was also found at the surface of the lower uterine segment endometrium. By immunohistochemistry, the tumors in the fallopian tube and in the cervix showed the same immunopheonotype. This included diffuse staining for WT-1, PAX-8, p16, and p53, and focal staining for the monoclonal carcinoembryonic antigen. The estrogen receptor was negative. Human papillomavirus-in situ hybridization was also negative. The focus of intramucosal tumor within the endometrium was similarly positive for WT-1 and p53 and negative for the estrogen receptor. The patient was subsequently treated with 6 cycles of carboplatinum and taxol. She remains well with no evidence of recurrent disease. The phenomenon of intramucosal tumor spread to the cervix mimicking primary invasive or in situ cervical adenocarcinoma may present a diagnostic challenge for the pathologist, requiring consideration of an appropriately wide differential diagnosis when interpreting cervical cytology and endocervical and endometrial biopsies.

Rutgers JK, Lawrence WD
A small organ takes center stage: selected topics in fallopian tube pathology.
Int J Gynecol Pathol. 2014; 33(4):385-92 [PubMed] Related Publications
In this paper we consider a number of non-neoplastic and neoplastic lesions of the fallopian tube. Emphasis has been placed on diagnostically difficult entities, some of which result in misdiagnosis and consequent alteration of treatment, including "pseudocarcinomas" that represent a florid epithelial response to acute and/or chronic salpingitis. Endometriosis-related lesions may cause infertility, or undergo malignant transformation to a Mullerian carcinoma, most frequently endometrioid and clear cell types. Pregnancy-related tubal lesions include the easily misdiagnosed metaplastic papillary tumor as well as several manifestations of ectopic pregnancy. Covered briefly are familial conditions such as the Peutz-Jeghers syndrome and its association with tubal mucinous metaplasia, clear cell papillary cystadenoma associated with von Hippel-Lindau syndrome, and the Li Fraumeni syndrome's germline p53 mutation and its association with distal tubal p53 signatures. Miscellaneous tumors discussed include the common adenomatoid tumor and the uncommon female adnexal tumor of probable Wolffian origin. Important issues including the updated staging of fallopian tube carcinomas, and the histopathologic variants of endometrioid carcinomas and their sometimes unusual patterns that engender the potential for confusion with other tumors are briefly noted. The final section covers the relatively recent and novel concept of the fallopian tube as the predominant site of origin of ovarian and peritoneal carcinomas. Discussed are the histologic, immunohistochemical, and molecular biologic evidence that support the tubal fimbria as the site of serous tubal intraepithelial carcinoma, possibly the immediate precursor to high-grade ovarian and peritoneal serous carcinoma.

Rabban JT, Garg K, Crawford B, et al.
Early detection of high-grade tubal serous carcinoma in women at low risk for hereditary breast and ovarian cancer syndrome by systematic examination of fallopian tubes incidentally removed during benign surgery.
Am J Surg Pathol. 2014; 38(6):729-42 [PubMed] Related Publications
Early detection of sporadic pelvic serous carcinoma remains an elusive goal. In women at high risk for hereditary breast and ovarian cancer syndrome who undergo prophylactic salpingectomy, systematic pathologic examination of the fallopian tubes will detect occult tubal cancer, mostly in the fimbriae, of a minority of women. Such tubal cancers are the putative precursor to advanced-stage pelvic cancer. We hypothesized that early tubal cancer detection can also be accomplished in women at low risk using a similar approach. In this study, we performed complete and systematic examination of the fallopian tubes removed during surgery performed for benign indications. Among 522 women, 4 cases of serous tubal intraepithelial carcinoma (STIC) were identified. Three of these cases would have gone undetected using the current standard of care of sampling only a single random section of the tube. The fourth case was accompanied by occult ovarian carcinoma. The fimbriae contained STIC in 3 of the 4 cases and atypical mucosa in 1 case in which the STIC was in the nonfimbriated portion of the tube. The morphologic and immunohistochemical features (aberrant p53 and MIB-1) of these STICs were similar to those expected in high-risk women. All 4 patients with STIC underwent BRCA1 and BRCA2 gene testing; no germline mutations were identified in any patient. An additional 11 specimens contained atypical mucosal proliferations that fell short of morphologic and immunohistochemical criteria for STIC. Two of these 11 fulfilled criteria for a serous tubal intraepithelial lesion, and the remaining atypical proliferations exhibited normal p53 and MIB-1. For most specimens, the fimbriae could be completely submitted in 1 or 2 cassettes per tube. These results demonstrate that systematic examination of the tubal fimbriae can serve as a form of early detection of sporadic tubal cancer without incurring significant labor or cost. We propose that the tubal fimbriae should be completely examined in all patients undergoing benign surgery even if there are no clinical features to suggest risk for hereditary breast and ovarian cancer syndrome.

Kietpeerakool C, Srisomboon J, Phongsaranantakul S, et al.
Survival and prognostic factors of patients with primary fallopian tube cancer receiving adjuvant paclitaxel and carboplatin chemotherapy.
J Obstet Gynaecol Res. 2014; 40(3):806-11 [PubMed] Related Publications
AIM: To determine the survival and prognostic factors of patients with primary fallopian tube cancer (PFTC) who had been treated with paclitaxel and carboplatin chemotherapy.
METHODS: The records of patients with PFTC who had been treated between 2002 and 2010, identified through the report of Chiang Mai University Hospital, were reviewed. All patients had pathological materials initially reported or reviewed by a gynecologic pathologist before initiation of treatment.
RESULTS: Thirty patients met the inclusion criteria. Median age was 51 years. Serous adenocarcinoma was observed in the majority of patients (76.7%). Approximately 46% of patients were in stage I–II. The 5-year progression-free survival (PFS) for all patients was 37.2%. The 5-year PFS was 75.0% for stage I, 51.4% for stage II and 18.5% for stage III. Median PFS of the entire cohort was 26.0 months with a 95% confidence interval (CI) of 18.7–33.3 months. This rate was 18.5 months (95% CI, 6.7–35.6) for stage III whereas it was not reached for patients of stage I–II. Serous histology and stage were noted to be significant independent predictors of PFS with an adjusted hazards ratio of 7.54 (95% CI, 1.34–42.4) and 6.19 (95% CI, 1.59–24.08), respectively.
CONCLUSION: The 5-year PFS of the whole cohort was 37.2% with a median survival of 26 months. International Federation of Gynecology and Obstetrics stage and histological subtype were a significant independent factor for predicting PFS.

Hunter SM, Ryland GL, Moss P, et al.
Genomic aberrations of BRCA1-mutated fallopian tube carcinomas.
Am J Pathol. 2014; 184(6):1871-6 [PubMed] Related Publications
Intraepithelial carcinomas of the fallopian tube are putative precursors to high-grade serous carcinomas of the ovary and peritoneum. Molecular characterization of these early precursors is limited but could be the key to identifying tumor biomarkers for early detection. This study presents a genome-wide copy number analysis of occult fallopian tube carcinomas identified through risk-reducing prophylactic oophorectomy from three women with germline BRCA1 mutations, demonstrating that extensive genomic aberrations are already established at this early stage. We found no indication of a difference in the level of genomic aberration observed in fallopian tube carcinomas compared with high-grade serous ovarian carcinomas. These findings suggest that spread to the peritoneal cavity may require no or very little further tumor evolution, which raises the question of what is the real window of opportunity to detect high-grade serous peritoneal carcinoma arising from the fallopian tube before it spreads. Nonetheless, the similarity of the genomic aberrations to those observed in high-grade serous ovarian carcinomas suggests that genetic biomarkers identified in late-stage disease may be relevant for early detection.

Coleman RL, Moon J, Sood AK, et al.
Randomised phase II study of docetaxel plus vandetanib versus docetaxel followed by vandetanib in patients with persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: SWOG S0904.
Eur J Cancer. 2014; 50(9):1638-48 [PubMed] Article available free on PMC after 01/09/2015 Related Publications
BACKGROUND: Vandetanib is an oral tyrosine kinase inhibitor of VEGFR-2/3, EGFR and RET, which has demonstrated clinical activity as a single agent and in combination with taxanes. We explored the efficacy, safety and toxicity of docetaxel and vandetanib in women with recurrent ovarian cancer (OC).
METHODS: Women with refractory or progressive OC were randomised 1:1 to docetaxel (75 mg/m(2), IV)+vandetanib (100mg daily, PO, D+V) or docetaxel (75 mg/m(2), D). Up to three additional cytotoxic regimens for recurrence and prior anti-angiogenic agents (as primary therapy) were allowed. The primary end-point was progression free survival (PFS). The study had 84% power to detect a PFS hazard ratio of 0.65, using a one-sided P of 0.1. This corresponds to an increase in median PFS from 3.6 months to 5.6 months. Patients progressing on D were allowed to receive single agent vandetanib (D → V).
RESULTS: 131 Patients were enrolled; two were excluded. 16% had received prior anti-angiogenic therapy. The median PFS estimates were 3.0 mos (D+V) versus 3.5 (D); HR: 0.99 (80% CI: 0.79-1.26). 61 Patients on D+V were assessable for toxicity; 20(33%) had treatment-related Grade (G) 4 events, primarily haematologic. Similarly, 17 (27%) of 64 patients receiving D had G4 events, primarily haematologic. 27 Evaluable patients crossed-over to V. 1/27(4%) experienced a G4 event. G3 diarrhoea was observed in 4% D → V patients. Median OS was 14 mos (D+V) versus 18 mos (D → V); HR(OS): 1.25 (80% CI: 0.93-1.68). Crossover vandetanib response was 4% (1/27 evaluable patients). High plasma IL-8 levels were associated with response to D+V.
CONCLUSIONS: Combination docetaxel+vandetanib did not prolong PFS relative to docetaxel alone in OC patients. No unexpected safety issues were identified.

Alvarez RD, Sill MW, Davidson SA, et al.
A phase II trial of intraperitoneal EGEN-001, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: a gynecologic oncology group study.
Gynecol Oncol. 2014; 133(3):433-8 [PubMed] Article available free on PMC after 01/09/2015 Related Publications
OBJECTIVE: The purpose of this phase II trial was to evaluate the toxicity and antitumor activity of EGEN-001 in platinum resistant recurrent ovarian cancer.
METHODS: Eligible patients had weekly IP infusion of EGEN-001 at a dose of 24mg/m(2). Toxicity and antitumor activity were evaluated using CTCAE and RESIST criteria, respectively. Co-primary endpoints were tumor response and survival without progression (PFS) for at least 6months. Survival without progression before going onto a subsequent therapy (EFS) for at least six months was also considered.
RESULTS: A total of 58 EGEN-001 cycles were administered to 20/22 enrolled patients (median 2cycles, range 1-9). The most frequently associated adverse events related specifically to EGEN-001 treatment were grade 1/2 fatigue, fever, chills, abdominal pain, nausea, vomiting, anemia, thrombocytopenia, and leukopenia. Three of 20 EGEN-001 treated patients evaluable for toxicity elected to withdraw from the study motivated in part by grade 1 treatment related toxicities. There were no patients with partial or complete response (0%; 90% CI 0-10.9%). Seven (35%) of 16 patients evaluable for response had stable disease, and 9 (45%) had progressive disease. Six (30%) patients had a PFS of greater than six months, although three had gone off study and onto other therapies before six months. The estimated six-month EFS was 15%. The median PFS and OS were 2.89 and 9.17months, respectively.
CONCLUSION: EGEN-001 at the dose and schedule evaluated was associated with some but limited activity and was seemingly less tolerated in platinum resistant recurrent ovarian cancer patients.

Nanaiah SP, Rathod PS, Rajkumar NN, et al.
Primary carcinoma of the fallopian tube: a review of a single institution experience of 8 cases.
ScientificWorldJournal. 2014; 2014:630731 [PubMed] Article available free on PMC after 01/09/2015 Related Publications
AIMS AND OBJECTIVES: To evaluate the clinicopathologic features, response to cytoreductive surgery and adjuvant platinum-based chemotherapy with or without paclitaxel.
MATERIALS AND METHODS: A retrospective observational study of 8 women with a histopathologic diagnosis of primary fallopian tube carcinoma (PFTC) from January 2000 to February 2013.
RESULTS: 4/8 (50%) of the women were in the early stage and an intraoperative frozen section was 100% effective in identifying fallopian tube carcinoma and then a staging laparotomy was performed. All 4/8 cases in the early stage had received and responded to single agent carboplatin and all are alive without clinical, radiological, or biochemical evidence of recurrence at the end of 2 years and the longest survivor has completed 13 years. Primary optimal cytoreductive surgery was achievable in 3/4 (75%) in advanced disease. All showed response to adjuvant paclitaxel and carboplatin (T+C), but all had succumbed to the disease following recurrence with mean progression-free survival of 19 months (range 15-21 months) and mean overall survival of 27 months (range 22-36 months).
CONCLUSION: The pivotal role played by a frozen section in diagnosing PFTC which is rare needs to be reemphasized, therefore justifying a primary staging laparotomy in an early stage. Prolonged survival observed in this group following an optimum tailored adjuvant single agent carboplatin is worth noting.

Staff S, Tolonen T, Laasanen SL, et al.
Quantitative analysis of γ-H2AX and p53 nuclear expression levels in ovarian and fallopian tube epithelium from risk-reducing salpingo-oophorectomies in BRCA1 and BRCA2 mutation carriers.
Int J Gynecol Pathol. 2014; 33(3):309-16 [PubMed] Related Publications
Mutations in BRCA1 and BRCA2 genes confer an increased lifetime risk for breast and ovarian cancer. Increased lifetime ovarian cancer risk among BRCA1/BRCA2 mutation carriers can be substantially decreased by risk-reducing salpingo-oophorectomy (RRSO), which also provides material for molecular research on early pathogenesis of serous ovarian cancer. RRSO studies have suggested fallopian tube as a primary site of serous high-grade ovarian cancer. In this study, the nuclear expression levels of γ-H2AX and p53 using immunohistochemical (IHC) study was quantitatively assessed in ovarian and fallopian tube epithelium derived from RRSOs in 29 BRCA1 and BRCA2 mutation carriers and in 1 patient with a strong family history of breast and ovarian cancer but showing an unknown BRCA status. Both p53 and γ-H2AX nuclear staining levels were significantly higher in BRCA1/2 mutation-positive fallopian tube epithelium compared with the control fallopian tube epithelium (P<0.006 and P=0.011, respectively). Nuclear expression levels of p53 and γ-H2AX were similar between the BRCA1/2 mutation-positive ovarian epithelium and controls. Both γ-H2AX and p53 showed significantly higher nuclear expression levels in BRCA1/2 mutation-positive fallopian tube epithelium compared with BRCA1/2 mutation-positive ovarian epithelium (P<0.0001 and P<0.0001, respectively). BRCA1/2 mutation-positive fallopian tube epithelium showed a positive correlation between the γ-H2AX and p53 nuclear expression levels (Pearson r=0.508, P=0.003). Our results of quantitative nuclear p53 and γ-H2AX expression levels in ovarian and fallopian tube epithelium derived from RRSO in high-risk patients support the previously suggested role of fallopian tube epithelium serving as a possible site of initial serous ovarian carcinogenesis.

Schwandt A, von Gruenigen VE, Wenham RM, et al.
Randomized phase II trial of sorafenib alone or in combination with carboplatin/paclitaxel in women with recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer.
Invest New Drugs. 2014; 32(4):729-38 [PubMed] Related Publications
BACKGROUND/PURPOSE: This study was designed to evaluate the response and toxicity of sorafenib alone or when combined with carboplatin and paclitaxel in patients with platinum-sensitive, recurrent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (EOC).
METHODS: Patients with recurrent platinum-sensitive EOC with no more than 2 prior courses of chemotherapy were randomized to single-agent sorafenib 400 mg twice daily or combination sorafenib 400 mg bid (days 2-19) with IV carboplatin (AUC 6) and IV paclitaxel 175 mg/m(2) (S+C/T) every 3 weeks. Single agent sorafenib could cross over to combination upon progression.
RESULTS: Patients were initially randomized to either arm, however, due to poor accrual, sorafenib arm was prematurely closed. A total of 13 patients were evaluable for response to sorafenib and 23 patients were evaluable for response to S+C/T. Objective response rate (RR) was 15 % for patients on sorafenib vs. 61 % for patients on S+C/T (p = 0.014); stable disease was seen in 62 % and 35 %, respectively. Clinical benefit rate (CBR) at 4 months (mos.) was 69 % for S and 65 % for S+C/T. The median progression free survival was 5.6 months on sorafenib vs. 16.8 months on S+C/T (p = 0.012) and there was no significant difference of overall survival between two arms (p = 0.974) with median overall survival 25.6 months under sorafenib vs. 25.9 months on S+C/T. Patients remained on trial for a median of 7.8 cycles on sorafenib and 5.4 cycles on S+C/T.
CONCLUSION: Sorafenib, alone or in combination with carboplatin and paclitaxel, has activity in patients with platinum-sensitive EOC. Sorafenib in combination with carboplatin and paclitaxel improved RR and PFS; however, there were increased grade and frequencies of toxicities.

Suprasert P, Manopunya M, Cheewakriangkrai C
Outcomes with single agent LIPO-DOX in platinum-resistant ovarian and fallopian tube cancers and primary peritoneal adenocarcinoma - Chiang Mai University Hospital experience.
Asian Pac J Cancer Prev. 2014; 15(3):1145-8 [PubMed] Related Publications
BACKGROUND: Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 mg/m2 every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

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