Radiation-associated Angiosarcoma Mimicking Fallopian Tube High-grade Serous Carcinoma in a Woman With De Novo Li-Fraumeni Syndrome.

We present a case study of a woman with history of rectal adenocarcinoma, and a new diagnosis of radiation-associated angiosarcoma mimicking fallopian tube high-grade serous carcinoma who was subsequently found to have de novo Li-Fraumeni syndrome. Our objective is to highlight angiosarcoma as a potential pitfall in the diagnosis of high-grade serous carcinoma.

Long-Term Survival After Surgery and Radiotherapy for Recurrent or Persistent Ovarian and Tubal Cancer.

OBJECTIVE: This study examines the factors associated with long-term disease-specific survival (DSS) and complications after radiotherapy (RT) for recurrent or persistent ovarian and tubal cancer. METHODS/MATERIALS: Between 1980 and 2015, 65 women with ovarian (57), tubal (3), or co-existent ovarian/endometrial carcinoma (5) received RT (>45 Gy) with curative intent for recurrent (45) or persistent cancer (20) found at second-look surgery. Surgery to debulk (± restage) was integrated into the management of all but 7 cases. RESULTS: Twenty-two women had no evidence of disease at last contact after a median of 15.6 years (range = 1.0-35.8 years). Of the 53 patients treated more than 10 years ago, 18 (34%) are in this long-term no evidence of disease group. Univariate analysis showed that the following factors were significantly associated with longer DSS (P < 0.05): initial stage I, II (vs III, IV); endometrioid histology (vs serous and other); no or 1 previous chemotherapy (vs ≥2); no macroscopic tumor before RT (vs macroscopic); localized tumor encompassed by a limited-volume RT field (vs more widespread tumor), and chemotherapy and RT (vs RT only). Multivariate analysis showed that endometrioid (vs other histology HR = 4.37, P = 0.017) and localized tumor (vs more widespread tumor, HR = 2.43, P = 0.017) were significantly associated with longer DSS.After RT to the pelvis and/or abdomen, 13 (21.7%) of 60 patients developed G3 or 4 bowel complications requiring surgery. In 10, these occurred in the presence of tumor, RT changes, and adhesions, and in 3, there was no sign of cancer. Six patients (9.2%) developed a subsequent malignancy. CONCLUSIONS: We conclude that there is a role for the use of RT in selected cases of localized recurrent or persistent ovarian cancer and may confer long-term survival. Surgery is useful to debulk and define the extent of tumor to be irradiated but may confer an increased risk of severe bowel complications.

Implementation and early clinical results utilizing Cs-131 permanent interstitial implants for gynecologic malignancies.

OBJECTIVE: Permanent interstitial brachytherapy is an ideal yet underutilized treatment modality for accessible, small volume gynecological malignancies. We present early clinical results utilizing a new permanent isotope, Cs-131. METHODS: A retrospective review was performed evaluating patients treated with Cs-131 permanent interstitial radiation at our institution from July 2011 through June 2013. Doses were most commonly prescribed and calculated to a depth of 5mm using Paterson-Parker planar implant rules for Au-198. This activity was converted to air-kerma strength (U). A conversion factor of 1.1 was applied based on RBE calculations, clinical observation and experience. RESULTS: 14 patients were identified among whom 17 Cs-131 implants were performed. Seven patients were implanted as sole therapy, and a median dose of 50 Gy was delivered. Ten implants were performed as boost within a more extensive radiation treatment plan. In these patients, a median implant dose of 27.5 Gy was used and the median total dose delivered in combination was 78.25 Gy. After a median follow up of 12 months, the actuarial local control rate was 84.4%. A very low level of grade 1-3 reactions was observed with no fistula formations or other severe side effects. CONCLUSIONS: Permanent interstitial brachytherapy with Cs-131 was well tolerated with favorable early results compared to other series. Cs-131 has multiple favorable properties, including minimal radiation exposure to treating staff, and should be considered as a therapeutic option in appropriately selected patients. A methodology for dose prescription, calculation of radioactivity required and distribution of the isotope is also presented.

Primary extramammary Paget's disease of the vulva: the clinicopathological features and treatment outcomes in a series of 43 patients.

OBJECTIVE: To characterize the clinicopathological features and evaluate the treatment outcomes for cases of primary extramammary Paget's disease of the vulva (EMPDV). METHODS: The medical records and pathology slides were reviewed and analyzed for 43 patients with primary EMPDV. RESULTS: The mean age of the patients was 68.6 years (range, 52-85). Intraepithelial EMPDV, invasive EMPDV and EMPDV with adnexal adenocarcinoma were observed in 33 (76.7%), 7 (16.3%) and 3 (7.0%) cases, respectively. Varied surgical procedures were initially performed in 35 (81.4%) cases. A positive incision margin was observed in 16 cases (47.0%). Definitive radiotherapy at a median dose of 60 Gy was performed in 8 (18.6%) patients. Six patients received postoperative radiotherapy due to a positive margin or lymph node metastasis after surgical excision. During a follow-up period of 6-169 months (median, 54), recurrence was observed in 12 (34.3%) patients. Nine (75.0%) patients underwent repeated surgery and 3 (25.0%) patients received radiotherapy. Long-term overall survival was observed in patients with intraepithelial EMPDV. The median overall survival was 124.5 months in intraepithelial cases, 70.8 months in invasive cases and 21.3 months in cases with adnexal adenocarcinoma (log rank, P=0.032). CONCLUSIONS: Intraepithelial EMPDV accounted for the majority of primary cases and had a better prognosis. Surgical excision was the standard curative treatment for EMPDV. Radiotherapy was an alternative choice for patients with medical contradiction or surgical difficulties. Postoperative radiotherapy could be considered in cases with positive surgical margin or lymph node metastasis. Recurrence was common and repeated excision was often necessary.

Outcomes after multiple lines of chemotherapy for platinum-resistant epithelial cancers of the ovary, peritoneum, and fallopian tube.

BACKGROUND: Platinum-resistant and refractory cancers of the ovary, fallopian tube, and peritoneum have a poor prognosis, yet in some cases, they can respond to multiple lines of chemotherapy. Uncertainty remains over optimal drug choice and when therapeutic focus should be switched from active therapy to supportive care. METHODS: A retrospective case note review was performed on 274 women treated for platinum-resistant/refractory ovarian, fallopian tube, or peritoneal carcinoma at the Christie Hospital between 2004 and 2008. Baseline data at onset of platinum resistance and outcomes from subsequent lines of therapy were recorded. RESULTS: A total of 689 lines of therapy were administered with a median overall survival from initiation of first-line therapy for platinum-resistant disease of 61 weeks. Twenty-eight percent of women commenced cytotoxic therapy in the last 3 months of life. Treatment efficacy declined rapidly with successive lines of therapy particularly if disease progression occurred during first-line therapy. Factors independently associated with worse overall survival at recognition of platinum resistance were performance status, presence of stage IV disease, elevated cancer antigen 125, and platinum-refractory disease. CONCLUSIONS: A significant proportion of women who were treated received therapy within the last few months of life with little clinical benefit. Disease progression on 2 consecutive lines of therapy should be used as a guide to discontinue cytotoxic treatment. A subset of patients with poor prognosis at the onset of platinum resistance, who may have little gain from anticancer treatment, can be identified.

Adjuvant intensity modulated whole-abdominal radiation therapy for high-risk patients with ovarian cancer FIGO stage III: final results of a prospective phase 2 study.

BACKGROUND: To assess late toxicity, quality of life and oncological outcome after consolidative whole abdominal radiotherapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high risk patients with advanced ovarian cancer FIGO stage III using IMRT (Intensity modulated radiation therapy). METHODS: The OVAR-IMRT-02 study is a multi-center single-arm phase-II-trial. Twenty patients with optimally debulked ovarian cancer stage FIGO III with complete remission after chemotherapy were treated with intensity modulated WART. A total dose of 30 Gy in 20 fractions was applied to the entire peritoneal cavity. Primary endpoint was treatment tolerability; secondary objectives were acute and chronic toxicities, quality of life, rates of therapy disruption/abortion, progression-free survival (PFS) and overall survival (OS). RESULTS: All patients completed treatment and 10/20 patients (50%) reached the final study follow-up of 36 months. Late side effects consisted of °1-°2 lower limb edema (44.5%), with one patient (5.6%) showing °3 edema. Three patients (16.7%) showed elevated gamma-Glutamyltransferase. There were no severe late side effects regarding renal or hepatic function or any gastrointestinal toxicity greater than °2. During WART, mean global health status decreased by 18.1 points (95%-CI: 7.1-29.0), but completely normalized after 6 months. The same trend was observed for the function scale scores. Kaplan-Meier-estimated 1-, 2- and 3-year PFS was 74, 51 and 40%, respectively. 1-, 2- and 3-year OS was 89, 83 and 83%, respectively. CONCLUSIONS: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late toxicity and minor impact on long-term quality of life. Together with the promising results for PFS and OS, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov ( NCT01180504 ). Registered 12 August 2010 - retrospectively registered.

Primary fallopian tube carcinoma in a 51-year-old postmenopausal woman--case report.

The case of a 51-year-old woman with a primary carcinoma of the left fallopian tube is presented. Laparotomy performed for an ovarian tumour revealed that the patient had normal ovaries, but a left fallopian tube was dilated and filled with a tumour mass. Histopathological examination revealed primary adenosquamous cell carcinoma of the fallopian tube.

[Triple synchronous primary gynaecological tumours. A case report]. / Tumores triple sincrónicos ginecológicos. Reporte de un caso.

BACKGROUND: Synchronous multiple primary malignancies in the female genital tract are infrequent. From 50 to 70% of them corresponds to synchronous cancers of the endometrium and ovary. To our knowledge, this is only the third case report in the international literature of three concurrent gynaecological cancers of epithelial origin. A case is presented, as well as a literature review due to the infrequency of its diagnosis and the lack of information on the subject. CLINICAL CASE: A 49-year-old woman, with previous gynaecological history of ovarian endometriosis. She underwent a hysterectomy and bilateral oophorectomy, as she had been diagnosed with endometrial hyperplasia with atypia. The final histopathology reported synchronous ovarian, Fallopian tube, and endometrial cancer. An extension study and complete surgical staging was performed, both being negative. She received adjuvant treatment of chemotherapy and radiotherapy. She is currently free of disease. CONCLUSIONS: The aetiology is uncertain. There is controversy relating to increased susceptibility of synchronous neoplasms to pelvic endometriosis and inherited genetic syndromes. Its diagnosis needs to differentiate them from metastatic disease. Additionally, they are problematical from a clinical, diagnostic, therapeutic, and prognostic point of view. The presentation of more cases of triple synchronous cancers is necessary for a complete adjuvant and surgical treatment.

Phase I study of 90Y-labeled B72.3 intraperitoneal administration in patients with ovarian cancer: effect of dose and EDTA coadministration on pharmacokinetics and toxicity.

The tumor-associated glycoprotein 72 (TAG-72) antigen is present on a high percentage of tumor types including ovarian carcinomas. Antibody B72.3 is a murine monoclonal recognizing the surface domain of the TAG-72 antigen and has been widely used in human clinical trials. After our initial encouraging studies (M. G. Rosenblum et al., J. Natl. Cancer Inst., 83: 1629-1636, 1991) of tissue disposition, metabolism, and pharmacokinetics in 9 patients with ovarian cancer, we designed an escalating dose, multi-arm Phase I study of 90Y-labeled B72.3 i.p. administration. In the first arm of the study, patients (3 pts/dose level) received an i.p. infusion of either 2 or 10 mg of B72.3 labeled with either 1, 10, 15, or 25 mCi of 90Y. Pharmacokinetic studies demonstrated that concentrations of 90Y-labeled B72.3 persist in peritoneal fluid with half-lives >24 h after i.p. administration. In addition, 90Y-labeled B72.3 was absorbed rapidly into the plasma with peak levels achieved within 48 h, and levels declined slowly thereafter. Cumulative urinary excretion of the 90Y label was 10-20% of the administered dose which suggests significant whole-body retention of the radiolabel. Biopsy specimens of bone and marrow obtained at 72 h after administration demonstrated significant content of the label in bone (0.015% of the dose/g) with relatively little in marrow (0.005% of the dose/g). The maximal tolerated dose was determined to be 10 mCi because of hematological toxicity and platelet suppression. This typically occurred on the 29th day after administration and was thought to be a consequence of the irradiation of the marrow from the bony deposition of the radiolabel. In an effort to suppress the bone uptake of 90Y, patients were treated with a continuous i.v. infusion of EDTA (25 mg/kg/12 h x 6) infused immediately before i.p. administration of the radiolabeled antibody. Patients (3 pts/dose level) were treated with doses of 10, 15, 20, 25, 30, 35, 40, or 45 mCi of 90Y-labeled B72.3 for a total of 38 patients. EDTA administration resulted in significant myeloprotection, which allowed escalation to the maximal tolerated dose of 40 mCi. Dose-limiting toxicity was thrombocytopenia and neutropenia. Studies of plasma and peritoneal fluid pharmacokinetics demonstrate no changes compared with patients without EDTA pretreatment. Cumulative urinary excretion of the radiolabel was not increased in patients pretreated with EDTA compared with the untreated group. However, analysis of biopsy specimens of bone and marrow demonstrated that bone and marrow content of the 90Y label was 15-fold lower (<0.001% injected dose/g) than a companion group without EDTA. Four responses were noted in patients who received 15-30 mCi of 90Y-labeled B72.3 with response durations of 1-12 months. These results demonstrate the myeloprotective ability of EDTA, which allows safe i.p. administration of higher doses of 90Y-labeled B72.3 and, therefore, clearly warrant an expanded Phase II trial in patients with minimal residual disease after standard chemotherapy or for the palliation of refractory ascites.

A 15-year overview of management and prognosis in primary fallopian tube carcinoma. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

143 women treated in 28 departments from 1980 to 1995 were retrospectively analysed to study the impact of prognostic factors in primary carcinoma of the fallopian tube. The mean age of the patients was 62.5 years. Sixty (42%) tumours were FIGO stage I, 28 (20%) stage II, 38 (27%) stage III, 17 (12%) stage IV. Complete radical resection was achieved in 102 (71%) patients. In 122 (85%) women, surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperative therapy consisted of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all cases was 43%. The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV (P < 0.00001). FIGO stage, histological grade and presence of residual tumour had an independent prognostic impact in multivariate analysis. In order to investigate the role of p53 in primary fallopian tube carcinomas, we analysed the immunohistochemical expression of p53 protein regarding survival and FIGO stage in 63 patients (44%). No statistical significance was observed.

Fallopian tube carcinoma.

Twenty-one patients with fallopian tube carcinoma from Yale-New Haven Medical Center are reviewed. Most patients who died of disease did so in the first two years after diagnosis, even following complete resection, clearly indicating the need for adjuvant therapy. Negative second-look surgery did not provide assurance of permanent remission. There was a high recurrence rate with Stage I and completely resected Stage II and III disease (8 of 14 patients). Some recurrences occurred late, up to nine years after initial diagnosis. We recommend whole abdomino-pelvic radiation if no disease greater than 2 cm3 bulk exists after surgery. Chemotherapy may be an alternative to radiation as primary adjuvant treatment in early stage disease. Chemotherapy for unresectable disease or recurrent disease has shown palliation with occasional prolonged survival but no patient with recurrent disease survived longer than two years.

The relevance of adjuvant therapy in primary carcinoma of the fallopian tube, stages I and II: irradiation vs. chemotherapy.

INTRODUCTION: Primary carcinoma of the Fallopian tube (FTC) is a rare but extremely aggressive neoplasm. It must be expected to cause up to 40% of tumor-related deaths even in Stage I, and up to 57% in Stage II. Due to its rarity, there exist only a few and divergent reports on the value of adjuvant therapy. Therefore the present study aims at evaluating the influence of postoperative adjuvant therapy on FTC by studying the effects of irradiation and chemotherapy on the overall survival of patients in Stages I and II. PATIENTS AND METHODS: We investigated 95 cases of FTC in Stages I (n = 66) and II (n = 29) in a retrospective multicenter study. Group I (n = 32) are patients who underwent a complete irradiation with cobalt or photon energies of 23 MV (administering a daily dose of 2 Gy resulted in a total of 45-52 Gy in the pelvic areas). Group II (n = 31) consists of those cases who received postoperative chemotherapy with platinum. Thirty-two women were excluded from this study because they had other chemotherapies, incomplete irradiation, or no adjuvant therapy at all. RESULTS: Median survival time was 57 months in Group I patients (95% confidence interval 33-81 months), compared to 73 months (95% confidence interval, 68-78 months) in the chemotherapeutically treated Group II. This difference did not prove to be statistically significant (p = 0.476).If primary surgical therapy is included in the evaluation, and patients with total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) are compared to those with additional radical lymphadenectomy (TAH+BSO+lymph nodes), the latter group's overall survival essentially improves but fails to reach statistical significance. Their 5-year survival rate is 83% against 58% in the TAH+BSO group (p = 0.12). CONCLUSION: Chemotherapy and irradiation are two adjuvant therapies that are similarly effective in FTC of Stages I and II, with chemotherapy being preferred at the present time. Primary surgical treatment, however, is of crucial impact on the prognosis of FTC.

Fallopian tube cancer: the role of radiation therapy.

Thirty-four patients with fallopian tube cancer were evaluated at the Mayo Clinic between 1964 and 1985 and received radiation therapy postoperatively. Employing a system analogous to FIGO ovarian cancer staging, there were 9 patients with stage I disease, 13 with stage II, and 12 with stage III/IV. Residual disease was present in 15 patients and absent in 19. Nodal metastases were documented in 12 patients or 35% (10 at presentation, two at relapse), with para-aortic nodes most commonly involved (67%) and 7 of the 12 having disease otherwise limited to the pelvis at presentation. Fifteen of 34 (44%) patients survived disease-free until intercurrent death or to a median follow-up of 70 months. Seven patients were treated with palliative intent for massive disease, and 27 patients were treated with curative intent (21 radiation alone, six radiation plus chemotherapy). Of those treated with curative intent, 15 patients received pelvic irradiation (with or without para-aortic nodal irradiation), 10 received whole abdominal irradiation, and 2 received intraperitoneal radiophosphorus. In the potentially curative group, seven of nine (78%) patients with stage I disease, five of 12 (42%) with stage II, and 2 of 6 (33%) with stage III have remained disease-free. Among the 21 patients with stage I or II disease, only four of the 11 (36%) patients who received pelvic irradiation alone were disease-free, but four patients had an isolated upper abdominal failure. In contrast, eight of 10 (80%) patients receiving treatment to the entire abdomen (including two patients who received 32P) were disease-free.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma of the fallopian tube. Experience with 41 patients.

Forty-one cases of primary fallopian tube carcinoma treated at our institution over the years 1946 to 1976 are described. The overall 5-year survival rate was 34.4%, although patients with early tumors had a 72.7% survival rate. The single most important factor affecting survival appeared to be the extent of disease at the time of diagnosis. Past and present treatment modalities are discussed, and proposals for management of this disease are outlined.

Primary adenocarcinoma of the fallopian tube.

Nineteen women with a mean age of 62 were treated for primary adenocarcinoma of the fallopian tube from 1960 to 1980. Common presentations were bleeding or discharge, pelvic mass, and pain. Cervical cytology was positive in five of eleven cases; endometrial curettings revealed adenocarcinoma in three of nine cases. Staging was by a system analogous to the International Federation of Gynecology and Obstetrics (FIGO) classification of ovarian carcinoma: 11% stage I, 44% stage II, 28% stage III, and 17% stage IV. Bleeding and abnormal cervical cytology were associated with earlier stage lesions and better prognosis. The most common treatment was excision of the primary tumor and gross intraperitoneal metastases. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed in 14 cases. Thirteen patients received 40-50 Gray of 2 MeV external beam pelvic radiation. Stages I and II had five-year survival of 100% and 63%. However, 38% of stage II patients had late extrapelvic relapses, and two early stage patients suffered serious complications of radiation therapy. All stage III and IV patients died of disease, 63% within the first 3 years. Based upon these results and review of other modern series, the importance of early diagnosis and complete surgical staging is emphasized, and stage-specific adjuvant therapy recommended.

[Clinical and pathological aspects of primary carcinoma of the fallopian tube (author's transl)]. / Zur Klinik und Pathologie des primären Tubenkarzinoms.

A report is presented of 24 cases of primary carcinoma of the Fallopian tube, histologically confirmed between 1956 and 1971 at the laboratory of the 2nd Gynaecological Department, University of Vienna, Austria. All patients underwent surgery. Total hysterectomy and bilateral salpingo-ophorectomy was performed in 16 cases. All patients received radiotherapy after surgery. All patients in whom the carcinoma was not confined to the Fallopian tubes (stages II to IV) died within 5 years (average 2.6 years). Patients with stage I lesions survived longer than 5 years only in those cases with more highly differentiated carcinomas (grades I and II). Histological grading, therefore, seems to enable a more reliable prognosis of stage I carcinoma of the Fallopian tube.

Role of radiotherapy in the management of primary carcinoma of the fallopian tube.

Primary fallopian tube carcinoma is a rare neoplasm. It may be postulated that postoperative loco-regional radiotherapy is a valuable adjunctive in the overall management of the tubal carcinoma. However, we can't advocate the efficacy of this approach authentically due to a very small number of cases. A prospective controlled and randomized trial with larger patient number may yield some definite conclusions regarding it's optimal management.

[Carcinoma of the fallopian tube. Clinical analysis of 40 cases]. / Pierwotny rak jajowodu. Analiza kliniczna 40 przypadków.

The results of clinical analysis of 40 cases of primary carcinoma of the fallopian tube are presented. All patients were treated with surgery and post operative external beam irradiation. Overall 5 years survival was 37% and symptom free survival 21%. The influence of following prognostic factors on the results of treatment had been evaluated: clinical stage, histologic grading and depth of infiltration of fallopian tube wall. Only the depth of infiltration proved to be statistically significant negative prognostic factor. The main cause of treatment failure was the intraperitonal dissemination of the disease. The results of treatment of recurrences was only palliative. No long term survivors were noted.