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.

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.

[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.

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.

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.

Brain metastases from fallopian tube carcinoma responsive to intra-arterial carboplatin and intravenous etoposide: a case report.

Fallopian tube carcinoma is the least common neoplasm of the female genital tract. Although rare, neurological complications such as brain metastases can develop. It remains unclear, however, what role chemotherapy has in the treatment of these patients and what route of administration is most effective. Intra-arterial (IA) regional administration of chemotherapy may increase intra-tumoral drug concentrations and improve efficacy. We report the case of a 47-year-old woman who developed bilateral fallopian tube cancer and multifocal brain metastases. After progression through radiation therapy and oral chemotherapy, she was placed on IA carboplatin (200 mg/m2/d x 2 days every 4 weeks) and intravenous etoposide (100 mg/m2/d x 2 days every 4 weeks). During treatment she had objective tumor shrinkage that has remained stable for more than 12 months. For patients with fallopian tube carcinoma that develop brain metastases and respond poorly to surgery and/or irradiation, multi-agent chemotherapy containing carboplatin should be considered. The effectiveness of carboplatin may be improved if administered by the IA route.

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.

Treatment of fallopian tube cancer. Review of the literature.

OBJECTIVE: To contribute toward the understanding of the therapeutic management of fallopian tube cancer. METHODS: Recent studies related to the treatment of fallopian tube cancer were reviewed. RESULTS: Current evidence indicates that even patients in early stages have nodal disease, and often experience relapses in distant sites. In advanced stages, survival prolongation by the use of platinum-based chemotherapy has been demonstrated. Aggressive cytoreductive surgery followed by chemotherapy and negative second-look laparotomy offer the possibility of long-term survival. However, a significant fraction of patients eventually relapses after negative second-look laparotomy, and a poor survival rate after positive second-look laparotomy has been observed. CONCLUSIONS: This series suggests the need for thorough evaluation of lymph nodes at the time of surgery. The use of platinum-based chemotherapy is probably the best adjuvant therapy for both early stages and advanced stages. The clinical value of second-look laparotomy will remain limited until effective salvage therapy is developed. The potential benefits of neoadjuvant chemotherapy and the use of paclitaxel will be increasingly important.

[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.

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.

Whole abdominal external beam radiation in the treatment of primary carcinoma of the fallopian tube.

Thirty-two patients with adenocarcinoma of the fallopian tube, treated between 1975 and 1990, were studied. Thirteen patients had stage I disease, 9 stage II, and 10 stage III. All patients underwent bilateral salpingo-oophorectomy, total abdominal hysterectomy, and subcolic omentectomy. All patients received postoperative primary whole abdominal external beam radiotherapy. Seventeen patients (53.1%) of the treated group survived NED for at least 5 years. Survival was 76.9% for stage I, 55.6% for stage II, and 20% for stage III. In the Cox multivariate analysis, two variables were independently related to survival: stage of disease and size of residual disease after surgery. Postoperative teleradiotherapy was totally ineffective in gross residual (>2 cm in diameter) disease (0% 5-year NED survivors) and not effective enough in small residual disease (<2 cm in diameter) (33% 5-year NED survivors). Despite postoperative whole abdominal external beam radiotherapy, 3 patients with microscopic, 4 with small, and 4 with gross residual disease did fail within the peritoneal cavity.

Radiation myelopathy after chemotherapy and radiation therapy for fallopian tube carcinoma.

Radiation myelopathy is a severe consequence of radiation to the spinal cord which rarely occurs with standard doses of radiation. This entity commonly results in different degrees of sensory and motor deficits. Diagnosis of radiation myelopathy in women with gynecologic malignancies may increase with the concomitant use of chemotherapy and radiation therapy. This paper reports the effect of this combination therapy in a 60-year-old woman with fallopian tube carcinoma.

[Radiotherapy in tubal carcinomas]. / Strahlentherapie beim Tubenkarzinom.

PURPOSE: Cancer of the fallopian tube is one of the rarest gynecological malignancies. The treatment of choice for this tumor is not well defined because of its very low incidence. The preferred primary treatment is surgical resection consisting of abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy. The value and extent of adjuvant radiotherapy is unclear so far. This retrospective analysis shows the experience at our clinic, which will be discussed in comparison with the existing literature. PATIENTS AND METHODS: From 1967 to 1994, 9 patients were treated at the Clinic and Polyclinic for Radiotherapy--Radio-Oncology of the University of Münster with adjuvant radiotherapy following surgery for carcinoma of the fallopian tube. The staging according to FIGO yielded 2/9 stage I, 4/9 stage II and 3/9 stage III patients. In 5/9 patients the tumor could be resected completely. In 3/9 cases the pelvis alone, in 5/9 cases the pelvis and para-aortal region were irradiated with doses ranging from 45 Gy to 50 Gy. In 1/9 cases the target volume comprised the whole abdomen. The treatment results were acquired retrospectively by analysis of the patients' records and inquiries among their general practitioners. RESULTS: Median survival of our patients was 25 months, 6/9 developed recurrence after a median time of 10.5 months. All of these were localized in the abdominal cavity; 1 patient also developed liver metastases. All patients with recurrent tumor died from their disease within a median period of 9 months. Of the other 3/9 patients, 2/3 died after 6 and 36 months, and 1 patient is still alive after 42 months; all of them without any sign of recurrence. CONCLUSION: Adjuvant radiotherapy of carcinoma of the fallopian tube seems to be indicated with the exception of little invasive tumors of FIGO stage I. From our findings, the target volume should comprise the whole abdomen. A smaller treatment volume (pelvis alone or plus the para-aortal region) can only be of any use in a palliative situation or as a salvage therapy.

Evaluation of adjuvant therapy after surgery for primary carcinoma of the fallopian tube.

OBJECTIVE: To evaluate the impact of postoperative therapy (chemotherapy vs. irradiation) on overall survival. DESIGN: A nationwide retrospective analysis. SETTING: Hanusch-Krankenhaus, Department of Gynaecology, SUBJECTS: 115 patients with histologically proved primary carcinoma of the Fallopian tube: 49 received six treatment cycles of a cis-platinum regimen (group I), 24 patients were treated by full irradiation using 50 Gray minimum (group II). The two groups had a similar distribution of stage I and II; in the more advanced stages chemotherapy was the predominant method of treatment. RESULTS: The five-year survival rate was 53% for women receiving irradiation as against 27% for those given cis-platinum. If the analysis was restricted to those patients with comparable stage I and stage II lesions, the p-value (0.07) was of borderline significance. There was no advantage in adding abdominal to pelvic irradiation (P = 0.62). CONCLUSIONS: Stage I and stage II carcinoma is probably better treated postoperatively by radiotherapy than chemotherapy. Chemotherapy may have more therapeutic potential in patients with more advanced lesions.