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Objective: Poly (ADP-ribose) polymerase inhibitors (PARPi) have become a new standard of care for the maintenance treatment of advanced epithelial ovarian cancer. This study aims to evaluate the efficacy and safety of combining stereotactic body radiotherapy with PARPi continuation as a strategy to treat ovarian cancer oligoprogression on PARPi., Methods: This is a multicenter retrospective study including ovarian cancer patients treated with stereotactic body radiotherapy and PARPi continuation for oligoprogression under PARPi maintenance therapy between June 2012 and May 2023 in three Italian centers. PARPi treatment was continued until further disease progression or unacceptable toxicity. The primary endpoint was the next-line systemic therapy-free interval. The Kaplan-Meier method was used to assess local control, progression-free survival, and overall survival. Univariate and multivariate Cox regression analyses were performed to evaluate potential clinical outcomes predictors., Results: 46 patients were included, with a total of 89 lesions treated over 63 radiotherapy treatments. Lymph nodes were the most frequently treated lesions (80, 89.9%), followed by visceral lesions (8, 9%) and one case with a bone lesion (1.1%). Median follow-up was 25.9 months (range 2.8-122). The median next-line systemic therapy-free interval was 12.4 months (95% CI 8.3 to 19.5). A number of prior chemotherapy lines greater than five was significantly associated with a reduced next-line systemic therapy-free interval (HR 3.21, 95% CI 1.11 to 9.32, p=0.032). At the time of analysis, 32 (69.6%) patients started a new systemic therapy regimen, while 14 (30.4%) remained on the PARPi regimen. The 2-year progression-free survival, local failure-free survival, and overall survival rates were 10.7%, 78.1%, and 76.5%, respectively. Four patients (8.7%) experienced acute toxicity with G1 gastrointestinal events., Conclusion: Stereotactic body radiotherapy combined with PARPi continuation may be an effective and safe strategy for managing ovarian cancer patients with oligoprogression on PARPi maintenance therapy. Prospective research is warranted to shed more light on this approach., Competing Interests: Competing interests: BAJ-F has received speakers fees from Roche, Bayer, Janssen, Carl Zeiss, Ipsen, Accuray, Astellas, Elekta, and IBA Astra Zeneca, all outside the current project., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Stereotactic body radiotherapy (SBRT) has shown promising results in the clinical setting of oligometastatic, persistent, or recurrent disease in several malignancies including ovarian cancer., Primary Objective: The MITO-RT3/RAD trial is a prospective, multicenter phase II study aimed at identifying potential predictors of response and clinical outcome after SBRT treatment., Study Hypothesis: Radiotherapy delivered by pre-defined SBRT treatment schedules and shared constraints could improve the rate of complete response., Trial Design: All patients accrued will be treated with a radiotherapy dose in the range of 30-50 Gy by 1, 3, or 5 SBRT daily fractions to all sites of active metastatic disease according to diagnostic imaging. Schedules of treatment and dose prescription have been established before considering target sites and healthy organ dose constraints. Follow-up and monitoring of side effects will be carried out every 3 months for the first year with imaging and clinical evalutation, and every 4 months within the second year; thereafter, surveillance will be carried out every 6 months. The best response on a per lesion basis will be evaluated by computed tomographic (CT) scan, positron emission tomography/CT, or magnetic resonance imaging in case of brain lesions, every 3 months., Major Inclusion/exclusion Criteria: The study includes patients with oligometastatic, persistent, or recurrent ovarian cancer for which salvage surgery or other local therapies are not feasible due to any relative contra-indication to further systemic therapy because of serious co-morbidities, previous severe toxicity, unavailability of potentially active systemic therapy, or patient refusal., Primary Endpoint: The primary endpoint of the study is the clinical complete response rate to SBRT by imaging on a per lesion basis., Sample Size: Approximately 205 lesions will be treated (90 lymph nodes and 115 parenchyma lesions)., Estimated Dates for Completing Accrual and Presenting Results: Fifty-two centers have expressed their intention to participate. Enrollment should be completed by March 2023 and analysis will be completed in September 2023., Trial Registration: NCT04593381., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Data supporting stereotactic body radiotherapy for oligometastatic patients are increasing; however, the outcomes for gynecological cancer patients have yet to be fully explored. Our aim is to analyze the clinical outcomes of stereotactic body radiotherapy in the treatment of patients with recurrent or oligometastatic ovarian cancer or cervical cancer., Methods: The clinical data of 29 patients (35 lesions) with oligometastatic cervical cancer (21 patients, 72%) and ovarian carcinoma (8 patients, 28%) who were treated with stereotactic body radiotherapy for metastatic sites were retrospectively evaluated. All patients had <5 metastases at diagnosis or during progression, and were treated with stereotactic body radiotherapy for oligometastatic disease. Patients with ≥5 metastases or with brain metastases and those who underwent re-irradiation for primary site were excluded. Age, progression time, mean biologically effective dose, and treatment response were compared for overall survival and progression-free survival., Results: A total of 29 patients were included in the study. De novo oligometastatic disease was observed in 7 patients (24%), and 22 patients (76%) had oligoprogression. The median follow-up was 15.3 months (range 1.9-95.2). The 1 and 2 year overall survival rates were 85% and 62%, respectively, and the 1 and 2 year progression-free survival rates were 27% and 18%, respectively. The 1 and 2 year local control rates for all patients were 84% and 84%, respectively. All disease progressions were observed at a median time of 7.7 months (range 1.0-16.0) after the completion of stereotactic body radiotherapy. Patients with a complete response after stereotactic body radiotherapy for oligometastasis had a significantly higher 2 year overall survival and progression-free survival compared with their counterparts. In multivariate analysis, early progression (≤12 months) and complete response after stereotactic body radiotherapy for oligometastasis were the significant prognostic factors for improved overall survival. However, no significant factor was found for progression-free survival in the multivariable analysis. No patients experienced grade 3 or higher acute or late toxicities., Conclusions: Patients with early detection of oligometastasis (≤12 months) and with complete response observed at the stereotactic body radiotherapy site had a better survival compared with their counterparts. Stereotactic body radiotherapy at the oligometastatic site resulted in excellent local control rates with minimal toxicity, and can potentially contribute to long-term survival., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Ovarian cancer relapses have been traditionally classified according to the platinum-free interval, leading to an arbitrary categorization of possible scenarios and treatment options. Its relevance in assessing treatment strategies has been revised in the last several years, as the panorama is constantly changing in the era of personalized medicine and targeted therapies. Factors to be considered while defining the best management of recurrent disease, and, consequently, the available treatment alternatives are increasing. Platinum remains one of the milestones of ovarian cancer treatment, but for some patients it might not be an ideal choice for several reasons other than limited platinum sensitivity. This review aims to analyze the scenarios in which platinum is not considered suitable in the management of patients with recurrent ovarian cancer, and the currently available alternatives., Competing Interests: Competing interests: AB and GM report personal fees and non-financial support from Tesaro, AstraZeneca, Pharmamar and Roche, outside the submitted work; LB reports personal fees and non-financial support from Tesaro, AstraZeneca, and Pharmamar outside the submitted work., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The most appropriate treatments for brain metastases from ovarian cancer have not been established mainly because of its rarity. The objective of this study was to describe clinical results of treatment and prognostic factors of patients with brain metastases from ovarian cancer treated at a single institution., Materials and Methods: We retrieved information from the electronic medical records of 56 consecutive patients (2.8%) with brain metastases, from a total of 2008 patients with ovarian cancer. Endpoints were the pattern of treatment failure, progression-free survival, and overall survival (OS)., Results: Radiation was the most common initial treatment for brain metastases (59%), followed by surgery (23%). The median progression-free survival was 9.8 months. Radiological progression was confirmed in 20 patients: 7 had leptomeningeal carcinomatosis (37%), 8 had local recurrence, and 5 had distant recurrence. Median OS was 11.25 months, and the 1-year OS rate was 48.2%. Patients received surgery for single metastasis as initial treatment showed median OS of 24.1 months, which was significantly prolonged compared with the other patients (P = 0.0002). Of the 48 patients who died, 29 (60%) died of systemic disease and 7 (15%) died of central nervous system progression. Karnofsky Performance Status greater than or equal to 70, control of systemic cancer, serous histology, and surgery for brain metastases were associated with improved OS in multivariable analysis (P < 0.05)., Conclusions: Surgical resection for single or symptomatic brain metastases from ovarian cancer prolonged OS significantly. Multimodality treatment, including control of systemic cancer, appeared to be an important factor in prolonging OS.

Objective: Stereotactic body radiation therapy (SBRT) has been successfully used to treat oligometastases of several primary tumors, but few experiences have been described in patients with gynecological oligometastatic cancer, particularly in ovarian neoplasm. The aim of this study was to evaluate the role of this new radiotherapy modality in a series of oligometastatic ovarian cancer patients., Materials and Methods: Clinical records of patients affected by oligometastatic ovarian carcinoma treated with SBRT were reviewed., Results: Twenty-six patients with 44 metastatic lesions (lymph nodes, 63.6%; liver, 31.8%; and lung, 4.5%) treated with SBRT between January 2011 and May 2017 were analyzed. After a median follow-up period of 28.5 months (range, 6-86 months), 17 patients (65.4%) were still alive at time of analysis: 6 are without evidence of disease, 11 experienced a disease progression. Eight patients died of disease, 1 died because of an heart attack while being disease free. The median local control (LC) was not reached. One-, 2-, and 5-year LCs were 92.9%. Median progression-free survival was 19 months, with 1-year progression-free survival of 69.3% and 38% at 2 years, 19% at 5 years. Median overall survival was 64.5 months, with all patients alive after 1 year, 92.7% at 2 years, and 61.7% at 5 years. Five (11.3%) cases experienced G2 toxicity; most common adverse effect was nausea and vomiting (3 cases [6.8%]) followed by abdominal pain (2 cases [4.5%]). None of the patients had grade 3 or grade 4 acute or late toxicity., Conclusions: In conclusion, SBRT is a feasible and safe approach for selected cases of oligometastatic ovarian cancer, with satisfactory results in terms of LC and disease free survival.

Objective: This study aimed to report response rates and predictors of response to palliative radiotherapy (RT) for recurrent ovarian cancer., Methods/materials: Database review identified 64 patients with symptomatic ovarian cancer recurrence who received a total of 76 courses of RT for 103 indications from March 2003 to August 2014. Radiotherapy indications were pain (44%), bleeding (32%), obstruction (15%), and other (9%). Responses were categorized as complete, partial, or none; all response (AR) was the sum of complete and partial responses. Response rates were compared using a χ test. Multivariate analysis was performed using logistic regression. Patients were followed up for symptom recurrence and death., Results: Response rates were significantly higher for pain (AR, 87%) and bleeding (93%) than for obstruction (62%) and other (60%; P < 0.01). Patients treated for pain at nonbony sites had higher response rates (AR 96%) compared with those treated at bony sites (75%; P = 0.04). Patients with clear cell histology had the lowest response rates (AR, 60%) compared with those with serous (82%), endometrioid (95%), or other Müllerian histology (85%; P = 0.01). Platinum status at diagnosis or the time of RT was not associated with response, nor was tumor size or number of prior chemotherapy regimens. On multivariate analysis, histology, RT indication, and RT dose were independent predictors of response (all P < 0.01)., Conclusions: Palliative RT provides relief of pain and bleeding in most patients with ovarian cancer recurrence. Patients with symptomatic obstruction, bony involvement, and clear cell histology may experience lower clinical response rates.

Objective: Our aim was to evaluate the population-based outcomes of stages I and II invasive ovarian mucinous carcinomas (MCs) treated with adjuvant platinum-based chemotherapy and abdominopelvic radiotherapy (XRT)., Methods: International Federation of Gynecology and Obstetrics stage I/II MC cases referred to the British Columbia Cancer Agency between 1984 and 2014 were reviewed. Chemotherapy (minimum of 3 cycles) and XRT were the institutional policy for stages IA/B (grade 2/3) and IC/II (any grade). Physician patterns of practice determined XRT use in eligible patients, allowing for the comparison of outcomes based on receipt of XRT treatment on disease-free survival (DFS) and overall survival (OS)., Results: We identified 129 patients. Univariate analyses on substages IA, IC no rupture, IC with intraoperative rupture, and IC with preoperative rupture demonstrated 10-year DFS rates of 67%, 67%, 67%, and 27% (P = 0.004), respectively, and OS rates of 72%, 72%, 67%, and 38% (P = 0.01), respectively. For all patients, adjuvant XRT demonstrated improved 10-year DFS (78% vs 36%, P = 0.05) and OS (83% vs 36%, P = 0.02). Subgroup analysis did not detect a benefit of adjuvant therapy for stage IA grade 1/2. Multivariate analysis confirmed the benefit of XRT on DFS (hazard ratio, 0.14; 95% confidence interval, 0.02-0.98; P = 0.047) and a trend to improved OS (hazard ratio, 0.12; 95% confidence interval, 0.009-1.64; P = 0.11), whereas decision tree analysis demonstrated a reduced rate of relapse (33% vs 77%) and death (20% vs 46%) with the use of XRT, exclusive of patients with preoperative rupture., Conclusions: This population-based retrospective study is the first to demonstrate that the use of adjuvant abdominopelvic XRT after chemotherapy can improve survival in patients diagnosed as having stage I/II MC. Patients with stage IA grade 1 and grade 2 MC can have adjuvant therapy omitted.

Objective: The aim of this review was to present the current radiation therapy status in recurrent ovarian cancer (OC) and explore potential solution to improve clinical outcomes in this setting of patients., Materials and Methods: PubMed search was performed. An attempt was made to include all relevant studies. Pertinent references cited in selected articles were also considered., Results: The role of radiation therapy in recurrent OC needs to be defined. This is the largest reported analysis of published data., Conclusions: Chemotherapy is the mainstay of recurrent OC treatment but prognosis remains very poor, and novel therapies are required to be integrated into this consolidated treatment regimen. Radiation therapy represents a valid alternative approach, even if no clear guidelines are available concerning it.

Objective: Given the relative chemo-resistant nature of clear-cell gynecologic cancers, we investigated the utility of radiation therapy (RT) to treat recurrent clear-cell carcinoma (CCC) of the ovary., Methods: A retrospective chart review of patients with recurrent CCC managed from 1994-2012 was conducted at 2 academic medical centers. Demographic and clinicopathologic factors were abstracted and evaluated using Pearson χ or t tests, Kaplan-Meier and Cox regression analyses., Results: Fifty-three patients had recurrent CCC, and 24 (45.3%) of these patients received RT. There were no significant differences in age, stage, optimal cytoreduction, platinum response, or the percentage of patients that received more than 3 regimens of chemotherapy between the 2 groups. Patients who received RT for recurrent CCC were more likely to have had a focal recurrence (62.5% vs 10.3%, P ≤ 0.001) and to have undergone secondary cytoreduction (70.8% vs 10.3%, P ≤ 0.001). Of patients who received RT, 73.9% underwent surgery with or before their treatment. Five-year survival after recurrence was significantly higher in the group that received RT, 62.9% versus 18.8% (P = 0.002). In a multivariate analysis, platinum-sensitive disease and RT were associated with improved survival from recurrence, (hazard ratio, 0.26; 95% confidence interval, 0.08-0.81; P = 0.02 and hazard ratio, 0.28; 95% confidence interval, 0.09-0.90, P = 0.03, respectively)., Conclusions: In this cohort of patients with recurrent CCC, platinum-sensitive disease and RT are associated with improved survival. However, it is important to note that the majority of these patients underwent surgery along with RT, and it may be that the benefit of RT is limited to those who undergo secondary cytoreduction.

Objectives: This study aimed to report on long-term effectiveness of involved field radiation therapy (IFRT) in the salvage of localized recurrent ovarian cancer (ROC)., Methods: A retrospective analysis of 27 patients with a diagnosis of epithelial ovarian cancer who received tumor volume-directed IFRT for localized extraperitoneal recurrences (either as consolidation after cytoreductive surgery (CRS) or as attempted salvage if unresectable) forms the basis of this report. All patients were heavily pretreated with multiple chemotherapy regimens. Involved field radiation therapy was primarily with external beam (median dose, 50.4 Gy). Local recurrence-free survival (LRFS) was defined as freedom from in-field recurrences and was considered as a measure of effectiveness of radiotherapy. Statistical analyses evaluated association between disease-free survival, overall survival, LRFS, and various prognostic factors. Comparison was also made with a similar but unmatched cohort with localized recurrences salvaged by additional chemotherapy instead of local therapies (NIFRT group)., Results: Of 27 patients, 17 had optimal CRS before RT. The actuarial survival at 5 and 10 years (in parenthesis) from date of radiation were LRFS (70% and 60%), overall survival (30% and 19%), and disease-free survival (33% and 20%). None of the NIFRT patients survived beyond 5 years from initiation of salvage chemotherapy., Conclusions: Long-term follow-up in this selected series confirmed the benefit of IFRT (±CRS) in localized ROC. Chemotherapy salvage in a similar NIFRT group was not equivalent, suggesting a role for locoregional therapies in selected patients with ROC.

Objective: The aim of this study was to evaluate the effectiveness and safety of percutaneous interstitial implantation with (125)I seed under computed tomographic (CT) guidance for recurrent ovarian cancer (ROC)., Materials and Methods: A retrospective review was performed on 17 patients with ROC who were treated with (125)I seed brachytherapy. Treatment planning system was used preoperatively to determine the estimated seeds number and distribution; (125)I seeds were implanted into recurrent lesions under CT guidance. Therapeutic effectiveness and complications were noted during follow-up time., Results: Months are counted from the time of (125)I seed brachytherapy, and the median duration of follow-up was 10.5 months (3-23 months). The objective response rates after 1, 3, 6, 12, and 18 months were 76.5%, 75.0%, 61.5%, 42.9%, and 40%, respectively. The pain relief rate was 61.5%, and the general living quality was improved dramatically. The median progression-free survival time was 5.4 months, the median overall survival time was 11.3 months, and the 1-year survival rate was 41.2%. Complications in this study were very mild; severe adverse events such as massive bleeding, intestinal fistula, and treatment-related deaths did not occur., Conclusions: Our initial experience showed that CT-guided (125)I seed interstitial implantation is safe and feasible in the treatment of patients with ROCs after multiple therapies.

Objective: Radiotherapy is associated with short-term and long-term morbidity. This study compared toxicity rates among patients with endometrial carcinoma (EC) treated with adjuvant external beam radiation therapy (EBRT) on a small pelvic field (SmPF) in comparison with a standard pelvic field (StPF) or an extended field (EF)., Methods: Patients with EC preoperatively diagnosed with high-grade histological disease (grade 3 endometrioid, papillary serous, clear cell, and mixed tumor type) or cervical involvement were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy in the University Medical Center Groningen between 1999 and 2008. Patients who received adjuvant EBRT were included in this study. External beam radiation therapy on SmPF (includes only the central pelvis and proximal vagina) was applied in case of negative lymph nodes after adequate lymphadenectomy (≥10 lymph nodes removed at the bilateral obturator and external iliac nodal stations). In case of positive pelvic lymph nodes or inadequate lymphadenectomy, EBRT on StPF was given. External beam radiation therapy on EF was applied in case of common iliac and/or para-aortic lymph node metastases. Retrospectively, using the Common Terminology Criteria for Adverse Events v3.0, acute toxicity was scored during radiotherapy, whereas late toxicity was scored, from 3 months onward after treatment., Results: Toxicity could be evaluated in 75 patients treated with SmPF (n = 33), StPF (n = 28), and EF EBRT (n = 14). Most patients with late adverse events had also reported toxicity during radiotherapy (71%). The most common late adverse events were gastrointestinal tract related, more frequently present in the StPF group (60.7%) compared to SmPF (33.3%; P = 0.032). In particular, nausea and anorexia were more frequent in the StPF group (32.1%) compared to the SmPF group (3.0%; P = 0.004), as well as ileus (14.3% vs 0%, P = 0.039, respectively)., Conclusions: Treatment with adjuvant EBRT on SmPF results in less gastrointestinal late adverse events compared to treatment with EBRT on StPF in patients with surgically staged EC.

Objective: To investigate whether an educational intervention would facilitate compliance with vaginal dilators and potentially reduce stenosis in women receiving radiotherapy as treatment for a gynecological malignancy., Methods: From 2002 to 2009, all patients undergoing pelvic radiotherapy (either external beam radiotherapy or brachytherapy) at our center for treatment of gynecological malignancies were educated about the use of vaginal dilators. Sixty patients agreed to participate in a prospective 12-month study to evaluate use. The patients had a structured educational intervention regarding dilator use. Assessment was prospectively performed via questionnaires at baseline, 3, 6, 9, and 12 months after completion of radiotherapy. Data collected included patients' demographics, treatment, incidence of stenosis, and usage of and attitudes toward dilator use., Results: The median age of the patients was 60 years. Primary disease site was the uterus (56.6%) and cervix (40.0%). At 12 months, 52% of patients were still using the dilators, and 35% were using the dilators at least 2 to 3 times per week. Frequency of dilator use was greater in those patients older than 50 years (P = 0.005), even after adjusting for sexual frequency, and in those experiencing pain on vaginal examination (P < 0.001). It was less frequent in those patients who were sexually active (P = 0.035). At 12 months, 11% of the patients had flimsy adhesions and 6.5% had partial stenosis. No patients had complete stenosis. The only independent predictor of stenosis was the treatment group with a hazard ratio of 0.200 (95% confidence interval, 0.059-0.685), favoring surgery and any radiotherapy reducing the risk of stenosis compared to definitive radiation therapy alone., Conclusions: Our educational intervention facilitates compliance with vaginal dilators. Surgery and adjuvant radiation therapy (with or without cisplatin as a radiation sensitizer) may predict a lower risk of vaginal stenosis compared to definitive radiation therapy alone.

Objective: To investigate disease control, survival outcomes, and tolerance of intraoperative electron beam radiation therapy (IOERT) as a component of treatment for women with recurrent ovarian malignancies., Methods: From November 1987 to January 2009, 20 patients with recurrent ovarian malignancies received IOERT after maximal surgical cytoreduction. Areas treated included the pelvis (14), para-aortic nodes (6), or inguinal nodes (1). The median IOERT dose was 12.5 Gy (range, 10-22.5 Gy). Sixteen patients also received perioperative external beam radiotherapy as a component of treatment (median, 50 Gy; range, 20-54.3 Gy). All patients were followed prospectively for outcome and toxicity evaluation., Results: Median follow-up for surviving patients was 76.2 months (range, 1.5-175.8 months). The 5-year Kaplan-Meier estimate of local control was 59%, and central control (within the IOERT field) was 76%. All local relapses occurred in patients who had microscopic margin-positive resections. The 5-year freedom from distant relapse was 37%. The median disease-free interval after IOERT was 14 months. The median survival was 30 months, and the 5-year Kaplan-Meier estimate of survival was 49%. Six patients (29%) experienced grade 3 or higher toxicities, 2 of which (10%) were at least partly attributable to IOERT. Three patients experienced grade 1 or 2 peripheral neuropathy related to IOERT., Conclusions: Combined modality therapy with external beam radiotherapy, surgery, and IOERT is an option for the treatment of localized recurrent ovarian cancer, with acceptable rates of in-field failure and toxicity. Durable disease control is possible in select women treated with this regimen.

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.

Ovarian cancer patients developing metastatic spinal cord compression (MSCC) are extremely rare and account for only 0.4% of MSCC patients. Only very few case reports are available in the literature. This analysis evaluates seven ovarian cancer patients treated for MSCC with radiotherapy alone. Data of 1,852 MSCC patients irradiated between 1992 and 2005 were retrospectively reviewed. Seven patients were identified with epithelial ovarian cancer. These seven patients were evaluated for functional outcome, ambulatory status, local control of MSCC, and survival. The patients received either short-course radiotherapy (1 x 8 Gy or 5 x 4 Gy, n= 2) or long-course radiotherapy (10 x 3 Gy, 15 x 2.5 Gy, or 20 x 2 Gy, n= 5). Improvement of motor function occurred in three of the seven patients, in three of the five patients after long-course radiotherapy, and none of the two patients after short-course radiotherapy. Two of the five nonambulatory patients regained the ability to walk after radiotherapy. No further deterioration of motor function was seen in another three of the seven patients, in two of the five patients after long-course radiotherapy, and one of the two patients after short-course radiotherapy. Deterioration occurred in one of the seven patients, in none of the five patients after long-course radiotherapy, and one of the two patients after short-course radiotherapy. Patients died after a median interval of 4 months (range 1-7 months) following radiotherapy. A recurrence of MSCC did not occur. Radiotherapy alone is effective in improving or maintaining motor function in MSCC patients with ovarian cancer and should be administered if decompressive surgery is not indicated.

This study assesses the feasibility and implementation of respiratory-gated whole-abdominal intensity-modulated radiation therapy (RG-WAIMRT). Three patients were treated with RG-WAIMRT. The planning target volume (PTV1) included the entire peritoneal cavity and a pelvic boost field was created (PTV2). The dose prescribed was 30 Gy to PTV1 and 14.4 Gy to PTV2. For comparison, a conventional three-dimensional (3D) plan was generated for each patient. In the WAIMRT plan, an average of 90% of PTV1 received 30 Gy compared to 70% for the conventional 3D plan. The percent volume receiving 30 Gy (V(30)) for liver averaged 54% (WAIMRT) vs 43% (3D). The percent volume receiving 20 Gy (V(20)) for kidneys averaged 19% vs 0%, and the mean V(20) for bone marrow was 74% vs 83%, respectively. Major acute toxicities were anemia (grade 2: 1/3), leukopenia (grade 3: 2/3 patients), and thrombocytopenia (grade 2: 1/3 patients, grade 3: 1/3 patients). One patient could not complete the whole-abdomen field after 19.5 Gy because of persistent nausea. No major subacute toxicity has been reported. WAIMRT demonstrated superior target coverage and reduced dose to bone marrow, with a slightly increased dose to liver and kidneys. WAIMRT is a novel and feasible technique for ovarian cancer treatment.

The value of consolidation therapy in advanced epithelial ovarian carcinoma patients is controversial. The aim of the present study was to assess the long-term survival of patients with a pathologically confirmed complete remission who had consolidation by single-dose, whole-abdominopelvic radiotherapy. Of 96 histologically confirmed stage II-IV epithelial ovarian carcinoma patients who underwent cytoreductive surgery followed by high-dose, platin-based chemotherapy, 57 were in complete clinical remission at the end of therapy and 50 underwent a second-look laparotomy. The study group comprises 32 consecutive patients who had no pathological evidence of disease and who received 800 cGy single-dose, whole-abdominal radiotherapy by an 8 MEV linear accelerator in a single fraction. The absolute 5-year survival and the actuarial 10-year survival were 78.7 and 63.3%, respectively. The survival was significantly better in patients who had < or =2 cm residual disease at the completion of the original operation. No severe postradiation complications were encountered. Mild complications were seen in three (9.4%) patients. Our data indicate a favorable long-term survival of patients with a negative second-look laparotomy who had consolidation with single-dose, whole-abdominal radiotherapy. These results seem to suggest that a collaborative, prospective, randomized multiarm study is indicated to solve the controversial issue of consolidation therapy.

In a prospective randomized trial, consolidation treatment with radiotherapy or chemotherapy was compared with no treatment in a series of 172 patients with epithelial ovarian carcinoma, FIGO stage III, with complete surgical remission after primary cytoreductive surgery and induction chemotherapy. In the subgroup with complete pathological remission, progression-free survival (PFS) was significantly (P = 0.032) better in the radiotherapy group (56%) than in the chemotherapy group (36%) and the untreated control group (35%). The number of recurrences was lowest in the radiotherapy group. The overall relapse rate was reduced by 33% and the pelvic recurrences by 43% by consolidation radiotherapy. On the other hand, treatment-related side effects were more frequent in the radiotherapy group.

Despite debulking surgery and multidrug chemotherapy, advanced stage ovarian cancer has a high mortality rate. Radioimmunotherapy (RIT) is a treatment modality using specific, radiolabeled antibodies that guide cytotoxic radionuclides to cancer cells. In the present study, the therapeutic efficacy of RIT with murine monoclonal antibody HMFG1 labeled with three different beta-radiation emitting radionuclides (90Yttrium, 186Rhenium, and 131Iodine) was assessed in athymic BALB/c mice with intraperitoneally growing NIH:OVCAR-3 ovarian carcinoma xenografts. Each of the three intraperitoneally administered radiolabeled antibody preparations (90Y-HMFG1, 186Re-HMFG1, and 131I-HMFG1) caused a significant delay in ascites formation and mortality as compared to the control groups treated with 90Y-labeled irrelevant antibody, nonradiolabeled HMFG1, or phosphate buffered saline. Intraperitoneally (ip) administered 90Y-HMFG1 was shown to have a significantly higher abdominal retention as compared to the intraperitoneally administered irrelevant antibody 90Y-G250. Furthermore, intraperitoneally administered 90Y-HMFG1 more effectively inhibited tumor growth than intravenously administered 90Y-HMFG1. It was concluded that in intraperitoneally located malignant disease with ascitic cell clusters and tumor deposits, intraperitoneal administration of RIT seemed preferable as compared to intravenous administration. The choice of the most optimal radionuclide in intraperitoneally located malignancies needs further research, but could well depend on tumor characteristics such as the size of the tumor lesions.

In a prospective randomized trial, consolidation treatment with radiotherapy or chemotherapy was compared with no treatment in a series of 172 patients with epithelial ovarian carcinoma, FIGO stage III, with complete surgical remission after primary cytoreductive surgery and induction chemotherapy. In the subgroup with complete surgical and pathologic remission, progression-free survival was significantly (P = 0.032) better in the radiotherapy group (56% at 5 years) than in the chemotherapy group (36% at 5 years) and the untreated control group (35% at 5 years). Overall survival was also most favorable in the radiotherapy group (69% at 5 years). The number of recurrences was lowest in the radiotherapy group. In the subgroup with microscopic residual carcinoma there were no significant differences in survival between the radiotherapy and the chemotherapy-treated patients. Early and late radiation reactions were recorded. Treatment-related side effects were seen most frequently in the radiotherapy group. Late intestinal radiation reactions of a severe type were recorded in 10%.

The purpose of this paper is to prospectively evaluate the effects of local radiation therapy upon localized ovarian cancer following chemotherapy. Patients with objective relapses or refractory disease but with localized epithelial ovarian cancers and who had undergone at least one regimen of chemotherapy were enrolled in this study. External irradiation was performed on all patients. Twenty patients, with a mean age of 53.8 +/- 10.3 y, were enrolled in this study. The median number of previous chemotherapies was 2. The interval between previous chemotherapy and radiation therapy was 4.5 months. The maximum diameter of the lesions was 3.6 +/- 1.8 cm. The irradiation dose was 52.3 +/- 8.3 Gy. Neither hematologic nor intestinal toxicity >grade 3 was observed. Forty-four disease sites, including the lymph nodes, vaginal cuff, pelvis, abdomen, subcutaneous regions, and the brain were irradiated. Thirty of these sites were symptom-free before irradiation. In patients with symptoms, the symptomatic relief was obtained in approximately 50% of patients. Smaller lesions (P = 0.024) and lymph nodes (P = 0.042) demonstrated better responses than larger lesions or other sites, respectively. Regression rates correlated with longer survivals (P = 0.0195) after radiation therapy. Survival was significantly better when radiation therapy was given before patients had symptoms (P = 0.001). Survival was also better in patients with lymph node disease only (P = 0.0069). We conclude that local radiation therapy may be one of the treatment options for relapsed or refractory but localized ovarian cancer, particularly when the tumor is small and/or located in the lymph nodes, even when patients had no symptoms.

The prognosis of patients with breast cancer symptomatically metastatic to the ovary is almost uniformly poor. In this case report, we present a 33-year-old para-4 with a symptomatic metastasis to the ovary. Previously, a modified radical mastectomy with adjuvant radiotherapy had been performed for invasive ductal carcinoma of the left breast. Laparotomy showed a 13-cm tumor of the left ovary; frozen section histology showed malignancy consistent with the previous breast cancer. The patient received adjuvant combination chemotherapy. About 5 years later, a carcinoma of the right breast was treated with conservative surgery and adjuvant radiation and chemotherapy. After a further 4 years, a recurrence at the left chest wall was treated with radiation. At the last follow-up, more than 13 years after the first breast cancer and 12 years after the ovarian metastasis, the patient was alive and well without evidence of disease. Bilateral oophorectomy is a therapeutic option in premenopausal patients with localized or advanced breast cancer. Our patient experienced long-term disease-free survival following an isolated metastasis to one ovary. This represents the first report of long-term survival of such a patient in the literature.

Epithelial ovarian cancer is a heterogeneous disease and many biologic and molecular factors are important for its development and progression, including growth rate, metastatic potential, chemo- and radiosensitivity, and prognosis. Even in the early stages (FIGO I-II), many questions persist about the biologic behavior, optimal treatment, and prognosis. In a series of 106 patients with epithelial ovarian cancers in FIGO stages IA-IIC, a number of known prognostic factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to two important growth factor receptors for oncogenesis (HER-2/neu and EGFR). Immunohistochemical techniques were used. All patients received adjuvant radiotherapy 4-6 weeks after the primary surgery. In a univariate analysis, the expression of the HER-2/neu receptor was not associated with any of the clinicopathologic factors studied or survival status. Positive EGFR staining was associated with poor survival in a univariate analysis. Co-expression of HER-2/neu and EGFR was most frequently seen in serous tumors and positive staining for HER-2/neu alone was associated with mucinous tumors. Both endometrioid and clear cell tumors belonged to the largest subgroup with concomitant negativity for both HER-2/neu and EGFR. In a multivariate Cox analysis, the tumor grade and EGFR status of the tumors were independent and significant prognostic factors. A therapeutic strategy for epithelial ovarian cancer might be to decrease EGFR expression by gene therapy in combination with adjuvant radiotherapy or chemotherapy.