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Mack N Barnes

Publications and source records attributed to Mack N Barnes.

At least 19 recordsLinked to original sources

A phase II trial of weekly topotecan for patients with secondary platinum-resistant recurrent epithelial ovarian carcinoma following the failure of second-line therapy.

OBJECTIVE: To determine the response rate, progression-free survival and toxicity associated with weekly topotecan administered to patients with platinum-sensitive recurrent epithelial ovarian (EOC) in the third-line setting. METHODS: Patients with measurable platinum-sensitive EOC following failure of second-line chemotherapy were eligible for this phase II study. All patients were initially treated with cytoreductive surgery and platinum/paclitaxel-based chemotherapy. Continuous, weekly topotecan was administered at a starting dose of 4 mg/m(2). Toxicity and efficacy were assessed at various time points after initiation of therapy. RESULTS: Twenty nine patients were enrolled in this prospective study. Toxicity was acceptable with grade 1/2 nausea being the most commonly experienced side effect (52%). Nine patients (31%) had grade 3/4 leukopenia; however, only 3 patients had febrile neutropenia. Thirteen patients had a treatment delay and six required dose reductions. Twenty two patients were evaluable for efficacy. The overall response rate for weekly topotecan was 13.6% [95% CI; -0.7-27.9%] with 1 complete response, and 2 partial responses. Twelve patients (54.5%), including 2 with minor responses, had stable disease for a median duration of 18 weeks. CONCLUSIONS: Weekly topotecan at the current schedule in the third-line setting in patients with platinum-sensitive recurrent EOC has modest clinical activity. Toxicity associated with this regimen is acceptable but growth factor support, dose reductions, or schedule alterations may need to be considered in many of these patients.

Adult↗

Bowel resection at the time of primary debulking for epithelial ovarian carcinoma: outcomes in patients treated with platinum and taxane-based chemotherapy.

BACKGROUND: Our goal was to determine the morbidity, disease-free survival, and overall survival of patients with bowel resection at primary cytoreductive surgery for advanced epithelial ovarian carcinoma in the era of platinum and taxane chemotherapy. STUDY DESIGN: We performed a retrospective study of patients undergoing bowel resection at the time of primary cytoreduction for advanced epithelial ovarian carcinoma, who subsequently received platinum and taxane chemotherapy, from 1996 to 2001. Data collected included demographics, stage, histology, debulking status, surgical morbidity, recurrence, and survival. Survival analysis and comparisons were performed using the Kaplan-Meier method and log-rank test. RESULTS: Of 48 patients (45 stage III; 3 stage IV), 25 patients (52%) were optimally debulked to < 1 cm of residual disease; the remaining 23 patients had residual disease > 1 cm. Four-year disease-free survival in the optimally debulked group was 24% versus 12% in the suboptimally debulked group (p=0.009). Four-year overall survival was 81% in the optimally debulked group versus 54% in the suboptimally debulked group (p=0.162). Five patients (10%) experienced a major postoperative complication including stroke, small bowel obstruction, anastomotic leak, entercutaneous fistula, and pelvic abscess. Two perioperative deaths occurred in the suboptimally debulked group. CONCLUSIONS: Patients with advanced epithelial ovarian carcinoma who undergo bowel resection as part of optimal cytoreduction and receive platinum and taxane chemotherapy have improved disease-free survival and a trend toward improved overall survival. Bowel resection at the time of primary cytoreductive surgery is associated with acceptable perioperative morbidity.

Adult↗

The use of bevacizumab to palliate symptomatic ascites in patients with refractory ovarian carcinoma.

OBJECTIVE: To evaluate our experience with the use of bevacizumab in patients with heavily pretreated recurrent ovarian carcinoma who have symptomatic ascites. METHODS: Four patients were identified who were previously heavily pretreated for recurrent ovarian carcinoma. Each had symptomatic ascites and required frequent therapeutic paracenteses. Each was treated with bevacizumab with the intent to palliate symptomatic ascites. Clinical data including demographic data and clinicopathologic variables was abstracted. RESULTS: The four patients demonstrated symptomatic relief of ascites. Toxicity was manageable in all patients with no grade 3/4 toxicity observed. In addition to symptomatic relief of ascites, no therapeutic paracenteses were required after initiation of therapy with bevacizumab. CONCLUSIONS: Bevacizumab may be a viable palliative option in patients with end stage ovarian carcinoma who have symptomatic ascites.

Angiogenesis Inhibitors↗

Efficacy and toxicity of the novel chemotherapeutic agent KW-2170 in recurrent epithelial ovarian cancer.

OBJECTIVES: KW-2170 is a novel DNA intercalating agent whose mechanism of action is similar to doxorubicin HCl, yet is associated with less cardiac toxicity. The objective of this study was to evaluate the activity and toxicity of this novel chemotherapeutic agent in patients with recurrent ovarian carcinoma. METHODS: A prospective phase II trial was performed in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma and measurable disease. Patients could have platinum-sensitive or refractory disease and could have received any number of prior treatments. One treatment cycle consisted of KW-2170 administered at a dose of 18 mg/m(2) weekly for 3 weeks followed by a 21-day rest period. Toxicity was assessed using the NCI Common Toxicity Criteria (Version 2.0), and dose reduction was allowed for significant toxicity. Response to therapy was assessed in patients who completed at least 2 cycles using RECIST criteria. RESULTS: A total of 28 patients were enrolled in this phase II trial at 5 separate centers. Of the 28 patients evaluated, all had stage III/IV disease at initial diagnosis. The median number of prior therapeutic regimens in these patients was 4 (range 1-8). The median number of KW-2170 cycles administered was 2 (range 1-5). Treatment-related toxicity in this heavily pretreated population was acceptable as only 6 patients (21%) had grade 3-4 neutropenia. Dose reductions occurred in 6 patients (21%) for grades 1-4 neutropenia, and no patient had febrile neutropenia. Four patients completed less than 1 cycle; 3 secondary to progressive disease, and one due to Gram-positive sepsis. Of patients receiving at least 2 full cycles, 10 patients (55%) had stable disease with a median of 4.5 months (range 3-10) to disease progression. All other patients were removed from the study after 1-2 cycles of therapy with no significant clinical effect noted. CONCLUSIONS: Although associated with relatively little toxicity, KW-2170 at the dose and schedule evaluated demonstrated little clinical activity in this heavily pretreated population of recurrent ovarian cancer patients. Whether KW-2170 would have greater clinical activity in a more treatment naive group of patients at an increased dose awaits clinical trial evaluation.

Acridines↗

Effectiveness of darbepoetin alfa versus epoetin alfa for the treatment of chemotherapy induced anemia in patients with gynecologic malignancies.

OBJECTIVE: Chemotherapy induced anemia (CIA) commonly occurs in gynecologic oncology patients. This often leads to treatment with erythropoietic stimulating agents in order to prevent chemotherapy delays, dose modifications and transfusion of red blood cells. Our objective was to determine the subsequent transfusion rates following administration of either darbepoetin alfa or epoetin alfa. METHODS: A single institution retrospective chart review was performed utilizing patients from January 2003 to September 2004 who received either darbepoetin alfa or epoetin alfa for CIA (Hgb < or = 10.0). Data collection variables included patient demographics, cancer diagnosis, chemotherapy treatment(s), laboratory data, erythropoeisis stimulation data, and transfusions. Sample size calculations were set to detect a 20% transfusion rate difference between the two groups. Chi-square, Fisher exact test and student t tests were used for statistical analysis. RESULTS: 123 patients were eligible for analysis (60 darbepoetin alfa; 62 epoetin alfa). 93% of darbepoetin alfa patients received 200 mg every other week, while 86% of epoetin alfa patients received 40,000 U weekly. The darbepoetin alfa and epoetin alfa groups were similar in respect to age, race, tumor type, histology, previous chemotherapy, number of chemotherapy agents, weeks of erythropoietic stimulation, and baseline serum levels of creatinine and hemoglobin. The mean baseline Hgb and change in Hgb was similar for each group (darbepoetin alfa = 11.2, 2.5 and epoetin alfa = 11.3, 2.3). Twenty one (35%) of the darbepoetin alfa patients received a transfusion of packed red blood cells compared to 12 (19%) of epoetin alfa patients (p = 0.05). CONCLUSIONS: This retrospective analysis powered to detect differences in transfusion rates revealed a statistically significant difference in transfusion rates between darbepoetin alfa and epoetin alfa for the treatment of CIA. These data warrant a randomized prospective trial in gynecologic oncology patients with careful attention to the timing of initiation of treatment, dosing regimens, and titration of growth factor.

Anemia↗

Pegylated liposomal doxorubicin consolidation therapy after platinum/paclitaxel-based chemotherapy for suboptimally debulked, advanced-stage epithelial ovarian cancer patients.

OBJECTIVE: To assess the feasibility of using pegylated liposomal doxorubicin (PLD) as a consolidation therapy in patients with advanced ovarian cancer who have attained a clinically defined complete response to initial platinum/paclitaxel-based chemotherapy. METHODS: Patients diagnosed with suboptimally debulked stage IIIC/IV epithelial ovarian cancer who attained a clinically defined complete response at the completion of platinum/paclitaxel-based chemotherapy were eligible for this protocol. Patients were treated with PLD at a dose of 40 mg/m(2) every 28 days for four cycles. A survival analysis was calculated using the Kaplan-Meier method. RESULTS: Of the 30 patients enrolled, 29 were evaluable. Twenty-three patients (79%) completed all four cycles of consolidation therapy. Palmar-plantar erythrodysesthesia was the most common toxicity. Six patients remained clinically without evidence of disease with a median follow-up of 35 months from the completion of primary chemotherapy. The median progression-free interval was 15 months, and median overall survival time was 31 months, with 47% of patients achieving a 4-year survival. CONCLUSIONS: Consolidation therapy with PLD chemotherapy administered to women with advanced epithelial ovarian cancer after initial chemotherapy appears feasible based on its toxicity profile. Considering the tolerability of this agent, further investigation is needed to depict the optimal dose and schedule needed for consolidation therapy.

Aged↗

A comparison of hand-assisted laparoscopy and conventional laparotomy for the surgical evaluation of pelvic masses.

OBJECTIVE: Although hand-assisted laparoscopic surgery (HALS) has been utilized in abdominal surgery, limited data exist on the feasibility and safety of HALS in the evaluation of pelvic masses. Our goal was to compare HALS to conventional laparotomy for pelvic masses in gynecologic patients. METHODS: A chart review identified patients who underwent a HALS or XLAP procedure for the evaluation of a pelvic mass from January 2003 to September 2004. RESULTS: 70 patients were analyzed-29 cases (HALS) and 41 controls (XLAP). The groups were comparable in terms of age (48 vs. 49 years), body mass index (29.1 vs. 29.8 m2), and mass size (11.0 vs. 11.3 cm). Operative times were similar between the groups (90 vs. 72 min, P = 0.9). HALS was associated with decreased estimated blood loss (108 vs. 207 cm3, P = 0.004), shorter hospital stay (2.8 vs. 4.2 days, P = 0.03), and fewer post-operative complications (4 vs. 11, P = 0.05). CONCLUSIONS: HALS is a safe and feasible alternative to conventional open laparotomy for the evaluation and surgical treatment of pelvic masses. In addition to similar operative times, HALS demonstrated a decreased estimated blood loss, complication rate, and length of hospital stay.

Adolescent↗

Adenoviruses with an RGD-4C modification of the fiber knob elicit a neutralizing antibody response but continue to allow enhanced gene delivery.

OBJECTIVE: The purpose of this study was to investigate the effect of preexisting neutralizing antibody (NAbs) in naive mice and the effect of induced NAbs in mice immunized with either an RGD or nonmodified Ad5 vector on the transduction efficiency of adenoviral vectors. METHODS: BALB/c mice were immunized with Ad5LucRGD, with the unmodified Ad5Luc1, or with Opti-MEM intraperitoneally (ip) from one to three times. Sera were collected on day 27 and serially diluted to block Ad5Luc1 or Ad5LucRGD prior to infection of SKOV3.ip1 human ovarian carcinoma cells with these same vectors. Forty-eight hours post Ad infection, a luciferase assay was performed to determine the titer of NAbs. RESULTS: Luciferase assay data showed that the gene transfer efficacy of Ad5LucRGD was 1.56-fold higher than Ad5Luc1 in the presence of serum from naive mice. In the presence of serum from Ad5Luc1-challenged mice, the transduction efficiency of Ad5LucRGD was 3.27-fold higher (single challenge) and 4.2-fold higher (triple challenge) than Ad5Luc1. In the presence of serum from Ad5LucRGD-challenged mice, the transduction efficiency of Ad5LucRGD was 2.24-fold higher (single challenge) and 2.53-fold higher (triple challenge) than Ad5Luc1. CONCLUSION: The RGD-modified human Ad vectors appear to be less recognizable than unmodified Ad to preexisting NAbs in mouse models. RGD-modified Ad vectors also appear to elicit a relatively lower level of NAbs that may also contribute to the higher gene transduction efficiency of these modified vectors. Therefore, RGD-modified Ad vectors may be reagents of clinical utility in the context of preformed anti-Ad immunity and in the setting of repetitive dosing.

Adenoviridae↗

Occult choriocarcinoma discovered by positron emission tomography/computed tomography imaging following a successful pregnancy.

BACKGROUND: Positron emission tomography (PET) is commonly used to detect occult or recurrent malignancy, including tumors of the female genital tract. Recently, there have been reports of PET scans used in patients with Gestational Trophoblastic Disease (GTD). CASE: A 22-year-old female presented with vaginal bleeding and elevated beta-hCG 7 months after a spontaneous vaginal delivery of a healthy infant. She had a history of molar pregnancy and persistent GTD requiring multi-agent chemotherapy. Metastatic evaluation with computed tomography and magnetic resonance imaging showed no evidence of GTD. A positron emission tomography/computed tomography (PET/CT) scan revealed a focus of metabolic activity in the left pelvis. The patient underwent an exploratory laparotomy that revealed metastatic choriocarcinoma in the left broad ligament. CONCLUSION: PET/CT may be useful in the evaluation of occult choriocarcinoma when conventional imaging fails to identify metastatic disease.

Adult↗

Feasibility of performing chemoprevention trials in women at elevated risk of ovarian carcinoma: initial examination of celecoxib as a chemopreventive agent.

BACKGROUND: A pilot study was undertaken to determine the feasibility of examining a COX-2 inhibitor (Celecoxib) as a chemopreventive agent in women at increased risk of ovarian cancer undergoing risk reducing salpingoophorectomy. METHODS: Women at elevated inherited risk of ovarian carcinoma pursuing risk reducing salpingoophorectomy were eligible for this trial. Ten patients were assigned to a control group while 10 patients were administered Celecoxib (400 mg/day) for 3 months prior to surgery. Demographic data at enrollment was collected. Serum, urine, peritoneal fluid, and resected tissues were obtained for correlative laboratory study. Evaluation of serum VEGF alterations was examined using an ELISA-based assay. RESULTS: Enrollment of patients was completed in 16 months. Of 29 eligible patients, 20 enrolled onto the study. One patient from each group did not complete surgical intervention. No significant differences were observed in the enrollment characteristics between the groups. No occult cases of ovarian cancer were identified and no differences in the presence of follicular cyst, hemorrhagic cysts, or inclusion cysts were noted on initial pathologic review. While the mean serum VEGF levels obtained following the administration of a COX-2 inhibitor were lower than the pre-administration in 5 of 6 patients, statistical significance in this difference was not observed (P = 0.359). However, this is most likely due to the small number of serum samples available. CONCLUSION: These results would suggest that chemoprevention trials in ovarian cancer will be eagerly embraced by this patient population.

Adult↗

Inter-patient variation in efficacy of five oncolytic adenovirus candidates for ovarian cancer therapy.

BACKGROUND: Gene therapy offers a new strategy for cancer treatment. Adenoviruses represent the most widely used gene therapy vector and feature an excellent safety record. Conditionally replicative adenoviruses (CRAds) effect solid tumor penetration and tumor selective oncolysis and consequently offer potential efficacy for metastatic disease treatment. We evaluated five CRAds as candidate clinical agents for ovarian cancer therapy: RGDCRADcox-2R, Ad5VEGFE1, Ad5/3VEGFE1, Ad5-Delta24RGD, and Ad5/3-Delta24. METHODS: DNA replication by these five CRAds, wild-type adenovirus, and an E1-deleted control was measured in purified primary ovarian cancer cell spheroids by quantitative PCR. CRAd-mediated oncolysis was quantified in ovarian cancer cell monolayers and three-dimensional spheroids by cellular viability assays. The therapeutic efficacy of each CRAd was tested by intraperitoneal administration in mice with peritoneally disseminated human ovarian cancer. RESULTS: An increase in viral DNA was noted in primary tumor cell spheroids for all replicative viruses tested. Variation was noted in viral DNA replication between patient samples. All five CRAds induced remarkable oncolysis. They also prolonged survival in vivo compared with the wild-type control group. CONCLUSIONS: All five CRAds tested showed robust DNA replication, oncolysis, and in vivo therapeutic efficacy. Each virus has potential for clinical testing, and such further testing will ultimately determine its safety and relative usefulness. Variation of CRAd DNA replication between different patient samples suggests that target tissue features, such as surface receptors and endogenous transcription factors, may affect CRAd infectivity and replicativity. Evaluation of such factors may become important to optimize cancer therapy for individual patients.

Adenocarcinoma↗

Primary lung large cell carcinoma metastatic to the vulva: a case report and review of the literature.

BACKGROUND: Metastatic cancer to the vulva is a rare diagnosis and is estimated to account for 5-8% of all vulvar cancers. CASE: A 57-year-old postmenopausal woman was referred for the evaluation of a new vulvar mass. CT scan of the pelvis demonstrated a 4 x 6 cm lobular mass of the left labia. An outpatient excisional biopsy revealed a poorly differentiated large cell carcinoma with prominent necrosis and focal perineural invasion consistent with a bronchogenic carcinoma. A subsequent PET scan of the chest revealed a large primary lung carcinoma confirmed by CT-guided biopsy that was identical to the vulvar tumor. CONCLUSION: This case represents the only literature described primary lung carcinoma presenting as a vulvar metastasis.

Carcinoma, Large Cell↗

The impact of aborted radical hysterectomy in patients with cervical carcinoma.

OBJECTIVE: To determine the impact of an aborted radical hysterectomy on morbidity and overall survival in patients undergoing surgical treatment for early stage cervical carcinoma. METHODS: Following IRB approval, a computerized database identified 304 women treated with radical surgery for early stage cervical carcinoma from 1994 to 2000 of which 23 (8%) had an aborted radical hysterectomy. RESULTS: Of the 23 patients, 17 patients had a IB(1) lesion, 4 patients had a IB(2) lesion, and 2 patients had a IIA lesion. Median age was 42 years (range 28-60). Twenty-one patients had squamous cell carcinoma and two patients had adenocarcinoma. Radical hysterectomy was aborted for the following reasons: 11 patients had pelvic extension, seven had positive pelvic nodes, and five patients had positive paraaortic nodes. All 23 patients received postoperative radiation therapy; additionally, 12 patients received concurrent chemotherapy consisting of platinum with or without 5-FU. There were four operative complications (17%) including deep vein thrombosis, wound infection, blood transfusion, and an ileus. Four patients (17%) had radiation-associated complications. Six of 23 (26%) patients experienced a recurrence. The 5-year overall survival was 83% with a median follow-up of 59 months (range 12-107 months). CONCLUSIONS: A small percentage of patients (8%) with early stage cervical carcinoma will have an aborted radical hysterectomy for pelvic extension or positive nodes. Fortunately, these patients still have a favorable prognosis with postoperative radiation therapy. Aborted radical surgery does not significantly increase overall complications.

Adenocarcinoma↗

Protrusio acetabuli presenting as a complex pelvic mass after total hip arthroplasty.

BACKGROUND: The differential diagnosis in an elderly woman with a complex pelvic mass includes benign and malignant diseases. CASE: A woman in her ninth decade was discovered to have both a breast mass and a pelvic mass at examination. After diagnostic breast biopsy results that confirmed invasive breast carcinoma, pelvic examination and ultrasonography were performed. The ultrasonogram demonstrated a large complex pelvic mass. The patient underwent an exploratory laparotomy at the time of her mastectomy. The pelvic mass was a protrusio acetabuli resulting from a prior right total hip arthroplasty. CONCLUSION: A complex pelvic mass secondary to protrusio acetabuli is a rare clinical finding.

Acetabulum↗

Immunohistochemical evaluation of the c-kit proto-oncogene in sarcomas of the uterus: a case series.

OBJECTIVE: To evaluate the incidence of c-kit expression in uterine sarcomas. STUDY DESIGN: Immunohistochemical evaluation for expression of c-kit was performed on specimens from 11 patients with pathologically documented uterine sarcomas. Histologic subtypes included 5 carcinosarcomas, 3 leiomyosarcomas and 3 endometrial stromal sarcomas. Histologic sections of formalin-fixed, paraffin-embedded hysterectomy specimens from patients with uterine sarcomas were immunostained with c-kit (CD117) antibody. Overall staining intensity was graded as strong, intermediate or weak. RESULTS: In all 11 patients with uterine sarcoma, c-kit immunostaining was positive. Four specimens demonstrated stronger staining intensity than did the gastrointestinal stromal tumor control. Five specimens demonstrated intermediate staining intensity. Two specimens demonstrated weak staining intensity. Furthermore, in the carcinosarcoma specimens both the epithelial and sarcomatous elements were positive for c-kit staining. CONCLUSION: In this case series, c-kit expression was demonstrated in all sarcomas of the uterus regardless of histologic type. These results suggest that such drugs as imatinib mesylate, which inhibit the c-kit tyrosine kinase, should be investigated for these mesenchymal neoplasms.

Biomarkers, Tumor↗

The secretory leukoprotease inhibitor (SLPI) promoter for ovarian cancer gene therapy.

BACKGROUND: Adenoviruses allow efficient transduction of dividing and non-dividing cells and their safety for the treatment of cancer has been established in clinical trials. However, one disadvantage is their promiscuous tropism. In this regard, tissue-specific promoters (TSPs) could be useful for directing transgene expression to target tissues and for reducing adverse effects in non-target tissues. We hypothesize that selective adenovirus-mediated transgene expression could be achieved through the use of the secretory leukoprotease inhibitor (SLPI) promoter in the context of ovarian cancer. METHODS: Adenoviruses containing the SLPI promoter driving reporter and suicide gene expression were created and tested in ovarian cancer cell lines and primary tumor cells isolated from patients. To evaluate the in vivo activation of the SLPI promoter in comparison to a ubiquitous promoter, intraperitoneal delivery was performed in tumor-bearing mice, followed by analysis of survival or gene expression in normal organs and tumor. RESULTS: The SLPI promoter retained its fidelity in an adenoviral context and was activated in both cell lines and primary cancer cells. The SLPI promoter was induced to a high degree in ovarian cancer cells while showing significantly reduced activity in normal tissues. The therapeutic efficacy of SLPI promoter-controlled gene expression was similar to the ubiquitous promoter in vitro and in an orthotopic murine model of peritoneally disseminated ovarian cancer, with higher activity than controls. CONCLUSIONS: The SLPI promoter is a potentially useful TSP for ovarian cancer and facilitates further development of targeting strategies for improved gene therapy of ovarian carcinomas.

Adenocarcinoma↗

Stage IC adenocarcinoma of the endometrium: survival comparisons of surgically staged patients with and without adjuvant radiation therapy.

OBJECTIVE: The goal of this study was to determine the outcomes of stage IC endometrial carcinoma patients who are managed with and without adjuvant radiation therapy after comprehensive surgical staging. METHODS: Patients with FIGO stage IC adenocarcinoma of the endometrium diagnosed from 1988 to 1999 were identified from tumor registry databases at four institutions. A retrospective chart review identified 220 women who underwent comprehensive surgical staging including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy, and peritoneal cytology. RESULTS: Of the 220 stage IC patients, 56 (25%) patients received adjuvant brachytherapy (BT), 19 (9%) received whole-pelvis radiation (WPRT), and 24 (11%) received both WPRT and BT. One hundred twenty-one patients (55%) did not receive adjuvant radiation. There were 6 recurrences (6%) in the radiated group and 14 (12%) in the observation group (P = 0.20). Seven of fourteen recurrences in the observation group were local, and all local recurrences were salvaged with radiation therapy. Two of seven distant recurrences in this group were also salvaged with surgery and chemotherapy. The overall salvage rate for the observation group was 64%. There was a statistical difference in 5-year disease-free survival between the radiated and observation groups (93% vs 75%, P = 0.013). However, the 5-year overall survival was similar in the two groups (92% vs 90%, P = 0.717). CONCLUSION: Adjuvant radiation therapy improves disease-free survival in surgical stage IC patients; however, overall survival is not improved with adjuvant radiation therapy since the majority of local recurrences in conservatively managed patients can be salvaged with radiation therapy.

Adenocarcinoma↗

Replication of an integrin targeted conditionally replicating adenovirus on primary ovarian cancer spheroids.

Replication competent viruses hold promise for treatment of advanced cancers resistant to available therapeutic modalities. Although preliminary clinical results have substantiated their efficacy, preclinical development of these novel approaches is limited by assay substrates. The evaluation of candidate agents could be confounded by differences between primary tumor cells and tumor cell lines, as discordance in the levels of surface receptors relevant for viral entry has been reported. Since primary tumor cells are difficult to analyze ex vivo for longitudinal observation of virus replication, we developed three-dimensional aggregates or spheroids of unpassaged and purified ovarian cancer cells as a means for prolonging primary tumor cell viability and as a three-dimensional in vitro model for replicative viral infection. Ovarian cancer cells purified from ascites samples were sustained for 30 days while retaining the infection profile with tropism modified and unmodified adenoviruses (Ads). Cell line and primary cell spheroids were used to quantitate the replication and oncolytic potency of replicative Ads in preclinical testing for human ovarian cancer trials. Therefore, spheroids provide a method to sustain purified unpassaged primary ovarian cancer cells for extended periods and to allow evaluation of replicative viruses in a three-dimensional model.

Adenoviridae↗