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Objective: To compare the outcomes of black and white women who have surgically staged endometrial carcinoma. Methods: We retrospectively compared the clinicopathologic factors, socioeconomic status, treatments, and outcomes of 70 black and 302 white women who were treated for surgically staged endometrial carcinoma at our institution. Results: Black women had higher-grade tumors, less favorable histologic findings, more comorbid illnesses, and lower socioeconomic indices. A nonsignificant trend was also seen toward more advanced-stage disease. The extent of surgical staging and types of adjuvant therapies were similar. On univariate analysis, black women had worse 5-year disease-free survival than white women (52.8% versus 75.2%; P = .001). Other significant factors included stage, grade, lymph node status, extension to the uterine serosa, cervical involvement, histology, adnexal involvement, lymphovascular invasion, myometrial invasion, positive peritoneal cytology, level of education, and household income. After controlling for pathologic and socioeconomic differences in multivariate analysis, race remained a significant prognostic factor ( P = .008; hazard rate 2.0; 95% confidence interval 1.2, 3.5). Conclusion: In a large cohort of surgically staged and uniformly treated patients with endometrial carcinoma, black race was associated with significantly worse outcomes, even after controlling for clinicopathologic and socioeconomic factors.

Objectives. Prostate-specific antigen (PSA) based end points are commonly used to report outcomes after treatment for prostate cancer. This study examines the influence of follow-up length on biochemical control (bNED) rates. Methods. We reviewed 437 patients with clinically localized prostate cancer treated with conformal radiotherapy without neoadjuvant androgen deprivation. Biochemical failure was defined as three consecutive PSA increases or an increase large enough to prompt androgen deprivation therapy. The failure date was projected back to the midpoint between the PSA nadir and the first PSA increase (or between the nadir and the initiation of androgen deprivation therapy). The analysis was performed by censoring patients with longer follow-up in a stepwise fashion, thus creating smaller subgroups with shorter follow-up intervals. Subgroup 1 (n = 191) and subgroup 2 (n = 273) were defined to include those patients monitored for up to 2 years and up to 3 years, respectively. Results. The median follow-up intervals for subgroup 1, subgroup 2, and the original study population were 1.1, 1.5, and 2.5 years. No significant differences were seen in pretreatment prognostic factors among the three groups. The 2-year bNED of subgroup 1, subgroup 2, and the original population was 86%, 77%, and 73%, respectively. Although subgroup 1 had a superior bNED compared with the original population (P = 0.04), no differences in clinical recurrence rates were seen among any of the three groups. Conclusions. Because of projecting the biochemical failure dates back according to commonly used bNED definitions, control rates are highly dependent on the length of follow-up.

The traditional approach to patients with stage II endometrial carcinoma is preoperative radiation therapy (RT) followed by surgery. Currently, many patients are treated with primary surgery and postoperative RT. We retrospectively reviewed the outcome of 44 stage II (32 IIA, 12 IIB) patients who underwent surgery and postoperative RT. Nine (20%) had microscopic cervical involvement noted before surgery, and 35 (80%) had occult involvement noted postoperatively. Postoperative RT consisted of whole pelvic RT (WPRT) (50%), vaginal brachytherapy (VB) (18%), or both (32%). At a median follow-up of 40 months, the 5-year actuarial disease-free survival was 72.4%. Two patients (4%) had recurrence in the pelvis (one vagina, one lateral pelvis). Eighteen stage IIA patients treated with WPRT alone and eight stage IIA patients, without deep myometrial invasion (MI), were treated with VB alone, and remained controlled in the pelvis. Extrapelvic recurrences occurred in 12 patients (25%), primarily in those with deep MI and/or grade 2-3 disease. Our results suggest that patients with stage II endometrial carcinoma with microscopic or occult cervical involvement treated with surgery and postoperative RT have a favorable outcome. A high rate of pelvic control is achieved with RT tailored to the pathologic findings.

OBJECTIVE: The goal of this study was to evaluate the effect of postoperative residual tumor size on the outcomes for patients with incompletely resected benign meningiomas who underwent radiotherapy (RT). METHODS: Fifty-four patients with incompletely resected benign meningiomas received postoperative RT between 1984 and 1995. Surgery consisted of partial resection for 43 patients (80%) and biopsy for 11 (20%). All patients underwent postoperative imaging (using computed tomography and/or magnetic resonance imaging), and the median residual tumor size was 3.5 cm (in greatest dimension). Thirty-eight tumors (69%) were

Objective: To evaluate outcomes of patients with stage IC endometrial carcinoma treated with external whole pelvic radiation but not vaginal brachytherapy. Methods: Sixty-one women with stage IC endometrial carcinoma had postoperative pelvic radiation without vaginal brachytherapy. The median age was 69 years (range 44 ‐ 87 years). Most subjects had histologic findings of adenocarcinoma (71%) and grade 2 or 3 disease (74%). The median pelvic irradiation dose was 48.6 Gy (range 43.2‐50.4 Gy). No patients received adjuvant chemotherapy or hormonal therapy. The median follow-up time was 69.5 months (range 7‐196 months). Results: The 5-year actuarial disease-free and overall survivals of the entire group were 86.7% and 97.6%, respectively. No patient developed local (vaginal) recurrence. One patient had recurrent disease in the lateral pelvis. Ten patients (16.4%) had distant (extrapelvic) metastases. No serious sequelae were noted, including vaginal necrosis, small bowel obstruction, proctitis, or fistulae. Conclusion: Local control was excellent in stage IC endometrial carcinoma treated with adjuvant radiation therapy alone. Attention needs to be focused on efforts to control extrapelvic recurrence in patients with this disease. (Obstet Gynecol 1999;93:599 ‐ 602. © 1999 by The American College of Obstetricians and Gynecologists.) Most patients with endometrial carcinoma present in stage I, and the mainstay of their treatment is surgery. However, those who have deep myometrial invasion without extrauterine disease (stage IC) are believed to be at risk of recurrence and often receive postoperative radiation therapy, which typically consists of a combination of external beam whole pelvic irradiation and vaginal brachytherapy. It remains unclear, however, whether both types of radiation are necessary. Pelvic radiation alone might be capable of sterilizing potential residual microscopic disease in the regional lymph nodes, obviating the need for brachytherapy. Although many investigators reported the outcomes of patients with stage I disease treated with surgery and adjuvant radiotherapy, 1‐10 few focused on the outcomes of patients treated with postoperative pelvic radiation alone. 11‐14 Most published reports included patients without deep myometrial invasion and at low risk for local (vaginal) recurrence. 15

To determine the optimal treatment volume in Hodgkin's disease patients undergoing high-dose chemotherapy (HDCT) and radiation therapy (RT), failure sites were reviewed in 56 patients. Twenty-one (38%) received involved-field RT (IFRT) before or after HDCT encompassing sites of prior disease. Failure sites were designated as previously involved (old) or uninvolved (new) sites. Seven patients (12%) died in the immediate post-HDCT period, leaving 49 evaluable (median follow-up, 41 months). Twenty-five patients (51%) relapsed (14 HDCT, 11 HDCT + IFRT): seven (28%) in old, eight (32%) in new, and ten (40%) in old and new sites. Six of the seven who relapsed in old sites received HDCT alone, whereas seven of the eight who relapsed in new sites received IFRT. Relapse in old sites was particularly common in patients failing to achieve a complete response. The most common new failure site was nodal, occurring in 11 patients and was primarily (10/11) adjacent to an old site. Although it controls prior disease, IFRT is insufficient in Hodgkin's disease patients undergoing HDCT. Relapse is common in new nodal sites and is primarily adjacent to prior sites. These results suggest that extended-field RT encompassing old and adjacent uninvolved nodal sites may be the optimal treatment volume in these patients. Radiat. Oncol. Invest. 7:353–359, 1999. © 1999 Wiley-Liss, Inc.

Objectives. The aim of this study was to examine factors underlying differences in outcome between African-American (AA) and Caucasian (C) patients undergoing radiation therapy (RT). Methods. Patient, tumor, treatment characteristics, and the outcome of 316 AA and 94 C cervical cancer patients who underwent RT were compared. Median follow-up was 72.4 months. Results. AA patients had a trend to a poorer 8-year cause-specific survival (47.9 vs 60.6%) ( P = 0.10) compared to C patients with a significant difference seen in stage IIB–IVA disease (34.3 vs 59.5%) ( P = 0.04). Several factors correlated with poor outcome were present in the AA group including lower mean hemoglobin levels during RT ( P = 0.001), lower median income ( P = 0.001), and less frequent intracavitary RT ( P = 0.09). In addition, while uncommon in C patients, health problems were major reasons for treatment protraction and inability to undergo intracavitary RT in the AA patients. Multivariate analysis demonstrated that race was not an independent prognostic factor after controlling for difference in patient, tumor, and treatment factors. Conclusions. AA cervical cancer patients possess multiple factors that adversely impact upon the efficacy of RT. These findings may add further insight into the observed differences in outcome of cervical cancer patients based on race.

Exposure to ionizing radiation is unavoidable for the many cancer patients that require radiotherapy as a component of their treatment. Radiation exposure also occurs from rare events, such as nuclear power plant malfunctions, terrorist attacks with “dirty bombs,” or detonation of nuclear weapons. The Chernobyl and Fukushima Daiichi disasters have demonstrated that the first responders to such emergencies have particularly high risks of radiation exposure. The types of ailments that victims suffer following total body exposures are dose-dependent (1). With total body exposures of

The primary objective of radiation oncology is to exploit the biological interaction of radiation within tissue to promote tumor death while minimizing damage to surrounding normal tissue. The clinical delivery of radiation relies on principles of radiation physics that define how radiation energy is deposited in the body, as well as technology that facilitates accurate tumor targeting. This review will summarize the current landscape of recent biological and technological advances in radiation oncology, describe the challenges that exist, and offer potential avenues for improvement.

Homologous recombination serves multiple roles in DNA repair that are essential for maintaining genomic stability. We here describe RI-1, a small molecule that inhibits the central recombination protein RAD51. RI-1 specifically reduces gene conversion in human cells while stimulating single strand annealing. RI-1 binds covalently to the surface of RAD51 protein at cysteine 319 that likely destabilizes an interface used by RAD51 monomers to oligomerize into filaments on DNA. Correspondingly, the molecule inhibits the formation of subnuclear RAD51 foci in cells following DNA damage, while leaving replication protein A focus formation unaffected. Finally, it potentiates the lethal effects of a DNA cross-linking drug in human cells. Given that this inhibitory activity is seen in multiple human tumor cell lines, RI-1 holds promise as an oncologic drug. Furthermore, RI-1 represents a unique tool to dissect the network of reaction pathways that contribute to DNA repair in cells.

BACKGROUND: A subset of patients with metastatic cancer in limited organs may benefit from metastasis-directed therapy. The authors investigated whether patients with limited metastases could be safely treated with metastasis-directed radiotherapy. METHODS: Patients with 1 to 5 metastatic cancer sites with a life expectancy of >3 months received escalating stereotactic body radiotherapy (SBRT) doses to all known cancer sites. Patients were followed radiographically with CT scans of the chest, abdomen, and pelvis and metabolically with fluorodeoxyglucose-positron emission tomography, 1 month after treatment, and then every 3 months. Acute toxicities were scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0, and late toxicities were scored using the Radiation Therapy Oncology Group late toxicity scoring system. RESULTS: Sixty-one patients with 113 metastases were enrolled from November 2004 to November 2009 on a prospective radiation dose escalation study. Median follow-up was 20.9 months. Patients tolerated treatment well; the maximal tolerated dose was not reached in any cohort. Eleven patients (18.3%) have not progressed. One and 2-year progression-free survival are 33.3% (95% confidence interval [CI], 22.8-46.1) and 22.0% (95% CI, 12.8-34.4); 1-year and 2-year overall survival are 81.5% (95% CI, 71.1-91.1) and 56.7% (95% CI, 43.9-68.9). Seventy-two percent of patients whose tumors progressed did so in limited (1-3) metastatic sites. CONCLUSIONS: Patients with 1 to 5 metastases can be safely treated to multiple body sites and may benefit from SBRT. Further investigation should focus on patient selection. Cancer 2011;. © 2011 American Cancer Society.

The use of ionizing radiation for the treatment of cancer dates back to the late 19th century, remarkably soon after Roentgen described X-rays in 1895 and the use of brachytherapy after Marie and Pierre Curie discovered radium in 1898. These initial efforts stimulated a revolution of conceptual and

Radiation therapy and chemotherapy are commonly used treatments for head and neck cancer. RAD51 is a highly conserved DNA repair protein that serves a central function in the homologous recombination pathway. High levels of RAD51 protein expression have been reported in number of human cancer cell lines, and studies suggest that RAD51 overexpression can increase cellular resistance to radiation and some chemotherapeutic drugs. In this study, RAD51 protein levels were quantified by immunohistochemistry in tumor samples from twelve head and neck cancer patients who received identical treatment with induction chemotherapy (paclitaxel and carboplatinum) followed by radiation therapy given concurrently with additional chemotherapy (paclitaxel, fluorouracil, hydroxyurea). Patients with high RAD51 protein levels in their pre-treatment tumor biopsies demonstrated poorer cancer-specific survival rates than patients with lower RAD51 levels (33.3% vs. 88.9% at 2 years; p=0.025). In addition, within a subgroup of patients with normal tumor cell p53 expression, there was a non-significant trend toward better induction chemotherapy response rates observed in the tumors with lower RAD51 protein levels. These results suggest that tumor cell RAD51 expression levels may influence the outcome of patients with head and neck cancer treated with chemotherapy and radiotherapy.

Radiation therapy and chemotherapy are commonly used treatments for head and neck cancer. RAD51 is a highly conserved DNA repair protein that serves a central function in the homologous recombination pathway. High levels of RAD51 protein expression have been reported in number of human cancer cell lines, and studies suggest that RAD51 overexpression can increase cellular resistance to radiation and some chemotherapeutic drugs. In this study, RAD51 protein levels were quantified by immunohistochemistry in tumor samples from twelve head and neck cancer patients who received identical treatment with induction chemotherapy (paclitaxel and carboplatinum) followed by radiation therapy given concurrently with additional chemotherapy (paclitaxel, fluorouracil, hydroxyurea). Patients with high RAD51 protein levels in their pre-treatment tumor biopsies demonstrated poorer cancer-specific survival rates than patients with lower RAD51 levels (33.3% vs. 88.9% at 2 years; p=0.025). In addition, within a subgroup of patients with normal tumor cell p53 expression, there was a non-significant trend toward better induction chemotherapy response rates observed in the tumors with lower RAD51 protein levels. These results suggest that tumor cell RAD51 expression levels may influence the outcome of patients with head and neck cancer treated with chemotherapy and radiotherapy.

Background/aims: The authors have previously reported a short term mean 15 month follow up of nasolacrimal intubation in adults. The effectiveness of this procedure for long term (mean 78 months) control of epiphoria is assessed here. Methods: 65 eyes from 40 patients who underwent nasolacrimal intubation were followed. Mean age at intubation was 59.2 years. The mean follow up period was 6.2 years. The results were based on long term symptomatic improvement. Results: Complete long term resolution of symptoms was reported in 50.7%. A partial improvement was reported in 38.5%, and no improvement in 10.7%. A better outcome was associated with a canalicular than nasolacrimal duct obstruction. On long term follow up 16.9% required dacrocysto-rhinostomy (DCR). Conclusion: Nasolacrimal intubation, a minimally invasive procedure is successful in the long term control of epiphora. Selection of patients with canalicular duct obstruction gives higher success rates with fewer patients subsequently requiring the DCR procedure.

Objectives: To compare normative beliefs about sexual health in young men and women from black Caribbean, black African, and white ethnic groups in order to better understand ethnic inequalities in sexual health. Methods: Focus group discussions with young people living in an area with known high prevalence of gonorrhoea and chlamydia. Groups were stratified by sex and self defined ethnicity. Results: 22 male and 20 female 16–25 year olds of black Caribbean, black African, and white ethnicity took part in eight discussions. Participants from black ethnic groups were more aware of gonorrhoea than white participants but all ethnic groups regarded these as being less important than unplanned pregnancy or HIV/AIDS. Most participants believed that they would have obvious symptoms if they had a sexually transmitted infection and could determine the cleanliness of sexual partners by visual or behavioural cues. Black Caribbean women were alone in acknowledging the likelihood of their partners having concurrent sexual relationships. Some black Caribbean women described negative attitudes of staff in genitourinary medicine clinics who were from the same ethnic background. Conclusion: In this focus group study we identified ethnic differences in terminology, awareness of sexually transmitted infections, non-exclusive sexual relationships, and experience of sexual health services but gender had a greater influence on normative beliefs. The similarities in norms for all ethnic groups might reflect common social and cultural exposures. The low priority given to sexually transmitted infections by young people from all ethnic groups needs to be addressed if they are to be tackled successfully.

Ionizing radiation (IR) has been used to treat human malignancies since the early part of the 20th century. To date, most of the advances in radiotherapy have focused on optimization of treatment delivery schedules and technologic improvements in the physical targeting of dose. By comparison, many of the discoveries regarding the molecular basis of DNA damage and repair have not yet been translated to clinical practice. This article offers some perspectives regarding modulators of radiation effects and the challenges faced as we approach newer molecular targets. Our goal is to frame the issues that contribute to the apparent disconnect between laboratory discoveries and improvements in clinically relevant therapeutics.

Objective: To determine the outcome, pattern(s) of failure, and optimal treatment volume in Stage IIIC endometrial carcinoma patients treated with surgery and postoperative radiation therapy (RT). Methods: Between 1983 and 1998, 30 Stage IIIC endometrial carcinoma patients were treated with primary surgery and postoperative RT at the University of Chicago. All underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, sampling of pelvic lymph nodes (PLN), and peritoneal cytology. All were noted to have PLN involvement. Para-aortic lymph nodes (PALN) were sampled in 26 cases, and were positive in 14 cases (54%). Twenty women received whole-pelvic RT (WPRT) and 10 (WPRT), plus paraortic RT (extended-field RT, EFRT). One EFRT patient also underwent concomitant whole-abdominal RT (WART). Adjuvant vaginal brachytherapy (VB) was delivered in 10, chemotherapy in 5, and hormonal therapy in 7 patients. Results: At a median follow-up of 32 months, the actuarial 5-year disease-free and cause-specific survivals of the entire group were 33.9% and 55.8%, respectively. Overall, 16 women (53%) relapsed. Sites of failure included the pelvis (23%), abdomen (13%), PALN (13%), and distant (40%). Of the 7 pelvic failures, 4 were vaginal (3 vaginal only). Patients treated with VB had a trend to a lower vaginal recurrence rate (0/10 vs. 4/20, p = 0.12) than those not receiving VB. All 4 PALN failures were in women treated with WPRT (2 negative, 1 unsampled, and 1 positive PALN). None of the 10 EFRT patients (2 negative, 8 positive PALN) recurred in the PALN. No patient developed an isolated abdominal recurrence. Two patients developed significant RT sequelae: chronic diarrhea in 1 patient treated with WPRT and VB, and small bowel obstruction in 1 patient treated with EFRT. Conclusion: FIGO Stage IIIC disease comprises a small percentage of endometrial carcinoma patients but carries a poor prognosis. Our failure pattern suggests that the optimal adjuvant RT volume is EFRT, even in women with negative PALN sampling. VB should also be administered to improve local control. The low rate of abdominal recurrence does not support the routine use of WART in these women. Given the predominance of failure in distant sites, attention should be focused on the development of systemic chemotherapy protocols.

To evaluate the risk of pelvic recurrence (PVR) in high-risk pathologic Stage I--IV endometrial carcinoma patients after adjuvant chemotherapy alone.Between 1992 and 1998, 43 high-risk endometrial cancer patients received adjuvant chemotherapy. All patients underwent primary surgery consisting of total abdominal hysterectomy and bilateral salpingo-oophorectomy. No patients received preoperative radiation therapy (RT). Regional lymph nodes and peritoneal cytology were sampled in 62.8% and 83.7% of cases, respectively. Most patients had Stage III--IV disease (83.7%) or unfavorable histology tumors (74.4%). None had evidence of extra-abdominal disease. All patients received 4-6 cycles of chemotherapy as the sole adjuvant therapy, consisting primarily of cisplatin and doxorubicin. Recurrent disease sites were divided into pelvic (vaginal, nonvaginal) and extrapelvic (para-aortic, upper abdomen, liver, and extra-abdominal). Median follow-up was 27 months (range, 2--96 months).Twenty-nine women (67.4%) relapsed. Seventeen (39.5%) recurred in the pelvis and 23 (55.5%) in extrapelvic sites. The 3-year actuarial PVR rate was 46.5%. The most significant factors correlated with PVR were cervical involvement (CI) (p = 0.01) and adnexal (p = 0.05) involvement. Of the 17 women who developed a PVR, 8 relapsed in the vagina, 3 in the nonvaginal pelvis, and 6 in both. The 3-year vaginal and nonvaginal PVR rates were 37.8% and 26%, respectively. The most significant factor correlated with vaginal PVR was CI (p = 0.0007). Deep myometrial invasion (p = 0.02) and lymph nodal involvement (p = 0.03) were both correlated with nonvaginal PVR. Nine of the 29 relapsed patients (31%) developed PVR as their only (6) or first site (3) of recurrence. Factors associated with a higher rate of PVR (as the first or only site) were CI and Stage I--II disease.PVR is common in high-risk pathologic Stage I-IV endometrial cancer patients after adjuvant chemotherapy alone. These results support the continued use of locoregional RT in patients undergoing adjuvant chemotherapy. Further studies are needed to test the addition of chemotherapy to locoregional RT.

The purpose of this report is to analyze the role and optimum integration of chemotherapy for invasive carcinoma of the esophagus in the combined modality setting. The charts of 157 patients with primary invasive nonmetastatic carcinoma of the esophagus treated with curative intent between 1984 and 1998 were reviewed. Various combinations of chemotherapy (C), radiotherapy (R), and surgery (S) were used. Chemotherapy was multiagent (typically 5-fluorouracil [5-FU]/cisplatin/hydroxyurea, 5-FU/cisplatin/leucovorin, or docetaxel/cisplatin) for all but seven patients treated with single agents. The clinical endpoints examined were overall survival (OS) and cause-specific survival (CSS). Multivariate analyses and pairwise comparisons were made for determination of the benefit of chemotherapy. On the multivariate analyses, only American Joint Committee on Cancer stage and chemotherapy were statistically significant determinants of both OS and CSS. Following are the results of the pairwise analyses: 3-year OS: (no C) versus (any C): 16% versus 27% (p = 0.02); (S) versus (C+S): 19% versus 34% (p = 0.35); (R) versus (C+R): 0% versus 13% (p = 0.05); (R + S) versus (C + R + S): 18% versus 33% (p = 0.03). The administration of adjuvant chemotherapy can improve survival in patients with invasive nonmetastatic esophageal carcinoma. This benefit appears to be greater when chemotherapy is given with radiotherapy (with or without surgery) than in the absence of radiotherapy, perhaps because of a radiosensitizing effect not possible when using surgery is the only local control modality.

PURPOSE: African-American (AA) men with prostate cancer present with advanced disease, relative to white (W) men. This report summarizes our clinical and biochemical control (bNED) rates after conformal radiotherapy (RT). In particular, we aim to characterize any race-based outcome differences seen after comparable treatment. PATIENTS AND METHODS: We reviewed 893 patients (418 AA and 475 W) with clinically localized prostate cancer treated between 1988 and 1997. Neoadjuvant hormonal blockade was used in 22.5% of cases, and all patients received conformal RT to a median dose of 68 Gy (range, 60 to 74.8 Gy). Biochemical failure was defined according to the American Society of Therapeutic Radiology and Oncology consensus definition. Median follow-up was 24 months (range, 1 to 114 months). RESULTS: The 5-year actuarial survival, disease-free survival, and bNED rates for the entire population were 80.5%, 70.0%, and 57.6%, respectively. When classified by prognostic risk category, the 5-year actuarial bNED rates were 78.7% for favorable, 57.7% for intermediate, and 39.8% for unfavorable category patients. AA men presented at younger ages and with more advanced disease. Controlled for prognostic risk category, AA and W men had similar 5-year actuarial bNED rates in favorable (78% v 79%, P = .91), intermediate (52% v 62%, P = .44), and unfavorable categories (36% v 45%, P = .09). Race was not an independent prognostic factor (P = .36). CONCLUSION: Conformal RT is equally effective for AA and W patients. More research is needed in order to understand and correct the advanced presentations in AA men. These data suggest a need for early screening in AA populations.

Synchronous ovarian primaries are infrequently found in patients with endometrial cancer. Although numerous investigators have examined the characteristics of these women, most include patients with tumors of similar histology, which may simply represent ovarian metastases. To overcome this problem, we present here patients found to have tumors of dissimilar histology. Of 499 patients with endometrial cancer undergoing primary surgery between 1980 and 1997, 18 (3.6%) were found to have endometrial and ovarian primaries of dissimilar histology. The median age was 64.2 years. Most had stage I, grades I and II, minimally invasive endometrial adenocarcinomas and stage IA mucinous or serous ovarian cystadenocarcinomas. Most ovarian tumors were either borderline or grades I and II. The 5-year actuarial disease-free (DFS) and cause-specific survivals of the entire group were 81.2% and 89.5%, respectively. Those with both stage I ovarian and endometrial primaries had a trend to a better DFS (100 versus 68.6%, p = 0.07) than did women with higher stage disease. Our data demonstrate that synchronous ovarian primaries of dissimilar histology are infrequently found in women undergoing surgery for endometrial cancer. These women seek treatment at a relatively advanced age, and have early-stage, low grade disease in both sites. Their outcome is favorable, particularly those with stage I disease in both sites.

Recent reports have suggested that the pathologic features of young patients with endometrial cancer are less favorable than previously thought. We retrospectively reviewed the characteristics and outcome of young patients with endometrial cancer at our institution. A total of 457 surgically staged patients were divided in 2 groups: Group A (ageor =45 years, n = 41) and B (age45, n = 416). Groups A and B had a similar distribution of tumor stage, grade, histology, lymphovascular invasion, synchronous ovarian primaries, and positive cytology. Although group A tumors had less myometrial invasion (MI) (p = 0.004) and were lower grade (p = 0.06), a trend to more frequent nodal involvement was seen in group A women (p = 0.09). Adverse pathologic features, in particular deep MI, were more common in group A patients older than age 40. Group A patients had a disease-free (p = 0.56) and cause-specific (p = (0.26) survival that was similar to that of group B patients. Young patients with endometrial cancer have a distribution of most pathologic features and equivalent outcome similar to that of older women. However, adverse features are not equally distributed in young women. A discordance may also exist between MI, grade, and nodal involvement.

Purpose. The purpose of this study was to compare the outcomes of early stage cervical cancer patients undergoing definitive radiation therapy (RT) with one versus two low-dose-rate intracavitary brachytherapy (ICB) applications. Methods and materials. Between 1983 and 1993, 140 stage IB–IIA patients underwent whole-pelvis RT (WPRT) and ICB. Prior to 1988, 56 patients (40%) received two ICB applications. After 1988, our policy was modified and subsequently 84 (60%) patients underwent one application. Patient, tumor, and treatment characteristics, outcome, and complications of the two groups were compared. Results. The groups were balanced in terms of race, hemoglobin level, histology, grade, treatment duration, chemotherapy, and follow-up. The single-application group, however, had more stage IB disease, had small (≤4 cm) tumors, and received higher WPRT and lower point A doses. Overall, the two groups had similar 5-year local control ( P = 0.83) and disease-free ( P = 0.23) and cause-specific ( P = 0.29) survival rates. Moreover, no differences were seen when analyzed by tumor size or stage. On multivariate analysis, the number of applications was not correlated with recurrence ( P = 0.59, hazard rate=1.1, 95% confidence interval=0.6–2.2). Chronic complications were similar in the two groups. Conclusion. Our nonselected comparison of one versus two ICB applications in early-stage cervical cancer patients reveals comparable outcomes and complication rates for the two approaches. These results support the use of a single application in early-stage patients undergoing definitive RT.

To evaluate the prognostic significance of and predictive factors for adnexal involvement (AI) in patients with endometrial carcinoma.We retrospectively reviewed the pathological features and outcomes of endometrial carcinoma patients. The prognostic significance of AI was examined by univariate and multivariate analyses. Median follow-up was 30.7 months.Of the 382 cases reviewed, 40 (10.5%) had AI. Patients with AI had a worse 5-year disease-free (DFS) survival (73.1 vs 37.1%, P0.0001) than patients without AI. However, patients with AI had multiple adverse features, including high grade disease, lymphovascular invasion, and additional sites of extrauterine disease. After controlling for these factors on multivariate analysis, AI lost its prognostic significance (P = 0.56). The 12 AI patients without other extrauterine disease had a favorable outcome (5-year DFS of 70.9%). Factors predictive of AI on logistic regression were metastatic disease, positive peritoneal washings, cervical involvement, and unfavorable histology.Endometrial carcinoma patients with AI have relatively poor prognoses. However, AI per se has little, if any, independent prognostic significance. The poor outcomes seen in these patients appear to result from the preponderance of other adverse pathologic factors.

RAD51 is the central strand exchange recombinase in somatic homologous recombination, providing genomic stability and promoting resistance to DNA damage. An important tool for mechanistic studies of RAD51 is the D-loop or strand assimilation assay, which measures the ability of RAD51-coated single-stranded DNA (ssDNA) to search for, invade and exchange ssDNA strands with a homologous duplex DNA target. As cancer cells generally overexpress RAD51, the D-loop assay has also emerged as an important tool in oncologic drug design programs for targeting RAD51. Previous studies have adapted the traditional gel-based D-loop assay by using fluorescence-based substrates, which in principle allow for use in high-throughput screening platforms. However, these existing D-loop methods depend on linear oligonucleotide DNA duplex targets, and these substrates enable recombinase-independent ssDNA annealing that can obscure the recombinase-dependent strand assimilation signal. This compelled us to fundamentally re-design this assay, using a fluorescent target substrate that consists of a covalently closed linear double-hairpin dsDNA. This new microplate-based method represents a fast, inexpensive and non-radioactive alternative to existing D-loop assays. It provides accurate kinetic analysis of strand assimilation in high-throughput and performs well with human RAD51 and Escherichia coli RecA protein. This advance will aid in both mechanistic studies of homologous recombination and drug screening programs.

7062 Background: Pemetrexed (pem, Alimta) is a multitargeted antifolate approved for second-line treatment of metastatic non-small cell lung cancer (NSCLC). Treatment failure with chemoradiotherapy...

SummaryThe cellular DNA repair hRAD51 protein has been shown to restrict HIV-1 integration both in vitro and in vivo. To investigate its regulatory functions, we performed a pharmacological analysis of the retroviral integration modulation by hRAD51. We found that, in vitro, chemical activation of hRAD51 stimulates its integration inhibitory properties, whereas inhibition of hRAD51 decreases the integration restriction, indicating that the modulation of HIV-1 integration depends on the hRAD51 recombinase activity. Cellular analyses demonstrated that cells exhibiting high hRAD51 levels prior to de novo infection are more resistant to integration. On the other hand, when hRAD51 was activated during integration, cells were more permissive. Altogether, these data establish the functional link between hRAD51 activity and HIV-1 integration. Our results highlight the multiple and opposite effects of the recombinase during integration and provide new insights into the cellular regulation of HIV-1 replication.