Journal Club

Members of the Ovarian Cancer Center team will periodically provide summaries and commentary on current topics of interest from select scientific journals.  Please bookmark this page and check for monthly updates to keep you abreast of the latest advances in ovarian cancer care.

Recent publications.....

Survival impact of multiple bowel resections in patients undergoing primary cytoreductive surgery for advanced ovarian cancer: A case-control study.

Salani R, Zahurak ML, Santillan A, Giuntoli RL 2nd, Bristow RE.

The incidence of primary fallopian tube cancer in the United States.

National Program of Cancer Registries, Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, 4770 Buford Highway, K-53, Atlanta, GA 30341, USA.

OBJECTIVE: The objective of this study was to report the incidence of primary fallopian tube carcinoma (PFTC) in the United States population and to describe associated demographic and clinical factors.

METHODS: A total of 3051 PFTC cases diagnosed from 1998 to 2003, reported from population-based cancer registries, were analyzed. Registries contributing data represent 83.1% of the U.S. population. Data are presented by age, race/ethnicity, U.S. census region, stage, histology, grade, and laterality. Trends in incidence over time from 1998 to 2003 are also presented.

RESULTS: The incidence rate was 0.41 per 100,000 women from 1998 to 2003. White, non-Hispanic women and women aged 60-79 had the highest incidence rates (p<0.0001). The majority (88%) of PFTCs were adenocarcinomas; serous adenocarcinomas accounted for 44% and endometrioid adenocarcinomas for 19% of adenocarcinoma diagnoses. Essentially half (49.9%) of PFTCs were poorly differentiated; 89% were unilateral at diagnosis. Stage at diagnosis was fairly evenly distributed among localized (36%), regional (30%), and distant (32%). Overall, rates of PFTC remained stable over time. Among women aged 65-69, incidence rates increased significantly by 3.8% per year from 1998 to 2003 (p<0.05).

CONCLUSIONS: This report provides characteristics of PFTC using the largest number of cases assembled in one study to date. Although the demographic characteristics of PFTC are similar to those of ovarian cancer, stage at diagnosis and the stable trend observed in PFTC are in contrast to ovarian cancer. Future studies should focus on examining the increasing trend of PFTC among 65- to 69-year-old women.

Is it justified to classify patients to Stage IIIC epithelial ovarian cancer based on nodal involvement only?

Cliby WA, Aletti GD, Wilson TO, Podratz KC.

Department of Obstetrics and Gynecology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.

BACKGROUND.: Stage IIIC epithelial ovarian cancer is generally associated with upper abdominal tumor implants of greater than 2 cm and carries a grave prognosis. A subset of patients is upstaged to Stage IIIC because of lymph node metastases, in which prognosis is not well defined. We undertook this study to describe the clinical behavior of occult Stage IIIC.

METHODS.: All consecutive patients found to have Stage IIIC epithelial ovarian cancer during a 9-year period (1994-2002) were analyzed for surgical procedures, pathology, and disease-free (DFS) and overall survival (OS).

RESULTS.: Thirty-six patients were upstaged to Stage IIIC by virtue of positive nodes. Nine had small volume upper abdominal disease (IIIA/B before upstaging), 15 had disease limited to the pelvis and 12 had disease confined to the ovaries. 32/36 patients had no gross residual disease at the conclusion of surgery. The 5-year DFS and OS survivals were 52% and 76% respectively, for all patients. We observed no significant difference in outcomes between patients upstaged from IIIA/B versus I-II stage disease. The outcomes were superior to a control group of patients cytoreduced to either no gross RD or RD<1 cm, who had large volume upper abdominal disease at beginning of surgery (p<0.001).

CONCLUSIONS.: Patients upstaged to Stage IIIC epithelial ovarian cancer for node involvement have an excellent 5-year OS relative to all patients with Stage IIIC disease. These data demonstrate the necessity for stratifying patients classified as having Stage IIIC disease based solely on nodal disease when comparing outcomes. This information is particularly valuable when counseling patients regarding prognosis.

Journal Club Archives

Frequency of Symptoms of Ovarian Cancer in Women Presenting to Primary Care Clinics

Barbara A. Goff, MD; Lynn S. Mandel, PhD; Cindy H. Melancon, RN; Howard G. Muntz, MD

JAMA. 2004;291:2705-2712.

Context  Women with ovarian cancer frequently report symptoms prior to diagnosis, but distinguishing these symptoms from those that normally occur in women remains problematic.

Objective  To compare the frequency, severity, and duration of symptoms between women with ovarian cancer and women presenting to primary care clinics.

Design, Setting, and Patients  A prospective case-control study of women who visited 2 primary care clinics (N = 1709) and completed an anonymous survey of symptoms experienced over the past year (July 2001-January 2002). Severity of symptoms was rated on a 5-point scale, duration was recorded, and frequency was indicated as number of episodes per month. An identical survey was administered preoperatively to 128 women with a pelvic mass (84 benign and 44 malignant).

Main Outcome Measures  Comparison of self-reported symptoms between ovarian cancer patients and women seeking care in primary care clinics.

Results  In the clinic population, 72% of women had recurring symptoms with a median number of 2 symptoms. The most common were back pain (45%), fatigue (34%), bloating (27%), constipation (24%), abdominal pain (22%), and urinary symptoms (16%). Comparing ovarian cancer cases to clinic controls resulted in an odds ratio of 7.4 (95% confidence interval [CI], 3.8-14.2) for increased abdominal size; 3.6 (95% CI, 1.8-7.0) for bloating; 2.5 (95% CI, 1.3-4.8) for urinary urgency; and 2.2 (95% CI, 1.2-3.9) for pelvic pain. Women with malignant masses typically experienced symptoms 20 to 30 times per month and had significantly more symptoms of higher severity and more recent onset than women with benign masses or controls. The combination of bloating, increased abdominal size, and urinary symptoms was found in 43% of those with cancer but in only 8% of those presenting to primary care clinics.

Conclusions  Symptoms that are more severe or frequent than expected and of recent onset warrant further diagnostic investigation because they are more likely to be associated with both benign and malignant ovarian masses.

Johns Hopkins ovarian cancer researchers presented the following abstracts at the March 2005 Annual Society of Gynecologic Oncologists meeting in Miami Beach, Florida.  More information on the meeting.

Program#/Poster#: 231
Presentation Title: The role of cytoreductive surgery for colon cancer metastatic to the ovary
Authors: Colleen C. McCormick, Robert L. Giuntoli II, Ginger J. Gardner, Richard D. Schulick, Robert E. Bristow. Johns Hopkins, Baltimore, MD
Objectives: To evaluate the survival impact of cytoreductive surgery among patients with colon cancer metastatic to the ovary.
Methods: All women diagnosed with primary colon cancer metastatic to the ovary at our institution from 1980-2004 were retrospectively identified from the tumor registry database. Survival analyses and comparisions were preformed using Kaplan-Meier plots and the log rank test.
Results: A total of 53 patients with colon cancer metastatic to the ovary were identified. Patients with metastatic disease confined to the ovaries (n=12) had a median overall survival time of 61 months (range 14-120 months) compared to 13 months (range 0.5-34 months) for women with more extensive metastasis (n=41) (p=0.03). For patients undergoing optimal cytoreduction (residual ¡Ü 1 cm) the median time to progression (PFS) was 11 months (range 1-32 months, n=28) compared to 4 months (range 2-12 months, n=14) for patients left with suboptimal residual disease (p=0.006). Optimal cytoreduction was associated with a significantly longer median overall survival time (OS) (31 months, range 0.5-120 months) compared to patients with suboptimal residual disease (median OS=7 months, range = 0.5-19 months) (p<0.001). The peri-operative mortality rate was 5.7%, and significant morbidity occurred in 7.5% of the cases. All major complications occurred in women with diffuse disease who underwent extensive cytoreductive surgery.
Conclusions: Colon cancer presenting as isolated ovarian metastasis is associated with a favorable survival outcome. For patients with ovarian and extra-ovarian metastatic disease, optimal cytoreduction is associated with prolonged PFS and OS. Further studies are warranted to further define those patients most likely to benefit from an aggressive surgical approach.

Program#/Poster#: 49
Presentation Title: Combined PET/CT for detecting recurrent ovarian cancer limited to retroperitoneal lymph nodes
Presentation Start/End Time: Wednesday, Mar 23, 2005, 8:00 AM - 8:08 AM
Authors: Robert E. Bristow, Robert L. Giuntoli II, Harpreet K. Pannu, Richard D. Schulick, Ginger J. Gardner, Richard L. Wahl, Elliot K. Fishman. The Johns Hopkins Medical Institutions, Baltimore, MD
Objectives: To evaluate the utility of combined positron emission tomography/computed tomography (PET/CT) for detecting recurrent epithelial ovarian cancer limited to retroperitoneal adenopathy.
Methods: Fourteen patients (median age = 53 years) with rising serum CA125 levels, and negative or equivocal conventional CT imaging ¡Ý6 months after primary therapy were retrospectively identified as having recurrent disease limited to retroperitoneal lymph nodes by combined PET/CT and underwent surgical reassessment of targeted nodal basins. Fisher¡¯s exact test was used to measure the ability of PET/CT to predict isolated retroperitoneal nodal disease.
Results: The median increase in serum CA125 from the baseline nadir level was 14U/ml (range = 2 - 76U/ml). There were 29 target nodes in 15 nodal basins (7 pelvic, 8 para-aortic) identified with increased metabolic uptake on combined PET/CT. For pelvic and para-aortic nodal basins, an average of 10.5 and 8.8 nodes were retrieved, respectively. Eleven patients (78.6%) had recurrent ovarian cancer in retroperitoneal lymph nodes targeted by PET/CT. Of 143 nodes retrieved, 59 contained recurrent ovarian cancer (median maximal nodal diameter = 2.5cm, range = 0.8 - 5.2cm). For all target nodal basins, the sensitivity, specificity, positive and negative predictive values, and accuracy for recurrent ovarian cancer in dissected lymph nodes were: 40.7% (24/59), 94.0% (79/84), 82.8% (24/29), 69.3% (79/114), and 72.0% (103/143) (p<0.001). PET/CT failed to identify microscopic disease in 59.3% of pathologically positive nodes.
Conclusions: Combined PET/CT demonstrates high positive predictive value in identifying recurrent ovarian cancer in retroperitoneal lymph nodes when conventional CT findings are negative or equivocal. The high incidence of occult disease within the target nodal basins suggests that regional lymphadenectomy may be necessary for complete secondary cytoreduction of recurrent disease.

Program#/Poster#: 128
Presentation Title: Ovarian cancer surgical care for the elderly: a population-based perspective
Authors: Teresa P. Diaz-Montes, Mariana L. Zahurak, Robert L. Giuntoli II, Ginger J. Gardner, Toby A. Gordon, Deborah K. Armstrong, Robert E. Bristow. Johns Hopkins Medical Institution, Baltimore, MD
Objectives: To characterize the short-term outcomes and cost of primary surgical care for ovarian cancer in women age ¡Ý80 years compared to younger women.
Methods: A statewide hospital discharge database was used to identify women undergoing primary surgery for ovarian cancer from 1990-2000. Logistic regression models were used to evaluate for significant differences in demographic characteristics and short-term outcomes relating to the index hospital admission comparing women aged ¡Ý80 years with those aged <79 years.
Results: A total of 2417 women were identified; women aged ¡Ý80 years comprised 7.0% (n=168) of cases. Compared to younger women, those aged ¡Ý80 years were significantly more likely to be admitted under emergent conditions (25.6% vs 14.9%, p<0.001) and less likely to undergo surgery at a university hospital (6.6% vs 18.6%. p=0.001). Ovarian cancer patients aged ¡Ý80 years were significantly more likely to have a longer hospital stay (median 10 days vs 7 days, p<0.0001) and a higher adjusted cost of hospital related care (median $76759 vs $52649, p<0.0001). The 30-day mortality rate was 2.3-fold higher for women aged ¡Ý80 years (5.4% vs 2.4%, p=0.036). For women aged ¡Ý80 years, there was a trend toward a higher risk of peri-operative death among low-volume hospitals (8.8%) compared to high-volume hospitals (3.0%, p=0.16).
Conclusions: Primary surgical care for ovarian cancer in women aged ¡Ý80 years is associated with utilization of significant health care resources and worse short-term outcomes compared to younger women. Additional research is needed to identify opportunities for improving the cost-effectiveness of care in this population.
  
Program#/Poster#: 127
Presentation Title: Ovarian malignancy in breast cancer patients with an adnexal mass
Authors: Fiona Simpkins, Deborah Armstrong, Marianna Zahurak, Frances Grumbine, Robert Bristow. NCI, Bethesda, MD, Johns Hopkins Hospital, Baltimore, MD, Greater Baltimore Medical Center, Baltimore, MD
Objectives: The objectives of this study were to estimate ovarian malignancy rate in breast cancer patients with an adnexal mass, and to identify variables predictive of malignancy.
Methods: This was a review from 1990-2002 including women with breast cancer diagnosed with an adnexal mass who subsequently underwent oophorectomy. Ovarian pathology was classified as benign, primary malignancy or metastatic breast cancer. Women with preoperative evidence of malignancy were excluded.
Results: Of 129 cases reviewed, benign ovarian cysts were found in 113 cases (88%) and malignant ovarian neoplasms were found in 16 cases (12%). Univariate logistic regression analyses were performed to determine predictors of malignancy. Complex masses were 29 times more likely to be malignant, p<.0001. Women with ER- breast cancer had an increased risk for malignant adnexal masses, OR=12.4 (95%CI: 2.4,65.1), p=.003. Patients with an elevated CA-125 had a 6.0 fold increased risk of malignancy, p=0.02. Adnexal mass size greater than 5 cm also increased the risk of malignancy, OR=4.6 (95%CI: 1.2,17.3), p=0.02. Malignant adnexal masses had a greater likelihood of being primary ovarian cancer than metastatic breast cancer by 7:1.
Conclusions: An isolated adnexal mass in the breast cancer patient is most commonly a benign ovarian cyst. Adnexal masses associated with an increased CA-125, complex architecture by ultrasound, or size greater than 5cm are significant predictors of malignancy and are indications for referral to a gynecologic oncologist.

Program#/Poster#: 228
Presentation Title: Diagnostic Criteria for Uterine Smooth Muscle Tumors; Continued Refinement is Necessary.
Authors: Robert L. Giuntoli II, Bobbie S. Gostout, Connie S. DiMarco, Daniel S. Metzinger, Stephen S. Cha, Jeff A. Sloan, Gary L. Keeney. The Johns Hopkins Medical Institutions, Baltimore, MD, Mayo Clinic, Rochester, MN, University of Louisville, Louisville, KY
Objectives: Our ability to predict outcomes of smooth muscle tumors of the uterus is less than ideal. The goal of this investigation is to determine the prognostic value of the current diagnostic criteria for uterine leiomyosarcoma (LMS) and leiomyoma variants.
Methods: Retrospective analysis of uterine LMS patients, treated from 1976 - 1999. Uterine LMS specimens were reevaluated using current criteria by a single pathologist, specializing in gynecologic diseases. Survival curves were generated using the Kaplan-Meier method.
Results: Primary specimens were available from 67 patients, who were diagnosed with uterine LMS during the study period. Surprisingly, only 47 specimens were felt to represent a uterine LMS on re-review. The other 20 patients were deemed to have a leiomyoma or a leiomyoma variant including 13 cellular leiomyoma, 5 atypical leiomyoma, and 2 leiomyoma. The median survival for patients with uterine LMS was 2.1 years with 97% of disease specific deaths occurring within 6 years of diagnosis. In contrast, median survival in patients with uterine leiomyoma or a leiomyoma variant was > 25 years with the 3 disease specific deaths occurring more than 6 years after diagnosis. The majority of patients found have nonmalignant smooth muscle tumors on re-review underwent surgery prior to 1980.
Conclusions: Contemporary diagnostic criteria for uterine LMS appear to more accurately predict outcome. However, even with expert pathologic review using current criteria for LMS of the uterus, disease specific deaths are seen in patients with leiomyoma variants and long term disease free survival is occasionally seen in patients with LMS. The inability to precisely anticipate clinical behavior points to the need for continued refinement of the current system.
  
Program#/Poster#: 215
Presentation Title: The Role of Secondary Cytoreduction in the Management of Uterine Leiomyosarcoma.
Authors: Robert L. Giuntoli II, Connie S. DiMarco, Daniel S. Metzinger, Bobbie S. Gostout. The Johns Hopkins Medical Institutions, Baltimore, MD, Mayo Clinic, Rochester, MN, University of Louisville, Louisville, KY
Objectives: The recurrence rate for even early stage uterine leiomyosarcoma (LMS) is significant. The optimal management of recurrent uterine LMS remains unclear. The goal of this investigation is to define better the role of secondary cytoreductive surgery, chemotherapy and radiation therapy in the treatment of recurrent uterine LMS.
Methods: Between 1976 and 1999, 208 patients were evaluated at our institution for LMS of the uterus. Charts were retrospectively reviewed and relevant clinical and pathologic data extracted. Survival curves were generated using the methods of Kaplan and Meier and compared using the log rank test. P values < 0.05 were considered significant.
Results: Recurrences developed in 62% (128/208) of patients. Persistent disease was noted in 10% (21/208) of patients. Only 27% (56/208) of patients remained free of disease. The recurrence pattern could not be determined in 1% (3/208). Median time to recurrence was 1.25 years. At the time of first recurrence, location of disease was reported as local only, distant only, and both distant and local in 22% (28/128), 58% (74/128), and 20% (26/128) of patients respectively. Univariate analysis demonstrated neither chemotherapy nor radiation therapy to be associated with improvement in disease specific survival from time of first recurrence. However, secondary cytoreductive surgery was associated with significantly improved disease specific survival from time of first recurrence (p=0.0001). Subset analysis demonstrated this survival advantage to be maintained for patients with either local (p=0.0018) or distant (p=0.0003) disease, but not for patients with both local and distant disease (p=0.651).
Conclusions: Several studies have suggested a survival advantage for resection of pulmonary metastases in patients with recurrent uterine LMS. Although limited by its retrospective nature, our investigation supports these findings and indicates similar utility for surgical intervention in patients with pelvic recurrences. As with secondary cytoreduction in ovarian cancer, surgery appears to be more effective for patients with isolated disease.

Program#/Poster#: 94
Presentation Title: Micropapillary serous ovarian carcinoma: Manifestation of extreme drug resistance compared to high-grade serous ovarian carcinoma.
Authors: Antonio Santillan, Yong-Wook Kim, Moon-Seok Cha, Marianna L. Zahurak, Ginger J. Gardner, Robert L. Giuntoli II, Ie-Ming Shih, Robert E. Bristow. The Johns Hopkins Medical Institutions, Baltimore, MD
Objectives: To evaluate the pattern of chemoresistance in patients (MPSC) and in high-grade serous ovarian carcinoma (HGSC) according to (EDR) assay testing.
Methods: Forty-four patients with recurrent ovarian cancer of serous histology who underwent cytoreductive surgery between 8/99 and 2/04 and had surgical specimens harvested for EDR testing were identified retrospectively from the tumor registry database. Thirteen patients were recurrent MPSC and 31 patients were recurrent HGSC. Fisher¡¯s exact test and exact logistic regression models were used to evaluate for significant differences between MPSC and HGSC in the frequency of EDR to individual chemotherapeutic agents.
Results: Compared to HGSC, MPSC tumors were significantly more likely to manifest EDR to the drugs paclitaxel (69% vs. 14%, p<.001) and carboplatin (50% vs. 17%, p=0.05). MPSC tumors also were significantly less likely than HGSC to have EDR to etoposide (0% vs. 44%, p=0.007) and to doxorubicin (8% vs. 45%, p=0.03). Exact logistic regression estimates confirmed that MPSC was associated with a significantly increased probability of EDR to paclitaxel OR=12.5 (95% CI: 2.3, 100.0, p=0.001) and carboplatin OR=4.8 (95% CI: 0.9, 25.0, p=0.07) and a significantly decreased probability of EDR to etoposide OR= 0.08 (95% CI: ¡Þ, 0.59, p=0.009) and doxorubicin OR= 0.12 (95% CI: 0.002, 1.00, p=0.05) compared to HGSC. There were no significant difference in EDR between MPSC and HGSC for cyclophosphamide (40% vs. 23%), gemcitabine (36% vs. 19%) and topotecan (8% vs. 21%).
Conclusions: These data suggest that extreme drug resistance to standard platinum-paclitaxel chemotherapy may be more prevalent among patients with MPSC compared to those with HGSC. Further investigation and clinical correlation are needed to clarify the role of chemotherapy treatment for patients with MPSC.
  
 
Program#/Poster#: 134
Presentation Title: The role of secondary cytoreductive surgery for isolated nodal recurrence in patients with epithelial ovarian cancer.
Authors: Antonio Santillan, Andrew J. Li, Amer Karam, Ginger J. Gardner, Robert L. Giuntoli II, Ilana Cass, Beth Y. Karlan, Robert E. Bristow. The Johns Hopkins Medical Institutions, Baltimore, MD, Cedars-Sinai Medical Center, Los Angeles, CA
Objective: To evaluate the feasibility of cytoreductive surgery for isolated nodal recurrence of epithelial ovarian cancer and subsequent survival outcome.
Methods: From a multi-institutional tumor registry database, twenty patients with epithelial ovarian cancer who underwent cytoreductive surgery for isolated nodal recurrence were identified. Demographic, diagnostic, operative, pathologic, and follow-up data were abstracted retrospectively. Overall survival was calculated using the Kaplan-Meier method.
Results: The median age at time of cytoreductive surgery for ovarian cancer recurrence was 51 years, 85% of patients initially had FIGO III/IV disease. All had high grade carcinomas at diagnosis. After primary cytoreductive surgery, all patients received platinum-paclitaxel based combination chemotherapy.
The median time from completion of the primary chemotherapy to nodal recurrence surgery was 20 months (range=10 to 52 months). The distribution of nodal involment was pelvic = 35% (n=7), para-aortic = 45% (n=9), inguinal = 15% (n=3) and pericardiac = 5% (n=1). The maximal nodal tumor diameter ranged from 2.5cm to 14cm, with a median of 3.0cm. Optimal secondary cytoreductive surgery (residual disease ¡Ü1cm) was achieved in 95% of patients). The median estimated intraoperative blood loss was 100cc (range= 10cc to 800cc). The length of hospitalization ranged from 2 days to 10 days, with a median of 4 days. For all the patients, no significant morbidity was experienced. At last follow-up, 5 patients (25%) have died of the disease, 9 are alive with disease, and 4 patients are without evidence. For all patients, the overall five year survival rate from initial diagnosis was 64%. The median post-recurrence overall survival time after cytoreduction of recurrent nodal disease was 35 months (range=22 to 49 months).
Conclusion: Complete secondary cytoreductive surgery for recurrent epithelial ovarian cancer presenting as an isolated node metastases is achievable in the majority of cases with limited morbidity, and is associated with a favorable long-term survival outcome.
  

Program#/Poster#: 44
Presentation Title: The risk of epithelial ovarian cancer recurrence in patients with rising serum CA125 levels within the normal range. 
Presentation Start/End Time: Tuesday, Mar 22, 2005, 8:38 AM - 8:48 AM
Authors: Antonio Santillan, Ruchi Garg, Marianna L. Zahurak, Ginger J. Gardner, Robert L. Giuntoli II, Robert E. Bristow. The Johns Hopkins Medical Institutions, Baltimore, MD
Objective: To evaluate the risk of epithelial ovarian cancer recurrence in patients with rising serum CA-125 levels that remain below the upper limit of normal (<35U/ml).
Methods: All patients treated for epithelial ovarian cancer between 9/97 and 3/03 were identified from the tumor registry database and screened retrospectively for the following inclusion criteria: (1) elevated serum CA125 at time of diagnosis, (2) complete clinical and radiographic response (CR) to initial treatment with normalization of serum CA125 (<35U/ml), (3) serial serum CA-125 determinations (1 to 6 month intervals) that remained within the normal range, and (4) clinical and radiographic determination of disease status at the time of last follow-up or recurrence. For statistical analyses, univariate regression models were used to compare absolute and relative changes in CA125 levels among patients with recurrent disease and those without ovarian cancer recurrence.
Results: A total of 39 patients satisfied study inclusion criteria; 22 patients manifested ovarian cancer recurrence at a median interval from CR of 11 months. The median follow-up time from CR to last contact was 32 months for the 17 patients in the no-recurrence group. Among the patients diagnosed with ovarian cancer recurrence, the median absolute CA-125 level was 21U/ml (range= 8U/ml to 33U/m) at the time of recurrence. A relative increase in CA125 of 50% (odds ratio [OR] =4.5, 95% confidence interval [CI]=1.5-13.5, p<0.01) and 100% (OR=20.7, 95%CI=2.4-181.5, p<0.01) were both significantly predictive of recurrence. From baseline nadir levels, an absolute increase in CA125 of 5U/ml (OR=6.2, 95%CI=2.2-18.0, p<0.01) and 10U/ml (OR=38.7, 95%CI=4.6-324.1, p<0.01) were also significantly associated with the likelihood of concurrent disease recurrence.
Conclusions: Among patients with epithelial ovarian cancer in complete clinical remission, a progressive low-level increase in serum CA125 levels is strongly predictive of disease recurrence and should be further investigated by appropriate radiographic imaging studies.
  

Program#/Poster#: 95
Presentation Title: A Potential Biomarker Complementary to CA125 in Detecting Early Stage Ovarian Cancer 
Authors: Zhen Zhang, Robert C. Bast Jr., Yinhua Yu, Andrew Berchuck, H.W.A. De Bruijn, A.G.J. Van der Zee, Daniel W. Chan. Johns Hopkins University, Baltimore, MD, U.T. M.D. Anderson Cancer Center, Houston, TX, Duke University Medical Center, Durham, NC, University Hospital Groningen, Groningen, The Netherlands
Objectives:
Early detection remains the most promising approach to improve long-term survival of patients with ovarian cancer. The heterogeneous nature of ovarian cancer makes it less likely that a single marker will be sufficient to detect all types of ovarian cancers. The discovery and identification of new biomarkers that are complementary to existing tumor markers such as CA125 are urgently needed. The objective of this study is to use mass spectrometry to analyze the differential proteomic expressions in clinical serum specimens to search for such new biomarkers.
Methods:
A total of 273 retrospective serum samples collected at two sites were used in the study. It included 40 stages I/II invasive epithelial ovarian cancer, and 13 patients with borderline tumors, all optimally staged by pathologists based on FIGO criteria. Among the stages I/II invasive cases, 13 were serous, 14 were mucinous, 9 were endometrioid, and 4 were clear cell. The samples included also 141 patients with benign pelvic masses and 79 healthy donors as controls. All samples were collected prior to the day of surgery or treatment, stored at -70¡ãC, and thawed immediately prior to assay. CA125 levels had been previously obtained using a CA125II radioimmunoassay. Serum samples were first fractionated via anion exchange chromatography by stepwise pH gradient elution and the proteomic expression data were determined using surface-enhanced laser desorption and ionization. A software package implementing the unified maximum separability analysis was used to discover the potential biomarkers. The Mann-Whitney U Test was used to assess the differential power of the discovered markers.
Results:
A potential biomarker from fraction pH4 spotted on the SAX ProteinChip demonstrated differentiating power in separating stage I/II ovarian cancer from healthy controls (p<0.005). A particular interesting observation was that this potential biomarker was significantly higher than the healthy controls among the ovarian cancer patients who had a serum CA125 below 35U/ml (p<0.0005). A second observation was that the potential marker was elevated mainly among the serous and mucinous cancer patients and not among the endometroid cancer patients.
Conclusions:
The discovered marker with further study and validation has the potential to be used in combination with CA125 to improve the detection of early stage ovarian cancer.