Asymptomatic Cancer Patients Research Articles

When is a bone scan study appropriate in asymptomatic men diagnosed with prostate cancer?

To determine when a bone scan investigation is appropriate in asymptomatic men diagnosed with prostate cancer. Between November 2005 and July 2006, 317 men with prostate cancer underwent a bone scan study; 176 men fulfilled the inclusion criteria. Prostate-specific antigen (PSA) cut-offs as well as univariate and multivariate logistic regression analyses using digital rectal examination finding, biopsy Gleason scores and age were performed to determine when a bone scan study is likely to be of value. Only 1/61 men (1.6%) with a serum PSA 20 ng/mL had a positive bone scan. However, 2/38 men (4.7%) with a serum PSA 20.1-40.0 ng/mL, 3/20 men (15%) with a serum PSA 40.1-60.0 ng/mL, 7/19 men (36.8%) with a serum PSA 60.1-100.0 ng/mL and 19/38 men (50%) with a serum PSA > 100.0 ng/mL had positive bone scans. Univariate and multivariate logistic regression analyses were uninformative in these groups. Based on our findings, a bone scan is of limited value in asymptomatic prostate cancer patients presenting PSA =or< 20 ng/mL. Therefore, this investigation can be eliminated unless a curative treatment is contemplated. Furthermore, digital rectal examination finding, biopsy Gleason score and age are unhelpful in predicting those who might harbor bone metastasis.

Lung cancer patients who are asymptomatic at diagnosis show favorable prognosis: A Korean Lung Cancer Registry Study

Purpose and methods The outcomes of lung cancer patients who were asymptomatic at diagnosis have never been reported as part of a large-scale study. A national survey of lung cancer in South Korea registered a total of 8788 patients diagnosed in 2005. We report the results herein, with an emphasis on the prognosis of the asymptomatic lung cancer patients. Results Adenocarcinoma was the most frequent (36.1%) histopathologic type, followed by squamous cell carcinoma (32.1%), large cell carcinoma (1.5%), and small cell carcinoma (13.5%). In most cases, lung cancer was detected with subjective symptoms, but 6.5% of cases had no symptoms indicative of lung cancer at the time of diagnosis. Compared to symptomatic patients, asymptomatic patients were younger, more often female, non-smokers, and more frequently presented with adenocarcinoma. Initial treatments were surgery (22.1%), radiation therapy (7.8%), chemo-radiation therapy (5.4%), and chemotherapy (38%), while 26.6% of patients were recorded to have supportive care only. Asymptomatic patients received surgery in 60.0% of cases, and they showed significantly longer survival times than symptomatic patients. Absence of symptoms at diagnosis significantly reduced the risk of death from non-small cell lung cancer, regardless of patient age, patient gender, stage at diagnosis, smoking history, or whether treatment was performed, but did not reduce the risk of death from small cell lung cancer. Conclusions Adenocarcinoma has grown to be the leading histopathologic type of lung cancer in South Korea. Absence of symptom at diagnosis is a favorable prognostic factor for patients with non-small cell lung cancer.

Cilengitide in asymptomatic metastatic androgen independent prostate cancer (AIPC) patients (pts): A randomized phase II trial

5144 Background: Integrins αvβ3 and αvβ5 are involved in PC metastasis by regulating cell adhesion, migration, invasion, motility and angiogenesis. αvβ3 integrin is important in bone metabolism and may play a role in PC growth in bone. Cilengitide is a selective, competitive inhibitor of αvβ3 and αvβ5 integrins. Methods: Chemo-naïve pts with asymptomatic progressive metastatic AIPCa were randomized to cilengitide 500 mg or 2,000 mg IV 2X/week (wk) in 6-wk cycles using Simon 2-stage optimal design. Disease was assessed q 12 wks. The primary end point was 6 month (m) objective progression rate (PgR) (excluding PSA). Historically a 75% PgR is expected. We hypothesized cilengitide would lower the 6 m PgR to 55%. > 6 pts/arm with no Pg were needed to move to 2nd stage. Pts with asymptomatic Pg at 1st assessment were permitted to receive 1 more cycle followed by reassessment. Secondary end points include safety, response rate, changes in circulating tumor cells (CTCs) and bone markers. Results: 44 pts were accrued to 1st stage. Arms were balanced at baseline except for younger age (median 68yrs vs 74yrs) and lower PSA (median 66ng/ml vs 141ng/ml) in the 2,000mg arm. Median number of cycles was 3/arm (500mg arm: 1–8; 2,000 mg arm: 1- 15). At 6 m, 3 pts (14%) on the 500mg arm and 6 pts (27%) on the 2,000mg arm had not progressed. Best objective response was stable disease (SD); 27% on the 500 mg arm, 36% on 2000mg arm. 50% of the 24 pts who had Pg at 1st assessment stayed on study for an additional cycle. There were 3 grade (G) 3 and no G4 toxicities. At 12 weeks, analysis of bone markers did not reveal significant biologic trends. At Pg, bone specific alkaline phosphatase and N-telopeptide increased in all pts, less so in pts on the 2000mg arm and in pts who obtained SD at 6m. CTCs increased over time in both arms. Conclusions: Cilengitide was well tolerated. The 2,000 mg arm had a modest but not clinically significant effect so 2nd stage was not pursued. Neither dose level decreased the 6 m PgR. Decreased level of bone markers correlated with a trend towards decreased PgR. The unique study design using a non-Pg endpoint, not acting on PSA changes, and confirming Pg after 1st assessment was feasible. Supported by CTEP, Prostate SPORE Grant P50 CA069568–09, PC051375, Merck KGaA, PC051382, Immunicon. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Johnson & Johnson Merck KGaA

Value of 18F-FDG PET-CT scan in the evaluation of recurrent asymptomatic epithelial ovarian cancer patients with rising serum CA-125

16535 Background: We conducted a pilot study to evaluate role of 18F-FDG PET- CT scan in the diagnosis of recurrent asymptomatic Epithelial Ovarian (EOC) cancer patients with rising serum CA-125. Methods: BetweenJuly 2006 and December 2007, 12 patients of recurrent EOC who were asymptomatic and had rising serum CA-125 on follow up were included in the study. All 12 patients (median age 53.5 years, range 40 to 75 years) had advanced disease at baseline (stage III, IV). They all had undergone cytoreductive surgery and platinum based chemotherapy and achieved complete response (clinical, normal CT scan and CA-125). At the detection of raised CA-125, patients underwent detailed clinical examination followed by contrast enhanced CT of whole abdomen. Patients with no evidence of disease clinically or on CT scan were further evaluated with 18F-FDG PET-CT. Those found to have increased uptake on FDG PET-CT underwent ultrasound guided fine needle aspiration cytology (FNAC) from that area. If the FNAC was positive they were considered as true positive, if negative, they were considered false positive. Patients, in whom FNAC was inconclusive or not possible, were followed closely for six months. If there was evidence of recurrence on clinical examination or on CT scan within this period, they were considered true positive else false positive. Patients with negative FDG PET-CT scan were also followed for six months, those who did not show any evidence of disease on clinical examination or CT scan were considered true negative. If they however showed evidence of recurrence during this period they were considered false negative. Results: All the twelve patients showed increased uptake on FDG PET-CT scan. Of these ten were true positive (seven positive on FNAC and three on follow up, two at 3 months and one at 4 months). There were two false positive (one on FNAC and the other on a follow up of 1year continues to be in remission). There was no true or false negative among the 12 patients analyzed. Conclusions: FDGPET-CT is a sensitive method to detect asymptomatic patients of recurrent epithelial ovarian cancer with only rising serum CA-125. However, a larger study is needed to confirm the results. No significant financial relationships to disclose.

First-Line Chemotherapy vs Bowel Tumor Resection Plus Chemotherapy for Patients With Unresectable Synchronous Colorectal Hepatic Metastases

Bowel resection followed by chemotherapy is a better management strategy than immediate chemotherapy in asymptomatic patients with colorectal cancer and unresectable liver-only metastases at presentation. Retrospective study. University hospital. Sixty-five consecutive symptom-free colorectal cancer patients with unresectable synchronous metastases confined to the liver undergoing bowel tumor resection plus systemic chemotherapy (42 patients [resection group]) or chemotherapy first (23 patients [chemotherapy group]). Long-term survival and identification of prognostic indicators of outcome. In the resection group, the mean and median overall survival times were shown to be significantly better than those in the chemotherapy group (P = .03). Performance status, basal serum levels of lactic dehydrogenase and alkaline phosphatase, percentage of liver involvement, potentially curative resection of the bowel tumor, and type of treatment (resection vs chemotherapy) were demonstrated to be the only variables significantly correlated with long-term survival. On multivariate analysis, performance status, extent of liver involvement, and type of treatment were shown to be the only covariates independently associated with survival rate. The rate of liver metastasis downstaging with subsequent curative hepatic resection was clearly associated with good performance status, limited liver involvement, and resection of the bowel tumor. Achieving complete cure in asymptomatic colorectal cancer patients with unresectable synchronous liver-only metastases appears to be mostly the result of shrinkage and resection of hepatic metastases. In patients with good performance status and limited liver involvement, bowel tumor resection appears to be the best treatment option for this purpose.

Performance of office hysteroscopy and endometrial biopsy for detecting endometrial disease in women at risk of human non-polyposis colon cancer: a prospective study

The objective of this study was to report the value of diagnostic hysteroscopy and endometrial biopsy for the detection of complex atypical hyperplasia or cancer in asymptomatic human non-polyposis colon cancer (HNPCC) patients. The secondary objective was to evaluate the accuracy of hysteroscopy, using endometrial biopsy as a gold standard. Consecutive patients at risk of HNPCC evaluated between January 1, 1999, and June 30, 2006 were included if they underwent diagnostic hysteroscopy at least once. Patients with a history of hysterectomy and those unwilling to undergo diagnostic hysteroscopy were not included. Yearly follow-up evaluations included diagnostic hysteroscopy, with endometrial biopsy. Hysteroscopic and histologic findings were recorded and compared. We included 62 patients, of whom 13 had mismatch repair gene mutations and 49 met Amsterdam II criteria. Of 125 attempted hysteroscopies, 11 (8%) failed. Hysteroscopy showed normally appearing mucosa in 46 cases, nonmalignant lesions in 65 cases, and possibly malignant lesions in 3 cases with abnormal uterine bleeding. Endometrial biopsy was attempted in 116 cases and failed in 12 (10%). Three cases each of simple hyperplasia and of cancer were diagnosed. No preinvasive or invasive lesions were found in asymptomatic women. When compared to endometrial biopsy, sensitivity of hysteroscopy was 100% for the detection of hyperplasia or cancer. No cases of cancer were diagnosed in asymptomatic patients in our study. However, diagnostic hysteroscopy ensured the diagnosis of endometrial adenocarcinoma in HNPCC women with bleeding. Nevertheless, usefulness and optimal modalities of screening remain to be determined.

Is There Any Effect of Tumor Burden on Hemostatic Parameters in Cancer Patients? A Case—Control Study of Hemostatic Abnormalities and Anticardiolipin Antibodies in Solid Tumors

Hemostatic complications are one of the leading causes of mortality in cancer patients. In the present study, we assessed the hemostatic parameters and anticardiolipin antibodies in patients with solid tumors (n = 104) and healthy controls (n = 25) and also find out whether the abnormalities in these hemostatic parameters vary related to tumor burden. Prothrombin time, activated partial thromboplastine time, D-dimer, and fibrinogen as hemostatic parameters were determined by photo-optometric clot detection system, and serum anticardiolipin levels were measured by enzyme-linked immunosorbent assay. The plasma levels of fibrinogen, D-dimer, and serum anticardiolipin IgM levels in cancer patients were significantly higher compared with those in controls (P < .001, P = .001, and P = .01, respectively). Only fibrinogen levels were significantly higher in metastatic group than nonmetastatic group (P < .001 ). Hemostatic abnormalities that are detected in asymptomatic cancer patients may not give any clue about tumor burden or stage of the cancer patients.

Can Cancer Be Diagnosed With a Blood Test During Routine Examinations?

Cancer can be detected in asymptomatic patients by a blood draw for tumor biomarkers during routine examinations in a doctor's office. The reliability of tumor biomarkers to diagnose cancer in asymptomatic patients is a frequently asked question in general practice as well as in an oncology setting.

Treatment options for the advanced asymptomatic prostate cancer patient: an active immunotherapy approach

Treatment options for the advanced asymptomatic prostate cancer patient: an active immunotherapy approach

EMD121974 (NSC 707544, cilengitide) in asymptomatic metastatic androgen independent prostate cancer (AIPCa) patients (pts): A randomized trial by the Prostate Cancer Clinical Trials Consortium (NCI 6372)

5137 Background: Integrins avβ3 and avβ5 are essential to PCa metastasis by regulating cell adhesion, migration, invasion and motility. Cilengitide is a potent and selective avβ3 and avβ5 integrin receptor antagonist that in phase I studies has shown clinical activity. Methods: Pts with asymptomatic, metastatic chemo-naive AIPCa with PSA or objective progression, no visceral disease, minimum PSA of 5ng/ml, and adequate organ function were randomized to cilengitide 500 mg or 2,000 mg IV 2X weekly in 6-week cycles, using modified randomized selection design. Disease status was assessed every 12 weeks. The primary end point is objective progression rate (not including PSA) at 6 months. The Simon 2-stage optimal design is used to accrue 53 pts/arm. After first stage (20 pts/arm), accrual continues if ≥ 6 pts have not progressed. If second stage accrual is initiated, at end of study, the better performing arm will be chosen for further study provided at least 18/53 pts in that arm have not progressed. Secondary end points include safety, response rates and correlative measures of cilengitide effect on circulating and bone marrow tumor and endothelial cells and on bone remodeling markers. Results: First stage accrual is complete with 42 pts registered. Median performance status is 0, median age is 71 years (range 52–85), and median PSA is 44ng/ml (range 5–870). Disease progression at registration was defined by PSA in 90%, soft tissue in 36% and bone in 31% of pts. Median number of cilengitide cycles is 3 (range 1–8). To date, 32/42 pts have received ≥ 2 cycles. The most common (&gt;5%) treatment related adverse events (AE): fatigue (38%), constipation (13%), anorexia (10%), leucopenia (8%) and nausea (8%). There were only 3 grade (G) 3 AEs (neutropenia, lymph node pain, lymph NOS) and no G4 AEs. Only 3 pts required dose modification. 25/42 pts were removed from protocol on or before 6 months, 6 pts received therapy for more than 6 months, and 11 are too early to assess. Conclusions: Cilengitide is well tolerated. Final results (efficacy, safety, correlative studies) of the first stage of accrual will be reported. Supported by CTEP, Prostate SPORE Grant P50 CA069568- 09, PC051375, Merck KGaA, PC051382. [Table: see text]

Brain metastases: epidemiology and pathophysiology

Metastases are the most common tumors of the central nervous system (CNS), but cancer databases are often incomplete leading to underestimation of the incidence of even symptomatic brain metastases. Brain imaging studies are not routinely performed on neurologically asymptomatic cancer patients and autopsy studies are outdated. Furthermore, while incidence rates for cancers are stable and mortality is decreasing due to earlier detection and better therapy, the incidence of brain metastases appears to be increasing. The pathophysiology of brain metastases is a complex multistage process, mediated by molecular mechanisms; from the primary organ, cancer cells must transform, grow and be transported to the CNS where they can lay dormant for various lengths of time before invading and growing further. Understanding the pathophysiology of brain metastases is of great importance, because it may lead to the development of more efficient therapies to combat brain tumor growth or to possibly make the CNS an undesirable environment for tumor progression.

Early detection of breast cancer based on gene-expression patterns in peripheral blood cells

IntroductionExisting methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. In this study, we investigated whether early detection of breast cancer is possible by analyzing gene-expression patterns in peripheral blood cells.MethodsUsing macroarrays and nearest-shrunken-centroid method, we analyzed the expression pattern of 1,368 genes in peripheral blood cells of 24 women with breast cancer and 32 women with no signs of this disease. The results were validated using a standard leave-one-out cross-validation approach.ResultsWe identified a set of 37 genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of these genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defense-related genes was increased in samples from breast cancer patients.ConclusionThe results show that a blood-based gene-expression test can be developed to detect breast cancer early in asymptomatic patients. Additional studies with a large sample size, from women both with and without the disease, are warranted to confirm or refute this finding.

Expression profiling of peripheral blood cells for early detection

Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. Especially, an accurate method for breast cancer detection based on peripheral blood as a clinical sample will be highly desirable because of the easy accessibility and less-invasive nature by which samples can be obtained. Results demonstrating that peripheral blood can be used to develop a gene expression based test for early detection of breast cancer will be presented. The rationale for using blood cells as monitors for a malignant disease elsewhere in the body is based on the hypothesis that a malignant growth will cause characteristic changes in the biochemical environment of blood. These changes will affect the expression pattern of certain genes in blood cells. We initially conducted a pilot study where the expression pattern of 1368 genes in peripheral blood cells of 24 females with breast cancer and 32 females with no signs of this disease were analyzed using macroarrays and the expression data analyzed by PAM. The results were validated using a standard leave-one-out cross-validation approach. We were able to identify a set of genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of the identified genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defence-related genes was increased in samples from breast cancer patients. In order to revalidate these findings and to increase the repertoire of informative genes, we have now extended the study with a larger number of breast cancer and non-breast cancer samples and used Agilent WG oligo arrays for large-scale gene expression analysis. The preliminary analysis of the data supports our previous finding that a blood-based gene expression test can potentially be developed to detect breast cancer in asymptomatic patients.

Use of changes in CA125 doubling time to detect activity of cytostatic agents in women relapsing with ovarian carcinoma. Study 1 - tamoxifen

5119 Background: Many new targeted-therapy agents with potential anti-cancer activity could be cytostatic rather than cytotoxic. Therefore standardised radiological response criteria such as RECIST may not detect activity of these agents in phase II trials. There is an urgent need for a method to screen for activity of these agents before embarking on large randomised trials. The main purpose of this study was to determine whether there is a predictable log-linear rise of CA125 levels in asymptomatic relapsing ovarian cancer patients and if so, whether a change in rate of rise of CA125 can be used to demonstrate activity of a cytostatic agent. For proof of principle, we used tamoxifen in this trial which has modest clinical activity, and so one would expect some changes in CA125 doubling time. Methods: Ovarian cancer patients with previously elevated CA125 levels that had successfully completed first relapse chemotherapy were eligible. Patients consented to monthly CA125 measurements, which became fortnightly once there was any rise in levels. Tamoxifen 20mg once daily was commenced once CA125 was either four times its upper limit of normal, or four times the nadir level if this was elevated at baseline. Log CA125 levels were plotted to look for linear trends. Results: So far out of the first 15 patients that have entered the study, 12 have had rising CA125 levels, out of whom 6 patients demonstrated a log-linear rise. The median number of samples from the start of the linear rise to start of tamoxifen was 5. A change in the slope of log linear CA125 levels was observed in 2 out of 6 patients started on Tamoxifen. Conclusions: Early results suggest that this approach to assessing new cytostatic agents in phase II trials does look feasible. A log linear rise was seen in 50% of patients. We aim to recruit 200 patients to reliably assess whether Tamoxifen has activity based on a change in slope of CA125. No significant financial relationships to disclose.

57 Rising PSA in asymptomatic prostate cancer patients after treatment with external beam radiotherapy (RT): follow-up without treatment

57 Rising PSA in asymptomatic prostate cancer patients after treatment with external beam radiotherapy (RT): follow-up without treatment

Use of tamoxifen in asymptomatic patients with recurrent small-volume ovarian cancer

Objectives. Tamoxifen, a well-tolerated oral hormonal agent with biological activity in ovarian cancer, is a potentially attractive option in asymptomatic patients with recurrent disease. Unfortunately, the clinical utility of the drug in this specific setting has not been well documented. Patients and methods. A retrospective review was conducted of patients with cancers of the ovary, fallopian tube, and primary cancer of the peritoneum at the Cleveland Clinic who experienced recurrence of the malignancy, in the absence of large volume disease (by physical exam and radiographic evaluation) or any cancer-related symptoms, and who received tamoxifen (20 mg [most patients] or 40 mg/day) before re-initiation of cytotoxic chemotherapy. Results. Fifty-six patients (45 after primary chemotherapy; 12 after second-line treatment) satisfied the criteria noted above. The median duration of treatment was 3 months (range 1–30 months), with 42% and 19% of patients remaining on tamoxifen for ≥6 and ≥12 months, respectively. Reasons for discontinuation were equally divided between three causes: (a) continued rise in CA-125 antigen level without symptoms or other objective signs of cancer; (b) evidence of progressive disease by physical exam or radiographic evaluation in the absence of symptoms; and (c) development of cancer-related symptoms. Conclusion. In the absence of data from a randomized controlled trial which defines optimal management of the asymptomatic ovarian cancer patient with documented recurrent disease, tamoxifen is a rational management option, although it remains unknown if the delay in subsequent administration of chemotherapy in some individuals for periods greater than 6–12 months results from a direct effect of this agent or simply reflects the natural history of disease in a subset of patients in this clinical setting.

Novel approaches to treating the asymptomatic hormone-refractory prostate cancer patient

For >50 years, the standard treatment for advanced prostate cancer has been hormonal therapy. However, all such treated patients eventually develop disease refractory to androgen suppression as manifested by increasing prostate-specific antigen (PSA) levels, progressive disease on radiographic imaging, and ultimately, symptomatic deterioration. Historical perceptions that treatment of hormone-refractory prostate cancer was a largely futile venture have faded over the past decade with the advances in new therapeutic strategies. With the use of PSA values to follow the progress of patients after definitive therapy, physicians are seeing more patients who have failed hormonal therapy yet have no symptoms from their disease. There are standard therapies available for patients who require palliation for symptoms, but there is no consensus on treatment for asymptomatic patients. To date, there has been no definitive increase in survival with any therapy in this group of patients. In addition, several novel drugs have advanced through preclinical testing into early clinical trials. It is these drugs—alone or in combination—that are designed to target strategic tumor pathways in these patients. This article will review a selection of agents that may be potentially useful in this population.

57 Rising PSA in asymptomatic prostate cancer patients after treatment with external beam Radiotherapy (RT): follow-up without treatment

57 Rising PSA in asymptomatic prostate cancer patients after treatment with external beam Radiotherapy (RT): follow-up without treatment

1096 What to do with asymptomatic prostate cancer patients with rising PSA after curative treatment with external beam radiotherapy (RT)?

1096 What to do with asymptomatic prostate cancer patients with rising PSA after curative treatment with external beam radiotherapy (RT)?

What to do for prostate cancer patients with a rising PSA?—a survey of Australian practice

Purpose: To document current Australian management of asymptomatic prostate cancer patients with prostate-specific antigen (PSA) relapse after radical treatment or considered unsuitable for radical treatment. Methods and materials: Four case scenarios—postprostatectomy PSA relapse, postradiotherapy (RT) with a slow or a rapidly rising PSA level, or no radical treatment—were presented. Management preferences, including (where relevant) RT, androgen ablation either immediate or delayed until a PSA rise or symptomatic progression, and other approaches, were identified. The preferred methods of androgen ablation were noted. Results: One hundred eighteen informative replies out of 324 e-mailed surveys were received. For postprostatectomy PSA relapse, 59% of respondents favored salvage RT. For post-RT with a slow or a rapidly rising PSA level and treatment of nonradical patients, there was no clear consensus of opinion, with respondents divided among the different options. A diverse range of PSA levels was cited for delayed intervention, with values ranging from 0.8 to 100 ng/mL. PSA doubling time proved a more consistent criterion for determining intervention. Most respondents favored the use of a luteinizing hormone-releasing hormone agonist as first-line androgen ablation, although patient choice was recognized as important in all decision making. Conclusion: A lack of available evidence underlies the diversity of opinion regarding the management of asymptomatic prostate cancer patients with a rising PSA. The need for randomized controlled trials in this area is highlighted.