Prospective Comparison of Geriatric Assessment and Provider's Assessment of Older Adults With Metastatic Breast Cancer in the Community.

BACKGROUND: Geriatric assessment (GA) is recommended for evaluating fitness of an older adult with cancer. Our objective was to prospectively evaluate the gaps that exist in the assessment of older adults with metastatic breast cancer (OA-MBC) in community practices (CP). METHODS: Self-administered GA was compared to provider's assessment (PA) of patients living with MBC aged ≥65 years treated in CP Providers were blinded to the GA results until PA was completed. McNemar's test was used to detect differences between PA and GA. RESULTS: One hundred patients were enrolled across 9 CP (median age 73.9). Geriatric assessment detected a total of 356 abnormalities in 96 patients; of which, 223 required interventions. African American and widowed/single patients were more likely to have abnormalities identified by GA. On average, across 100 patients, PA did not detect 25.5% of GA-detected abnormalities, mostly in functional status, social support, nutrition, and cognition. These differences were less pronounced among providers with more clinical experience. Patients with abnormal Timed Up and Go tests more likely had additional abnormalities in other domains, and more abnormalities that were not identified by PA. Providers were "surprised" by GA results in 33% of cases, mainly with cognitive or social support findings, and reported plans for management change for 39% of patients based on GA findings. CONCLUSIONS: Including a GA in the care of OA-MBC in CP is beneficial for the detection of multiple abnormalities not detected by routine PA.

Prognostic Significance of MUC-1 in Circulating Tumor Cells in Patients With Metastatic Pancreatic Adenocarcinoma.

OBJECTIVES: Development of targeted therapies for pancreatic cancer could be enhanced by a reliable method for noninvasive tumor cell assessment. In this pilot study, we isolated and phenotypically characterized circulating tumor cells (CTCs) from patients with metastatic pancreatic cancer and explored their relationship to clinical outcome. METHODS: Peripheral blood from 50 patients was collected at treatment initiation and first disease evaluation for CTC enumeration and phenotyping by CellSearch® system. Expression of human mucin 1 (MUC-1) was performed. RESULTS: Forty-eight and 37 patients had evaluable samples at baseline and first disease evaluation, respectively. The cohort was 62% male, with a median age of 63 years. At least 1 CTC per 7.5 mL was detected in 23 patients (48%) pretreatment and 11 patients (30%) at first disease evaluation. No difference was seen in overall survival between patients with 1 or more CTCs versus no CTC at baseline (P = 0.14). Patients with MUC-1 expressing CTC (n = 10) had shorter median overall survival compared with those with MUC-1 negative CTC (n = 13; 2.7 vs 9.6 m; P = 0.044). CONCLUSIONS: Circulating tumor cell enumeration and phenotypic characterization from metastatic pancreatic cancer patients are feasible. No correlation was found between CTC isolation and survival. However, the presence of MUC-1 expressing CTC demonstrated a trend toward inferior survival.

Circulating tumor cells in colorectal cancer: past, present, and future challenges.

Recent advances in immunomagnetic separation and flow cytometry have made the detection and characterization of circulating tumor cells (CTC) a reality. This technology has already demonstrated prognostic significance in breast and prostate cancer. In the current review, we will review the historical and current data regarding the enumeration and identification of CTC in colorectal cancer. With immunomagnetic separation techniques, CTC can reliably and reproducibly be identified within 1 to 2 cells in a 7.5 mL sample of peripheral blood. Prospective studies have demonstrated a significant adverse impact on survival with the presence of > or = 3 CTC per 7.5 mL blood. Approximately one quarter of patients with metastatic disease will be categorized in this poor prognosis group. In addition, change in number of cells on treatment has prognostic significance. While CTC enumerated through immunomagnetic separation are a clear prognostic factor for patients with mCRC, the future challenge is to study whether treatment decision-making should be impacted by their level. Low cell yield in mCRC is a potential hinderance to answering these important clinical questions at present. CTC can also be isolated and studied with flow cytometry, FISH, and RT-PCR, allowing real-time assessment of tumor biology. Future advances in this field will improve both the detection and manipulation of these cells. Improvements in detection and characterization of CTC will hopefully lead to refinement of the surgical and chemotherapeutic treatment of colorectal cancer.

Effect of melanoma on immune function in the regional lymph node basin.

PURPOSE: To determine if melanoma within the tumor microenvironment will result in immunosuppression within the draining lymph node as measured by down-regulation of T-cell receptor zeta (TCR zeta) expression. EXPERIMENTAL DESIGN: Patients with clinical stage I to III melanoma undergoing wide local excision and sentinel lymph node biopsy or therapeutic lymph node dissection were consented to have a portion of their lymph node sampled. Lymph nodes were classified as macroscopically involved (TI), microscopically involved (MI), noninvolved with positive wide excision (NI+), or noninvolved with negative wide excision (NI-). Lymphocytes were stained using antibodies to TCR zeta and other immune cells and analyzed via flow cytometer. Reverse transcription-PCR was used to assess for mediators of immunosuppression. RESULTS: Fifty patient lymph node samples (15 TI, 7 MI, 9 NI+, and 19 NI-) were evaluated. Increasing involvement of tumor in the lymph node was associated with decreasing TCR zeta chain expression (TI 56%, MI 76%, and NI- 89%). Differences between TI and MI (P = 0.005), TI and NI- (P = 0.0001), and MI and NI- (P = 0.019) were statistically significant. There was also a significant difference between TCR zeta chain expression of NI+ and NI- (73% versus 89%; P = 0.0016). A trend toward increased arginase expression in tumor-involved lymph nodes was detected by reverse transcription-PCR. CONCLUSIONS: Melanoma involvement of regional nodes is associated with loss of TCR zeta expression that is inversely related to tumor burden. Residual melanoma within the wide local excision specimen is associated with TCR zeta loss in noninvolved sentinel lymph nodes, suggesting that immune modulation precedes tumor spread.

Symptoms and signs of primary melanoma: important indicators of Breslow depth.

BACKGROUND: Operative management of patients with cutaneous melanoma is guided primarily by the pathologic determination of Breslow depth. Differentiating early from more advanced melanoma is not always straightforward and may be complicated by pathologic misdiagnosis, inappropriate biopsy techniques, or poor specimen handling. Inconsistencies between the patient's history and the pathologist's interpretation may alert the physician to the possibility of misdiagnosis. In this setting, awareness of the signs and symptoms (S/S) of thin versus intermediate or deep melanoma may be helpful in guiding management. The authors performed a prospective evaluation of the S/S reported by patients who presented at Memorial Sloan-Kettering Cancer Center with invasive primary melanoma. METHODS: The authors prospectively evaluated 369 patients with a detailed questionnaire regarding their S/S at the time of their initial visit. Multivariate logistic regression was employed to study the association between S/S reported by the patient and Breslow depth of the primary lesion, adjusting for gender, age, and anatomic site. Patients were grouped by the Breslow depth of their primary tumors into three categories for analysis: those with thin (< or = 1.0 mm), intermediate (1.0-4.0 mm), and thick (> or = 4.0 mm) lesions. RESULTS: Gender, age, and primary site were not significantly predictive of increasing category of Breslow depth. Most patients reported at least one S/S (n=278 [75%]). The most common S/S reported was an increase in size (n=187 [51%]), followed by a change in color (n=147 [40%]). Bleeding (n=95 [26%]), lump (n=86 [23%]), itching (n=83 [22%]), skin breakdown (n=66 [18%]), and pain (n=24 [7%]) were less common. In a multivariate analysis, the S/S most strongly associated with an increased category of Breslow depth was bleeding (odds ratio [OR] 7.5), followed by pain (OR 3.3), lump (OR 2.2), itching (OR 1.9), and change in size (OR 1.7). The only S/Ss not independently associated with an increasing category of Breslow depth were a change in color and skin breakdown. The presence of one or more S/S was associated significantly with an increased category of Breslow depth of the primary melanoma (1 or 2 S/S vs. no S/S: OR, 4; > or= 3 S/S vs. no S/S: OR, 24). CONCLUSION: Most S/Ss of cutaneous melanoma are associated with an increasing risk of a deep primary lesion. Understanding this relationship can be valuable in patient management, especially when pathologic data are incomplete or inconsistent with the patient's history.