Biomedical subjects

Robert B Livingston

Publications and source records attributed to Robert B Livingston.

18 recordsLinked to original sources

PubMed2004

Sequencing of tamoxifen and radiotherapy after breast-conserving surgery in early-stage breast cancer.

PURPOSE: Tamoxifen (TAM) is thought to exert a cytostatic effect on hormone-sensitive breast cancer cells. Some preclinical studies show reduced radiosensitivity in irradiated malignant mammary epithelial cells when pretreated with TAM; other studies refute these results. Recent randomized clinical trials suggest an antagonistic effect of TAM on cytotoxic therapy, with improved disease-free survival (DFS) with sequential versus concurrent TAM. An exploratory analysis was undertaken to evaluate the optimal sequencing of TAM and radiotherapy (RT) after breast-conserving surgery. PATIENTS AND METHODS: Southwest Oncology Group trial 8897 (Intergroup 0102) randomly assigned node-negative women with T1-3 breast cancers to cyclophosphamide, doxorubicin, fluorouracil (CAF); CAF --> TAM; cyclophosphamide, methotrexate, fluorouracil (CMF); and CMF --> TAM. For this analysis, data are reported only in the TAM groups. RT was allowed either before adjuvant therapy (sequential [SEQ] RT; 107 patients) or after chemotherapy but concurrent with TAM (concurrent [CONC] RT; 202 patients). Survival data were adjusted for receptor status, age, and tumor size. RESULTS: With a median follow-up of 10.3 years, 10-year DFS values were 83% and 83% for CONC versus SEQ RT groups (log-rank P = .73; P = .76 adjusted for patient characteristics), and 10-year overall survivals were 88% and 90%, respectively (log-rank P = .59; adjusted P = .65). Patterns of failure showed no increase in in-breast recurrence rates between CONC RT and SEQ RT groups, with 10-year local recurrence rates of 7% for CONC RT and 5% for SEQ RT (hazard ratio, 0.73; 95% CI, 0.26 to 2.04; P = .54). CONCLUSION: The current analysis does not suggest an adverse effect on local or systemic control with CONC versus SEQ TAM and RT in node-negative breast cancer. A randomized trial is encouraged to validate these results.

Aged↗

PubMed2004

HER-2 testing in breast cancer using parallel tissue-based methods.

CONTEXT: Testing for HER-2 oncogene in breast cancer has increased because of its role as a prognostic and predictive factor. Some advocate gene testing by fluorescence in situ hybridization (FISH) vs protein testing by immunohistochemistry as the method which most accurately evaluates and predicts response to the anti-HER-2 antibody, trastuzumab. However, critical examination of FISH on a screening basis has yet to be performed. OBJECTIVES: To determine the correlation between FISH and immunohistochemistry results by determining HER-2/neu gene status on tumor sections with indeterminate immunohistochemistry results (2+ score), confirm gene amplification on tumor sections with positive results (3+ score), and verify gene status on tumor sections with negative results (0 or 1+ score). DESIGN, SETTING, AND PATIENTS: A quality control and quality assurance program for HER-2 testing by FISH, which used tumor specimens from 2963 patients (median age, 56 years) with breast cancer received from 135 hospitals and cancer centers in 29 states, was performed at a reference laboratory from January 1, 1999, to May 15, 2003. Every specimen evaluated by FISH was parallel tested with immunohistochemistry tests. MAIN OUTCOME MEASURES: With FISH as the presumed standard testing method, the positive and negative predictive values and sensitivity and specificity of immunohistochemistry were calculated. RESULTS: A total of 3260 clinical HER-2 tests by FISH were performed on 2963 serially referred breast cancer specimens. Of these, 2933 tests were successful and 2913 breast cancer specimens had both FISH and immunohistochemistry results available. With FISH as the standard testing method, the positive predictive value of positive immunohistochemistry score (3+) was 91.6%, and the negative predictive value of negative immunohistochemistry score (0 or 1+) was 97.2%. The sensitivity of immunohistochemistry tests, including tumor sections with scores of 2+ or 3+, was 92.6% and the specificity of immunohistochemistry tests with scores of 3+ was 98.8%. The FISH test had a significantly higher failure rate (5% vs 0.08%) and reagent cost (140 dollars vs 10 dollars), and longer testing (36 hours vs 4 hours) and interpretation times (7 minutes vs 45 seconds) vs immunohistochemistry tests. CONCLUSIONS: A testing algorithm for HER-2 determination is most efficient by using immunohistochemistry as the method of choice, with FISH performed for cancers with indeterminate results (2+ score). Successful quality control and quality assurance programs are a prerequisite for such approaches.

Adult↗

PubMed2004

Potential of chemotherapy-herb interactions in adult cancer patients.

GOALS OF WORK: The purpose of this study was to examine the specific herbs or vitamins (HV) used by patients receiving chemotherapy. Specifically, the following aspects were investigated: (1) HV use among adult cancer patients receiving chemotherapy, (2) the frequency of potential chemotherapy-HV interactions, (3) communication patterns between oncologists and their cancer patients taking HV, and (4) patients' reactions to two hypothetical scenarios of chemotherapy-HV interactions. PATIENTS AND METHODS: Adult cancer patients receiving chemotherapy at a university-based outpatient clinic over a 1-month period were sent a validated eight-page questionnaire regarding the use of complementary/alternative medicine, focusing on HV use. A total of 76 patients participated; relevant medical information was obtained from study participants' charts. The chemotherapy received was compared with HV use to assess for potentially detrimental chemotherapy-HV interactions. RESULTS: HV use in patients receiving chemotherapy was common (78%), with 27% of the study participants being at risk of a detrimental chemotherapy-HV interaction. Most patients (>85%) would discontinue their HV or ask their medical oncologist for advice if a detrimental chemotherapy-HV interaction was suspected. Although most patients discussed HV use with their oncologist, the majority also relied on their friends and naturopathic physician for information regarding HV. CONCLUSIONS: Considerable potential exists for detrimental chemotherapy-HV interactions. Methods to improve communication of HV use between cancer patients receiving chemotherapy and health-care practitioners are necessary to identify and minimize the risk of these interactions.

Adult↗

PubMed2004

Combined use of MRI and PET to monitor response and assess residual disease for locally advanced breast cancer treated with neoadjuvant chemotherapy.

RATIONALE AND OBJECTIVES: The purpose of the study was to evaluate the hypothesis that magnetic resonance imaging (MRI) and positron emission tomography (PET) are complementary and valuable in monitoring response and assessing residual disease of locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy. We sought to determine if the combination of the two modalities was more accurate than either alone and could provide better guidance in patient management. MATERIALS AND METHODS: Sixteen lesions in 15 women with LABC were evaluated with MRI, PET, and clinical breast examination (CBE) before and after neoadjuvant chemotherapy. The pre- and posttherapy maximal tumor sizes on MRI and CBE and standard uptake values (SUVs) on PET served as the measurements for clinical response classification and residual disease assessment. Pathologic assessment provided the reference for macroscopic and microscopic pathologic tumor response and residual disease. RESULTS: PET correctly predicted lack of pathologic response in five of six cases (83%); CBE predicted correctly in one of six (17%) cases, and MRI predicted correctly in zero of six cases. When PET predicted response, MRI defined the extent of macroscopic pathologic residual disease accurately in 9 of 10 cases (90%). When posttherapy MRI showed complete response (CR) in eight cases, macroscopic pathologic complete response (mCR) was observed in all eight cases (100%). CONCLUSION: Our study suggests that combined use of MRI and PET is complementary and offers advantages over CBE. PET was more accurate in predicting pathologic nonresponse. Complete response by MRI correlated well with macroscopic pathologic complete response.

Adolescent↗

PubMed2004

Prolonged survival in patients with resected non-small cell lung cancer and single-level N2 disease.

OBJECTIVES: To test the hypothesis that patients with non-small cell lung cancer and single-level N2 metastases constitute a favorable subgroup of patients with mediastinal metastases, we analyzed the results of the Eastern Cooperative Oncology Group 3590 (a randomized prospective trial of adjuvant therapy in patients with resected stages II and IIIa non-small cell lung cancer) by site of primary tumor and pattern of lymph node metastases. METHODS: Accurate staging was ensured by mandating either systematic sampling or complete dissection of the ipsilateral mediastinal lymph nodes. The overall survival of patients with left lung non-small cell lung cancer and metastases in only 1 of lymph node levels 5, 6, or 7 and right lung non-small cell lung cancer with metastases in only 1 of levels 4 or 7 was compared with that of patients with N1 disease originating in the same lobe. RESULTS: The median survival of the 172 patients with single-level N2 disease was 35 months (95% confidence interval: 27-40 months) versus 65 months (95% confidence interval: 45-84 months) for the 150 patients with N1 disease (median follow-up 84 months, P =.01). However, among patients with left upper lobe tumors, survival was not significantly different between patients with N1 disease and patients with single-level N2 disease (49 vs 51 months, P =.63). The median survival of the 71 patients with single-level N2 metastases without concomitant N1 disease (skip metastases) was 59 months (95% confidence interval: 36-107 months) versus 26 months (95% confidence interval: 16-36 months) for the 145 patients with both N1 and N2 metastases (P =.001). CONCLUSIONS: Survival of patients with left upper lobe non-small cell lung cancer and metastases to single-level N2 lymph nodes is not significantly different from that of patients with N1 disease. The presence of isolate N2 skip metastases is associated with improved survival when compared with patients with both N1 and N2 disease. Survival should be reported by the lobe of primary tumor and metastatic pattern to guide future clinical trial development, treatment strategies, and revisions of the TNM staging system.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Evaluation of the internal mammary lymph nodes by FDG-PET in locally advanced breast cancer (LABC).

The presence of internal mammary (IM) lymph node metastases in breast cancer predicts outcome and may alter treatment. Standard imaging has limited usefulness for evaluation of the IM chain because of low sensitivity. Our preliminary studies suggested that [F-18]-2-fluoro-d-glucose positron emission tomography (FDG-PET) improves the detection of IM and mediastinal metastases. We therefore performed a retrospective review of women who underwent FDG-PET prior to treatment to determine the benefit of PET for imaging IM disease. The records of 28 consecutive patients undergoing FDG-PET prior to neoadjuvant chemotherapy for suspected locally advanced breast cancer (LABC) were reviewed. The presence of abnormal IM uptake on FDG-PET was noted. IM uptake on FDG PET was compared with standard radiographic imaging and was correlated with putative risk factors for IM involvement and with clinical patterns of failure. Patients did not undergo IM biopsy; however, patterns of failure were assessed to validate the FDG-PET findings. Clearly abnormal FDG uptake in the IM nodes was seen in 7 of 28 women (25%). Prospective conventional chest imaging failed to identify IM metastases in any patient. IM uptake on PET was associated with large size of the primary tumor (P = 0.03) and with inflammatory disease (P = 0.04). The presence of IM FDG uptake predicted failure by a pattern consistent with spread from IM lymph node metastasis. FDG-PET appears to be a useful noninvasive modality to detect IM metastases in LABC. Pathologic verification in a prospective study is necessary to confirm these findings.

Adult↗

PubMed2003

A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer.

BACKGROUND: In hormone-dependent breast cancer, five years of postoperative tamoxifen therapy--but not tamoxifen therapy of longer duration--prolongs disease-free and overall survival. The aromatase inhibitor letrozole, by suppressing estrogen production, might improve the outcome after the discontinuation of tamoxifen therapy. METHODS: We conducted a double-blind, placebo-controlled trial to test the effectiveness of five years of letrozole therapy in postmenopausal women with breast cancer who have completed five years of tamoxifen therapy. The primary end point was disease-free survival. RESULTS: A total of 5187 women were enrolled (median follow-up, 2.4 years). At the first interim analysis, there were 207 local or metastatic recurrences of breast cancer or new primary cancers in the contralateral breast--75 in the letrozole group and 132 in the placebo group--with estimated four-year disease-free survival rates of 93 percent and 87 percent, respectively, in the two groups (P< or =0.001 for the comparison of disease-free survival). A total of 42 women in the placebo group and 31 women in the letrozole group died (P=0.25 for the comparison of overall survival). Low-grade hot flashes, arthritis, arthralgia, and myalgia were more frequent in the letrozole group, but vaginal bleeding was less frequent. There were new diagnoses of osteoporosis in 5.8 percent of the women in the letrozole group and 4.5 percent of the women in the placebo group (P=0.07); the rates of fracture were similar. After the first interim analysis, the independent data and safety monitoring committee recommended termination of the trial and prompt communication of the results to the participants. CONCLUSIONS: As compared with placebo, letrozole therapy after the completion of standard tamoxifen treatment significantly improves disease-free survival.

Adult↗

PubMed2003

Second primary tumors following adjuvant therapy of resected stages II and IIIa non-small cell lung cancer.

The occurrence of second primary tumors (SPTs) following adjuvant therapy for resected stages II and IIIa non-small cell lung cancer (NSCLC) was investigated. Data regarding SPTs were prospectively collected in all patients accrued to Eastern Cooperative Group Oncology E3590 (a phase III trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC). Four hundred eighty-eight patients were accrued to the study, 242 to the RT arm and 246 to the CRT arm. Median follow-up was 73 months. Thirty patients (6.1%) developed 33 SPTs, 20 in the RT arm and ten in the CRT arm. Ten SPTs occurred within the upper aerodigestive tract, six in the RT arm and four in the CRT arm. Twenty-three SPTs occurred in other organs, 17 in the RT arm and six in the CRT arm. Median time to detection of a SPT for those patients randomized to RT and CRT was 43 and 36 months, respectively. The incidence of SPTs was 1.8% per patient-year of follow-up. Excluding skin tumors, the relative risk of death following diagnosis of a SPT for patients randomized to the CRT arm as compared with those randomized to RT alone was 2.26 (95% confidence interval, 0.78-5.58, P=0.12). Patients are at risk for developing a SPT following resection of stages II and IIIa NSCLC. The majority of SPTs occur outside the aerodigestive tract. Following development of a non-skin SPT, the survival difference between patients who had received adjuvant CRT and those treated with adjuvant RT alone was not significant.

Adult↗

PubMed2003

Myalgias and arthralgias associated with paclitaxel.

Paclitaxel-induced myalgias and arthralgias occur in a significant fraction of patients receiving therapy with this taxane, potentially impairing physical function and quality of life. Paclitaxel-induced myalgias and arthralgias are related to individual doses; associations with the cumulative dose and infusion duration are less clear. Identification of risk factors for myalgias and arthralgias could distinguish a group of patients at greater risk, leading to minimization of myalgias and arthralgias through the use of preventive therapies. Optimal pharmacologic treatment and possibilities for the prevention of myalgias and arthralgias associated with paclitaxel are unclear, partially due to the small number of patients treated with any one medication. The effectiveness of nonsteroidal anti-inflammatory drugs (NSAIDs) is the most frequently documented pharmacologic intervention, although no clear choice exists for patients who fail to respond to NSAIDs. However, the increasing use of weekly paclitaxel could necessitate daily administration of NSAIDs for myalgias and arthralgias and leave patients at risk for adverse effects. This concern may also limit the use of corticosteroids for the prevention and treatment of paclitaxel-induced myalgias and arthralgias. Data from case reports suggest that gabapentin (Neurontin), glutamine, and, potentially, antihistamines (e.g., fexofenadine [Allegra]) could be used to treat and/or prevent myalgias and arthralgias. Given the safety profile of these medications, considerable enthusiasm exists for evaluating their effectiveness in the prevention and treatment of paclitaxel myalgias and arthralgias, particularly in the setting of weekly paclitaxel administration.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy.

UNLABELLED: Locally advanced breast cancer (LABC) is commonly treated with neoadjuvant chemotherapy followed by definitive surgery. The factors influencing the response of LABC to presurgical chemotherapy are incompletely understood. To characterize in vivo tumor biology in patients with LABC, we performed serial measurements of blood flow and glucose metabolism in LABC patients over the course of neoadjuvant chemotherapy and compared measurements with response. METHODS: Thirty-five patients with newly diagnosed LABC underwent (18)F-FDG and (15)O-water PET imaging before therapy and after 2 mo of chemotherapy. Tumor metabolism was estimated from graphical analysis of dynamic (18)F-FDG studies and was expressed as the metabolic rate of (18)F-FDG (MRFDG). Blood flow was estimated from dynamic images after bolus (15)O-water injection using a 1-compartment model. Metabolism and blood flow data were analyzed with and without partial-volume corrections to account for changes in tumor size over the course of therapy. Changes in tumor blood flow and metabolism were compared with response to chemotherapy and with patient survival. RESULTS: For all patients, the mean MRFDG after 2 mo of chemotherapy decreased by 54% and the mean blood flow by 21%. Responders showed a greater decline in MRFDG than did nonresponders; however, the difference was of borderline significance (P = 0.05) after correction for partial-volume effects. Patients who responded had a decline in tumor blood flow, whereas nonresponders had an average increase (-32% vs. +48%, P < 0.005); the difference between responders and nonresponders remained significant after partial-volume correction (P < 0.01). There was also a statistically significant association between the pathologic degree of response and the percentage change in blood flow at 2 mo with and without partial-volume correction; this was not the case for MRFDG. The change in blood flow after 2 mo of therapy predicted disease-free and overall survival. CONCLUSION: Although both resistant and responsive LABC tumors have an average decline in MRFDG over the course of chemotherapy, resistant tumors have an average increase in blood flow. Patients whose tumors fail to have a decline in blood flow after 2 mo of therapy have poorer disease-free and overall survival. Further investigations are needed to elucidate the tumor biology underlying these findings.

Adult↗

PubMed2002

Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America.

BACKGROUND: To determine the changes in clinical trials and outcomes of patients with limited-stage small cell lung carcinoma (SCLC) treated on Phase III randomized trials initiated in North America between 1972 and 1992. METHODS: Phase III trials from 1972 to 1992 for patients with limited-stage SCLC were identified. Patients with limited-stage SCLC treated during a similar time interval were also evaluated in the Surveillance, Epidemiology, and End Results (SEER) database. Trends were tested in the number of trials, in the number and gender of patients entered on trial, and in survival duration over time. RESULTS: Thirty trials involving 6564 patients were eligible for analyses. Nineteen trials (61%) involving 3626 patients were initiated within the first half of this time period (1972-1981). The median of median survival times of all patients treated on the control arms of the Phase III trials initiated between 1972 and 1981 and between 1982 and 1992 were 12.0 months (range, 10-16 months) and 17.0 months (range, 11-20 months), respectively (P < 0.001). Of 26 studies available for survival analysis, 5 (19%) showed a statistically significant survival prolongation in the experimental arm compared with the control arm with a median prolongation of 3.4 months (range, 1-5.2 months). All five evaluated some aspect of thoracic radiation therapy. Over a similar time period, there was a 6.4-month increase in the median survival of limited-stage SCLC patients listed in the SEER database (P < 0.0001) and a more than doubling of the 5-year survival from 5.2% to 12.1% (P = 0.0001). CONCLUSIONS: Analyses of the patients with limited-stage SCLC treated on Phase III trials in North America initiated between 1972 and 1992 and those listed in the SEER database show significant improvements in median survivals. Furthermore, the 5-year survival of patients with limited-stage SCLC listed in the SEER database has more than doubled over the last 25 years. Further research will be needed to determine the relative contribution of improved therapy, supportive care, and stage migration to this prolongation in survival.

Adult↗

PubMed2002

Dose-dense anthracycline-based chemotherapy for node-positive breast cancer.

PURPOSE: Theoretical considerations and clinical experience suggest that dose-dense chemotherapy may be superior to other approaches using the same drugs. We studied a dose-dense combination of doxorubicin and cyclophosphamide, with or without fluorouracil, as adjuvant therapy. PATIENTS AND METHODS: Patients with resected breast cancer were treated if they were node-positive and estrogen receptor-negative, positive for overexpression of Her-2-neu, or had four or more involved nodes. Doxorubicin was given weekly to a total dose of 480 mg/m(2). Cyclophosphamide 60 mg/m(2) was given daily by mouth during the period of doxorubicin treatment. The first 30 patients received fluorouracil at 300 mg/m(2)/wk intravenously concurrently with doxorubicin administration. In the last 22, it was omitted because of symptomatic hand-foot syndrome in the majority of patients. Filgrastim (granulocyte colony-stimulating factor [G-CSF]) was administered during chemotherapy every day except the day of intravenous administration and continued until 1 week after the completion of the chemotherapy. RESULTS: Between October 20, 1992, and June 10, 1997, we enrolled 52 patients. The mean delivered dose-intensity for doxorubicin was 18.6 mg/m(2)/wk. Hospitalization was required in 6% of patients for reversible febrile neutropenia. There were no acute treatment-related deaths, but one patient subsequently died of acute leukemia with a characteristic translocation for anthracycline-related exposure. At 5 years, the event-free survival was 86% for all patients (95% confidence interval, 75% to 95%). CONCLUSION: Continuous dose-dense chemotherapy with G-CSF support produced encouraging results, which seem to be superior to those expected with "standard" doxorubicin and cyclophosphamide chemotherapy. It deserves a test in the form of a randomized trial where this approach to anthracycline-based treatment is compared with intermittent administration.

Adult↗

PubMed2002

Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019.

PURPOSE: There are no published survival data after chemoradiotherapy (chemoRT) in pathologically documented stage IIIB non-small-cell lung cancer. Studies of radiotherapy (RT) alone or chemotherapy followed by RT yield 5-year survivals less than 10%. The Southwest Oncology Group (SWOG) employed the same concurrent chemoRT induction regimen used in its predecessor trimodality trial to determine the efficacy, safety, and long-term outcome of replacing postinduction surgery with additional chemoRT. PATIENTS AND METHODS: Eligible patients for SWOG-9019 had pathologic documentation of T4N0/1, T4N2, or N3 stage IIIB non-small-cell lung cancer. They had pulmonary function adequate to withstand combined-modality therapy, identical to the requirements of the previous trial with postchemoRT surgery. Induction therapy was two cycles of cisplatin plus etoposide (PE) concurrent with once-daily thoracic RT (45 Gy). In the absence of progressive disease, RT was completed to 61 Gy, with two additional cycles of cisplatin plus etoposide. RESULTS: Fifty eligible patients were accrued with tumor-node (TN) substage confirmed on central review: 18, T4N0/1; 12, T4N2; and 20, N3. Grade 4 neutropenia was the most common toxicity (32%). Grade 3/4 esophagitis occurred in 12% and 8%. Median follow-up was 52 months, and overall median survival was 15 months (10 to 22, 95% confidence interval). Three- and 5-year survivals were 17% and 15% (5-year T4N0/1, 17%; T4N2, 13%; and N3, 15%). CONCLUSION: Feasibility and long-term survival support the application of these results as a standard against which mature outcomes of chemoRT trials with new chemotherapy agents can be compared. These results also justify use of the SWOG-9019 approach as a control arm in ongoing phase III trials.

Adult↗

PubMed2002

[Tc-99m]-sestamibi uptake and washout in locally advanced breast cancer are correlated with tumor blood flow.

OBJECTIVES: To determine the influence of breast tumor blood flow on MIBI kinetics, we compared MIBI uptake and washout to [O-15]-water PET estimates of blood flow in patients with locally advanced breast cancer. METHODS: Prior to therapy, 37 patients underwent MIBI and [O-15]-water PET imaging; 22/37 also had MIBI washout analysis. Twenty-five patients underwent serial imaging over the course of chemotherapy. RESULTS: MIBI uptake and blood flow had a significant positive correlation pre-therapy. The change in MIBI uptake over the course of therapy also correlated with the change in blood flow. The half-time of MIBI washout inversely correlated with blood flow, indicating faster MIBI washout with higher blood flow. CONCLUSIONS: Blood flow strongly influences early MIBI uptake and can be a factor affecting the rate of MIBI washout in breast tumors. We present a model of MIBI kinetics in tumors which forms a hypothesis for further mechanistic studies of MIBI uptake and washout in breast cancer.

Blood Flow Velocity↗

PubMed2002

Use of serial FDG PET to measure the response of bone-dominant breast cancer to therapy.

RATIONALE AND OBJECTIVES: The authors performed this study to determine the feasibility of using quantitative 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) to monitor the response of breast cancer bone metastases to therapy. MATERIALS AND METHODS: Twenty-four women with stage IV bone-dominant breast carcinoma were included in this study. Whole-body FDG PET imaging was performed at serial time points during the course of therapy. FDG PET scans were interpreted quantitatively by using the maximum standard uptake value (SUV) of the most conspicuous bone lesion at baseline FDG PET. PET results were compared to the overall assessment of response (response, stable disease, progressive disease) with a combination of conventional imaging, change in tumor marker values, and subjective symptom changes by experienced medical oncologists blinded to the findings at FDG PET. Changes in FDG SUV were also correlated quantitatively to the changes in a particular tumor marker (CA 27.29). RESULTS: The changes in FDG SUV with therapy showed correlation with the overall clinical assessment of response (P < .01). The percentage change in FDG uptake with therapy showed strong correlation with the percentage change in tumor marker value (P < .01). CONCLUSION: Preliminary results indicate that serial whole-body FDG PET can help quantitatively assess the response of breast cancer bone metastases to therapy. Prospective trials are needed to further investigate its accuracy.

Adult↗

PubMed2002

Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy.

UNLABELLED: Locally advanced breast cancer (LABC) is commonly treated with neoadjuvant chemotherapy followed by definitive surgery. The factors influencing the response of LABC to presurgical chemotherapy are incompletely understood. To characterize in vivo tumor biology in patients with LABC, we measured pretherapy blood flow and glucose metabolism in LABC, compared measurements with clinical and pathologic parameters, and examined blood flow and response to subsequent neoadjuvant chemotherapy. METHODS: Thirty-seven patients with newly diagnosed LABC underwent (18)F-FDG and (15)O-water PET imaging. Thirty-one of these patients underwent neoadjuvant chemotherapy, and response was evaluated by serial measurements of tumor size and pathologic examination after definitive surgery after chemotherapy. Tumor metabolism was estimated from graphic analysis of dynamic (18)F-FDG studies and was expressed as the metabolic rate of (18)F-FDG (MRFDG). Blood flow was estimated from dynamic images after bolus (15)O-water injection using a 1-compartment model. Tumor blood flow and metabolism were compared with clinical and pathologic parameters and with response to chemotherapy. RESULTS: Both blood flow and metabolism were significantly higher in tumor than in normal breast. Tumor blood flow and metabolism were correlated but highly variable. There were weak associations of metabolism with patient age and tumor grade and of blood flow with estrogen receptor status. There was a statistically significant trend for patients with a high MRFDG to have a poorer response to therapy (P = 0.001). Response was not significantly correlated with any other parameters. A low ratio of MRFDG to blood flow was the best predictor of macroscopic complete response (CR) (P = 0.02 vs. non-CR). Preliminary analysis of patient follow-up showed the ratio of MRFDG to blood flow to also be predictive of disease-free survival. CONCLUSION: Despite uniformly large tumor size, blood flow and metabolism in LABC are highly variable. High glucose metabolism predicts a poor response to neoadjuvant chemotherapy, and low MRFDG relative to blood flow is a predictor of CR. Further work is needed to elucidate the biologic mechanisms underlying these findings.

Adult↗

PubMedDate not supplied

An axillary recurrence of breast cancer following a negative sentinel lymph node biopsy.

In many parts of the United States, lymphatic mapping and sentinel lymph node biopsy has almost replaced axillary lymph node dissection (ALND) as the axillary staging procedure of choice for small, clinically node-negative breast cancers. However, the long-term outcome of patients undergoing a sentinel lymph node biopsy as the only axillary procedure in patients with tumor-free sentinel nodes remains to be determined. We present the first reported case of axillary recurrence in a patient with breast cancer following a tumor-negative sentinel lymph node biopsy. Whether sentinel lymph node biopsy can replace ALND in the management of patients with early breast cancer remains to be answered.

Axilla↗

PubMedDate not supplied

Detection of locoregional and distant recurrences in breast cancer patients by using FDG PET.

Cases of recurrence of breast cancer can pose considerable diagnostic and therapeutic challenges for the oncologic team. The prognosis and management decisions are based on knowledge of the true extent of disease. Conventional staging methods, including physical examination, assessment of levels of tumor markers, cross-sectional imaging, and bone scintigraphy, may not reliably demonstrate the extent of disease in all cases. Physical examination and cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging) can be problematic because (a) the sequelae of previous surgery and radiation therapy can be difficult to distinguish from recurrent neoplasms and (b) early metastatic disease (small lesions) can be difficult to distinguish from benign lesions that are too small to characterize. Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) can help clarify inconclusive findings from physical examination and cross-sectional imaging. FDG PET is more sensitive than CT in detection of lymphatic spread of disease to locoregional and mediastinal nodes. Metastases at distant sites including the lung, bone, and the liver are also readily detected at FDG PET. FDG PET has been proved accurate in restaging cases of recurrent breast cancer and will likely aid in directing therapy in these cases.

Bone Neoplasms↗