Showing papers in "Cancer in 2006"

Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study.

Abstract: BACKGROUND Aberrant DNA methylation, which results in leukemogenesis, is frequent in patients with myelodysplastic syndromes (MDS) and is a potential target for pharmacologic therapy. Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters. METHODS A total of 170 patients with MDS were randomized to receive either decitabine at a dose of 15 mg/m2 given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m2 per course) and repeated every 6 weeks, or best supportive care. Response was assessed using the International Working Group criteria and required that response criteria be met for at least 8 weeks. RESULTS Patients who were treated with decitabine achieved a significantly higher overall response rate (17%), including 9% complete responses, compared with supportive care (0%) (P < .001). An additional 12 patients who were treated with decitabine (13%) achieved hematologic improvement. Responses were durable (median, 10.3 mos) and were associated with transfusion independence. Patients treated with decitabine had a trend toward a longer median time to acute myelogenous leukemia (AML) progression or death compared with patients who received supportive care alone (all patients, 12.1 mos vs. 7.8 mos [P = 0.16]; those with International Prognostic Scoring System intermediate-2/high-risk disease, 12.0 mos vs. 6.8 mos [P = 0.03]; those with de novo disease, 12.6 mos vs. 9.4 mos [P = 0.04]; and treatment-naive patients, 12.3 mos vs. 7.3 mos [P = 0.08]). CONCLUSIONS Decitabine was found to be clinically effective in the treatment of patients with MDS, provided durable responses, and improved time to AML transformation or death. The duration of decitabine therapy may improve these results further. Cancer 2006. © 2006 American Cancer Society.

Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients.

Abstract: BACKGROUND Hospitalization for febrile neutropenia (FN) in cancer patients is associated with considerable morbidity, mortality, and cost. The study was undertaken to better define mortality, length of stay (LOS), cost, and risk factors associated with mortality and prolonged hospitalization in cancer patients with FN. METHODS The longitudinal discharge database derived from 115 US medical centers was used to study all adult cancer patients hospitalized with FN between 1995 and 2000, comprising a total of 41,779 patients. Primary outcomes included mortality, LOS, and cost per episode. RESULTS Overall, in-hospital mortality was 9.5%. Patients without any major comorbidities had a 2.6% risk of mortality, whereas 1 major comorbidity was associated with a 10.3% and more than 1 major comorbidity with a ≥21.4% risk of mortality, respectively. Mean (median) length of stay was 11.5 (6) days, and the mean (median) cost was $19,110 ($8,376) per episode of FN. Patients hospitalized for ≥10 days (35% of all patients) accounted for 78% of overall cost. Independent major risk factors for inpatient mortality included invasive fungal infections, Gram-negative sepsis, pneumonia and other lung disease, cerebrovascular, renal, and liver disease. Main predictors for LOS ≥10 days included leukemia, invasive fungal infections, other types of infection, and several comorbid conditions. CONCLUSION Factors associated with increased mortality, LOS, and cost in hospitalized adult cancer patients with FN include patient characteristics, type of malignancy, comorbidities, and infectious complications. These factors may be useful in identifying patients at increased risk of serious medical complications and mortality for more aggressive supportive care measures. Cancer 2006. © 2006 American Cancer Society.

Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis.

Abstract: BACKGROUND Lymphatic mapping with sentinel lymph node biopsy has the potential for reducing the morbidity associated with breast carcinoma staging. It has become a widely used technology despite limited data from controlled clinical trials. METHODS A systematic review of the world's literature of sentinel lymph node (SLN) biopsy in patients with early-stage breast carcinoma was undertaken by using electronic and hand searching techniques. Only studies that incorporated full axillary lymph node dissection (ALND), regardless of SLN results, were included. Individual study results along with weighted summary measures were estimated using the Mantel–Haenszel method. The correlations of outcomes with the study size, the proportion of positive lymph nodes, the technique used, and the study quality were evaluated. RESULTS Between 1970 and 2003, 69 trials were reported that met eligibility criteria. Of the 8059 patients who were studied, 7765 patients (96%) had successfully mapped SLNs. The proportion of patients who had successfully mapped SLNs ranged from 41% to 100%, with > 50% of studies reporting a rate 10%. Significant inverse correlations were observed between the FNR and both the number of patients studied (r = − 0.42; P < 0.01) and the proportion of patients who had successfully mapped SLNs nodes (r = − 0.32; P = 0.009). CONCLUSIONS Lymphatic mapping with SLN biopsy is used widely to reduce the complications associated with ALND in patients with low-risk breast carcinoma. This systematic review revealed a wide variation in test performance. Cancer 2006. © 2005 American Cancer Society.

Metastatic patterns in adenocarcinoma

Abstract: BACKGROUND Unique metastatic patterns cited in the literature often arise from anecdotal clinical observations and autopsy reports. The authors analyzed clinical data from a large number of patients with histologically confirmed, distant-stage adenocarcinoma to evaluate metastatic patterns. METHODS Tumor registry data were collected between 1994-1996 on 11 primary tumor sites and 15 metastatic sites from 4399 patients. The primary and metastatic sites were cross-tabulated in various ways to identify patterns, and the authors developed algorithms by using multinomial logistic regression analysis to predict the locations of primary tumors based on metastatic patterns. RESULTS Three primary tumors had single, dominant metastatic sites: ovary to abdominal cavity (91%), prostate to bone (90%), and pancreas to liver (85%). The liver was the dominant metastatic site for gastrointestinal (GI) primary tumors (71% of patients), whereas bone and lung metastases were noted most frequently in non-GI primary tumors (43% and 29%, respectively). In a study of combinations of liver, abdominal cavity, and bone metastases, 86% of prostate primary tumors had only bone metastases, 80% of ovarian primary tumors had only abdominal cavity metastases, and 74% of pancreas primary tumors had only liver metastases. A single organ was the dominant source of metastases in 7 sites: axillary lymph node from the breast (97%), intestinal lymph node from the colon (84%), thoracic lymph node from the lung (66%), brain from the lung (64%), mediastinal lymph node from the lung (62%), supraclavicular lymph node from the breast (51%), and adrenal gland from the lung (51%). CONCLUSIONS The algorithms that the authors developed achieved a cross-validated accuracy of 64% and an accuracy of 64% on an 1851-patient independent test set, compared with 9% accuracy when a random classifier was used. Cancer 2006. © 2006 American Cancer Society.

Fatigue in long-term breast carcinoma survivors: a longitudinal investigation.

Abstract: BACKGROUND A longitudinal study was designed to evaluate the prevalence, persistence, and predictors of posttreatment fatigue in breast carcinoma survivors METHODS A sample of 763 breast carcinoma survivors completed questionnaires at 1–5 and 5–10 years after diagnosis, including the RAND 36-item Health Survey, Center for Epidemiological Studies – Depression scale (CES-D), Breast Cancer Prevention Trial Symptom Checklist, and demographic and treatment-related measures RESULTS Approximately 34% of study participants reported significant fatigue at 5–10 years after diagnosis, which is consistent with prevalence estimates obtained at 1–5 years after diagnosis Approximately 21% reported fatigue at both assessment points, indicating a more persistent symptom profile Longitudinal predictors of fatigue included depression, cardiovascular problems, and type of treatment received Women treated with either radiation or chemotherapy alone showed a small improvement in fatigue compared with those treated with both radiation and chemotherapy CONCLUSIONS Fatigue continues to be a problem for breast carcinoma survivors many years after cancer diagnosis, with 21% reporting persistent problems with fatigue Several factors that may contribute to long-term fatigue are amenable to intervention, including depression and comorbid medical conditions Cancer 2006 © 2006 American Cancer Society

Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study.

Abstract: BACKGROUND Different scoring systems currently are being used to stratify patients with differentiated thyroid carcinoma (DTC) into risk groups. DTC is usually subdivided into papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). The objective of the current study was to identify those factors that predict long-term unfavorable prognosis and to evaluate the predictive accuracy of the TNM staging system. METHODS The authors conducted a nested case–control study within the cohort of all patients (n = 5123) diagnosed with DTC in Sweden between 1958–1987 who survived at least 1 year after diagnosis. One control, matched by age at diagnosis, gender, and calendar period, was randomly selected for each case (patients who died of DTC). All patients were classified at the time of diagnosis according to the TNM staging system. The effect of prognostic factors on DTC mortality was evaluated using conditional logistic regression. RESULTS Patients with widely invasive FTC experienced a significantly higher mortality compared with PTC patients. The grade of differentiation was found to influence mortality significantly. Patients with TNM Stage IV disease had a higher mortality rate compared with patients with Stage II disease (odds ratio [OR] = 9.1; 95% confidence interval [95% CI], 5.7–14.6). Patients with lymph node metastases experienced a higher mortality (OR = 2.5; 95% CI, 1.6–4.1) and patients with distant metastasis at the time of diagnosis were found to have a nearly 7-fold higher mortality rate (OR = 6.6; 95% CI, 4.1–10.5). Incomplete surgical excision was associated with higher mortality, particularly in patients with Stage I disease. CONCLUSIONS In the current study, the following were found to be clinically significant prognostic factors for patients with DTC: histopathologic subgroup, TNM staging including lymph node metastases and distant metastases, and completeness of the surgical excision.Cancer 2006. © 2005 American Cancer Society.

Acute myeloid leukemia: epidemiology and etiology.

Abstract: Acute myeloid leukemias (AMLs) are infrequent, yet highly malignant neoplasms responsible for a large number of cancer-related deaths. The incidence has been near stable over the last years. It continuously shows 2 peaks in occurrence in early childhood and later adulthood. With an incidence of 3.7 per 100,000 persons and an age-dependent mortality of 2.7 to nearly 18 per 100,000 persons, there is a rising awareness in the Western world of AML's special attributes resulting from an ever-aging population. To objectively describe epidemiologic data on this patient population, recent publications were evaluated to make transparent the current trends and facts. A review of the literature is presented, reflecting highlights of current research with respect to AML etiology. To estimate outcome and discuss informed treatment decisions with AML patients of different age groups and different biologic risk categories, it is mandatory to consider that the outcome results reported in clinical trials were until now heavily biased toward younger patients, whereas the overall dismal prognosis documented in population-based studies most likely reflects the exclusion of older patients from aggressive treatment. The etiology for most cases of AML is unclear, but a growing knowledge concerning leukemogenenic agents within chemotherapy regimens for other malignancies is already available. This includes specific associations of the most frequent balanced translocations in AML, including the "good-risk" abnormalities comprised by the core binding factor leukemias (i.e., AML with the translocation (8;21) and inversion of chromosome 16, and acute promyelocytic leukemia with the translocation (15;17)). In contrast to these genetic alterations, epigenetic lesions, e.g., promoter silencing by hypermethylation of the p15/INK4b and other genes, are increasingly recognized as important in the pathogenesis of AML.

Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome.

Abstract: BACKGROUND Elderly patients (age ≥ 65 years) with acute myeloid leukemia (AML) generally have a poor prognosis. AML-type therapy results are often derived from studies in younger patients and may not apply to elderly AML. Many investigators and oncologists advocate, at times, only supportive care or frontline single agents, Phase I–II studies, low-intensity regimens, or ‘targeted’ therapies. However, baseline expectations for outcomes of elderly AML with ‘standard’ AML-type therapy are not well defined. The aim was to develop prognostic models for complete response (CR), induction (8-week) mortality, and survival rates in elderly AML, which would be used to advise oncologists and patients of expectations with standard AML type therapy, and to establish baseline therapy results against which novel strategies would be evaluated. METHODS A total of 998 patients age ≥ 65 years with AML or high-risk myelodysplastic syndrome (> 10% blasts) treated with intensive chemotherapy between 1980 and 2004 were analyzed. Univariate and multivariate analyses of prognostic factors associated with CR, induction (8-week) mortality, and survival used standard methods. RESULTS The overall CR rate was 45% and induction mortality 29%. Multivariate analysis of prognostic factors identified consistent independent poor prognostic factors for CR, 8-week mortality, and survival. These included age ≥ 75 years, unfavorable karyotypes (often complex), poor performance (3–4 ECOG [Eastern Cooperative Oncology Group]), longer duration of antecedent hematologic disorder, treatment outside the laminar airflow room, and abnormal organ functions. Patients could be divided into: 1) a favorable group (about 20% of patients) with expected CR rates above 60%, induction mortality rates of 10%, and 1-year survival rates above 50%; 2) an intermediate group (about 50–55% of patients) with expected CR rates of 50%, induction mortality rates of 30%, and 1-year survival rates of 30%; and 3) an unfavorable risk group (about 25–30% of patients) with expected CR rates of less than 20%, induction mortality rates above 50%, and 1-year survival rates of less than 10%. CONCLUSIONS Prognostic models, based on standard readily available baseline characteristics, were developed for elderly patients with AML, which may assist in therapeutic and investigational decisions. These predictive models, based on a retrospective analysis, will require validation in independent study groups. Cancer 2006. © 2006 American Cancer Society.

Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution.

Abstract: BACKGROUND The evaluation variables influencing systemic and local recurrence and final outcome are extremely important in defining risk-adapted treatments for patients with nonmetastatic osteosarcoma of the extremity. METHODS A homogeneous group of 789 patients treated at a single institution between March 1983 and March 1999 with different protocols of neoadjuvant chemotherapy, with a minimum followup of 5 years, were retrospectively evaluated in relation to gender, age, serum levels of alkaline phosphatase, tumor site and size of the pathologic fracture, type of surgery, protocol of chemotherapy, surgical margins, and histologic response to preoperative treatment. RESULTS The 5-year event-free survival (EFS) and overall survival rates were 60.1% and 67.5%, respectively. Upon univariate analysis, EFS was significantly related to the age of patients, serum value of alkaline phosphatase, tumor volume, histologic subtype, type of surgery, surgical margins, histologic response to preoperative treatment, and chemotherapy protocol. Local recurrences (4.8%) were significantly correlated with surgical margins. The 5-year postrecurrence EFS survival was 17% and was significantly lower for patients who had a local recurrence and metastases than for those with metastases only. Patients who had a recurrence only in the lung had a postrecurrence survival rate significantly better than others, correlated with the number of metastatic nodules and the length of the disease-free interval. CONCLUSIONS Upon multivariate analysis, age ≤ 14 years, high serum levels of alkaline phosphatase, tumor volume > 200 mL, a two-drug regimen chemotherapy, inadequate surgical margins, and poor histologic response to treatment maintained independent prognostic values on the outcome of nonmetastatic osteosarcoma of the extremities. These factors must be considered when deciding risk-adapted treatments for osteosarcoma patients. Cancer 2006. © 2006 American Cancer Society.

Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia

Abstract: Background Adult Burkitt-type lymphoma (BL) and acute lymphoblastic leukemia (B-ALL) are rare entities composing 1% to 5% of non-Hodgkin lymphomas NHL) or ALL. Prognosis of BL and B-ALL has been poor with conventional NHL or ALL regimens, but has improved with dose-intensive regimens. Methods To evaluate the addition of rituximab, a CD20 monoclonal antibody, to intensive chemotherapy in adults with BL or B-ALL, 31 patients with newly diagnosed BL or B-ALL received the hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen with rituximab. Their median age was 46 years; 29% were 60 years or older. Rituximab 375 mg/m(2) was given on Days 1 and 11 of hyper-CVAD courses and on Days 1 and 8 of methotrexate and cytarabine courses. Results Complete remission (complete response [CR]) was achieved in 24 of 28 (86%) evaluable patients; 3 had a partial response, and 1 had resistant disease. There were no induction deaths. The 3-year overall survival (OS), event-free survival, and disease-free survival rates were 89%, 80%, and 88%, respectively. Nine elderly patients achieved CR with all of them in continuous CR (except 1 death in CR from infection), with a 3-year OS rate of 89%. Multivariate analysis of current and historical (those treated with hyper-CVAD alone) groups identified age and treatment with rituximab as favorable factors. Conclusions The addition of rituximab to hyper-CVAD may improve outcome in adult BL or B-ALL, particularly in elderly patients.

Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study.

Abstract: Background Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for approximately 36,000 diagnoses of invasive carcinoma annually. The most common histologic type, endometrioid adenocarcinoma (EC), accounts for 75-80% of patients. The objective of this work was to estimate the prevalence of concurrent carcinoma in women with a biopsy diagnosis of the precursor lesion, atypical endometrial hyperplasia (AEH). Methods This prospective cohort study included women who had a community diagnosis of AEH. Diagnostic biopsy specimens were reviewed independently by three gynecologic pathologists who used International Society of Gynecologic Pathologists/World Health Organization criteria. Study participants underwent hysterectomy within 12 weeks of entry onto protocol without interval treatment. The hysterectomy slides also were reviewed by the study pathologists, and their findings were used in the subsequent analyses. Results Between November 1998 and June 2003, 306 women were enrolled on the study. Of these, 17 women were not included in the analysis: Two patients had unreadable slides because of poor processing or insufficient tissue, 2 patients had only slides that were not endometrial, the slides for 5 patients were not available for review, and 8 of the hysterectomy specimens were excluded because they showed evidence of interval intervention, either progestin effect or ablation. In total, 289 patients were included in the current analysis. The study panel review of the AEH biopsy specimens was interpreted as follows: 74 of 289 specimens (25.6%) were diagnosed as less than AEH, 115 of 289 specimens (39.8%) were diagnosed as AEH, and 84 of 289 specimens (29.1%) were diagnosed as endometrial carcinoma. In 5.5% (16 of 289 specimens), there was no consensus on the biopsy diagnosis. The rate of concurrent endometrial carcinoma for analyzed specimens was 42.6% (123 of 289 specimens). Of these, 30.9% (38 of 123 specimens) were myoinvasive, and 10.6% (13 of 123 specimens) involved the outer 50% of the myometrium. Among the women who had hysterectomy specimens with carcinoma, 14 of 74 women (18.9%) had a study panel biopsy consensus diagnosis of less than AEH, 45 of 115 women (39.1%) had a study panel biopsy consensus diagnosis of AEH, and 54 of 84 women (64.3%) had a study panel diagnosis of carcinoma. Among women who had no consensus in their biopsy diagnosis, 10 of 16 women (62.5%) had carcinoma in their hysterectomy specimens. Conclusions The prevalence of endometrial carcinoma in patients who had a community hospital biopsy diagnosis of AEH was high (42.6%). When considering management strategies for women who have a biopsy diagnosis of AEH, clinicians and patients should take into account the considerable rate of concurrent carcinoma.

Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases.

Abstract: BACKGROUND. Medullary thyroid cancer (MTC) is a rare cancer. There is a relative paucity of data over the last decade with regard to the prognosis of these patients. Therefore, the authors used the population-based Surveillance, Epidemiology, and End Results (SEER) registry to update what to their knowledge is one of the largest series of patients with MTC reported to date. METHODS. All patients with a diagnosis of MTC with active follow-up in the SEER database from 1973 to 2002 were included. Univariate and multivariate regression analyses were used to assess the associations between demographic, clinical, and pathologic characteristics of patients and survival. RESULTS. A total of 1252 patients with MTC were identified over 29 years of follow-up. In all, 87% of patients were white and 60% were female, with a mean age of 50 years. Although many variables were significant on univariate analysis, SEER stage and age at diagnosis were found to be the strongest predictors of survival in the multivariate analysis. Prognosis was poor in patients with advanced disease (hazards ratio [HR], 4.47), or those age >65 years (HR, 6.55). Patients who underwent surgery fared better than those who did not. Overall, 51% of patients had less than the currently recommended treatment guidelines for MTC. Adjuvant radiation therapy was found to be independently associated with a decreased survival (HR, 1.65). CONCLUSIONS. Stage of disease and age at diagnosis were found to be the strongest predictors of survival for patients with MTC. To the authors' knowledge there has been no change in stage at diagnosis or asignificant improvement in survival noted over the last 30 years. Many patients underwent surgery that was deemed less than optimal for stage of disease. Cancer 2006. © 2006 American Cancer Society.

Annual report to the nation on the status of cancer, 1975-2003, featuring cancer among U.S. Hispanic/Latino populations.

Abstract: BACKGROUND The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries collaborate annually to provide U.S. cancer information, this year featuring the first comprehensive compilation of cancer information for U.S. Latinos. METHODS Cancer incidence was obtained from 90% of the Hispanic/Latino and 82% of the U.S. populations. Cancer deaths were obtained for the entire U.S. population. Cancer screening, risk factor, incidence, and mortality data were compiled for Latino and non-Latino adults and children (incidence only). Long-term (1975–2003) and fixed-interval (1995–2003) trends and comparative analyses by disease stage, urbanicity, and area poverty were evaluated. RESULTS The long-term trend in overall cancer death rates, declining since the early 1990s, continued through 2003 for all races and both sexes combined. However, female lung cancer incidence rates increased from 1975 to 2003, decelerating since 1991 and breast cancer incidence rates stabilized from 2001 to 2003. Latinos had lower incidence rates in 1999–2003 for most cancers, but higher rates for stomach, liver, cervix, and myeloma (females) than did non-Latino white populations. Latino children have higher incidence of leukemia, retinoblastoma, osteosarcoma, and germ-cell tumors than do non-Latino white children. For several common cancers, Latinos were less likely than non-Latinos to be diagnosed at localized stages. CONCLUSIONS The lower cancer rates observed in Latino immigrants could be sustained by maintenance of healthy behaviors. Some infection-related cancers in Latinos could be controlled by evidence-based interventions. Affordable, culturally sensitive, linguistically appropriate, and timely access to cancer information, prevention, screening, and treatment are important in Latino outreach and community networks. Cancer 2006. Published 2006 by the American Cancer Society.

Emerging implications of nanotechnology on cancer diagnostics and therapeutics

Abstract: Nanotechnology is multidisciplinary field that involves the design and engineering of objects <500 nanometers (nm) in size. The National Cancer Institute has recognized that nanotechnology offers an extraordinary, paradigm-changing opportunity to make significant advances in cancer diagnosis and treatment. In the last several decades, nanotechnology has been studied and developed primarily for use in novel drug-delivery systems (e.g. liposomes, gelatin nanoparticles, micelles). A recent explosion in engineering and technology has led to 1) the development of many new nanoscale platforms, including quantum dots, nanoshells, gold nanoparticles, paramagnetic nanoparticles, and carbon nanotubes, and 2) improvements in traditional, lipid-based nanoscale platforms. The emerging implications of these platforms for advances in cancer diagnostics and therapeutics form the basis of this review. A widespread understanding of these new technologies is important, because they currently are being integrated into the clinical practice of oncology.

Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity.

Abstract: RESULTS. After review by 4 pathologists, 78 patients were included in the study. Sixty-one of 78 patients (78%) had encapsulated tumors (18 invasive, 43 noninvasive), and 17 patients had nonencapsulated tumors (infiltrative/diffuse). The gender distribution, age at presentation, and tumor size did not differ between patients with encapsulated and nonencapsulated FVPTC. Patients who had encapsulated FVPTC had a significantly lower rate of marked intratumor fibrosis (18%), extrathyroid extension (5%), and positive margins (2%) compared with patients who had nonencapsulated tumors (88%, 65%, and 50% respectively; P < .0001). Regional lymph node metastases were present in 14 of 78 patients (18%), and no patients had distant metastases. The lymph node metastatic rate was significantly higher in patients who had nonencapsulated tumors (11 of 17 patients; 65%) compared with patients who had encapsulated neoplasms (3 of 61 patients; 5%; P < .0001). In addition, lymph node metastases were not detected in any noninvasive, encapsulated FVPTCs. With a median follow-up of 10.8 years, only 1 patient developed a recurrence, which occurred in an encapsulated FVPTC that had numerous invasive foci. None of the patients with noninvasive, encapsulated FVPTCs developed recurrences, including 31 patients who underwent lobectomy alone, with a median follow-up of 11.1 years. CONCLUSIONS. FVPTC appeared to be a heterogeneous disease composed of 2 distinct groups: an infiltrative/diffuse (nonencapsulated) subvariant, which resembles classic papillary carcinoma in its metastatic lymph node pattern and invasive growth, and an encapsulated form, which behaves more like FTA/FTC. Patients who had noninvasive, encapsulated FVPTCs did not develop lymph node metastases or recurrences and could be treated by lobectomy alone. If the current findings are confirmed, then strong consideration should be given to reclassifying encapsulated FVPTC as an entity that is close to the FTA/FTC class of tumors. Cancer 2006;107:1255–64. � 2006 American Cancer Society.

Tumor infiltrating Foxp3+ regulatory T‐cells are associated with recurrence in pathologic stage I NSCLC patients

Abstract: BACKGROUND. Early stage lung cancer has a variable prognosis, and there are currently no markers that predict which patients will recur. This study examined the relation between tumor-regulatory T (Treg) cells and total tumor-infiltrating T-cell lymphocytes (TIL) to determine whether they correlated with recurrence. METHODS. The authors reviewed all patients in our tissue databank from 1996 to 2001 and identified 64 consecutive pathologic stage I non-small cell lung cancer (NSCLC) patients who had surgical resection and at least a 2.5 years disease-free follow-up or documented recurrence within 2 years. Immunohistochemical analyses were performed on paraffin-embedded lung cancer tissue and the relation between Treg cells, TIL, and disease-specific survival was determined. A risk index was devised deductively for various possible combinations of Treg cells and TIL. RESULTS. Treg cells and TIL were detected in 33 of 64 (51%) and 53 of 64 (83%) patients, respectively. When data were analyzed by using a Treg/TIL Combination Risk Index, patients with high-risk and intermediate-risk indices had hazard ratios of 8.2 (P = .007) and 3.3 (P = .109), respectively. CONCLUSIONS. Patients with stage I NSCLC who have a higher proportion of tumor Treg cells relative to TIL had a significantly higher risk of recurrence. These data may be useful, particularly if combined with a panel of tumor markers, to suggest at the time of diagnosis which patients with seemingly early-stage NSCLC will relapse. Cancer 2006. © 2006 American Cancer Society.

Primary malignant hepatic epithelioid hemangioendothelioma: a comprehensive review of the literature with emphasis on the surgical therapy.

Abstract: Malignant hepatic epithelioid hemangioendothelioma (HEH) is a rare malignant tumor of vascular origin with unknown etiology and a variable natural course. The authors present a comprehensive review of the literature on HEH with a focus on clinical outcome after different therapeutic strategies. All published series on patients with HEH (n = 434 patients) were analyzed from the first description in 1984 to the current literature. The reviewed parameters included demographic data, clinical manifestations, therapeutic modalities, and clinical outcome. The mean age of patients with HEH was 41.7 years, and the male-to-female ratio was 2:3. The most common clinical manifestations were right upper quadrant pain, hepatomegaly, and weight loss. Most patients presented with multifocal tumor that involved both lobes of the liver. Lung, peritoneum, lymph nodes, and bone were the most common sites of extrahepatic involvement at the time of diagnosis. The most common management has been liver transplantation (LTx) (44.8% of patients), followed by no treatment (24.8% of patients), chemotherapy or radiotherapy (21% of patients), and liver resection (LRx) (9.4% of patients). The 1-year and 5-year patient survival rates were 96% and 54.5%, respectively, after LTx; 39.3% and 4.5%, respectively, after no treatment, 73.3% and 30%, respectively, after chemotherapy or radiotherapy; and 100% and 75%, respectively, after LRx. LRx has been the treatment of choice in patients with resectable HEH. However, LTx has been proposed as the treatment of choice because of the hepatic multicentricity of HEH. In addition, LTx is an acceptable option for patients who have HEH with extrahepatic manifestation. Highly selected patients may be able to undergo living-donor LTx, preserving the donor pool. The role of different adjuvant therapies for patients with HEH remains to be determined.

Malignant peripheral nerve sheath tumors: Prognostic factors and survival in a series of patients treated at a single institution

Abstract: BACKGROUND. The authors explored the prognostic factors and clinical outcomes of patients who had malignant peripheral nerve sheath tumors (MPNST) with and without neurofibromatosis type 1 (NF-1). METHODS. Two hundred five patients with localized MPNST who underwent surgery at the Istituto Nazionale per lo Studio e la Cura dei Tumori (Milan, Italy) over 25 years were reviewed. Forty-six patients had concomitant NF-1 syndrome, and 159 patients did not. Local recurrence, distant metastases, and survival rates were studied. RESULTS. One hundred thirty patients presented with primary disease, and 75 patients had locally recurrent tumors. The disease-specific mortality rate was 43% at 10 years, with a continuously disease-free survival rate of no greater than 40%. Presentation with either primary or recurrent disease, tumor size, and tumor site (trunk vs. extremity) were the strongest independent predictors of survival. Margin status and radiation therapy also played a role, mostly related to their effect on local outcome. Pathologic grade influenced distant metastases, but only a trend for survival could be observed. No significant independent differences between patients with and without NF-1 were observed. CONCLUSIONS. To the authors' knowledge, this was among the largest single-institution series to date. The results confirmed that patients with MPNST share similar prognostic factors with patients who have other soft tissue sarcomas and have some of the worst clinical outcomes. The presence of NF-1 syndrome per se did not affect survival, but patients with NF-1 were more likely to have larger tumors. Therefore, such patients should be followed carefully to detect disease as early as possible. Cancer 2006. © 2006 American Cancer Society.

Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase.

Abstract: BACKGROUND. In patients with cancer, one of the main mechanism of resistance to antimetabolite drugs is related to higher levels of thymidylate synthase (TS) activity. METHODS. To investigate the association between TS expression and histopathologic data, 56 resection specimens from patients with nonsmall cell lung carcinoma (NSCLC) were collected consecutively. TS messenger RNA (mRNA) was evaluated in tumor specimens by using real-time polymerase chain reaction (PCR) analysis; protein expression was evaluated by using immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded (FFPE) specimens; and the analysis of TS transcriptional regulation activity was performed by using real-time PCR analysis in snap-frozen normal and tumor specimens. RESULTS. The amplification of the TS gene from FFPE tissues was obtained from all samples, with a median level (unit-less ratio) of 1.45 (range, 0.34–5.24); whereas positive TS status at IHC (>10% positive cells) was detected in 56% of samples. It is noteworthy that TS expression was significantly higher in squamous cell carcinoma compared with adenocarcinoma when both mRNA levels (2.17 vs. 1.16; P < .0001) and protein levels (P = .0269) were considered in FFPE specimens, and a strong association was observed between mRNA and protein expression (P = .00017). Moreover, higher TS levels were observed in high-grade tumors (P = .0389 and P = .0068 for mRNA and protein quantification, respectively). The analysis in snap-frozen samples revealed that the TS gene was up-regulated strongly in tumors (P = 3.8 × 10−12), and an 8-fold increase (as a cut-off value) in the TS mRNA ratio between tumor and corresponding normal tissue was detected in 32 of 56 patients (57%) bearing preferentially squamous cell tumors (P = .0022) and high-grade tumors (P < .001). CONCLUSIONS. Data from the current study consistently indicated higher TS expression levels in squamous cell and in high-grade carcinomas. This information may be useful in selecting which patients with NSCLC should receive treatment with TS-inhibiting agents. Cancer 2006. © 2006 American Cancer Society.

Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients.

Abstract: BACKGROUND. The purpose of the current study was to determine the potential therapeutic role of lymphadenectomy in women with endometrioid corpus cancer. METHODS. Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology, and End Results Program between 1988–2001. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS. In all, 12,333 women (median age, 64) underwent surgical staging with lymph node assessment, including 9,009, 1,211, 1,223, and 890 with Stage I-IV disease. Over the time intervals 1988–1992, 1993–1997, and 1998–2001, the percentage of patients undergoing lymph node staging increased from 22.6%, 29.6%, to 40.9% (P 20) was associated with improved 5-year disease-specific survivals across all 5 groups at 75.3%, 81.5%, 84.1%, 85.3%, and 86.8%, respectively (P < .001). For Stage IIIC-IV patients with nodal disease, the extent of node resection significantly improved the survival from 51.0%, 53.0%, 53.0%, 60.0%, to 72.0%, (P < .001). However, no significant benefit of lymph node resection in low-risk patients could be demonstrated (Stage IA, all grades; Stage IB, Grades 1 and 2 disease; P = .23). In multivariate analysis, a more extensive node resection remained a significant prognostic factor for improved survival in intermediate/high-risk patients after adjusting for other factors including age, year of diagnosis, stage, grade, adjuvant radiotherapy, and the presence of positive nodes (P < .001). CONCLUSIONS. The findings of the current study suggest that the extent of lymph node resection improves the survival of women with intermediate/high-risk endometrioid uterine cancer. Cancer 2006. © 2006 American Cancer Society.

Adolescents and young adults with cancer: the scope of the problem and criticality of clinical trials.

Abstract: In the U.S., older adolescents and young adults with cancer have benefited less from therapeutic advances than did either younger or older patients. One factor that may explain this deficit is the relative lack of participation of patients in this age group on clinical trials of therapies that could improve their outcome. Comparisons were made of the participation of cancer patients on clinical trials in the U.S., as a function of patient age, with the change in national cancer mortality rate; and Surveillance, Epidemiology, End Results (SEER) cancer survival rate as a function of age. The participation rate in cancer treatment trials has been strikingly lower in 15-34-year-olds than in younger or older patients. The nadir has been apparent for both males and females in all of the major ethnic and racial groups. The national cancer mortality reduction and SEER survival improvement shows a similar age dependence. In the U.S., the age-dependence of cancer treatment trial participation, and of improvement in survival prolongation and cancer death rates, are correlated. Regardless of whether there is a causal relationship, the impact on the older adolescent and young adult U.S. population is substantial, adversely affecting the national cost of healthcare, the person-years of life lost, the loss of young people entering the job market, and the scientific knowledge and social implications of cancer during adolescence and early adulthood. National initiatives are underway to address these issues, with special emphasis on increasing the availability and access to clinical trials designed for older adolescents and young adults.

Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy.

Abstract: BACKGROUND Prostate carcinoma (PCa) is one of the most common malignancies in men. Androgen-deprivation therapy (ADT) is used frequently in the treatment of recurrent and metastatic PCa, rendering these men hypogonadal. Because male hypogonadism is associated with an unfavorable metabolic profile, and men with PCa have high cardiovascular mortality, the authors evaluated the effects of long-term ADT on fasting glucose levels, insulin levels, and insulin resistance. METHODS To evaluate the long-term effects of ADT on fasting glucose and insulin resistance in men with PCa who received ADT and to determine whether these metabolic alterations are a result of hypogonadism, the authors conducted a cross-sectional study at a university-based research institution in the United States. In total, 53 men were evaluated, including 18 men with PCa who received ADT for at least 12 months prior to the onset of the study (the ADT group), 17 age-matched men with nonmetastatic PCa who had undergone prostatectomy and/or received radiotherapy and who were not receiving ADT (the non-ADT group), and 18 age-matched controls (the control group). None of the men had a known history of diabetes mellitus. RESULTS The mean age was similar in all 3 groups (P = 0.33). Serum total testosterone levels (P < 0.0001) and free testosterone levels (P < 0.0001) were significantly lower in the ADT group compared with the other groups. Men in the ADT group had a higher BMI compared with the other groups (overall P = 0.005). After adjustment for age and BMI, men in the ADT group had significantly higher fasting levels of the following parameters: 1) Glucose levels were 131.0 ± 7.43 mg/dL in the ADT group compared with 103.0 ± 7.42 mg/dL in the non-ADT group (P = 0.01) and 99.0 ± 7.58 mg/dL in the control group (P < 0.01). 2) Insulin levels were 45.0 ± 7.25 uU/mL in the ADT group compared with 24.0 ± 7.24 uU/mL in the non-ADT group (P = 0.05) and 19.0 ± 7.39 uU/mL in the control group (P = 0.02). 3) Leptin levels were 25.0 ± 2.57 ng/mL in the ADT group compared with 12.0 ± 2.56 ng/mL in the non-ADT group (P < 0.01) and 6.0 ± 2.62 ng/mL in the control group (P < 0.01). 4) The homeostatic model assessment for insulin resistance (HOMAIR) = 17.0 ± 2.78 in the ADT group compared with HOMAIR = 6.0 ± 2.77 in the non-ADT group (P < 0.01) and HOMAIR = 5.0 ± 2.83 in the control group (P = 0.01). There was a significant negative correlation between total and free testosterone levels with fasting glucose, insulin, leptin, and HOMAIR. CONCLUSIONS The current data suggested that men with PCa who are receiving long-term ADT are at risk for developing insulin resistance and hyperglycemia, thus leading to their increased risk of cardiovascular disease. This adverse metabolic profile developed independent of age and BMI and appeared to be a direct result of androgen deprivation. Cancer 2006. © 2005 American Cancer Society.

Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder.

Abstract: BACKGROUND. Perioperative cisplatin-based chemotherapy has shown benefit in patients with high-risk localized urothelial bladder cancer, but it is not widely used. Renal impairment may be a major factor limiting its use. The current study was designed to determine the proportion of patients ineligible to receive adjuvant cisplatin-based chemotherapy based on inadequate renal function alone. METHODS. Patients who underwent radical cystectomy for urothelial cancer of the bladder with evidence of extravesical disease (≥pT3 or any N+) were identified. Patients who received neoadjuvant chemotherapy were excluded. Serum creatinine immediately before and nadir serum creatinine after cystectomy were used to calculate creatinine clearance (CrCl) or glomerular filtration rate (GFR) using the Cockroft-Gault (CG), Jelliffe, and Modification of Diet in Renal Disease (MDRD) study formulas. A cutoff of CrCl <60 mL/min or GFR <60 mL/min/1.73 m2 was used to determine ineligibility for cisplatin-based chemotherapy. The proportion of patients ineligible by each formula was compared by univariate logistic regression. Univariate linear regression was performed to determine the effect of age on CrCl or GFR. RESULTS. Most patients were pT3 or greater; 39% were lymph node-positive. The overall proportion of patients ineligible for cisplatin-based chemotherapy was 28% by the CG formula, 52% by Jelliffe, and 24% by MDRD. Concordance between formulas was low. With all formulas the probability of ineligibility increased with age: by the CG equation, >40% of patients age >70 years were ineligible. CONCLUSIONS. The widespread use of cisplatin-based perioperative chemotherapy in patients with high-risk localized bladder cancer may be significantly limited by the high prevalence of baseline renal insufficiency in this population. This finding is most striking in the elderly. Better selection of patients who may safely receive cisplatin and more effective regimens devoid of cisplatin are required to optimize outcomes in this group of patients. Cancer 2006. © 2006 American Cancer Society.

Radiation-induced xerostomia in patients with head and neck cancer: a literature review

Abstract: A dry mouth or xerostomia is one of the most common complications during and after radiotherapy for head and neck cancer, because irreparable damage is caused to the salivary glands, which are included in the radiation fields. Xerostomia not only significantly impairs the quality of life of potentially cured cancer patients, it may also lead to severe and long-term oral disorders. Because management of xerostomia is rarely effective, prevention is paramount. Several strategies have been developed to avoid radiation-induced salivary dysfunction without compromising definitive oncologic treatment. These include salivary gland-sparing radiation techniques, such as 3-dimensional conformal or intensity-modulated radiotherapy, concomitant cytoprotectants, and surgical salivary gland transfer. However, these preventive approaches are not applicable to all patients, and comprehensive scientific research that incorporates new biological insights is warranted to optimize the therapeutic index of radiotherapy for head and neck cancer.

Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero

Abstract: BACKGROUND As women in the US delay childbearing, it has been hypothesized that the incidence of breast cancer diagnosed during pregnancy will increase. There are very little prospective data on the treatment of pregnant women with breast cancer with chemotherapy and even less data on the outcomes of their children who were exposed to chemotherapy in utero. METHODS Fifty-seven pregnant breast cancer patients were treated on a single-arm, multidisciplinary, institutional review board-approved protocol with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant (n = 32) or neoadjuvant (n = 25) setting. Parents/guardians were surveyed by mail or telephone regarding outcomes of children exposed to chemotherapy in utero. RESULTS Of the 57 women, 40 are alive and disease-free, 3 have recurrent breast cancer, 12 died from breast cancer, 1 died from other causes, and 1 was lost to follow-up. Of the 25 patients who received neoadjuvant FAC, 6 had a pathologic complete response, whereas 4 had no tumor response to chemotherapy and eventually died from their disease. All women who delivered had live births. One child has Down syndrome and 2 have congenital anomalies (club foot; congenital bilateral ureteral reflux). The children are healthy and those in school are doing well, although 2 have special educational needs. CONCLUSIONS Breast cancer can be treated with FAC chemotherapy during the second and third trimesters without significant short-term complications for the majority of children exposed to chemotherapy in utero. Longer follow-up of the children is needed to evaluate possible late side effects such as impaired cardiac function and fertility. Cancer 2006. © 2006 American Cancer Society.

Racial differences in doctors' information-giving and patients' participation.

Abstract: BACKGROUND Whether doctor-patient communication differs by race was investigated in patients with pulmonary nodules or lung cancer. METHODS Eligible patients (n = 137) had pulmonary nodules or lung cancer and were seen in thoracic surgery or oncology clinics for initial treatment recommendations at a large southern Veterans Affairs Medical Center from 2001–2004. Doctor-patient consultations were audiotaped. Audiotapes were transcribed, unitized into utterances, and utterances were coded as doctors' information-giving or patients' and companions' active participation (asking questions, expressing concerns, and making assertions). Data were compared by patient race and doctor-patient racial concordance using t-tests or chi-square tests as appropriate. Mixed linear regression was used to determine the independent predictors of doctor's information-giving after controlling for clustering of patients by doctor. RESULTS Patient age, gender, marital status, clinical site, and health status were similar by race (P > .20), but black patients were somewhat less likely to have education beyond high school and to bring a companion to the visit (P = .06) than white patients. Black patients and their companions received significantly less information from doctors (49.3 vs. 87.3 mean utterances; P < .001) and produced significantly fewer active participation utterances (21.4 vs. 37.2; P < .001) than white patients. In mixed regression analyses, after adjusting for patients' and companions' participation, clustering by doctor, and other factors, race no longer predicted information-giving (P = .54). Patients in racially discordant interactions received significantly less information and were significantly less active participants (P < .001) when compared with patients in racially concordant interactions, and after controlling for patients' participation and other factors using mixed regression, racial discordance did not predict information-giving. CONCLUSIONS The results indicate a pattern of communication that may perpetuate patient passivity and limited information exchange where black patients and patients in discordant interactions do less to prompt doctors for information and doctors in turn provide less information to these patients. Cancer 2006. © 2006 American Cancer Society.

Successes and failures of the teachable moment: smoking cessation in cancer patients.

Abstract: BACKGROUND Successful cancer treatment can be significantly compromised by continued tobacco use. Because motivation and interest in smoking cessation increase after cancer diagnosis, a window of opportunity exists during which healthcare providers can intervene and assist in the quitting process. METHODS The authors conducted a comprehensive literature review to discuss 1) the benefits of smoking cessation in cancer patients, 2) current knowledge regarding smoking cessation interventions targeted to cancer patients, and 3) treatment models and state-of the-art guidelines for intervention with cancer patients who smoke. The authors present clinical cases to illustrate the challenging nature of smoking cessation treatment for cancer patients. RESULTS Continued smoking after cancer diagnosis has substantial adverse effects on treatment effectiveness, overall survival, risk of second primary malignancies, and quality of life. Although some encouraging results have been demonstrated with smoking cessation interventions targeted to cancer patients, few empirical studies of such interventions have been conducted. A range of intervention components and state-of-the-art cessation guidelines are available that can be readily applied to cancer patients. Case illustrations highlight the crucial role of healthcare providers in promoting smoking cessation, the harmful impact of nicotine addiction manifested in delayed and failed reconstructive procedures, and unique problems encountered in treating patients who have particular difficulty quitting. CONCLUSIONS Despite the importance of stopping smoking for all cancer patients, the diagnosis of cancer is underused as a teachable moment for smoking cessation. More research is needed to empirically test cessation interventions for cancer patients, and attention must be given to complex and unique issues when tailoring cessation treatment to these individuals. Cancer 2006. © 2005 American Cancer Society.

Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma

Abstract: BACKGROUND The current study was conducted to characterize the risks and clinical consequences of oral mucositis (OM) in patients with head and neck carcinoma (HNC) who are receiving radiation therapy. METHODS Data regarding 450 HNC patients who had received radiation therapy were collected via chart review from 154 U.S. medical and radiation oncologists. Information obtained included patient characteristics, treatments received, highest recorded grade of OM during radiation therapy (none, mild, moderate, or severe), and outcomes potentially associated with mucosal injury. RESULTS The mean age (± standard deviation [SD]) of the study subjects was 61.3 years (12.3 yrs); the majority of patients (80%) were men. Primary tumor locations included the oropharynx (26.4%), larynx (26.4%), oral cavity including the lip (24.4%), hypopharynx (13.6%), and nasopharynx (9.1%). The majority of tumors were new and were classified as AJCC Stages III or IV. The majority of patients (83%) received standard radiation therapy; the mean (± SD) cumulative dose was 6285 centigrays (cGy) (± 1158 cGy). Approximately 33% of the patients received concomitant chemotherapy. The majority of patients (83%) developed OM; 29% developed severe OM. Patients with severe OM were more likely to have nasopharyngeal or oropharyngeal tumors (adjusted odds ratio [OR] of 10.1 [95% confidence interval (95% CI), 2.1–49.9] and 6.9 [95% CI, 2.4–19.7], respectively), and to have received cumulative radiation doses > 5000 cGy (OR of 10.4; 95% CI, 2.9–37.1) and concomitant chemotherapy (OR of 3.3; 95% CI, 1.4–8.0). Patients with OM had more unplanned breaks in radiation therapy (OR of 3.8; 95% CI, 1.7–8.5) and hospital admissions (OR of 3.5; 95% CI, 1.3–9.5). CONCLUSIONS HNC patients with nasopharyngeal or oropharyngeal tumors, and those who receive cumulative radiation doses > 5000 cGy or concomitant chemotherapy, are more likely to develop OM. Patients with OM are at a higher risk of unplanned breaks in radiation therapy and hospitalization. Cancer 2006. © 2005 American Cancer Society.

The metabolic syndrome and risk of incident colorectal cancer.

Abstract: BACKGROUND The authors tested the hypothesis that the metabolic syndrome (≥3 of the following components: high blood pressure, increased waist circumference, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, or diabetes/hyperglycemia) is a risk factor for colorectal cancer. METHODS Data from the Atherosclerosis Risk in Communities (ARIC) multicenter prospective cohort study were used. Metabolic syndrome components and other risk factors were collected during 1987 to 1989 from the 14,109 men and women in these analyses. One hundred ninety-four incident colorectal cancers were identified through the Year 2000. Multivariate Cox proportional hazards regression analyses were used to examine associations. RESULTS Baseline metabolic syndrome (≥3 components vs. 0 components) had a positive association with age-adjusted and gender-adjusted colorectal cancer incidence (relative risk [RR], 1.49; 95% confidence interval [95%CI], 1.0-2.4); this association was attenuated after multivariate adjustment (RR, 1.39; 95%CI, 0.9-2.2). There was a dose-response association between colorectal cancer incidence and the number of metabolic syndrome components present at baseline (P for trend = .006) after multivariate adjustment. Analysis of gender revealed that the multivariate-adjusted association of metabolic syndrome with colorectal cancer was stronger in men (RR, 1.78; 95%CI, 1.0-3.6) and weaker in women (RR, 1.16; 95%CI, 0.6-2.2). CONCLUSIONS In this population-based cohort, metabolic syndrome was a risk factor for incident colorectal cancer in men but not women. Evidence is growing that the metabolic syndrome may be a marker for a physiologic milieu of growth that encourages tumor initiation, promotion, and/or progression. Cancer 2006. © 2006 American Cancer Society.

Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the Pre-Operative "Arimidex" Compared to Tamoxifen (PROACT) trial.

Abstract: BACKGROUND The Pre-Operative “Arimidex” Compared to Tamoxifen (PROACT) study was a randomized, multicenter study comparing anastrozole with tamoxifen as a preoperative treatment of postmenopausal women with large, operable (T2/3, N0-2, M0), or potentially operable (T4b, N0-2, M0) breast cancer. The effect of preoperative endocrine therapy in patients scheduled for mastectomy or with inoperable tumors at baseline was also investigated. METHODS Patients with hormone receptor-positive breast cancer received anastrozole (n = 228) or tamoxifen (n = 223) with or without chemotherapy for 12 weeks before primary surgery. RESULTS Objective responses for anastrozole and tamoxifen occurred in 39.5% and 35.4% of patients, respectively (ultrasound measurements), and 50.0% and 46.2% of patients, respectively (caliper measurements). In hormonal therapy-only patients (n = 314), feasible surgery at baseline improved after 3 months in 43.0% of patients receiving anastrozole and 30.8% receiving tamoxifen (P = .04). In the intent-to-treat population, improvement in feasible surgery at baseline to actual surgery at 3 months was found to be numerically higher in the anastrozole group compared with the tamoxifen group, although this difference did not reach significance. Drug-related adverse events were reported in 20.2% and 18.1% of patients, respectively, in the anastrozole and tamoxifen groups. CONCLUSIONS Anastrozole is an effective and well-tolerated preoperative therapy, producing clinically beneficial tumor downstaging and reductions in tumor volume. These effects enable more minimal surgical interventions in patients scheduled for mastectomy, and mastectomy in patients with previously inoperable tumors. Anastrozole appears to be at least as effective as tamoxifen in this setting, and more effective than tamoxifen in certain clinically relevant subgroups. Cancer 2006. © 2006 American Cancer Society.