American Cancer Society (american + cancer_society)

Distribution by Scientific Domains

Selected Abstracts

Are men shortchanged on health?

Perspective on life expectancy, morbidity, mortality in men, women in the United States
Summary Background:, Significant gender disparities exist in life expectancy and major disease morbidity. There is an urgent need to understand the major issues related to men's health that contributes to these significant disparities. It is hypothesized that men have higher and earlier morbidities, in addition to behavioral factors that contribute to their lower life expectancy. Methods:, Data was collected from CDC: Health United States, 2007; American Heart Association, American Obesity Association, and American Cancer Society. Results:, Men have lower life expectancy than women in most countries around the world including United States. This gender disparity is consistent regardless of geography, race and ethnicity. More men die of 12 out of the 15 leading causes of death than women. In addition, men have higher morbidity and mortality in coronary heart disease (CHD), hypertension, diabetes, and cancer. Conclusions:, Men's lower life expectancy may be explained by biological and clinical factors such as the higher incidence of cardiovascular metabolic disease and cancer. In the context of public health, raising awareness of cardiovascular and metabolic health is needed to reduce the gender disparity. In addition, consideration of preventive and early detection/intervention programs may improve men's health. [source]

Contributions of the American Cancer Society to Coordinated School Health Programs: A Changing View of Schools

John R. Seffrin
No abstract is available for this article. [source]

Ongoing capacity building in the American Cancer Society (ACS) 1995,2001

Donald W. Compton
The authors' case study narrative is about the seven-year process of building an ECB structure at this nationwide, not-for-profit health organization. [source]

Crossing the Borders: An International Breast Health Educational Initiative , A Collaboration Between the American Cancer Society and the University of Florida, Jacksonville

Shahla Masood MD
No abstract is available for this article. [source]

American Cancer Society (ACS) Facilitators Boost Colorectal Screening in Primary Care

Article first published online: 31 DEC 200
No abstract is available for this article. [source]

Chromosome 9p deletions identify an aggressive phenotype of clear cell renal cell carcinoma

CANCER, Issue 20 2010
Jeffrey La Rochelle MD
Abstract BACKGROUND: The authors investigated whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccRCC) predicted worse disease-specific survival (DSS) and recurrence-free survival (RFS) and whether it was associated with more aggressive behavior in small renal masses. METHODS: In total, 703 ccRCC tumors were analyzed using fluorescence in situ hybridization (316 tumors) and cytogenetics (388 tumors). Tumor grade, classification, and size; 9p status; Eastern Cooperative Oncology Group performance status (ECOG PS); lymph node involvement; and the presence of metastasis were recorded. Outcomes were stratified by 9p status, and a Cox proportional hazards models was constructed using TNM staging, ECOG PS, tumor size, tumor grade, and 9p status. RESULTS: Deletions of 9p were detected in 97 tumors (13.8%). At presentation, 9p-deleted tumors were larger and were more likely to be high grade (grade 3 or 4), to have a high tumor (T) classification (T3-T4), and to have lymph node or distant metastases (P < .01). The median DSS for patients with and without 9p deletions was 37 months and 82 months, respectively (P < .01). In patients with localized disease, the median RFS in those who had 9p deletions was 53 months and was not reached in those without 9p deletions (P < .01). In patients who had localized lesions that measured ,4 cm in greatest dimension, 9p-deleted tumors were more likely to recur (19% vs 2%; P = .01). CONCLUSIONS: Deletion of chromosome 9p in ccRCC occurred in 14% of patients and was associated with higher grade and T classification, and the presence of lymph node and distant metastases. In addition, 9p deletion independently conferred a worse prognosis for patients with localized ccRCC, and most noteworthy, in patients with localized, small renal masses. Preoperatively identifying patients with 9p deletions will improve risk stratification and will help to select appropriate patients for surveillance protocols or aggressive treatment. Cancer 2010. © 2010 American Cancer Society. [source]

Underuse of colorectal cancer screening among men screened for prostate cancer

CANCER, Issue 20 2010
A teachable moment?
Abstract BACKGROUND: Evidence suggests that colorectal cancer (CRC) screening reduces disease-specific mortality, whereas the utility of prostate cancer screening remains uncertain. However, adherence rates for prostate cancer screening and CRC screening are very similar, with population-based studies showing that approximately 50% of eligible US men are adherent to both tests. Among men scheduled to participate in a free prostate cancer screening program, the authors assessed the rates and correlates of CRC screening to determine the utility of this setting for addressing CRC screening nonadherence. METHODS: Participants (N = 331) were 50 to 70 years old with no history of prostate cancer or CRC. Men registered for free prostate cancer screening and completed a telephone interview 1 to 2 weeks before undergoing prostate cancer screening. RESULTS: One half of the participants who underwent free prostate cancer screening were eligible for but nonadherent to CRC screening. Importantly, 76% of the men who were nonadherent to CRC screening had a regular physician and/or health insurance, suggesting that CRC screening adherence was feasible in this group. Furthermore, multivariate analyses indicated that the only significant correlates of CRC screening adherence were having a regular physician, health insurance, and a history of prostate cancer screening. CONCLUSIONS: Free prostate cancer screening programs may provide a teachable moment to increase CRC screening among men who may not have the usual systemic barriers to CRC screening, at a time when they may be very receptive to cancer screening messages. In the United States, a large number of men participate in annual free prostate cancer screening programs and represent an easily accessible and untapped group that can benefit from interventions to increase CRC screening rates. Cancer 2010. © 2010 American Cancer Society. [source]

Efficacy and toxicity of reirradiation using intensity-modulated radiotherapy for recurrent or second primary head and neck cancer

CANCER, Issue 20 2010
David J. Sher MD
Abstract BACKGROUND: Patients with locally recurrent squamous cell cancer of the head and neck (SCCHN) are reported to have a poor prognosis and limited therapeutic options. Optimal management is selectively applied and morbid. Both surgical resection and chemoradiotherapy are reported to result in median survivals of approximately 12 months. Intensity-modulated radiotherapy (IMRT) is a highly conformal approach for delivering RT. This study reported the experience of the Dana-Farber Cancer Institute (DFCI) with IMRT-based chemoradiotherapy with or without surgery for locally recurrent SCCHN. METHODS: The current study was a retrospective study of all patients treated at DFCI who were diagnosed with nonmetastatic second primary or recurrent SCCHN and who received reirradiation based on IMRT. The primary endpoint was overall survival (OS), and secondary endpoints were locoregional (LRC) and distant control and acute and chronic toxicity. RESULTS: Thirty-five patients were treated from August 2004 until December 2008. Recurrent disease was treated in the oral cavity (4 patients), larynx/hypopharynx (13 patients), oropharynx (7 patients), nasopharynx (2 patients), and neck (9 patients). The median radiation dose was 60 Gray (Gy), and all patients received concurrent chemotherapy. The median follow-up was 2.3 years. The 2-year actuarial OS and LRC rates were 48% and 67%, respectively. Approximately 91% and 46%, respectively, of all patients developed at least 1 acute and late grade 3 toxicity. Four (11%) late deaths occurred in patients with no evidence of disease (2 aspiration events, 1 oropharyngeal hemorrhage, and 1 infectious death). CONCLUSIONS: Aggressive chemoradiotherapy with IMRT was found to be feasible and resulted in favorable survival outcomes in comparison with published reports. Acute and late toxicities were substantial. The apparently improved LRC appears to carry a significant risk of developing late complications. Cancer 2010. © 2010 American Cancer Society. [source]

Predictors of anticoagulation in hospice patients with lung cancer,

CANCER, Issue 20 2010
Holly M. Holmes MD
Abstract BACKGROUND: Guidelines recommend lifelong anticoagulation in patients with cancer and a history of thromboembolism, but the use of anticoagulation in hospice has not been described. A retrospective study of medication data was conducted to determine patterns of anticoagulant use and predictors of type of anticoagulant prescribed for hospice patients with lung cancer. METHODS: Medication data were evaluated for 16,896 hospice patients with lung cancer in 2006 to determine patient and hospice characteristics that predicted anticoagulant prescription. Independent predictors of warfarin versus low molecular weight heparin (LMWH) prescription were identified using a logistic regression model. RESULTS: One of every 11 patients was prescribed an anticoagulant, most commonly warfarin. Compared with patients prescribed LMWH, patients prescribed warfarin were older (71.6 vs 65.8 years, P<.001), were more likely white (81.2% vs 74.3%, P = .03), had a longer stay in hospice (median 21 days vs 17 days, P = .001), and were more likely to have ,3 comorbid illnesses (37.5% vs 25.0%, P<.001). The strongest independent predictor of type of anticoagulant prescribed was geographic region, with hospices in the Northeast more likely to prescribe LMWH. CONCLUSIONS: Anticoagulant use is prevalent in patients with lung cancer enrolled in hospice. This study highlights the need to understand the benefits and risks of anticoagulation at the end of life. Cancer 2010. © 2010 American Cancer Society. [source]

Peak oxygen consumption and long-term all-cause mortality in nonsmall cell lung cancer,

CANCER, Issue 20 2010
Lee W. Jones PhD
Abstract BACKGROUND: Identifying strong markers of prognosis is critical to optimize treatment and survival outcomes in patients with nonsmall cell lung cancer (NSCLC). The authors investigated the prognostic significance of preoperative cardiorespiratory fitness (peak oxygen consumption [VO2peak]) among operable candidates with NSCLC. METHODS: By using a prospective design, 398 patients with potentially resectable NSCLC enrolled in Cancer and Leukemia Group B 9238 were recruited between 1993 and 1998. Participants performed a cardiopulmonary exercise test to assess VO2peak and were observed until death or June 2008. Cox proportional models were used to estimate the risk of all-cause mortality according to cardiorespiratory fitness category defined by VO2peak tertiles (<0.96 of 0.96-1.29/>1.29 L/min,1) with adjustment for age, sex, and performance status. RESULTS: Median follow-up was 30.8 months; 294 deaths were reported during this period. Compared with patients achieving a VO2peak <0.96 L/min,1, the adjusted hazard ratio (HR) for all-cause mortality was 0.64 (95% confidence interval [CI], 0.46-0.88) for a VO2peak of 0.96 to 1.29 L/min,1, and 0.56 (95% CI, 0.39-0.80) for a VO2peak of >1.29 L/min,1 (Ptrend = .0037). The corresponding HRs for resected patients were 0.66 (95% CI, 0.46-0.95) and 0.59 (95% CI, 0.40-0.89) relative to the lowest VO2peak category (Ptrend = .0247), respectively. For nonresected patients, the HRs were 0.78 (95% CI, 0.34-1.79) and 0.39 (95% CI, 0.16-0.94) relative to the lowest category (Ptrend = .0278). CONCLUSIONS: VO2peak is a strong independent predictor of survival in NSCLC that may complement traditional markers of prognosis to improve risk stratification and prognostication. Cancer 2010. © 2010 American Cancer Society. [source]

Trends in incidence and survival of pediatric and adolescent patients with germ cell tumors in the United States, 1975 to 2006

CANCER, Issue 20 2010
Jenny N. Poynter PhD
Abstract BACKGROUND: Pediatric germ cell tumors (GCTs) are rare and heterogeneous tumors with uncertain etiology. In the current study, data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program were used to evaluate trends in incidence and survival of GCTs in boys and girls ages ,19 years. To the authors' knowledge, few studies to date have evaluated trends in pediatric GCTs. Results from these analyses may provide clues to the etiology of GCTs. METHODS: Frequencies, incidence rates, and 5-year relative survival rates stratified by sex were evaluated overall and by demographic subgroups based on age (birth to 9 years and 10-19 years), race (white, black, and other), and ethnicity (non-Hispanic and Hispanic) as sample size permitted. RESULTS: In whites, the incidence of GCTs was lower for females than males in the 10-year to 19-year age group (rate ratio [RR], 0.47; 95% confidence interval [95% CI], 0.42-0.53), whereas the rates were similar in the age group for birth to 9 years. In contrast, incidence rates were higher in black females than in black males in both age groups (RR, 2.01 [95%CI, 1.08-3.84] in those ages birth to 9 years; RR, 3.30 [95% CI, 2.13-5.28] in those ages 10-19 years). The incidence of ovarian GCT was significantly higher in Hispanic compared with non-Hispanic girls in the groups aged 10 to 19 years. Incidence rates increased during the study period in boys ages 10 to 19 years (annual percentage change [APC], 1.2; 95% CI, 0.4-2.1) and girls ages birth to 9 years (APC, 1.9; 95% CI, 0.3-2.5). CONCLUSIONS: The incidence of pediatric GCTs in the United States appears to be increasing only in certain subgroups, suggesting that the etiology is not completely overlapping in all age groups. Differences in incidence patterns by race and ethnicity merit further investigation. Cancer 2010. © 2010 American Cancer Society. [source]

Invasive neuroendocrine carcinoma of the breast

CANCER, Issue 19 2010
A distinctive subtype of aggressive mammary carcinoma
Abstract BACKGROUND: Neuroendocrine carcinoma (NEC) of the breast, a pathologic entity newly defined in the 2003 World Health Organization classification of tumors, is a rare type of tumor that is not well recognized or studied. The purpose of this first case-controlled study is to reveal the clinicopathologic features, therapeutic response, and outcomes of patients with NEC of the breast. METHODS: Seventy-four patients with NEC of the breast who were treated at The University of Texas M. D. Anderson Cancer Center were analyzed; 68 of them had complete clinical follow-up. Two cohorts of invasive mammary carcinoma cases were selected to pair with NEC to reveal demographic, pathologic, and clinical features at presentation, along with therapeutic response to treatment and patient outcomes. RESULTS: NEC was more likely to be estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative. Despite similar age and disease stages at presentation, NEC showed a more aggressive course than invasive ductal carcinoma, with a higher propensity for local and distant recurrence and poorer overall survival. High nuclear grade, large tumor size, and regional lymph node metastasis were significant negative prognostic factors for distant recurrence-free survival; high nuclear grade and regional lymph node metastasis were also significant negative prognostic factors for overall survival. Although endocrine therapy and radiation therapy showed a trend toward improved survival, the small number of cases in this study limited the statistical power to reveal therapeutic benefits in NEC of the breast. CONCLUSIONS: NEC is a distinct type of aggressive mammary carcinoma. Novel therapeutic approaches should be explored for this uniquely different clinical entity. Cancer 2010. © 2010 American Cancer Society. [source]

Concomitant weekly cisplatin and altered fractionation radiotherapy in locally advanced head and neck cancer

CANCER, Issue 19 2010
Heather E. Newlin MD
Abstract BACKGROUND: Both concomitant chemotherapy and altered fractionation radiotherapy (RT) have been shown to improve outcomes for patients with locoregionally advanced head and neck squamous cell carcinomas. However, both strategies also increase acute toxicity, and it is questionable whether the 2 can be safely combined. Traditional concomitant chemotherapy regimens include high-dose cisplatin given at 100 mg/m2 every 3 weeks. The authors' purpose was to report efficacy and toxicity after weekly cisplatin (30 mg/m2/wk) concurrent with altered fractionation RT. METHODS: One hundred twenty-one patients with American Joint Committee on Cancer stages II (3%), III (13%), or IV (84%) squamous cell carcinomas of the oropharynx (70%), hypopharynx (20%), or larynx (10%) were treated between 2000 and 2006 at the University of Florida with hyperfractionated RT (55 patients) or concomitant boost RT (66 patients) and concomitant cisplatin (30 mg/m2/wk). RESULTS: Median follow-up was 2.9 years; median follow-up on survivors was 3.6 years. Seventy-nine percent of patients completed ,6 cycles of chemotherapy; 94% received ,7200 centigrays. Seven (6%) patients changed from cisplatin to carboplatin because of bone marrow toxicity. Gastrostomy tube feeding was required in 54% of patients either before (16%) or during RT (38%). Two (1.6%) patients died from therapy-related complications. The 5-year outcomes were: local control, 83%; locoregional control, 79%; distant metastasis-free survival, 88%; cause-specific survival, 76%; and overall survival, 59%. Seven (6%) patients had severe late complications. Three (3%) patients required a permanent gastrostomy tube. CONCLUSIONS: Concomitant weekly cisplatin with altered fractionation RT is a safe and effective treatment regimen. Cancer 2010. © 2010 American Cancer Society. [source]

The antitumor activity of NK012, an SN-38,incorporating micelle, in combination with bevacizumab against lung cancer xenografts

CANCER, Issue 19 2010
Hirotsugu Kenmotsu MD
Abstract BACKGROUND: It has been demonstrated that NK012, a novel 7-ethyl-10-hydroxycamptothecin (SN-38)-incorporating polymeric micelle, exerts significantly more potent antitumor activity against various human tumor xenografts than irinotecan (CPT-11) (a water-soluble prodrug of SN-38). Combination therapy of anticancer agents with bevacizumab (Bv), an anti-vascualr endothelial growth factor humanized monoclonal antibody, has more potently inhibited tumor growth than either agent alone. In the current study, the authors examined the antitumor effect of NK012 in combination with Bv against human lung cancer. METHODS: Nude mice bearing lung adenocarcinoma (PC-14 or A549 xenografts) were administered NK012 at SN-38-equivalent doses of 5 mg/kg or 30 mg/kg in combination with or without Bv at 5 mg/kg. CPT-11 at a dose of 66.7 mg/kg was administered with or without Bv at a dose of 5 mg/kg in the same experimental model. To evaluate interaction with Bv, the pharmacokinetics and microvessel density in tumors that were treated on each regimen were analyzed. RESULT: In vitro, the growth-inhibitory effect of NK012 was 50-fold more potent than that of CPT-11 and was almost equivalent to that of SN-38. In vivo studies revealed that the combination of NK012 plus Bv had significantly greater antitumor activity against human lung cancer xenografts compared with NK012 alone (PC-14, P = .0261; A549, P < .001). The pharmacokinetic profile of NK012 revealed that coadministration of Bv did not interfere with the accumulation of NK012. CONCLUSIONS: In this study, significant antitumor activity was noted with NK012 in combination with Bv against lung cancer cells. The current results warrant the clinical evaluation of NK012 in lung cancer. Cancer 2010. © 2010 American Cancer Society. [source]

Influence of patients' preferences and treatment site on cancer patients' end-of-life care,

CANCER, Issue 19 2010
Alexi A. Wright MD
Abstract BACKGROUND: Research suggests that patients' end-of-life (EOL) care is determined primarily by the medical resources available, and not by patient preferences. The authors examined whether patients' desire for life-extending therapy was associated with their EOL care. METHODS: Coping with Cancer is a multisite, prospective, longitudinal study of patients with advanced cancer. Three hundred one patients were interviewed at baseline and followed until death, a median of 4.5 months later. Multivariate analyses examined the influence of patients' preferences and treatment site on whether patients received intensive care or hospice services in the final week of life. RESULTS: Eighty-three of 301 patients (27.6%) with advanced cancer wanted life-extending therapy at baseline. Patients who understood that their disease was terminal or who reported having EOL discussions with their physicians were less likely to want life-extending care compared with others (23.4% vs 42.6% and 20.7% vs 44.4%, respectively; P , .003). Patients who were treated at Yale Cancer Center received more intensive care (odds ratio [OR], 3.14; 95% confidence interval [CI], 1.16-8.47) and less hospice services (OR, 0.52; 95% CI, 0.29-0.92) compared with patients who were treated at Parkland Hospital. However, in multivariate analyses that controlled for confounding influences, patients who preferred life-extending care were more likely to receive intensive care (adjusted OR [AOR], 2.91; 95% CI, 1.09-7.72) and were less likely to receive hospice services (AOR, 0.45; 95% CI, 0.26-0.78). Treatment site was not identified as a significant predictor of EOL care. CONCLUSIONS: The treatment preferences of patients with advanced cancer may play a more important role in determining the intensity of medical care received at the EOL than previously recognized. Future research is needed to determine the mechanisms by which patients' preferences for care and treatment site interact to influence EOL care. Cancer 2010. © 2010 American Cancer Society. [source]

Breast cancer subtypes and response to systemic treatment after whole-brain radiotherapy in patients with brain metastases

CANCER, Issue 18 2010
Anna Niwi, ska MD
Abstract BACKGROUND: The aim of this study was to assess the role of systemic treatment after whole-brain radiotherapy (WBRT) in immunohistochemically defined biological subsets of breast cancer patients with brain metastases. METHODS: The group of 420 consecutive breast cancer patients with brain metastases treated at the same institution between the years of 2003 to 2009 was analyzed. Patients were divided into 4 immunohistochemically biological subsets, based on the levels of estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptors, and labeled as luminal A, luminal B, HER2, and triple-negative. Survival from brain metastases with and without systemic treatment after WBRT was calculated in 4 subsets. RESULTS: In the entire group, the median survival from brain metastases in patients without and with systemic treatment after WBRT was 3 and 10 months, respectively (P < .0001). In the triple-negative subset, the median survival from brain metastases with and without systemic treatment was 4 and 3 months (P = .16), and in the luminal A subset, it was 12 and 3 months, respectively (P = .003). In the luminal B subset, the median survival without further treatment, after chemotherapy and/or hormonal therapy, and after chemotherapy and/or hormonal therapy with targeted therapy was 2 months, 9 months, and 15 months, respectively (P < .0001). In the HER2 subset, the median survival was 4 months, 6 months, and 13 months, respectively (P < .0001). No significant response to systemic treatment was noted in the triple-negative breast cancer population. CONCLUSIONS: Systemic therapy, ordered after WBRT, appears to improve survival in patients with the luminal A, luminal B, and HER2 breast cancer subtypes. Targeted therapy was found to have an additional positive impact on survival. In patients with triple-negative breast cancer, the role of systemic treatment after WBRT appears to be less clear, and therefore this issue requires further investigation. Cancer 2010. © 2010 American Cancer Society. [source]

SERPINE1 intron polymorphisms affecting gene expression are associated with diffuse-type gastric cancer susceptibility

CANCER, Issue 18 2010
Hyoungseok Ju PhD
Abstract BACKGROUND: A primary inhibitor of plasminogen activators, SERPINE1 (serpin peptidase inhibitor 1, clade E, member 1, also known as plasminogen activator inhibitor type 1), is an important regulator in tumorigenesis and is highly expressed in many cancers. METHODS: Five tag single nucleotide polymorphisms (SNPs) and 1 insertion polymorphism within SERPINE1 were genotyped in 1101 unrelated Korean individuals (a case group of 612 patients with gastric cancer and a control group of 489 healthy individuals). Associations with susceptibility to diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer were assessed using multivariate logistic regression analyses adjusted for age and sex. Allelic differences in the contribution to gene expression were measured using luciferase assays. RESULTS: SNP c.1162+162C>T (rs2227692) in intron 7 was associated with susceptibility to DGC but not with susceptibility to intestinal-type gastric cancer. The minor allele-carrying genotypes C/T and T/T had 1.6-fold greater odds of DGC than the C/C genotype (P = .00084). This SNP was linked to a repeat-number variation c.1162+604AAAG(11_17), a deletion (del) variation c.1162+664_1162+673del, and another SNP c.1162+859T>A (rs2070683) in intron 7 based on the sequencing of 5 patients and 5 controls. The risk haplotype of the 4 variations exhibited a 30% greater gene expression level than the nonrisk haplotype in luciferase reporter assays (P = .025). In contrast, DGC susceptibility was not associated with the c.,1969_,1968insG polymorphism (rs1799768) in the promoter, commonly known as 4G/5G, in which the minor 5G allele is less active in transcription than the major 4G allele. CONCLUSIONS: An association between SERPINE1 and DGC susceptibility was observed with 4 correlated polymorphisms in intron 7 rather than the 4G/5G polymorphism in the promoter, although all polymorphisms affected gene expression. Cancer 2010. © 2010 American Cancer Society. [source]

Efficacy and safety of the combination of rituximab, fludarabine, and mitoxantrone for rituximab-naive, recurrent/refractory follicular non-Hodgkin lymphoma with high tumor burden,

CANCER, Issue 18 2010
A multicenter phase 2 trial by the Groupe d'Etude des Lymphomes de l'Adulte (GELA), Groupe Ouest Est des Leucémies et Autres Maladies du Sang (GOELAMS)
Abstract BACKGROUND: This phase 2 trial was undertaken to evaluate the efficacy and safety of rituximab combined with intravenous fludarabine and mitoxantrone (R-FM) for patients with recurrent/refractory follicular lymphoma who had high tumor burden according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria. METHODS: Fifty patients were enrolled who had received a maximum of 2 previous regimens, including 1 cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/CHOP-like regimen but no previous exposure to rituximab, fludarabine, or mitoxantrone. At baseline, 58% of patients had bulky disease (lesion >7cm), 56% had high-risk Follicular Lymphoma International Prognostic Index (FLIPI) scores (range, 3-5), and 22% were refractory. Treatment consisted of 4 courses of R-FM (rituximab 375 mg/m2 intravenously on Day 1, fludarabine 25 mg/m2 intravenously on Days 2 through 4, and mitoxantrone 10 mg/m2 intravenously on Day 2, recycling at Day 28) and consolidation with 2 courses of fludarabine and mitoxantrone (the same regimen without rituximab). RESULTS: The best response (84% overall response rate including 68% complete response/complete response unconfirmed) was achieved after 4 courses of R-FM. Response rates were high regardless of age, refractoriness to last previous therapy, and FLIPI score. After a median follow-up of 4 years, the 3-year progression-free survival rate was 47%, the event-free survival rate was 41%, and the 3-year overall survival rate was 66%. Grade ,3 neutropenia and infections were the most common toxicities and occurred in 72% and 14% of patients, respectively. CONCLUSIONS: Cytoreduction with 4 courses of R-FM was safe and highly efficient in patients with recurrent/refractory follicular lymphoma who had high tumor burden; however, better consolidation than FM is needed to further improve outcome. Cancer 2010. © 2010 American Cancer Society. [source]

A prospective study of aromatase inhibitor-associated musculoskeletal symptoms and abnormalities on serial high-resolution wrist ultrasonography

CANCER, Issue 18 2010
N. Lynn Henry MD
Abstract BACKGROUND: Nearly half of women treated with aromatase inhibitors (AI) develop AI-associated musculoskeletal symptoms (AIMSS) such as arthralgias, but to the authors' knowledge the etiology is unclear. The upper extremities are frequently affected, especially the wrists, hands, and fingers. AI use may also increase the risk of developing carpal tunnel syndrome. Tendon sheath fluid and tenosynovial changes have been demonstrated by imaging symptomatic patients who were treated with AIs. The authors hypothesized that these abnormalities are correlated with AIMSS. METHODS: Thirty consecutive patients in whom adjuvant therapy with letrozole or exemestane was initiated on a prospective clinical trial enrolled in a pilot study evaluating tendon and joint abnormalities at baseline and after 3 months of AI therapy. Patients underwent high-resolution ultrasonography of the wrists bilaterally and completed the Health Assessment Questionnaire (HAQ) and pain Visual Analog Scale (VAS). AIMSS were defined as an increase in the HAQ or VAS score during AI therapy that exceeded a predefined cutoff. RESULTS: Twenty-five patients completed both the baseline and 3-month assessments. During the first 12 months of AI therapy, 15 patients developed AIMSS, and 13 discontinued therapy because of musculoskeletal symptoms. There was a trend toward an association between the presence of tendon sheath abnormalities on wrist ultrasound at baseline and the development of AIMSS (P = .06). CONCLUSIONS: Clinically relevant musculoskeletal symptoms develop in women treated with AIs, leading to treatment discontinuation in a substantial percentage of these patients. However, in the current study, patient-reported symptoms were not found to be associated with changes visible on wrist ultrasonography. Cancer 2010. © 2010 American Cancer Society. [source]

Adenovirus-mediated expression of truncated E2F-1 suppresses tumor growth in vitro and in vivo

CANCER, Issue 18 2010
Jorge G. Gomez-Gutierrez PhD
Abstract BACKGROUND: Adenovirus (Ad)-mediated E2F-1 gene transfer induces apoptosis in cancer cells in vitro and in vivo, but clinical application of E2F-1 in cancer gene therapy remains controversial because of the oncogenic potential of E2F-1. This barrier can be circumvented by using the truncated form of the E2F-1 gene (E2Ftr) (amino acids 1 through 375), which lacks the E2F-1 transactivation domain and cell cycle-promoting effects. METHODS: The authors constructed 3 adenoviral vectors that expressed E2Ftr under regulation of the tetracycline (Tet)-off system (AdTet-E2Ftr1, AdTet-E2Ftr2, and AdTet-E2Ftr3). These vectors were compared for E2Ftr expression and apoptosis induction in cancer cells and normal cells. E2Ftr antitumor activity in vivo also was assessed in a melanoma xenograft model. RESULTS: One of the 3 vectors, AdTet-E2Ftr3, had the highest E2Ftr protein expression levels, which were correlated with the greatest induction of apoptosis and inhibition of cancer cell growth. E2Ftr induced apoptosis in a variety of cancer cell lines independent of p53 status with little cytotoxicity in normal cell lines. In a mouse melanoma xenograft model, AdTet-E2Ftr3 exhibited an approximately 80% decrease in tumor size compared with controls in vivo. CONCLUSIONS: The current results indicated that AdTet-E2Ftr3 is a novel anticancer agent that has significant therapeutic activity in vitro and in vivo. Cancer 2010. © 2010 American Cancer Society. [source]

Prognostic factors derived from a prospective database dictate clinical biology of anal cancer

CANCER, Issue 17 2010
The intergroup trial (RTOG 98-11)
Abstract BACKGROUND: Only 4 prospective randomized phase 3 trials have been reported for anal cancer. A prognostic factor analysis for anal cancer from a prospective database has been published from only 1 study (N = 110). To confirm and uncover new prognostic factors, we analyzed the prospective database of intergroup RTOG 98-11. METHODS: Univariate and multivariate analyses of the baseline characteristics for 5-year overall survival (OS) and disease-free survival (DFS) were carried out. Various combinations of tumor diameter and clinically positive nodes (N+) were analyzed to identify subgroups. RESULTS: A total of 644 were assessable and analyzed. Tumor diameter >5 cm was associated with poorer 5-year DFS (P = .0003) and poorer 5-year OS (P = .0031), and N+ was associated with poorer 5-year DFS (P , .0001) and poorer 5-year OS (P = , .0001) in the multivariate analysis. In stratified analyses, N+ had more adverse influence on DFS and OS than did tumor diameter. Patients with >5-cm tumor and N+ had the worst DFS (only 30% at 3 years compared with 74% for the best group; <5 cm primary and N0) and OS (only 48% at 4 years compared with 81% for the best group; <5 cm primary and N0). Men had worse DFS (P = .02) and OS (P = .016). These factors maintained their influence in each treatment arm. CONCLUSIONS: This prospective prognostic factor analysis establishes tumor diameter as an independent prognosticator of poorer 5-year DFS and OS and confirms N+ and male sex as poor prognostic factors. This analysis also uncovers novel subgroups (derived from combining prognostic factors) with incremental worsening of DFS and OS. Cancer 2010. © 2010 American Cancer Society. [source]

Increased exposure to bacterial antigen RpL7/L12 in early stage colorectal cancer patients

CANCER, Issue 17 2010
Annemarie Boleij MSc
Abstract BACKGROUND: Intestinal bacteria have long been implicated in colorectal cancer pathology, and many reports point to a close linkage between Streptococcus bovis biotype I (recently renamed Streptococcus gallolyticus) infections and tumors of the human colon. This work aims to investigate the humoral immune response to this bacterium during different stages of colorectal cancer. METHODS: The presence of serum antibodies against S. bovis antigen RpL7/L12, previously assigned as a potential diagnostic antigen, was evaluated in Dutch (n = 209) and American (n = 112) populations using a newly developed enzyme-linked immunosorbent assay. RESULTS: The analyses consistently showed that an immune response against this bacterial antigen was increased in polyp patients and stage I/II colorectal cancer patients as compared with asymptomatic individuals. This was not paralleled by increased antibody production to endotoxin, an intrinsic cell wall component of the majority of intestinal bacteria, which implies that the humoral immune response against RpL7/L12 is not a general phenomenon induced by the loss of colonic barrier function. Notably, increased anti-RpL7/L12 levels were not or were only mildly detected in late stage colorectal cancer patients having lymph node or distant metastasis. CONCLUSIONS: These findings are indicative of an increased exposure to antigen RpL7/L12 during early stages of colon carcinogenesis and suggest that intestinal bacteria such as S. bovis constitute a risk factor for the progression of premalignant lesions into early stage carcinomas. Clearly, the current findings emphasize the necessity for further studies on the possible etiologic relationship between intestinal bacteria and human colorectal cancer. Cancer 2010. © 2010 American Cancer Society. [source]

Clonal origin of multifocal hepatocellular carcinoma

CANCER, Issue 17 2010
Kurt B. Hodges MD
Abstract BACKGROUND: Hepatocellular carcinoma is the most common primary tumor of the liver. Patients frequently have multiple histologically similar, but anatomically separate tumors. The clonal origin of multiple hepatocellular carcinomas is uncertain. METHODS: The authors analyzed 31 tumors from 12 different patients (11 women, 1 man), who had multiple hepatocellular carcinomas involving 1 or both lobes. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue using laser capture microdissection. DNA was analyzed for loss of heterozygosity (LOH), X chromosome inactivation status, and TP53 gene mutations. RESULTS: Ten (83%) of the 12 patients showed LOH in at least 1 of the analyzed microsatellite markers. Concordant LOH patterns between separate hepatocellular carcinomas in individual patients were seen in 8 (80%) of 10 cases, whereas discordant patterns were seen in 2 (20%) of 10 cases. Five (50%) of 10 informative female patients showed identical nonrandom X chromosome inactivation patterns in multiple tumors; 1 case showed discordant nonrandom X chromosome inactivation pattern. TP53 mutations were identified in 8 (67%) of 12 patients. Tumors in 7 (88%) of these 8 patients showed different point mutations. Three patients (Cases 4, 5, and 10) had tumors with additional TP53 point mutations, indicating additional genetic abnormalities in these tumors. CONCLUSIONS: The data suggested that the significant proportion of patients with multifocal hepatocellular carcinomas have tumors of common clonal origin. Cancer 2010. © 2010 American Cancer Society. [source]

High response rate after intratumoral treatment with interleukin-2

CANCER, Issue 17 2010
Results from a phase 2 study in 51 patients with metastasized melanoma
Abstract BACKGROUND: Systemic high-dose interleukin-2 (IL-2) achieved long-term survival in a subset of patients with advanced melanoma. The authors reported previously that intratumorally applied IL-2 induced complete local responses of all metastases in >60% of patients. The objectives of the current study were to confirm those results in a larger cohort and to identify patient or regimen characteristics associated with response. METHODS: Patients with melanoma who had a median of 12 injectable metastases received intratumoral IL-2 treatments 3 times weekly until they achieved clinical remission. The initial dose of 3 million international units was escalated, depending on the individual patient's tolerance. RESULTS: Forty-eight of 51 patients were evaluable. Only grade 1/2 toxicity was recorded. A complete response that lasted ,6 months was documented in 70% of all injected metastases. A complete local response of all treated metastases was achieved in 33 patients (69%), including 11 patients who had between 20 and 100 metastases. Response rates were higher for patients who had stage III disease compared with patients who had stage IV disease. No objective responses of distant untreated metastases were observed. The 2-year survival rate was 77% for patients with stage IIIB/IIIC disease and 53% for patients with stage IV disease. Efficacy and survival did not differ between patients who had ,20 lesions and patients who had <20 lesions. CONCLUSIONS: Intratumoral IL-2 treatment elicited complete local responses in a high percentage of patients. Further studies will be required to investigate the mode of action of this treatment and its impact on survival. Cancer 2010. © 2010 American Cancer Society. [source]

Risk factors for central venous catheter thrombotic complications in children and adolescents with cancer,,

CANCER, Issue 17 2010
S. Revel-Vilk MD
Abstract BACKGROUND: The use of central venous catheters (CVCs) has greatly improved the quality of care in children with cancer, yet these catheters may cause serious infectious and thrombotic complications. The aim of this prospective registry study was to assess the host and CVC-related risk factors for CVC-created thrombotic complications. METHODS: Patients undergoing CVC insertion for chemotherapy were followed prospectively for CVC complications. At the time of enrollment, demographic, clinical, and CVC-related data, and family history of thrombosis were collected. Survival and Cox regression analyses were performed. RESULTS: A total of 423 CVCs were inserted into 262 patients for a total of 76,540 catheter days. The incidence of CVC-related deep-vein thrombosis (DVT) was 0.13 per 1000 catheter-days (95% confidence interval [CI], 0.06-0.24). Insertion of peripherally inserted central catheters (PICCs) and insertion in an angiography suite significantly increased the risk of symptomatic CVC-related DVT. The incidence of CVC occlusion was 1.35 per 1000 catheter-days (95% CI, 1.1-1.63). Positive family history of thrombosis significantly increased the risk of CVC occlusion (hazard ratio [HR], 2.16; 95% CI, 1.2-3.8). The CVC-related risk factors were insertion of Hickman catheters, insertion in angiography suite, and proximal-tip location. Patients developing at least 1 episode of both CVC occlusion and infection had an increased risk for developing symptomatic CVC-related DVT (HR, 4.15; 95% CI, 1.2-14.4). CONCLUSIONS: Both patient-related and CVC-related factors are associated with higher risk of symptomatic thrombotic complications. These risk factors could be used in the clinical setting and in developing future studies for CVC thromboprophylaxis. Cancer 2010. © 2010 American Cancer Society. [source]

Germ cell-specific heat shock protein 70-2 is expressed in cervical carcinoma and is involved in the growth, migration, and invasion of cervical cells

CANCER, Issue 16 2010
Manoj Garg PhD
Abstract BACKGROUND: Cervical cancer is a major cause of death among women worldwide, and the most cases are reported in the least developed countries. Recently, a study on DNA microarray gene expression analysis demonstrated the overexpression of heat shock protein 70-2 (HSP70-2) in cervical carcinoma cells (HeLa). The objective of the current study was to evaluate the association between HSP70-2 expression in cervical carcinogenesis and its potential role in various malignant properties that result in disease progression. METHODS: HSP70-2 expression was examined in various cervical cancer cell lines with different origins and in clinical cervical cancer specimens by reverse transcriptase-polymerase chain reaction (RT-PCR), flow cytometry, and immunohistochemistry (IHC) analyses. A plasmid-based, short-hairpin RNA approach was used specifically to knock down the expression of HSP70-2 in cervical tumor cells in vitro and in vivo to examine the role of HSP70-2 on various malignant properties. RESULTS: RT-PCR and IHC analyses revealed HSP70-2 expression in 86% of cervical cancer specimens. Furthermore, knockdown of HSP70-2 expression significantly reduced cellular growth, colony formation, migration, and invasion in vitro and reduced tumor growth in vivo. A significant association of HSP70-2 gene and protein expression was observed among the various tumor stages (P = .046) and different grades (P = .006), suggesting that HSP70-2 expression may be an indicator of disease progression. CONCLUSIONS: The current findings suggested that HSP70-2 may play an important role in disease progression in cervical carcinogenesis. Patients who had early stage disease and low-grade tumors had HSP70-2 expression, supporting its potential role in early detection and aggressive treatment modalities for cervical cancer management. Cancer 2010. © 2010 American Cancer Society. [source]

Long-term outcomes for patients with limited stage follicular lymphoma,

CANCER, Issue 16 2010
Involved regional radiotherapy versus involved node radiotherapy
Abstract BACKGROUND: Given the indolent behavior of follicular lymphoma (FL), it is controversial whether limited stage FL can be cured using radiotherapy (RT). Furthermore, the optimal RT field size is unclear. The authors of this report investigated the long-term outcomes of patients with limited stage FL who received RT alone and studied the impact of reducing the RT field size from involved regional RT (IRRT) to involved node RT with margins up to 5 cm (INRT,5 cm). METHODS: Eligible patients had limited stage, grade 1 through 3A FL diagnosed between 1986 and 2006 and treated were with curative-intent RT alone. IRRT encompassed the involved lymph node group plus ,1 adjacent, uninvolved lymph node group(s). INRT,5 cm covered the involved lymph node(s) with margins ,5 cm. RESULTS: In total, 237 patients were identified (median follow-up, 7.3 years) and included 48% men, 54% aged >60 years, stage IA disease in 76% of patients, elevated lactate dehydrogenase (LDH) in 7% of patients, grade 3A tumors in 12% of patients, and lymph node size ,5 cm in 19% of patients. The 2 RT groups were IRRT (142 patients; 60%) and INRT,5 cm (95 patients; 40%). At 10 years, the progression-free survival (PFS) rate was 49%, and the overall survival (OS) rate was 66%. Only 2 patients developed recurrent disease beyond 10 years. The most common pattern of first failure was a distant recurrence only, which developed in 38% of patients who received IRRT and in 32% of patients who received INRT,5 cm. After INRT,5 cm, 1% of patients had a regional-only recurrence. Significant risk factors for PFS were lymph nodes ,5 cm (P = .008) and male gender (P = .042). Risk factors for OS were age >60 years (P < .001), elevated LDH (P = .007), lymph nodes ,5 cm (P = .016), and grade 3A tumors (P = .036). RT field size did not have an impact on PFS or OS. CONCLUSIONS: Disease recurrence after 10 years was uncommon in patients who had limited stage FL, suggesting that a cure is possible. Reducing RT fields to INRT,5 cm did not compromise long-term outcomes. Cancer 2010. © 2010 American Cancer Society. [source]

Improved survival in patients with early stage low-grade follicular lymphoma treated with radiation,

CANCER, Issue 16 2010
A Surveillance, End Results database analysis, Epidemiology
Abstract BACKGROUND: External beam radiation therapy (RT) is the standard treatment for stage I-II, grade 1-2 follicular lymphoma. Because of an indolent natural history, some advocate alternative management strategies, including watchful waiting for this disease. The relative improvement in outcomes for patients treated with and without RT has never been tested in randomized trials. METHODS: The Surveillance, Epidemiology, and End Results database was queried for adult patients with stage I-II, grade 1-2 follicular lymphoma diagnosed from 1973 to 2004. Retrievable patient data included age, sex, race, stage, extranodal disease, and treatment with RT within the first year after diagnosis. Actuarial overall survival (OS) and disease-specific survival (DSS) were analyzed. RESULTS: A total of 6568 patients were identified. DSS at 5, 10, 15, and 20 years in the RT group was 90%, 79%, 68%, and 63% versus 81%, 66%, 57%, and 51% in the no RT group (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.55-0.68; P < .0001). OS at 5, 10, 15, and 20 years in the RT group was 81%, 62%, 45%, and 35% versus 71%, 48%, 34%, and 23% in patients not receiving RT (HR, 0.68; 95% CI, 0.63-0.73; P < .0001). On multivariate analysis, upfront RT remained independently associated with improved DSS (P < .0001, Cox HR, 0.65; 95% CI, 0.57-0.72) and OS (P < .0001; Cox HR, 0.73; 95% CI, 0.67-0.79). Lymphoma was the most common cause of death (52%). Only 34% of patients received upfront RT. CONCLUSIONS: Upfront RT was associated with improved DSS and OS compared with alternate management approaches, a benefit that persisted over time. This benefit suggests that watchful waiting with administration of salvage therapies on progression/relapse do not compensate for inadequate initial definitive treatment. Although it is the standard of care for this disease, RT for early stage low-grade follicular lymphoma is greatly underused in the US population; increased use of upfront RT could prevent thousands of deaths from lymphoma in these patients. Cancer 2010. © 2010 American Cancer Society. [source]

Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study,,

CANCER, Issue 16 2010
70 milligrams twice daily, Efficacy, tolerability of 140 milligrams once daily
Abstract BACKGROUND: In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome-positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow-up are reported. METHODS: Patients were stratified according to whether they had CML in myeloid blast phase (MBP-CML) or in lymphoid blast phase (LBP-CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily. RESULTS: In patients with MBP-CML, the major hematologic response rate was 28% for both regimens; and, in patients with LBP-CML, the major hematologic response rate was 42% for once-daily dasatinib and 32% for twice-daily dasatinib. The major cytogenetic response rates were 25% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective rates in patients with LBP-CML were 50% and 40%. The overall survival rate at 24 months was 24% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective values in patients with LBP-CML were 21% and 16%. Adverse events indicated a trend toward improved tolerability for the once-daily regimen. CONCLUSIONS: The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70-mg twice-daily regimen in patients with imatinib-resistant, blast phase CML. Cancer 2010. © 2010 American Cancer Society. [source]

Trends in PSA, age and prostate cancer detection among black and white men from 1990-2006 at a tertiary care center

CANCER, Issue 16 2010
Jeannette M. Potts MD
Abstract BACKGROUND: Prostate cancer is the most frequently diagnosed malignancy in men in the United States, with even higher prevalence and death rates among black men. The authors sought to compare trends in prostate-specific antigen (PSA), age, and prostate-cancer detection among black and white men in our region during a 16-year period. METHODS: This was a retrospective study of patient archives between 1990 through 2006. Data collection was accomplished by examining patients' charts and electronic medical records. Data from 5570 patients, of whom 911 were black, were analyzed statistically by testing and comparing parameters over time. RESULTS: During this 16-year period, mean age at the time of initial diagnostic prostate biopsy did not change in either group, despite what we had believed about the effects of patient education and screening campaigns. However, prostate-cancer detection rates did decrease during the time period studied. Over time, the authors also observed significant decreases in the sensitivity and specificity of PSA as a screening tool. Indeed, analysis of more recent cases demonstrated a positive predictive value comparable to a coin toss. While Gleason scores remained relatively stable over time, reporting of prostate intraepithelial neoplasia (PIN) and inflammation increased. CONCLUSIONS: Using lower PSA thresholds, promoting younger screening age, and increasing efforts to educate the public have not seemed to influence age at time of diagnostic testing, which may reflect other factors such as usefulness of screening, physician referral patterns, patient compliance, and other sociodemographic issues. The usefulness of PSA as a screening tool appears to be diminishing. Cancer 2010. © 2010 American Cancer Society. [source]