Showing papers in "Cancer in 2008"

Barriers to recruiting underrepresented populations to cancer clinical trials: a systematic review.

Abstract: Racial and ethnic minorities, older adults, rural residents, and individuals of low socioeconomic status are underrepresented among participants in cancer-related trials. The authors conducted a systematic review to determine the barriers to participation of underrepresented populations in cancer-related trials. Their search included English-language publications that reported original data on the recruitment of underrepresented groups to cancer treatment or prevention trials between 1966 and December 2005 in multiple electronic databases. They also hand-searched titles in 34 journals from January 2003 to December 2005 and they examined reference lists for eligible articles. Titles and abstracts were reviewed to identify relevant studies. Data on barriers to participation were synthesized both qualitatively and based on statistically significant associations with trial enrollment. Of 5257 studies that were cited, 65 studies were eligible for inclusion in the current analysis, including 46 studies on recruitment into cancer therapeutic trials, 15 studies on recruitment into prevention trials, and 4 studies on recruitment into both prevention and treatment trials. Numerous factors were reported as barriers to participation in cancer-related trials. However, only 20 of the studies reported statistically significant associations between hypothesized barriers and enrollment. The available evidence had limitations in quality regarding representativeness, justification of study methods, the reliability and validity of data-collection methods, potential for bias, and data analysis. The results indicated that underrepresented populations face numerous barriers to participation in cancer-related trials. The current systematic review highlighting the literature on recruitment of underrepresented populations to cancer trials and may be used as the evidence base toward developing an agenda for etiologic and intervention research to reduce the disparities in participation in cancer-related trials.

A Systematic Meta-Analysis of Randomized Controlled Trials of Adjuvant Chemotherapy for Localized Resectable Soft-Tissue Sarcoma

Abstract: Background The use of adjuvant chemotherapy to treat adults with localized resectable soft-tissue sarcoma remains controversial. The objective of this systematic review was to update the 1997 meta-analysis of randomized controlled trials (RCTs) to reassess the efficacy of doxorubicin-based chemotherapy with respect to recurrence and survival. Methods A comprehensive literature search was performed to identify RCTs of adjuvant chemotherapy for adult patients diagnosed with localized resectable soft-tissue sarcoma. Two reviewers independently assessed eligibility and quality of the studies using a modified version of the Detsky Quality Scale. The outcome measures were local, distant, and overall recurrence and survival calculated through the fixed effect or random effect model. Results Four new eligible trials were identified allowing for a total of 18 trials representing 1953 patients to be included in the analysis. The odds ratios (OR) for local recurrence was 0.73 (95% confidence interval [CI] 0.56-0.94; P = .02) in favor of chemotherapy. For distant and overall recurrence the OR was 0.67 (95% CI 0.56-0.82; P = .0001) in favor of chemotherapy. In terms of survival, doxorubicin alone had an OR of 0.84 (95% CI, 0.68-1.03; P = .09), which as not statistically significant. However, the OR for doxorubicin combined with ifosfamide was 0.56 (95% CI, 0.36-0.85; P = .01) in favor of chemotherapy. Conclusions This updated meta-analysis confirms the marginal efficacy of chemotherapy in localized resectable soft-tissue sarcoma with respect to local recurrence, distant recurrence, overall recurrence, and overall survival. These benefits are further improved with the addition of ifosfamide to doxorubicin-based regimens, but must be weighed against associated toxicities.

Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium.

Abstract: Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings, possibly because of small sample sizes in individual studies and differences between studies in patients, tumor types, and methods of classification. Individual studies generally have lacked samples of sufficient size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in promoting understudied groups, such as pediatric brain tumors; the etiology of rare glioma subtypes, such as oligodendroglioma; and meningioma, which, although it is not uncommon, has only recently been registered systematically in the United States. There also is a pressing need for more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. In this report, BTEC epidemiologists reviewed the group's consensus on the current state of scientific findings, and they present a consensus on research priorities to identify which important areas the science should move to address.

Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases.

Abstract: Purpose To characterize the outcomes of patients with metastatic triple negative breast cancers, including the risk and clinical consequences of central nervous system (CNS) relapse

Trends in childhood cancer incidence in the U.S. (1992-2004).

Abstract: BACKGROUND. The etiology of most pediatric neoplasms remains elusive. Examination of population-based incidence data provides insight regarding etiology among various demographic groups and may result in new hypotheses. The objective of the current study was to present updated information regarding childhood cancer incidence and trends in the U.S. overall and among demographic subgroups, including Asian/Pacific Islanders and Hispanics, for whom to the authors' knowledge trends have not been previously examined. METHODS. Data obtained by 13 registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program were evaluated to assess incidence and trends of common primary cancers diagnosed between 1992 and 2004 among children aged birth to 19 years. Frequencies, age-adjusted incidence rates, and joinpoint regression results, including annual percent change (APC) in incidence rates (and 95% confidence intervals [95% CI]), were calculated. RESULTS. Between 1992 and 2004, a modest, nonsignificant increase in the average annual incidence rate (APC, 0.4%; 95% CI, −0.1%–0.8%) was observed for all pediatric cancer diagnoses combined. There was a suggestion of an increase in leukemia (APC, 0.7%; 95% CI, −0.1%–1.5%), and acute lymphoblastic leukemia in particular (APC, 0.8%; 95% CI, −0.4%–1.9%), whereas rates for central nervous system tumors overall were stable (APC, −0.1%; 95% CI, −1.1%–1.0%); 2 joinpoints were observed for astrocytoma. Rate increases were noted for hepatoblastoma (APC, 4.3%; 95% CI, 0.2%–8.7%) and melanoma (APC, 2.8%; 95% CI, 0.5%–5.1%). Differences by demographic group (sex, age, and race/ethnicity) are also described. CONCLUSIONS. The observed trends reinforce an ongoing need for population-based surveillance and further etiologic studies. Cancer 2008. © 2007 American Cancer Society.

Physical and psychological long-term and late effects of cancer

Abstract: The number of long-term cancer survivors (> or =5 years after diagnosis) in the U.S. continues to rise, with more than 10 million Americans now living with a history of cancer. Along with such growth has come increasing attention to the continued health problems and needs of this population. Many cancer survivors return to normal functioning after the completion of treatment and are able to live relatively symptom-free lives. However, cancer and its treatment can also result in a wide range of physical and psychological problems that do not recede with time. Some of these problems emerge during or after cancer treatment and persist in a chronic, long-term manner. Other problems may not appear until months or even years later. Regardless of when they present, long-term and late effects of cancer can have a negative effect on cancer survivors' quality of life. This article describes the physical and psychological long-term and late effects among adult survivors of pediatric and adult cancers. The focus is on the prevalence and correlates of long-term and late effects as well as the associated deficits in physical and emotional functioning. In addition, the emergence of public health initiatives and large-scale research activities that address the issues of long-term cancer survivorship are discussed. Although additional research is needed to fully understand and document the long-term and late effects of cancer, important lessons can be learned from existing knowledge. Increased awareness of these issues is a key component in the development of follow-up care plans that may allow for adequate surveillance, prevention, and the management of long-term and late effects of cancer.

Patient navigation: State of the art or is it science?

Abstract: First implemented in 1990, patient navigation interventions are emerging today as an approach to reduce cancer disparities. However, there is lack of consensus about how patient navigation is defined, what patient navigators do, and what their qualifications should be. Little is known about the efficacy and cost-effectiveness of patient navigation. For this review, the authors conducted a qualitative synthesis of published literature on cancer patient navigation. By using the keywords 'navigator' or 'navigation' and 'cancer,' 45 articles were identified in the PubMed database and from reference searches that were published or in press through October 2007. Sixteen studies provided data on the efficacy of navigation in improving timeliness and receipt of cancer screening, diagnostic follow-up care, and treatment. Patient navigation services were defined and differentiated from other outreach services. Overall, there was evidence of some degree of efficacy for patient navigation in increasing participation in cancer screening and adherence to diagnostic follow-up care after the detection of an abnormality. The reported increases in screening ranged from 10.8% to 17.1%, and increases in adherence to diagnostic follow-up care ranged from 21% to 29.2% compared with control patients. There was less evidence regarding the efficacy of patient navigation in reducing either late-stage cancer diagnosis or delays in the initiation of cancer treatment or improving outcomes during cancer survivorship. There were methodological limitations in most studies, such as a lack of control groups, small sample sizes, and contamination with other interventions. Although cancer-related patient navigation interventions are being adopted increasingly across the United States and Canada, further research will be necessary to evaluate their efficacy and cost-effectiveness in improving cancer care.

Renal cell cancer stage migration: analysis of the National Cancer Data Base.

Abstract: BACKGROUND. Evidence exists to suggest a pattern of increasing early diagnosis of renal cell carcinoma (RCC). The aim of the study was to analyze patterns of disease presentation and outcome of RCC by AJCC stage using data from the National Cancer Data Base (NCDB) over a 12-year period. METHODS. The NCDB was queried for adults diagnosed between 1993 and 2004 presenting with ICD-O-2 of 3 renal cell tumors arising in the kidney. Cases were classified by demographics, 2002 AJCC stage (6th edition), and histology. The Cochran-Armitage Test for Trend was used to determine statistical significance of trends over time. Cox regression multivariate analysis was used to evaluate the impact of stage and histology on relative survival. SPSS 14.0 was used for analyses. RESULTS. Between 1993 and 2004 a total of 205,963 patients from the NCDB fit our case definition of RCC. Comparisons between 1993 and 2004 data show an increase in stage I disease and decrease in stage II, III, and IV disease (P ≤ .001). The size of stage I tumors also decreased from a mean of 4.1 cm in 1993 to 3.6 cm in 2003. In multivariate analysis, stage, but not histology, predicted relative survival. A 3.3% increase in survival was found for patients diagnosed in 1998 compared with patients diagnosed in 1993. CONCLUSIONS. A greater proportion of newly diagnosed patients with RCC currently present with stage I disease compared with earlier years. Stage predicts relative survival for patients with kidney cancer. More recently diagnosed patients have improved relative survival. Cancer 2008. © 2008 American Cancer Society.

Guideline implementation for breast healthcare in low-income and middle-income countries: overview of the Breast Health Global Initiative Global Summit 2007.

Abstract: Breast cancer outcomes in low- and middle-income countries (LMCs) correlate with the degree to which 1) cancers are detected at early stages, 2) newly detected cancers can be diagnosed correctly, and 3) appropriately selected multimodality treatment can be provided properly in a timely fashion. The Breast Health Global Initiative (BHGI) invited international experts to review and revise previously developed BHGI resource-stratified guideline tables for early detection, diagnosis, treatment, and healthcare systems. Focus groups addressed specific issues in breast pathology, radiation therapy, and management of locally advanced disease. Process metrics were developed based on the priorities established in the guideline stratification. The groups indicated that cancer prevention through health behavior modification could influence breast cancer incidence in LMCs. Diagnosing breast cancer at earlier stages will reduce breast cancer mortality. Programs to promote breast self-awareness and clinical breast examination and resource-adapted mammographic screening are important early detection steps. Breast imaging, initially with ultrasound and, at higher resource levels with diagnostic mammography, improves preoperative diagnostic assessment and permits image-guided needle sampling. Multimodality therapy includes surgery, radiation, and systemic therapies. Government intervention is needed to address drug-delivery problems relating to high cost and poor access. Guideline dissemination and implementation research plays a crucial role in improving care. Adaptation of technology is needed in LMCs, especially for breast imaging, pathology, radiation therapy, and systemic treatment. Curricula for education and training in LMCs should be developed, applied, and studied in LMC-based learning laboratories to aid information transfer of evidence-based BHGI guidelines.

Neuroendocrine tumor epidemiology: contrasting Norway and North America.

Abstract: BACKGROUND. The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program has proven to be a significant resource in US neuroendocrine tumor (NET) epidemiology. Norway also holds a robust and detailed cancer registry: the Norwegian Registry of Cancer (NRC). METHODS. SEER NET data were compared with corresponding NRC data in the time period 1993 to 2004 to determine whether there are differences in NET epidemiology between Norway and the United States. RESULTS. The SEER and NRC reported 17,312 and 2030 NETs, respectively. The overall Caucasian SEER NET incidence was 4.44, compared with 3.24 in the NRC. In the SEER white subset, bronchopulmonary NETs were the most common (incidence = 1.42; 32% of all NETs), compared with small intestinal NETs in the NRC (0.81; 26%). A marked increase in SEER NET incidence (37%-40%) was observed in the period 2000 to 2004, compared with 1993 to 1997; an even more pronounced increase (72%) was seen in the NRC. African Americans exhibited a remarkably high overall NET incidence of 6.50; furthermore, among African Americans, rectal NETs were most common (1.65; 27%). Small intestinal NET incidence was ∼30% higher in men compared with women in all populations. The highest 5-year survival rates were for rectal NETs (74%-88%) in both databases, whereas prostatic NETs had the worst outcome (0%-23%). At diagnosis, NETs were localized in 27% to 46% of patients. CONCLUSIONS. NET incidence in the US Caucasian population and in Norway is similar, but considerably higher (∼50%) among African Americans. NETs have been regarded as indolent tumors; however, the 5-year survival is only ∼55%. Cancer 2008. © 2008 American Cancer Society.

HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women.

Abstract: Human papillomavirus (HPV) is a necessary cause of cervical cancer. In addition, on the basis of the fulfillment of a combination of viral as well as epidemiological criteria, it is currently accepted that a proportion of anal, oropharyngeal, vulvar, and vaginal cancers among women and anal, oropharyngeal, and penile cancers among men are etiologically related to HPV. At these noncervical sites with etiologic heterogeneity, HPV-associated cancers represent a distinct clinicopathological entity, which is generally characterized by a younger age at onset, basaloid or warty histopathology, association with sexual behavior, and better prognosis, when compared with their HPV-negative counterparts. Currently available estimates indicate that the number of HPV-associated noncervical cancers diagnosed annually in the US roughly approximates the number of cervical cancers, with an equal number of noncervical cancers among men and women. Furthermore, whereas the incidence of cervical cancers has been decreasing over time, the incidence of anal and oropharyngeal cancers, for which there are no effective or widely used screening programs, has been increasing in the US. The efficacy of HPV vaccines in preventing infection at sites other than the cervix, vagina, and vulva should, therefore, be assessed (eg, oral and anal). Given that a substantial proportion of cervical cancers (approximately 70%) and an even greater proportion of HPV-associated noncervical cancers (approximately 86% to 95%) are caused by HPV16 and 18 (HPV types that are targeted by the currently available vaccines), current HPV vaccines may hold great promise (provided equivalent efficacy at all relevant anatomic sites) in reducing the burden of HPV-associated noncervical cancers, in addition to cervical cancers.

Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST).

Abstract: BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most frequent sarcoma of the intestinal tract and often shows constitutive activation of either the KIT or PDGFRA receptor tyrosine kinases because of gain-of-function mutation Although the efficacy of tyrosine kinase inhibitors in metastatic GIST depends on tumor mutation status, there have been conflicting reports on the prognostic importance of KIT mutation in primary GIST METHODS: A total of 127 patients were studied who presented to our institution from 1983 to 2002 with localized primary GIST and underwent complete gross surgical resection of disease The majority of tumors originated in the stomach (58%) or small intestine (28%) By using polymerase chain reaction (PCR) and direct sequencing, a KIT mutation was found in 71% of patients and a PDGFRA mutation in 6% RESULTS: After a median follow-up of 47 years, recurrence-free survival was 83%, 75%, and 63% at 1, 2, and 5 years, respectively On multivariate analysis recurrence was predicted by > or =5 mitoses/50 high-power fields, tumor size > or =10 cm, and tumor location (with patients having small bowel GIST doing the worst) In particular, a high mitotic rate conferred a hazard rate of 146 (95% confidence interval, 65-324) Specific KIT mutations had prognostic importance by univariate but not multivariate analysis Patients with KIT exon 11 point mutations and insertions had a favorable prognosis Those with KIT exon 9 mutations or KIT exon 11 deletions involving amino acid W557 and/or K558 had a higher rate of recurrence, whereas patients without a tyrosine kinase mutation had intermediate outcome CONCLUSIONS: In the absence of therapy with tyrosine kinase inhibitors, recurrence in completely resected primary GIST is independently predicted by mitotic rate, tumor size, and tumor location

Bronchopulmonary neuroendocrine tumors

Abstract: Bronchopulmonary neuroendocrine tumors (BP-NETs) comprise approximately 20% of all lung cancers and represent a spectrum of tumors arising from neuroendocrine cells of the BP-epithelium. Although they share structural, morphological, immunohistochemical, and ultrastructural features, they are separated into 4 subgroups: typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large-cell neuroendocrine carcinoma (LCNEC), and small-cell lung carcinoma (SCLC), which exhibit considerably different biological characteristics. The clinical presentation includes cough, hemoptysis, and obstructive pneumonia but varies depending on site, size, and growth pattern. Less than 5% of BP-NETs exhibit hormonally related symptoms such as carcinoid syndrome, Cushing, acromegaly, and SIADH. SCLC is the most common BP-NET, while LCNEC is rare, approximately 10% and < or =1%, respectively, of all lung cancers. Both SCLC and LCNEC progress rapidly, are aggressively metastatic, and exhibit a poor prognosis. The incidence of BP-carcinoids (TC and AC) in the US was 1.57 of 100,000 in 2003 (an unexplained and substantial increase over the last 30 years, approximately 6% per year). No curative treatment except for radical surgery (almost never feasible) exists. The slow-growing TC exhibit a fairly good prognosis ( approximately 88%, 5-year survival), whereas AC demonstrate a 5-year survival of approximately 50%, and the highly malignant LCNEC and SCLC5-year survival of 15% to 57% and <5%, respectively. This review provides a broad overview on BP-NETs and focuses on the evolution of the disease, general features, and current diagnostic and therapeutic options.

Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System.

Abstract: Myelodysplastic syndromes (MDS) are a heterogeneous group of neoplastic bone marrow disorders characterized by dysplastic changes in the myeloid lineages and a variable percentage of blasts. Approximately 50% of patients have chromosomal aberrations. The presenting laboratory features are marked by anemia (usually macrocytic) and neutropenia/thrombocytopenia.1–3 The disease heterogeneity is accounted for in part by several consistent pretreatment prognostic factors, which are incorporated into prognostic models such as the French-American-British (FAB), World Health Organization (WHO), and International Prognostic Scoring System (IPSS) classifications.4–6 The IPSS has achieved widespread use in clinical practice as well as in investigational studies to stratify patients and to assess the benefit of new therapies within prognostic subsets. The original IPSS classification mostly involved patients with newly diagnosed, untreated MDS (only 8% received minimal prior therapy) and excluded patients who had secondary MDS and chronic myelomonocytic leukemia (CMML) with white blood cell (WBC) counts >12 × 109/L.6 The effect of the duration of the antecedent hematologic disorder (AHD) on outcome in patients with MDS also was not specified. Recent studies have suggested that a need for transfusions is an adverse factor and have proposed different cytogenetic categories for prognostic classifications.7–9 Application of the IPSS to modern investigations and to patient prognostication is limited by a few issues: 1) most patients who are referred for investigational trials already have failed some form of therapy (growth factors, chemotherapy) and have had MDS for some time, 2) 20% to 30% of patients with MDS have secondary MDS, 3) patients who have CMML with a WBC count >12 × 109/L are excluded, 4) patients with poor performance or organ dysfunctions (ie, excluded from investigational therapy) are not accounted for, and 5) the effect of erythrocyte transfusion dependence has not been considered. In the current analysis, we attempted to address some of these issues by 1) applying the IPSS to MDS categories that were excluded from the original study (secondary MDS, duration of AHD, CMML with high WBC counts, prior therapy) and 2) using multivariate analysis to propose and validate a new risk model for MDS.

Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG

Abstract: BACKGROUND. The aim was to assess the relevant distribution of the novel PET tracer 68Ga-DOTATATE in neuroendocrine tumors (NETs) with combined positron emission tomography / computed tomography (PET/CT) and compare its performance with that of 18F-FDG PET/CT. METHODS. The imaging findings with 68Ga-DOTATATE and 18F-FDG on 38 consecutive patients with a diagnosis of primary or recurrent NET were compared and correlated with tumor grade on histology based on ki67 and mitotic index. RESULTS. The sensitivity of 68Ga-DOTATATE PET/CT was 82% (31 of 38) and that of 18F-FDG PET/CT was 66% (25 of 38). The sensitivity of combined 68Ga-DOTATATE and 18F-FDG PET/CT was 92% (35 of 38). There was greater uptake of 68Ga-DOTATATE than 18F-FDG in low-grade NET (median SUV 29 vs 2.9, P < .001). In high-grade NET there was higher uptake of 18F-FDG over 68Ga-DOTATATE (median SUV 11.7 vs 4.4, P = .03). There was a significant correlation with predominant tumor uptake of 68Ga-DOTATATE or 18F-FDG and tumor grade on histology (P < .0001). CONCLUSIONS. 68Ga-DOTATATE PET/CT is a useful novel imaging modality for NETs and is superior to 18F-FDG for imaging well-differentiated NET. Functional imaging with both 68Ga-DOTATATE and 18F-FDG has potential for a more comprehensive tumor assessment in intermediate- and high-grade tumors. Cancer 2008. ©2008 American Cancer Society.

Inherited pancreatic endocrine tumor syndromes: Advances in molecular pathogenesis, diagnosis, management, and controversies

Abstract: Pancreatic endocrine tumors (PETs) can occur as part of 4 inherited disorders, including Multiple Endocrine Neoplasia type 1 (MEN1), von Hippel-Lindau disease (VHL), neurofibromatosis 1 (NF-1) (von Recklinghausen disease), and the tuberous sclerosis complex (TSC). The relative frequency with which patients who have these disorders develop PETs is MEN1>VHL>NF-1>TSC. Over the last few years, there have been major advances in the understanding of the genetics and molecular pathogenesis of these disorders as well in the localization and the medical and surgical treatment of PETs in such patients. The study of PETs in these disorders not only has provided insights into the possible pathogenesis of sporadic PETs but also has presented several unique management and treatment issues, some of which are applicable to patients with sporadic PETs. Therefore, the study of PETs in these uncommon disorders has provided valuable insights that, in many cases, are applicable to the general group of patients with sporadic PETs. In this article, these areas are reviewed briefly along with the current state of knowledge of the PETs in these disorders, and the controversies that exist in their management are summarized briefly and discussed.

Psychologic Intervention Improves Survival for Breast Cancer Patients: A Randomized Clinical Trial

Abstract: BACKGROUND. The question of whether stress poses a risk for cancer progression has been difficult to answer. A randomized clinical trial tested the hypothesis that cancer patients coping with their recent diagnosis but receiving a psychologic intervention would have improved survival compared with patients who were only assessed. METHODS. A total of 227 patients who were surgically treated for regional breast cancer participated. Before beginning adjuvant cancer therapies, patients were assessed with psychologic and behavioral measures and had a health evaluation, and a 60-mL blood sample was drawn. Patients were randomized to Psychologic Intervention plus assessment or Assessment only study arms. The intervention was psychologist led; conducted in small groups; and included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment and care. Earlier articles demonstrated that, compared with the Assessment arm, the Intervention arm improved across all of the latter secondary outcomes. Immunity was also enhanced.

Preoperative assessment enables the early diagnosis and successful treatment of lymphedema

Abstract: BACKGROUND. The incidence of breast cancer (BC)-related lymphedema (LE) ranges from 7% to 47%. Successful management of LE relies on early diagnosis using sensitive measurement techniques. In the current study, the authors demonstrated the effectiveness of a surveillance program that included preoperative limb volume measurement and interval postoperative follow-up to detect and treat subclinical LE. METHODS. LE was identified in 43 of 196 women who participated in a prospective BC morbidity trial. Limb volume was measured preoperatively and at 3month intervals after surgery. If an increase >3% in upper limb (UL) volume developed compared with the preoperative volume, then a diagnosis of LE was made, and a compression garment intervention was prescribed for 4 weeks. Upon reduction of LE, garment wear was continued only during strenuous activity, with symptoms of heaviness, or with visible swelling. Women returned to the 3-month interval surveillance pathway. Statistical analysis was a repeated-measures analysis of variance by time and limb (P � .001) comparing the LE cohort with an age-matched control group. RESULTS. The time to onset of LE averaged 6.9 months postoperatively. The mean (� standard deviation) affected limb volume increase was 83 mL (� 119 mL;

Quality of life of family caregivers of cancer survivors: across the trajectory of the illness.

Abstract: BACKGROUND. Cancer affects not only the quality of life (QOL) of individuals with the disease but also that of their family members and close friends. The impact on various aspects of the family caregivers' QOL is significant throughout the trajectory of the illness. The authors reviewed literature on the QOL of family caregivers at the acute and middle- to long-term survivorship phases as well as the bereavement phase. METHODS. By using several databases, the authors searched the literature published in English from 1996 through July 2007. Keywords searched included cancer, carcinoma, family, family member, caregivers, and quality of life. Several criteria were used to guide the literature review: Articles had to be published in refereed journals and had to use rigorous methods, sample, and validated measures. RESULTS. The findings suggested that the QOL of family caregivers of individuals with cancer varies along the illness trajectory. This highlights were importance of assessing the ongoing adjustment of the caregivers over time. However, there were few theory-driven studies, and significant gaps remain in the current understanding of the effects of family caregiving beyond the time of diagnosis and treatment. CONCLUSIONS. Accumulating evidence has supported the concept that cancer affects not only the patients/survivors but also their family members. However, theoretically and methodologically rigorous research on various aspects of the family's QOL, including not only the psychological but also the physical, spiritual, and behavioral adjustment to cancer in the family, remains sparse. Family-based interventions across the trajectory of the illness also are needed. Cancer 2008. © 2008 American Cancer Society.

Incidence of early pseudo‐progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide

Abstract: BACKGROUND. Radiotherapy (RT) plus concomitant and adjuvant temozolomide (TMZ) is now the standard of care for patients with newly diagnosed glioblastoma. The occurrence of pseudo-progression directly after RT is a recognized phenomenon, but to the authors' knowledge its incidence after combined RT/TMZ is unknown. The occurrence of early pseudo-progression was retrospectively assessed in a cohort of malignant glioma patients treated with RT/TMZ. METHODS. The pre-RT and post-RT brain scans from patients treated with RT/TMZ for a malignant glioma were reviewed. Scans were made before the start of RT, 4 weeks after the end of RT, and every 3 months thereafter. In addition, information was collected regarding clinical signs and symptoms, dexamethasone dose, histology, and survival. RESULTS. Eighty-five patients were identified. In 36 patients (42%) the first followup scan 4 weeks after the end of RT indicated disease progression. Of these 36 patients, 18 (50%) were diagnosed with pseudo-progression. None of the patients received additional treatment other than TMZ. Six of 18 patients with pseudo-progression and 12 of the 18 patients with real tumor progression developed new clinical signs and symptoms during RT or in the first 4 weeks thereafter. CONCLUSIONS. Up to 50% of malignant glioma patients treated with RT/TMZ and progression immediately after RT develop pseudo-progression. The current study data support the idea to continue TMZ in the case of progressive lesions immediately after RT/TMZ. Surgery should be considered in symptomatic cases. The inclusion of patients with progressive lesions developing direcdy after chemoradiation in studies regarding recurrent gliomas will lead to an overestimation of the results.

Active Surveillance for the Management of Prostate Cancer in a Contemporary Cohort

Abstract: Author(s): Dall'Era, Marc A; Konety, Badrinath R; Cowan, Janet E; Shinohara, Katsuto; Stauf, Frank; Cooperberg, Matthew R; Meng, Maxwell V; Kane, Christopher J; Perez, Nanette; Master, Viraj A; Carroll, Peter R | Abstract: BackgroundActive surveillance followed by selective treatment for men who have evidence of disease progression may be an option for select patients with early-stage prostate cancer. In this article, the authors report their experience in a contemporary cohort of men with prostate cancer who were managed with active surveillance.MethodsAll men who were managed initially with active surveillance were identified through the authors' institutional database. Selection criteria for active surveillance included: prostate-specific antigen (PSA)l10 ng/mL, biopsy Gleason sum 0.75 ng/mL per year), was a secondary outcome. Chi-square and log-rank tests were used to compare groups. The association between clinical characteristics and receipt of active treatment was analyzed by using Cox proportional hazards regression.ResultsThree hundred twenty-one men (mean age [+/-standard deviation]: 63.4+/-8.5 years) selected active surveillance as their initial management. The overall median follow-up was 3.6 years (range, 1-17 years). The initial mean PSA level was 6.5+/-3.9 ng/mL. One hundred twenty men (37%) met at least 1 criterion for progression. Overall, 38% of men had higher grade on repeat biopsy, and 26% of men had a PSA velocityg0.75 ng/mL per year. Seventy-eight men (24%) received secondary treatment at a median 3 years (range, 1-17 years) after diagnosis. Approximately 13% of patients with no disease progression elected to obtain treatment. PSA density at diagnosis and rise in Gleason score on repeat biopsy were associated significantly with receipt of secondary treatment. The disease-specific survival rate was 100%.ConclusionsSelected individuals with early-stage prostate cancer may be candidates for active surveillance. Specific criteria can be and need to be developed to select the most appropriate individuals for this form of management and to monitor disease progression. A small attrition rate can be expected because of men who are unable or unwilling to tolerate surveillance.

Cryoablation or Radiofrequency Ablation of the Small Renal Mass: A Meta-analysis

Abstract: Background: The incidence of renal cell carcinoma(RCC) is rising due to incidental detection of small renal masses(SRMs). While surgical resection remains the standard of care, cryoablation and radiofrequency ablation(RFA) have emerged as minimally-invasive treatment alternatives. We performed a comparative meta-analysis evaluating cryoablation and RFA as primary treatment for SRMs.

The impact of socioeconomic status on survival after cancer in the United States : findings from the National Program of Cancer Registries Patterns of Care Study.

Abstract: BACKGROUND. Understanding the ways in which socioeconomic status (SES) affects mortality is important for defining strategies to eliminate the unequal burden of cancer by race and ethnicity in the United States. METHODS. Disease stage, treatment, and 5-year mortality rates were ascertained by reviewing medical records, and SES was determined by analyzing income and education at the census tract level for 4844 women with breast cancer, 4332 men with prostate cancer, and 4422 men and women with colorectal cancer who were diagnosed in 7 U.S. states in 1997. RESULTS. Low SES was associated with more advanced disease stage and with less aggressive treatment for all 3 cancers. The hazard ratio (HR) for 5-year all-cause mortality associated with low SES was elevated after a diagnosis of breast cancer when the analysis was adjusted for age (HR, 1.59; 95% confidence interval [CI], 1.35-1.87). Adjustment for mediating factors of race/ethnicity, comorbid conditions, cancer stage, and treatment reduced the association. The age-adjusted mortality risk associated with low SES was elevated after a diagnosis of prostate cancer (HR, 1.33; 95% CI, 1.13-1.57), and multivariate adjustments for mediating factors also reduced that association. There was less association between SES and mortality after a diagnosis of colorectal cancer. For all 3 cancer sites, low SES was a much stronger predictor of mortality among individuals aged <65 years and among individuals from racial/ethnic minority groups. CONCLUSIONS. The current results indicated that low SES is a risk factor for all-cause mortality after a diagnosis of cancer, largely because of a later stage at diagnosis and less aggressive treatment. These findings support the need to focus on SES as an underlying factor in cancer disparities by race and ethnicity. Cancer 2008. © 2008 American Cancer Society.

Adrenocortical carcinoma in the United States: Treatment utilization and prognostic factors

Abstract: BACKGROUND. Adrenocortical carcinoma (ACC) is a rare tumor with a relatively poor prognosis. The authors' objectives were to examine treatment utilization and factors associated with long-term survival after resection of ACC in a large, national, patient population. METHODS. Patients diagnosed with ACC from 1985 to 2005 were identified from the National Cancer Data Base (NCDB). Patient, tumor, treatment, and hospital factors associated with survival after resection were examined. RESULTS. For the current study, 3982 patients with ACC were identified. Median age at diagnosis was 55 years. Median tumor size was 13 cm. Of the patients with nodes examined, 26.5% had nodal metastases. Distant metastases were found on presentation in 21.6% of patients. A total of 57.4% of patients underwent surgical resection alone, whereas 16.0% underwent resection with adjuvant chemotherapy or radiation. A total of 19.4% had margin-positive resections. Treatment utilization remained unchanged from 1985 to 2005 (P = .28). Median follow-up was 24 months. Overall 5-year survival for all patients who underwent resection was 38.6% (median survival, 31.9 months). Multivariable analysis demonstrated a higher risk of death with increasing age, poorly differentiated tumors, involved margins, and nodal or distant metastases. Overall survival remained unchanged from 1985 to 2000 (P = .08). CONCLUSIONS. ACC carries a poor prognosis for patients commonly presenting with large, locally invasive tumors, involved margins, and metastatic disease. Survival is not affected by size but is diminished with increasing age, poorly differentiated tumors, involved margins, and the presence of regional and distant disease. Identification of novel therapies may help to increase survival, which has remained unchanged over the last 20 years. Cancer 2008. © 2008 American Cancer Society.

Screening and referral for psychosocial distress in oncologic practice: use of the Distress Thermometer.

Abstract: BACKGROUND. The objectives of this study were to validate the Distress Thermometer (DT) in the Netherlands and to examine its correspondence with a 46-item Problem List, possible risk factors, and the wish for a referral. METHODS. A cross-sectional group of 277 cancer patients who were treated at 9 hospitals filled in the DT and the Hospital Anxiety and Depression Scale and rated the presence and severity of problems (response rate, 49%). RESULTS. Receiver operating characteristic analyses identified an ideal cutoff score of 5 on the DT with a positive predictive value of 39% and a negative predictive value of 95%. The Problem List appeared to be a reliable measure. Five items on the Problem List correlated strongly with the DT, 13 items had a moderately strong correlation, 26 items were correlated weakly, and 2 items were not correlated significantly. Emotional control, nervousness, pain, and physical fitness appeared to contribute independently to the DT score. The percentage of patients scoring 5( n5 118 patients; 43%) who wanted (14%) or maybe wanted (29%) a referral was significantly higher than the percentage of patients with DT scores <5 (5% and 13%, respectively) who wanted or maybe wanted a referral. Intensively treated patients reported more distress than those who only underwent surgery. No other clear risk factors for distress were identified. CONCLUSIONS. The DT appeared to be a good instrument for routine screening and ruling out elevated distress. Emotional and physical problems contributed mainly to distress. Experiencing clinically elevated distress did not necessarily suggest that patients wanted a referral. Screening for distress and the wish for a referral can facilitate providing support for those patients who most need and want it. Cancer 2008;113:870–8. � 2008 American Cancer Society.

Prognostic Relevance of a Novel TNM Classification System for Upper Gastroenteropancreatic Neuroendocrine Tumors

Abstract: BACKGROUND. Neuroendocrine tumors (NETs) of the gastroenteropancreatic (GEP) system comprise a rare but challenging group of malignant neoplasms and occur at virtually any site of the GEP system. In 2006, a new TNM classification system was proposed for the staging and grading of upper GEP NETs. METHODS. The prognostic relevance of the TNM classification system was analyzed retrospectively in 202 patients from a referral center with histologically proven foregut NET. Patients were classified according to previous classification systems and the TNM classification. Survival data were acquired and statistical analyses were performed by using log-rank and Cox regression testing. RESULTS. Primary tumors were gastric (n = 48), duodenal (n = 23), and pancreatic (n = 131). During the observation period, 21% of patients died. The overall 5- and 10-year survival rates were 75% and 64%, respectively. Previous classification systems discriminated between low-grade and high-grade malignant NETs but did not allow further prognostic differentiation. In contrast, the proposed TNM classification was able to differentiate significantly between different tumor stages (stages I-III vs stage IV; P < .01) and cellular proliferation rates according to Ki-67 labeling (grade 1 vs grade 2, P = .04; grade 1 vs grade 3 and grade 2 vs grade 3, P < .01). Cox regression analysis confirmed an increased risk of reduced survival for patients with stage III or IV NET and grade 2 or 3 NET. CONCLUSIONS. The current results demonstrated the prognostic relevance of the newly proposed TNM classification system for foregut NETs with statistical significance for the subgroups of both the staging classification and the grading system. Thus, the new classification system provides a valid and powerful tool for prognostic stratification of GEP NETs in clinical practice and research. Cancer 2008. © 2008 American Cancer Society.

Intimacy and relationship processes in couples' psychosocial adaptation to cancer.

Abstract: The authors highlighted the importance of viewing cancer from a relationship perspective. This perspective not only considers the marital relationship as a resource that individual partners draw upon but also highlights the importance of focusing attention onto the relationship and engaging in communication behaviors aimed at sustaining and/or enhancing the relationship during stressful times. On the basis of existing conceptualizations, empiric research on couples and cancer, and the authors' perspective on the literature, they formulated the relationship intimacy model of couples' psychosocial adaptation to cancer as a first step toward building a framework for researchers and clinicians to inform their work in this area. The model proposes that patients and their partners engage in behaviors that either promote or undermine the level of closeness in their relationship and that the closeness of the marital relationship is an important determinant of patient and partner psychologic adaptation to cancer. Preliminary data from a couples' intimacy-enhancing intervention for breast cancer patients and their partners supported the model. Of the 25 couples who consented to participate in the intervention and completed the preintervention surveys, 15 couples completed all 5 sessions, and 12 couples completed the follow-up survey. The current results suggested that the intervention improved patient and partner perceptions of the closeness of their relationship and reduced their distress. The authors also discuss limitations of the relationship intimacy model as well as future directions for empiric and clinical research on couples' psychosocial adaptation to cancer. Cancer 2008. © 2008 American Cancer Society.

High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma : a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006

Abstract: BACKGROUND The treatment of metastatic renal cell carcinoma (RCC) with high-dose interleukin-2 (HD IL-2) has resulted in durable tumor regression in a minority of patients. The current study presents the authors’ 20-year experience administering this immunotherapeutic agent.

Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer.

Abstract: BACKGROUND. The purpose of this study was to investigate whether tumor-infiltrating immune cells in biopsy specimens can be used to predict the clinical outcome of stage IV nonsmall cell lung cancer (NSCLC) patients. METHOD. The authors performed an immunohistochemical study to identify and count the number of CD68+ macrophages, c-kit+ mast cells, and CD8+ T cells in both cancer nests and cancer stroma in pretreatment biopsy specimens obtained from 199 patients with stage IV NSCLC treated by chemotherapy, and then analyzed for correlations between the number of immune cells and clinical outcome, including chemotherapy response and prognosis. RESULTS. There was no correlation between the number of immune cells in either cancer nests or stroma and chemotherapy response. Patients with more tumor-infiltrating macrophages in cancer nests than in cancer stroma (macrophages, nests > stroma) had significantly better survival than nests stroma) showed significantly better survival than in nests < stroma cases (MST 388 days vs 256 days; P = .0070). The proportion of tumor-infiltrating macrophages or CD8+ T cells between cancer nests and stroma became independent prognostic factors in the multivariate analysis. Neither the number of mast cells in nests nor in stroma correlated with the clinical outcome. CONCLUSIONS. Evaluation of the numbers of macrophages and CD8+ T cells in cancer nests and stroma are useful biomarkers for predicting the prognosis of stage IV NSCLC patients treated with chemotherapy, but could fail to predict chemotherapy response. Cancer 2008. © 2008 American Cancer Society.

Geographic access to cancer care in the U.S.

Abstract: BACKGROUND Although access to cancer care is known to influence patient outcomes, to the authors' knowledge, little is known regarding geographic access to cancer care, and how it may vary by population characteristics. This study estimated travel time to specialized cancer care settings for the continental U.S. population and calculated per capita oncologist supply. METHODS The closest travel times were estimated using a network analysis of the road distance weighted by travel speeds from the population or geographic centroid of every ZIP area in the continental U.S. to that of the nearest cancer care setting under consideration: National Cancer Institute (NCI)-designated Cancer Centers, academic medical centers, and oncologists. Alaska and Hawaii were excluded because travel in these states is often not road-based. Population and geographic characteristics including race/ethnicity, income, education, and region were derived from U.S. Census 2000 data and from rural-urban commuting area classifications. Oncologist supply per 100,000 residents in Hospital Referral Regions (pHRRs) was estimated by region. RESULTS Travel times of ≤1 hour were estimated for 45.2% of the population to the nearest NCI Cancer Center, 69.4% to the nearest academic-based care, and 91.8% to any specialized cancer care. Native Americans, nonurban dwellers, and residents in the South had the longest travel times to the nearest NCI Cancer Center compared with the overall U.S. population (median [interquartile range (IQR)] in minutes: 155 [62–308], 173 [111–257], and 164 [70–272], vs 78 [27–172], respectively). Travel burdens persisted for Native Americans and nonurban populations across all 3 cancer care settings. For all population strata, travel times markedly increased as the degree of cancer care specialization increased. The median oncologist supply for pHRRs was 2.83 per 100,000 individuals. CONCLUSIONS There are population groups with limited access to the most specialized cancer care settings. Cancer 2008. © 2008 American Cancer Society.