Showing papers in "Cancer in 2004"

Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients

Abstract: BACKGROUND A frequent complication of anticancer treatment, oral and gastrointestinal (GI) mucositis, threatens the effectiveness of therapy because it leads to dose reductions, increases healthcare costs, and impairs patients' quality of life. The Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an international multidisciplinary panel of experts to create clinical practice guidelines for the prevention, evaluation, and treatment of mucositis. METHODS The panelists examined medical literature published from January 1966 through May 2002, presented their findings at two separate conferences, and then created a writing committee that produced two articles: the current study and another that codifies the clinical implications of the panel's findings in practice guidelines. RESULTS New evidence supports the view that oral mucositis is a complex process involving all the tissues and cellular elements of the mucosa. Other findings suggest that some aspects of mucositis risk may be determined genetically. GI proapoptotic and antiapoptotic gene levels change along the GI tract, perhaps explaining differences in the frequency with which mucositis occurs at different sites. Studies of mucositis incidence in clinical trials by quality and using meta-analysis techniques produced estimates of incidence that are presented herein for what to our knowledge may be a broader range of cancers than ever presented before. CONCLUSIONS Understanding the pathobiology of mucositis, its incidence, and scoring are essential for progress in research and care directed at this common side-effect of anticancer therapies. Cancer 2004;100(9 Suppl):1995–2025. © 2004 American Cancer Society.

Annual report to the nation on the status of cancer, 1975–2001, with a special feature regarding survival

Abstract: BACKGROUND The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information regarding cancer occurrence and trends in the U.S. This year's report features a special section on cancer survival. METHODS Information concerning cancer cases was obtained from the NCI, CDC, and NAACCR and information concerning recorded cancer deaths was obtained from the CDC. The authors evaluated trends in age-adjusted cancer incidence and death rates by regression models and described and compared survival rates over time and across racial/ethnic populations. RESULTS Incidence rates for all cancers combined decreased from 1991 through 2001, but stabilized from 1995 through 2001 when adjusted for delay in reporting. The incidence rates for female lung cancer decreased (although not statistically significant for delay adjusted) and mortality leveled off for the first time after increasing for many decades. Colorectal cancer incidence rates also decreased. Death rates decreased for all cancers combined (1.1% per year since 1993) and for many of the top 15 cancers occurring in men and women. The 5-year relative survival rates improved for all cancers combined and for most, but not all, cancers over 2 diagnostic periods (1975–1979 and 1995–2000). However, cancer-specific survival rates were lower and the risk of dying from cancer, once diagnosed, was higher in most minority populations compared with the white population. The relative risk of death from all cancers combined in each racial and ethnic population compared with non-Hispanic white men and women ranged from 1.16 in Hispanic white men to 1.69 in American Indian/Alaska Native men, with the exception of Asian/Pacific Islander women, whose risk of 1.01 was similar to that of non-Hispanic white women. CONCLUSIONS The continued measurable declines for overall cancer death rates and for many of the top 15 cancers, along with improved survival rates, reflect progress in the prevention, early detection, and treatment of cancer. However, racial and ethnic disparities in survival and the risk of death from cancer, and geographic variation in stage distributions suggest that not all segments of the U.S. population have benefited equally from such advances. Cancer 2004. Published 2004 by the American Cancer Society.

The prevalence of pituitary adenomas: a systematic review.

Abstract: BACKGROUND Pituitary adenomas display an array of hormonal and proliferative activity. Once primarily classified according to size (microadenomas, < 1 cm; macroadenomas, ≥ 1 cm), these tumors are now further classified according to immunohistochemistry and functional status. With these additional classifications in mind, the goals of the current study were to determine the prevalence of pituitary adenomas and to explore the clinical relevance of the findings. METHODS The authors conducted a metaanalysis of all existing English-language articles in MEDLINE. They used the search string (pituitary adenoma or pituitary tumor) and prevalence and selected relevant autopsy and imaging evaluation studies for inclusion. RESULTS The authors found an overall estimated prevalence of pituitary adenomas of 16.7% (14.4% in autopsy studies and 22.5% in radiologic studies). CONCLUSIONS Given the high frequency of pituitary adenomas and their potential for causing clinical pathologies, the findings of the current study suggest that early diagnosis and treatment of pituitary adenomas should have far-reaching benefits. Cancer 2004. © 2004 American Cancer Society.

Stereotactic hypofractionated high-dose irradiation for stage I nonsmall cell lung carcinoma: clinical outcomes in 245 subjects in a Japanese multiinstitutional study.

Abstract: BACKGROUND Stereotactic irradiation (STI) has been actively performed using various methods to achieve better local control of Stage I nonsmall cell lung carcinoma (NSCLC) in Japan. The authors retrospectively evaluated results from a Japanese multiinstitutional study. METHODS Patients with Stage I NSCLC (n = 245; median age, 76 years; T1N0M0, n=155; T2N0M0, n=90) were treated with hypofractionated high-dose STI in 13 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. A total dose of 18–75 gray (Gy) at the isocenter was administered in 1–22 fractions. The median calculated biologic effective dose (BED) was 108 Gy (range, 57–180 Gy). RESULTS During follow-up (median, 24 months; range, 7–78 months), pulmonary complications of National Cancer Institute-Common Toxicity Criteria Grade > 2 were observed in only 6 patients (2.4%). Local progression occurred in 33 patients (14.5%), and the local recurrence rate was 8.1% for BED ≥ 100 Gy compared with 26.4% for < 100 Gy (P < 0.05). The 3-year overall survival rate of medically operable patients was 88.4% for BED ≥ 100 Gy compared with 69.4% for < 100 Gy (P < 0.05). CONCLUSIONS Hypofractionated high-dose STI with BED < 150 Gy was feasible and beneficial for curative treatment of patients with Stage I NSCLC. For all treatment methods and schedules, local control and survival rates were better with BED ≥ 100 Gy compared with < 100 Gy. Survival rates in selected patients (medically operable, BED ≥ 100 Gy) were excellent, and were potentially comparable to those of surgery. Cancer 2004. © 2004 American Cancer Society.

Clinical practice guidelines for the prevention and treatment of cancer therapy–induced oral and gastrointestinal mucositis†

Abstract: BACKGROUND Oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary track mucositis increases mortality and morbidity and contributes to rising health care costs. Consequently, the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an expert panel to evaluate the literature and to create evidence-based guidelines for preventing, evaluating, and treating mucositis. METHODS Thirty-six panelists reviewed literature published between January 1966 and May 2002. An initial meeting in January 2002 produced a preliminary draft of guidelines that was reviewed at a second meeting the same year. Thereafter, a writing committee produced a report on mucositis pathogenesis, epidemiology, and scoring (also included in this issue), as well as clinical practice guidelines. RESULTS Panelists created recommendations from higher levels of evidence and suggestions when evidence was of a lower level and there was a consensus regarding the interpretation of the evidence by the panel. Panelists identified gaps in evidence that made it impossible to recommend or not recommend use of specific agents. CONCLUSIONS Oral/GI mucositis is a common side effect of many anticancer therapies. Evidence-based clinical practice guidelines are presented as a benchmark for clinicians to use for routine care of appropriate patients and as a springboard to challenge clinical investigators to conduct high-quality trials geared toward areas in which data are either lacking or conflicting. Cancer 2004;100(9 Suppl):2026–2046. © 2004 American Cancer Society.

Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer

Abstract: BACKGROUND. The incidence of anal cancer has increased among both men (160%) and women (78%) from 1973 to 2000 in the U.S. The authors conducted a population-based case– control study of anal cancer to examine factors that may account for this increase. METHODS. Men (n 119 patients) and women (n 187 patients) who were diagnosed with anal cancer between 1986 and 1998 in the Seattle area were ascertained through the local Surveillance, Epidemiology, and End Results registry. Control participants (n 1700) were ascertained through random-digit telephone dialing. Participants were interviewed in person and provided blood samples. Archival tumor tissue was tested for human papilloma virus (HPV) DNA, and serum samples were tested for HPV type 16 (HPV-16). RESULTS. Overall, 88% of tumors (all histologies) in the study were found to be positive for HPV. HPV-16 was the most frequent HPV type detected (73% of all tumors), followed by HPV-18 (6.9%), regardless of gender. However, 97.7% of tumors from men who were not exclusively heterosexual contained HPV DNA. The risk of anal cancer increased among men (odds ratio [OR], 5.3; 95% confidence interval [95% CI], 2.4 –12.0) and women (OR, 11.0; 95% CI, 5.5–22.1) who had 15 sexual partners during their lifetime. Among men who were not exclusively heterosexual and women, receptive anal intercourse was related strongly to the risk of anal cancer (OR, 6.8 [95% CI, 1.4 –33.8] and OR, 2.2 [95% CI, 1.4 –3.3], respectively). Current smokers among men and women were at particularly high risk for anal cancer, independent of age and other risk factors (OR, 3.9 [95% CI, 1.9 – 8.0] and OR, 3.8 [95% CI, 2.4 – 6.2], respectively). CONCLUSIONS. The high proportion of tumors with detectable HPV suggests that infection with HPV is a necessary cause of anal cancer, similar to that of cervical cancer. Increases in the prevalence of exposures, such as cigarette smoking, anal intercourse, HPV infection, and the number of lifetime sexual partners, may account for the increasing incidence of anal cancer in men and women. Cancer 2004;101:270 – 80. © 2004 American Cancer Society.

Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management.

Abstract: Cytotoxic chemotherapy suppresses the hematopoietic system, impairing host protective mechanisms and limiting the doses of chemotherapy that can be tolerated. Neutropenia, the most serious hematologic toxicity, is associated with the risk of life-threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcomes. The authors reviewed the recent literature to provide an update on research in chemotherapy-induced neutropenia and its complications and impact, and they discuss the implications of this work for improving the management of patients with cancer who are treated with myelosuppressive chemotherapy. Despite its importance as the primary dose-limiting toxicity of chemotherapy, much concerning neutropenia and its consequences and impact remains unknown. Recent surveys indicate that neutropenia remains a prevalent problem associated with substantial morbidity, mortality, and costs. Much research has sought to identify risk factors that may predispose patients to neutropenic complications, including febrile neutropenia, in an effort to predict better which patients are at risk and to use preventive strategies, such as prophylactic colony-stimulating factors, more cost-effectively. Neutropenic complications associated with myelosuppressive chemotherapy are a significant cause of morbidity and mortality, possibly compromised treatment outcomes, and excess healthcare costs. Research in quantifying the risk of neutropenic complications may make it possible in the near future to target patients at greater risk with appropriate preventive strategies, thereby maximizing the benefits and minimizing the costs.

Breast carcinoma in men: a population-based study.

Abstract: BACKGROUND Male breast carcinoma is an uncommon disease, and most previous studies have been single-institution series that were limited by extremely small sample sizes. The goals of the current study were to fill in the major gaps in knowledge regarding the incidence, presenting characteristics, prognostic factors, and survival rates of male breast carcinoma and to determine how breast carcinoma differs between men and women. METHODS Data from the National Cancer Institute Surveillance, Epidemiology, and End Results 1973–1998 database were used. Age-adjusted incidence rates were calculated. Characteristics of the patients and presenting tumors were compared between men and women. Univariate and multivariate analyses were performed to determine the effect of each variable on overall survival. Survival rates by disease stage were compared for men and women. RESULTS Over the years of the study, the incidence of male breast carcinoma increased significantly from 0.86 to 1.08 per 100,000 population (P < 0.001). Men had a higher median age at diagnosis (P < 0.001) and were more likely to have lymph node involvement (P < 0.001), a more advanced stage at diagnosis (P < 0.001), and tumors that were positive for estrogen receptor (ER) (P < 0.001) and progesterone receptor (PR) (P < 0.001). In multivariate analysis, larger tumor size and lymph node involvement were associated with shortened survival. Tumor grade and ER/PR status did not appear to independently influence survival. Relative survival rates by stage of disease for men and women were similar. CONCLUSIONS Although it remains a rare disease, the incidence of male breast carcinoma is increasing. Breast carcinoma in men has some epidemiologic and biologic differences from breast carcinoma in women. Cancer 2004. © 2004 American Cancer Society.

Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind, placebo-controlled trial.

Abstract: Background The authors previously reported the efficacy of a dose of 4 mg of zoledronic acid in reducing skeletal complications in patients with bone metastases secondary to lung carcinoma and other solid tumors (except carcinomas of the breast and prostate). In the current study, they update these results and report the long-term efficacy and safety of 21 months of treatment with zoledronic acid in a randomized, placebo-controlled trial. Methods A total of 773 patients were randomized to receive zoledronic acid (4 mg or 8 mg) or placebo via a 15-minute infusion every 3 weeks for 21 months. The 8-mg dose later was reduced to 4 mg (8/4-mg group). The primary efficacy endpoint was the percentage of patients at 21 months with >/= 1 skeletal-related event (SRE) (pathologic fracture, spinal cord compression, radiation therapy to bone, or surgery to bone). Secondary analyses (time to first SRE, annual incidence of SREs, and multiple-event analysis) included hypercalcemia of malignancy. Results Fewer patients treated with zoledronic acid developed at least 1 SRE at 21 months compared with patients treated with placebo (39% of those treated at the 4-mg dose [P =0.127] and 36% of those treated at the 8/4-mg dose [P = 0.023], compared with 46% of those treated with placebo). Furthermore, 4 mg of zoledronic acid significantly delayed the median time to first SRE (236 days with 4 mg vs. 155 days with placebo; P = 0.009) and significantly reduced the annual incidence of SREs (1.74 per year with the 4-mg dose vs. 2.71 per year with placebo; P = 0.012). Moreover, the 4-mg dose of zoledronic acid was found to reduce the risk of developing a skeletal event by 31% (hazard ratio of 0.693; P = 0.003). Zoledronic acid was found to be well tolerated with long-term use; the most commonly reported adverse events in all treatment groups included bone pain and the transient, acute-phase reactions of nausea, anemia, and emesis. Conclusions To the authors' knowledge, zoledronic acid is the first bisphosphonate to demonstrate long-term safety and efficacy in this patient population.

Human prostate cancer risk factors.

Abstract: Prostate cancer has the highest prevalence of any nonskin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating androgens will develop microscopic prostate cancer if they live long enough. This review is a contemporary and comprehensive, literature-based analysis of the putative risk factors for human prostate cancer, and the results were presented at a multidisciplinary consensus conference held in Crystal City, Virginia, in the fall of 2002. The objectives were to evaluate known environmental factors and mechanisms of prostatic carcinogenesis and to identify existing data gaps and future research needs. The review is divided into four sections, including 1) epidemiology (endogenous factors [family history, hormones, race, aging and oxidative stress] and exogenous factors [diet, environmental agents, occupation and other factors, including lifestyle factors]); 2) animal and cell culture models for prediction of human risk (rodent models, transgenic models, mouse reconstitution models, severe combined immunodeficiency syndrome mouse models, canine models, xenograft models, and cell culture models); 3) biomarkers in prostate cancer, most of which have been tested only as predictive factors for patient outcome after treatment rather than as risk factors; and 4) genotoxic and nongenotoxic mechanisms of carcinogenesis. The authors conclude that most of the data regarding risk relies, of necessity, on epidemiologic studies, but animal and cell culture models offer promise in confirming some important findings. The current understanding of biomarkers of disease and risk factors is limited. An understanding of the risk factors for prostate cancer has practical importance for public health research and policy, genetic and nutritional education and chemoprevention, and prevention strategies.

The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: Results of a prospective, randomized, longitudinal trial

Abstract: BACKGROUND Retrospective trials have reported that chemotherapy-induced cognitive dysfunction was experienced by a subset of patients with breast carcinoma. However, recent evidence indicated that a subset also exhibited impaired cognitive function at baseline, before the start of chemotherapy. A prospective, longitudinal trial that incorporates baseline neuropsychologic evaluations is necessary to determine to what extent cognitive dysfunction is attributable to chemotherapy in this population. METHODS Eighteen women with breast carcinoma underwent a comprehensive neuropsychologic evaluation before treatment and at short-term and long-term intervals after chemotherapy. The incidence, nature, severity, and chronicity of cognitive dysfunction developing in patients with breast carcinoma treated with a standard dose of adjuvant chemotherapy were assessed. RESULTS Before the start of systemic therapy, 33% of women in the current cohort exhibited cognitive impairment. At the short-term postchemotherapy time point, 61% of the cohort exhibited a decline relative to baseline in 1 or more domains of cognitive functioning and reported greater difficulty in maintaining their ability to work. The most common domains of cognitive dysfunction were related to attention, learning, and processing speed. At the long-term postchemotherapy time point, approximately 50% of patients who experienced declines in cognitive function demonstrated improvement, whereas 50% remained stable. Self-reported ability to perform work-related activities also improved over this interval. Neither impairment at baseline nor subsequent treatment-related cognitive decline exhibited any statistically significant correlation with affective well-being or with demographic or clinical characteristics. CONCLUSIONS The current study is the first longitudinal trial to report evidence of an association between cognitive dysfunction and chemotherapy in a subgroup of women with nonmetastatic breast carcinoma. The importance of using prospective research designs, appropriate cognitive measures, and statistical methods to evaluate subgroup effects was discussed. Identification of mechanisms associated with cognitive dysfunction and of risk factors contributing to subgroup vulnerability is necessary. Cancer 2004. © 2004 by the American Cancer Society.

Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000.

Abstract: BACKGROUND. Anal cancer is a rare malignancy of the anogenital tract that historically has affected women at a greater rate than men. METHODS. The authors analyzed changing trends in incidence rates and 5-year relative survival percentages for patients with anal cancer. The publicly available data used in the current study were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program, a system of population-based tumor registries in the United States. RESULTS. The incidence of anal cancer was similar for men and women between 1994 and 2000 (2.04 per 100,000 and 2.06 per 100,000, respectively), the most recent period for which data were available, whereas men had lower rates than did women between 1973 and 1979 (1.06 per 100,000, compared with 1.39 per 100,000), the earliest period for which data were available. In addition, recently, black men had higher incidence rates than did other race-specific and gender-specific groups (2.71 per 100,000). From the earliest period for which data were available to the most recent period, relative 5-year survival improved from 59% to 73% among women, was unchanged among men (60%), and decreased from 45% to 27% among black men. Eighteen percent of patients who had distant disease were alive at 5 years, compared with 78% of patients who had localized disease. CONCLUSIONS. The incidence of anal cancer in the United States increased between 1973 and 2000, particularly among men. There were higher incidence rates and lower survival rates for black men compared with other race-specific and gender-specific groups. Later disease stage was inversely associated with the survival rate, indicating that earlier detection may improve the survival of patients with anal cancer. Cancer 2004;101:281– 8. © 2004 American Cancer Society.

Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia

Abstract: Background Modern intensive chemotherapy regimens have improved the prognosis for patients with adult acute lymphocytic leukemia (ALL). With these regimens, the complete response rates are now reported to be > 80%, and the long-term survival rates range from 30% to 45%. The current analysis updated the long-term results with the original hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) program, with a median follow-up time of 63 months. Methods Between 1992 and 2000, 288 patients were treated with Hyper-CVAD. The median age of the patients was 40 years, and 59 patients (20%) were > or = age 60 years. The incidence of Philadelphia chromosome (Ph)-positive ALL was 17%, and the incidence of of T-cell ALL was 13%. Results A complete response (CR) was achieved in 92% of patients. The induction mortality rate was 5% (2% if the patient's age was or = 60 years). With a median follow-up time of 63 months, the 5-year survival rate was 38% and the 5-year CR duration rate was 38%. Multivariate analysis of prognostic factors for CR duration identified the following adverse factors: age > or = 45 years, leukocytosis > or = 50 x 10(9)/L, poor performance status (an Eastern Cooperative Oncology Group score of 3-4), Ph-positive disease, French-American-British L2 morphology, > 1 course to achieve CR, and Day 14 bone marrow blasts > 5%. Patients were divided into low-risk (risk score 0-1; 37%), intermediate risk (risk score 2-3; 36%), and poor-risk groups (risk score > or = 4; 27%) with 5-year CR duration rates of 52%, 37%, and 10%, respectively. Conclusions Compared with the previous VAD regimens, Hyper-CVAD was associated with significantly better CR rates, CR duration, and survival. The long-term follow-up results of Hyper-CVAD were favorable. Comparison of Hyper-CVAD with other established adult ALL regimens is warranted.

Patterns and predictors of colorectal cancer test use in the adult U.S. population.

Abstract: BACKGROUND Screening is effective in reducing the incidence and mortality of colorectal cancer. Rates of colorectal cancer test use continue to be low. METHODS The authors analyzed data from the National Health Interview Survey concerning the use of the home-administered fecal occult blood test (FOBT) and sigmoidoscopy/colonoscopy/proctoscopy to estimate current rates of colorectal cancer test use and to identify factors associated with the use or nonuse of tests. RESULTS In 2000, 17.1% of respondents reported undergoing a home FOBT within the past year, 33.9% reported undergoing an endoscopy within the previous 10 years, and 42.5% reported undergoing either test within the recommended time intervals. The use of colorectal cancer tests varied by gender, race, ethnicity, age, education, income, health care coverage, and having a usual source of care. Having seen a physician within the past year had the strongest association with test use. Lack of awareness and lack of physician recommendation were the most commonly reported barriers to undergoing such tests. CONCLUSIONS Less than half of the U.S. population age ≥ 50 years underwent colorectal cancer tests within the recommended time intervals. Educational initiatives for patients and providers regarding the importance of colorectal cancer screening, efforts to reduce disparities in test use, and ensuring that all persons have access to routine primary care may help increase screening rates. Cancer 2004. © 2004 American Cancer Society.

Prostate-specific antigen: a review of the validation of the most commonly used cancer biomarker.

Abstract: BACKGROUND The widespread use of prostate-specific antigen (PSA) screening has had a tremendous impact on all aspects of the management of prostate carcinoma. Although PSA-based screening has resulted in a stage migration to more organ-confined tumors at the time of diagnosis, and has been temporally associated with a decrease in prostate carcinoma mortality, PSA screening is imperfect. A recent analysis of results from the Prostate Cancer Prevention Trial (PCPT) has provided insight into the positive predictive value of PSA in the so-called “normal” range. METHODS The history of the discovery, initial studies, and subsequent widespread application of PSA screening is reviewed. RESULTS The application of PSA for screening preceded the development of current prostate biopsy techniques and an upper limit of normal was established without complete disease ascertainment. More recent modifications of PSA-based screening have been adopted clinically without sufficient validation. With current methods, overdiagnosis of clinically unimportant disease almost certainly occurs and high-grade, aggressive disease may not be detected sufficiently early to allow successful treatment. CONCLUSIONS To the authors' knowledge, the optimal upper limit of normal for PSA for prostate carcinoma screening is unknown. New biomarkers of disease are needed; these must be linked with disease prognosis and must be validated in rigorously designed clinical trials. Cancer 2004. © 2004 American Cancer Society.

Is breast cancer survival improving

Abstract: BACKGROUND Despite advances in therapies for breast cancer, improvement in survival for patients with recurrent or metastatic breast cancer has been difficult to establish. The objective of the current study was to determine whether the survival of women with recurrent breast cancer has improved from 1974 to 2000. METHODS The authors analyzed the survival experience of 834 women who developed recurrent breast cancer between November 1974 and December 2000. All patients had been treated previously with adjuvant anthracycline-based protocols. Patients were divided into five consecutive groups based on year of breast cancer recurrence, and survival was compared across the five groups. Because some prognostic variables were divided unevenly divided among the cohorts, a multivariate model was created to determine the association of year of recurrence and survival after accounting for other prognostic factors. RESULTS In the unadjusted analysis, there was a statistically significant improvement in survival across the five groups, and the more recent cohorts had longer survival (P < 0.001). Other variables that predicted longer survival after breast cancer recurrence included smaller initial tumor size, lower stage of disease, fewer lymph nodes involved, longer disease-free interval, estrogen receptor–positive tumors, and nonvisceral dominant site of disease recurrence. In the multivariate analysis, which adjusted for these prognostic factors, year of recurrence was associated with a trend toward improved survival, with a 1% reduction in risk for each increasing year. CONCLUSIONS For these cohorts of patients, the authors present data suggesting that the prognosis for patients with recurrent breast cancer improved between 1974 and 2000. Cancer 2004;100:44–52. © 2003 American Cancer Society.

The natural history of incidentally detected small renal masses.

Abstract: BACKGROUND The incidence of renal cell carcinoma (RCC) is increasing, largely due to the widespread use of cross-sectional imaging. Most renal tumors are detected incidentally as small, asymptomatic masses. To study their natural history, the authors prospectively followed a series of patients with this type of lesion who were unsuited for or refused surgery. METHODS Twenty-nine patients with 32 masses that measured < 4 cm in greatest dimension (25 solid masses and 7 complex cystic masses) were studied. The primary outcome was tumor size, which was calculated as volume over time. All patients were followed with serial abdominal imaging, and each mass had at least three follow-up measurements. The median follow-up was 27.9 months (range, 5.3–143.0 months). RESULTS Overall, the average growth rate did not differ statistically from zero growth (P = 0.09; 95% confidence interval, − 0.005–0.2 cm per year) and was not associated with either initial size (P = 0.28) or mass type (P = 0.41). Seven masses (22%) reached 4 cm in greatest dimension after 12–85 months of follow-up. Eight masses (25%) doubled their volumes within 12 months. Overall, 11 masses (34%) fulfilled 1 of these 2 criteria of rapid growth. Nine tumors were removed surgically after an average of 3.1 years of follow-up because it was believed that they were growing fast. No patient had disease progression. CONCLUSIONS Approximately one-third of small renal masses that are presumed RCCs grow if they are managed conservatively and are followed with serial imaging. The growth rate is slow or undetectable in the majority of patients. These observations raise the possibility of a period of initial observation in selected patients, particularly the elderly or infirm. Cancer 2004;100:738–45. © 2004 American Cancer Society.

Adenocarcinoma of the small bowel: presentation, prognostic factors, and outcome of 217 patients

Abstract: BACKGROUND Primary adenocarcinoma of the small bowel is a rare neoplasm, and to the authors' knowledge, few studies to date have addressed the topic. METHODS In the current study, the records of 217 patients with small bowel adenocarcinoma were reviewed retrospectively for the presentation, prognostic factors, treatment modalities, and outcome. RESULTS The median age of the patients was 55 years and there were 133 (61%) males. Tumors originated in the duodenum in 113 (52%) patients, the jejunum in 54 (25%) patients, the ileum in 28 (13%) patients, and in nonspecified sites in 22 (10%) patients. Patients with proximal tumors were diagnosed for the most part using endoscopy (i.e., 46 of 108 [43%]), whereas laparotomy enabled diagnosis in 16 of 28 (57%) patients with distal tumors. Based on TNM staging, 9 (4%) patients had Stage I disease, 43 (20%) patients had Stage II disease, 86 (39%) patients had Stage III disease, and 75 (35%) patients had Stage IV disease. The liver was the most common site of metastasis in 44 (59%) patients. Cancer-directed surgery was performed in 146 (67 %) patients, including the Whipple procedure in 36 patients (17%). The median overall survival time was 20 months. The 5-year overall survival rate was 26%. Cancer-directed surgery, early-stage disease, and lymph node involvement ratio were significantly associated with overall survival by univariate analysis. However, only cancer-directed surgery and lymph node involvement ratio were independent predictors of overall survival in a multivariate analysis (adjusted rate ratio = 0.14; 95% confidence interval [95% CI], 0.04–0.46; P = 0.001 and adjusted rate ratio = 0.25; 95% CI, 0.12–0.53; P < 0.001, respectively). CONCLUSIONS Performing an oncologic surgery resulted in the best outcome in patients with nonmetastatic disease. Because cancer-directed surgery is associated with high morbidity and mortality in primary centers, these patients should be referred to a tertiary center for adequate treatment. Cancer 2004. © 2004 American Cancer Society.

Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma.

Abstract: BACKGROUND Research suggests that stress-reduction programs tailored to the cancer setting help patients cope with the effects of treatment and improve their quality of life. Yoga, an ancient Eastern science, incorporates stress-reduction techniques that include regulated breathing, visual imagery, and meditation as well as various postures. The authors examined the effects of the Tibetan yoga (TY) practices of Tsa lung and Trul khor, which incorporate controlled breathing and visualization, mindfulness techniques, and low-impact postures in patients with lymphoma. METHODS Thirty-nine patients with lymphoma who were undergoing treatment or who had concluded treatment within the past 12 months were assigned to a TY group or to a wait-list control group. Patients in the TY group participated in 7 weekly yoga sessions, and patients in the wait-list control group were free to participate in the TY program after the 3-month follow-up assessment. RESULTS Eighty nine percent of TY participants completed at least 2–3 three yoga sessions, and 58% completed at least 5 sessions. Patients in the TY group reported significantly lower sleep disturbance scores during follow-up compared with patients in the wait-list control group (5.8 vs. 8.1; P < 0.004). This included better subjective sleep quality (P < 0.02), faster sleep latency (P < 0.01), longer sleep duration (P < 0.03), and less use of sleep medications (P < 0.02). There were no significant differences between groups in terms of intrusion or avoidance, state anxiety, depression, or fatigue. CONCLUSIONS The participation rates suggested that a TY program is feasible for patients with cancer and that such a program significantly improves sleep-related outcomes. However, there were no significant differences between groups for the other outcomes. Cancer 2004. © 2004 American Cancer Society.

Incidence of chemotherapy-induced nausea and emesis after modern antiemetics

Abstract: BACKGROUND The authors determined the incidence of acute and delayed chemotherapy-induced nausea and emesis (vomiting) (CINV) among patients receiving highly (HEC) or moderately (MEC) emetogenic chemotherapy. They also assessed whether physicians and nurses accurately recognized the incidence of acute and delayed CINV in their own practices. METHODS A prospective, observational study of adult patients receiving HEC or MEC for the first time was performed. Before patient enrollment, medical oncologists and oncology nurses estimated the incidence of acute (Day 1) and delayed (Days 2–5) CINV after first administration of HEC and MEC in their own practices. Eligible patients from their practices then completed a 6-day diary including emetic episodes, nausea assessment, and antiemetic medication use. Observed incidence rates of acute and delayed CINV were compared with physician/nurse predictions. RESULTS Twenty-four physicians and nurses and 298 eligible patients (67 receiving HEC and 231 receiving MEC) were recruited from 14 oncology practices in 6 countries. Greater than 35% of patients overall experienced acute nausea, whereas 13% experienced acute emesis. Delayed nausea and emesis were observed in 60% and 50% of HEC patients, respectively, and in 52% and 28% of MEC patients, respectively. Delayed symptoms appeared without acute symptoms after HEC (emesis, 38%; nausea, 33%) and MEC (emesis, 19%; nausea, 21%). Physicians and nurses accurately predicted the incidence of acute CINV but underestimated the incidence of delayed nausea and emesis after HEC by 21 and 28 percentage points, respectively, and delayed nausea after MEC by 28 percentage points. Greater than 75% of physicians and nurses underestimated the incidence of delayed CINV after both HEC and MEC. CONCLUSIONS Physicians and nurses markedly underestimated the incidence of delayed nausea and emesis after both HEC and MEC. Delayed nausea and emesis, which may appear even in the absence of acute nausea and emesis, remain important targets for improved therapeutic intervention. Cancer 2004. © 2004 American Cancer Society.

Under use of necessary care among cancer survivors

Abstract: Comorbid conditions are the major threat to life for many cancer survivors, yet little is known about the quality of the noncancer-related health care they receive. The authors analyzed the Medicare claims of 14,884 Medicare-eligible, 5-year colorectal carcinoma survivors who were diagnosed initially while they lived in a region monitored by the Surveillance, Epidemiology, and End Results (SEER) Program and compared them with matched controls who had no history of cancer drawn from the Medicare 5% sample. In both univariable and multivariable analyses, cancer survivorship was associated with an increased likelihood of not receiving recommended care across a broad range of chronic medical conditions (odds ratio, 1.19, 95% confidence interval, 1.12-1.27). For example, colorectal carcinoma survivors were less likely than controls to receive appropriate follow-up for heart failure, necessary diabetic care, or recommended preventive services. Having both primary care physicians and oncologists involved in follow-up appeared to ameliorate this effect significantly. African-American, poor, and elderly patients were less likely to receive necessary care in both groups. Whether it was due to patient factors, physician factors, or both, cancer survivors appear to be a vulnerable patient population, because their cancer diagnosis may shift attention away from important noncancer problems and providers. In addition, there may be lack of clarity around the relative roles primary care and specialist physicians will play in a survivor's care. Special attention and education are needed to ensure that survivors receive optimal medical services.

Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey.

Abstract: BACKGROUND Advances in the diagnosis and surgical treatment of hepatocellular carcinoma (HCC) have improved the prognosis for patients with HCC who undergo liver resection. The objective of this study was to evaluate prognostic predictors for patients with HCC who underwent liver resection in a Japanese nationwide data base. METHODS In this study, the authors analyzed 12,118 patients with HCC in a Japanese nationwide data base who underwent liver resection between 1990 and 1999 and compared them with a previous analysis of patients between 1982 and 1989. All patients were evaluated for prognostic factors. RESULTS During the last decade, the increases in patients who were without hepatitis B virus surface antigen, who had small tumors, and who had portal vein invasion were noted. The 5-year overall survival rates for patients with HCC improved to 50.5%, compared with < 40% in the previous analysis. A multivariate analysis using a stratified Cox proportional hazards model according to associated liver disease indicated that age, degree of liver damage, α-fetoprotein level, maximal tumor dimension, number of tumors, intrahepatic extent of tumor, extrahepatic metastasis, portal vein invasion, hepatic vein invasion, surgical curability, and free surgical margins were independent prognostic predictors for patients with HCC. Operative mortality decreased from 2.3% in 1990–1991 to 0.6% in 1998–1999. CONCLUSIONS Outcomes and operative mortality rates in patients with HCC improved during the last decade. Age, degree of liver damage, α-fetoprotein level, maximal tumor dimension, number of tumors, intrahepatic extent of tumor, extrahepatic metastasis, portal vein invasion, hepatic vein invasion, surgical curability, and free surgical margins were prognostic factors for patients with HCC who underwent liver resection. Cancer 2004. © 2004 American Cancer Society.

Cervical adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for 1976-2000

Abstract: BACKGROUND Although cervical carcinoma incidence and mortality rates have declined in the U.S. greatly since the introduction of the Papanicolaou smear, this decline has not been uniform for all histologic subtypes. Therefore, the authors assessed the differential incidence rates of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the cervix by race and disease stage for the past 25 years. METHODS Data from nine population-based cancer registries participating in the U.S. Surveillance, Epidemiology, and End Results (SEER) Program were used to compute incidence rates for cervical carcinoma diagnosed during 1976–2000 by histologic subtype (SCC and AC), race (black and white), age, and disease stage (in situ, localized, regional, or distant). RESULTS In black women and white women, the overall incidence of invasive SCC declined over time, and the majority of tumors that are detected currently are in situ and localized carcinomas in young women. The incidence of in situ SCC increased sharply in the early 1990s. AC in situ (AIS) incidence rates increased, especially among young women. In black women, invasive AC incidence rose linearly with age. CONCLUSIONS Changes in screening, endocervical sampling, nomenclature, and improvements in treatment likely explain the increased in situ cervical SCC incidence in white women and black women. Increasing AIS incidence over the past 20 years in white women has not yet translated into a decrease in invasive AC incidence. Etiologic factors may explain the rising invasive cervical AC incidence in young white women; rising cervical AC incidence with age in black women may reflect either lack of effective screening or a differential disease etiology. Cancer 2004;100:1035–44. © 2004 American Cancer Society.

Preferential brain locations of low-grade gliomas.

Abstract: BACKGROUND The objectives of this study were to register the brain locations in a consecutive series of low-grade gliomas (LGGs) and compare these localizations with the locations of de novo glioblastomas (GBMs) that were collected during the same period in an effort to analyze whether LGGs are situated in preferential areas and to review the pathophysiologic hypothesis of such a phenomenon. METHODS One hundred thirty-two patients with LGG and 102 patients with GBM who were followed consecutively between 1996 and 2003 by the authors were reviewed, whatever their treatment. Using anatomic, three-dimensional magnetic resonance imaging, the location of each tumor was analyzed accurately according to a classification system based on the proximity of eloquent areas previously reported by the authors. RESULTS One hundred nine LGGs (82.6%), compared with 55 GBMs (53.9%), were situated within functional regions (P < 0.001). More specifically, 36 LGGs (27.3%), compared with 11 GBMs (10.8%), were localized in the region of the supplementary motor area (SMA) (P < 0.001); and 33 LGGs (25%), compared with 11 GBMs (10.8%), were located within the insula (P < 0.001). CONCLUSIONS The current findings suggest that LGGs are located preferentially in “secondary” functional areas (immediately near the so-called primary eloquent regions), especially within the SMA and the insular lobe. This preferential localization may be explained by developmental, cytomyeloarchitectonic, neurochemical, metabolic, and functional reasons. A better knowledge of the pathophysiologic mechanisms underlying preferential LGGs locations may improve understanding of the genesis and natural history of these tumors and, subsequently, their management. Cancer 2004. © 2004 American Cancer Society.

Squamous cell carcinoma in situ at oropharyngeal and hypopharyngeal mucosal sites

Abstract: BACKGROUND Head and neck squamous cell carcinoma typically is diagnosed at an advanced stage, and the prognosis for patients with this type of malignancy is poor. Detection of these lesions at an earlier stage (e.g., as carcinoma in situ) would be of clear benefit to patients. However, it has been extremely difficult to detect carcinoma in situ at head and neck mucosal sites during routine endoscopy, even after numerous passes of the endoscope through the oral cavity and the pharynx. METHODS The current clinical investigation was performed during routine endoscopic screening or surveillance procedures. The authors used a novel optical technique, known as narrowband imaging (NBI) that allows noninvasive visualization of the microvascular structure of an organ's surface using reflected light. RESULTS Between April 2002 and August 2003, 34 consecutive superficial lesions were found in 18 patients. Multifocal carcinoma was found in 5 patients (28%). The median age of the patients examined was 59.5 years (range, 43–71 years), and 83% of all patients were male. All lesions exhibited a microvascular proliferation pattern on magnified NBI. Thirteen patients with a combined total of 29 lesions underwent endoscopic resection under general anesthesia. The pyriform sinus was the most frequent primary site (66%; 19 of 29 lesions). The median tumor diameter was 20 mm (range, 1.3–40 mm). Twenty-one lesions (72%) were histologically confirmed to be carcinoma in situ, and the remaining lesions showed evidence of microinvasion (0.05–1 mm) beneath the epithelium. Vascular invasion was observed in only one lesion. The median hospital stay was 10 days (range, 4–18 days). All patients were discharged without severe complications. After a median follow-up period of 8 months (range, 1–16 months), there were no cases of local disease recurrence. CONCLUSION The authors stress the importance of endoscopic detection of superficial carcinoma at oropharyngeal and hypopharyngeal mucosal sites. NBI is a promising and potentially powerful tool for identifying carcinomas at an earlier stage during routine endoscopic examination. Cancer 2004. © 2004 American Cancer Society.

Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution.

Abstract: BACKGROUND The optimal treatment strategy for synovial sarcoma (SS) is subject to debate, and different strategies have been used for pediatric and adult patients. The current retrospective analysis examined a large group of patients of all ages who were treated at a single institution over a 30-year period. METHODS The study included 271 patients who ranged in age from 5 years to 87 years; 255 had localized disease, which was macroscopically resected in 215 cases and deemed unresectable at diagnosis in 40 cases. Chemotherapy was administered to 41% of patients, corresponding to 76% of patients age ≤ 16 years and < 20% of older patients; 28% of patients with macroscopically resected disease received chemotherapy on an adjuvant basis. RESULTS The 5-year event-free survival rate for the study cohort as a whole was 37%, although this rate varied with age (66%, 40%, and 31% for patients age ≤ 16 years, 17–30 years, and > 30 years, respectively). Chemotherapy was used more commonly for children than for adults. Among patients with surgically resected disease, the 5-year metastasis-free survival (MFS) rate was 60% for those who were treated with chemotherapy and 48% for those who were not; the benefit associated with chemotherapy use appeared to be greatest for patients age ≥ 17 years who had tumors measuring > 5 cm (MFS, 47% [chemotherapy] vs. 27% [no chemotherapy]). In the subgroup of patients with measurable disease, the rate of tumor response to chemotherapy was approximately 48%. CONCLUSIONS Although the authors await more convincing proof of the efficacy of adjuvant chemotherapy in the treatment of adult soft tissue sarcoma, they recommend that patients with high-risk SS (tumor size > 5 cm) be the first to be considered for this type of treatment. Cancer 2004. © 2004 American Cancer Society.

Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion

Abstract: BACKGROUND Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial. METHODS Overall, 1130 patients with breast carcinoma who had all types of bone metastases (osteolytic, mixed, or osteoblastic by radiology) were randomized to receive treatment with either 4 mg of Zol or 8 mg of Zol as a 15-minute infusion or 90 mg of Pam as a 2-hour infusion every 3–4 weeks for 12 months. A skeletal-related event (SRE) was defined as a pathologic fracture, spinal cord compression, radiotherapy, or surgery to bone. RESULTS Among all patients with BC, the proportion of those who had an SRE (primary endpoint) was comparable between treatment groups (43% of patients who received 4 mg of Zol vs. 45% of patients who received Pam). Among patients who had breast carcinoma with at least 1 osteolytic lesion (n = 528 patients), the proportion with an SRE was lower in the 4-mg Zol group compared with the Pam group (48% vs. 58%), but this did not reach statistical significance (P = 0.058). The time to first SRE was significantly longer in the 4-mg Zol group compared with the Pam group (median, 310 vs. 174 days; P = 0.013). Moreover, multiple-event analysis demonstrated significant further reductions in the risk of developing SREs over the reduction achieved with Pam (30% in the osteolytic subset [P = 0.010] and 20% for all patients with BC [P = 0.037]). CONCLUSIONS The current data indicate that treatment with 4 mg of Zol was more effective than 90 mg of Pam in reducing skeletal complications in a subset of patients with breast carcinoma who had at least 1 osteolytic lesion at study entry. Cancer 2004;100:36–43. © 2003 American Cancer Society.

Early-stage cervical carcinoma, radical hysterectomy, and sexual function. A longitudinal study.

Abstract: BACKGROUND Limited knowledge exists concerning the impact of radical hysterectomy (RH) alone on the sexual function of patients with early-stage cervical carcinoma. The authors investigated the longitudinal course of self-reported sexual function after RH. METHODS The current study was comprised of 173 patients with lymph node-negative, early-stage cervical carcinoma who had undergone RH and pelvic lymphadenectomy. They were assessed prospectively using a validated self-assessment questionnaire 5 weeks and 3 months, 6 months, 12 months, 18 months, and 24 months after RH. Results were compared with an age-matched control group from the general population. RESULTS Compared with control women, patients experienced severe orgasmic problems and uncomfortable sexual intercourse due to a reduced vaginal size during the first 6 months after RH, severe dyspareunia during the first 3 months, and sexual dissatisfaction during the 5 weeks after RH. A persistent lack of sexual interest and lubrication were reported throughout the first 2 years after RH. Long-term lack of sexual interest and insufficient vaginal lubrication were confirmed by the patient's self-reported changes 12 months after RH compared with before the cancer diagnosis and by a pre-post comparison within patients. However, most of the patients who were sexually active before their cancer diagnosis were sexually active again 12 months after surgery (91%), although with a decrease in sexual frequency reported. CONCLUSIONS RH had a persistent and negative impact on patients' sexual interest and vaginal lubrication whereas the majority of other sexual and vaginal problems disappeared over time. Sexual and vaginal problems in the short-term and long-term after RH should be discussed with the patient before and after surgery. Cancer 2004;100:97–106. © 2003 American Cancer Society.

Persistent area socioeconomic disparities in U.S. incidence of cervical cancer, mortality, stage, and survival, 1975-2000.

Abstract: BACKGROUND Temporal cervical cancer incidence and mortality patterns and ethnic disparities in patient survival and stage at diagnosis in relation to socioeconomic deprivation measures have not been well studied in the United States. The current article analyzed temporal area socioeconomic inequalities in U.S. cervical cancer incidence, mortality, stage, and survival. METHODS County and census tract poverty and education variables from the 1990 census were linked to U.S. mortality and Surveillance, Epidemiology, and End Results cancer incidence data from 1975 to 2000. Age-adjusted incidence and mortality rates and 5-year cause-specific survival rates were calculated for each socioeconomic group and differences in rates were tested for statistical significance at the 0.05 level. RESULTS Substantial area socioeconomic gradients in both incidence and mortality were observed, with inequalities in cervical cancer persisting against a backdrop of declining rates. Cervical cancer incidence and mortality rates increased with increasing poverty and decreasing education levels for the total population as well as for non-Hispanic white, black, American Indian, Asian/Pacific Islander, and Hispanic women. Patients in lower socioeconomic census tracts had significantly higher rates of late-stage cancer diagnosis and lower rates of cancer survival. Even after controlling for stage, significant differences in survival remained. The 5-year survival rate among women diagnosed with distant-stage cervical cancer was approximately 30% lower in low than in high socioeconomic census tracts. CONCLUSIONS Census-based socioeconomic measures such as area poverty and education levels could serve as important surveillance tools for monitoring temporal trends in cancer-related health inequalities and targeting interventions. Cancer 2004. Published 2004 by the American Cancer Society.