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Showing papers in "Cancer in 2011"


Journal ArticleDOI
15 Jan 2011-Cancer
TL;DR: In vitro data indicate that the combination of capecitabine and temozolomide is synergistic for induction of apoptosis in neuroendocrine tumor cell lines.
Abstract: BACKGROUND Temozolomide is an active agent in metastatic pancreatic endocrine carcinomas. In vitro data indicate that the combination of capecitabine and temozolomide is synergistic for induction of apoptosis in neuroendocrine tumor cell lines. The authors retrospectively evaluated the efficacy of capecitabine and temozolomide in 30 patients with metastatic pancreatic endocrine carcinomas to assess response rate, progression free survival (PFS), and overall survival (OS).

666 citations


Journal ArticleDOI
15 Oct 2011-Cancer
TL;DR: This study investigates whether BRAF mutant CRC is further defined by a distinct pattern of metastatic spread and explores the impact of BRAF mutation and microsatellite instability (MSI) on prognosis in metastatic CRC.
Abstract: BACKGROUND: It is hypothesized that BRAF mutant cancers represent a discrete subset of metastatic colorectal cancer (CRC) defined by poorer survival. This study investigates whether BRAF mutant CRC is further defined by a distinct pattern of metastatic spread and explores the impact of BRAF mutation and microsatellite instability (MSI) on prognosis in metastatic CRC. METHODS: By using prospective clinical data and molecular analyses from 2 major centers (Royal Melbourne Hospital and The University of Texas MD Anderson Cancer Center), patients with known BRAF mutation status were analyzed for clinical characteristics, survival, and metastatic sites. RESULTS: The authors identified 524 metastatic CRC patients where BRAF mutation status was known; 57 (11%) were BRAF mutant tumors. BRAF mutant tumors were significantly associated with right-sided primary tumor, MSI, and poorer survival (median, 10.4 months vs 34.7 months, P < .001). A distinct pattern of metastatic spread was observed in BRAF mutant tumors, namely higher rates of peritoneal metastases (46% vs 24%, P = .001), distant lymph node metastases (53% vs 38%, P = .008), and lower rates of lung metastases (35% vs 49%, P = .049). In additional survival analyses, MSI tumors had significantly poorer survival compared with microsatellite stable tumors (22.1 months vs 11.1 months, P = .017), but this difference was not evident in the BRAF mutant population. CONCLUSIONS: The pattern of metastatic spread observed in this study further defines BRAF mutant CRC as a discrete disease subset. The authors demonstrated that, unlikely early stage disease, MSI is associated with poorer survival in metastatic CRC, although this is driven by its association with BRAF mutation. Cancer 2011;. © 2011 American Cancer Society.

616 citations


Journal ArticleDOI
15 Jan 2011-Cancer
TL;DR: There is an overview of available evidence for optimal use of Erwinia asparaginase in the treatment of ALL and debate on the optimal formulation and dosage of these agents continues.
Abstract: Asparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive asparaginase treatment improves clinical outcomes in childhood ALL. Three asparaginase preparations are available: the native asparaginase derived from Escherichia coli (E. coli asparaginase), a pegylated form of this enzyme (PEG-asparaginase), and a product isolated from Erwinia chrysanthemi, ie, Erwinia asparaginase. Clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli asparaginase, lead to inactivation of E. coli asparaginase in up to 60% of cases. Current treatment protocols include E. coli asparaginase or PEG-asparaginase for first-line treatment of ALL. Typically, patients exhibiting sensitivity to one formulation of asparaginase are switched to another to ensure they receive the most efficacious treatment regimen possible. Erwinia asparaginase is used as a second- or third-line treatment in European and US protocols. Despite the universal inclusion of asparaginase in such treatment protocols, debate on the optimal formulation and dosage of these agents continues. This article provides an overview of available evidence for optimal use of Erwinia asparaginase in the treatment of ALL.

486 citations


Journal ArticleDOI
15 Apr 2011-Cancer
TL;DR: The outcomes of advanced melanoma patients who developed brain metastases were reviewed to identify significant prognostic factors for overall survival (OS).
Abstract: BACKGROUND: One of the most common and deadly complications of melanoma is brain metastases. The outcomes of advanced melanoma patients who developed brain metastases were reviewed to identify significant prognostic factors for overall survival (OS). METHODS: An institutional database of advanced melanoma patients enrolled on clinical trials in the Department of Melanoma Medical Oncology from 1986 to 2004 was reviewed and patients who developed brain metastases were identified. Date of diagnosis, patient age, pattern of brain involvement, timing relative to extracranial metastases, prior response to systemic therapy, and treatments given for brain metastases were assessed as potential prognostic factors for OS. RESULTS: Among 743 melanoma patients enrolled in clinical trials for regional or systemic metastatic disease, 330 (44%) patients developed brain metastases. The median OS after the diagnosis of brain metastases was 4.7 months. Diagnosis before 1996, increased number of parenchymal brain metastases, leptomeningeal involvement, and development of brain metastases after receiving systemic therapy for extracranial metastases were found to be significant prognostic factors for OS. Among patients who received systemic therapy as the initial treatment of brain metastases, patients who previously responded to systemic therapies had longer survival than patients who had not responded. CONCLUSIONS: The era, pattern, and timing of melanoma brain metastases were found to be strongly associated with survival. Previous responsiveness to systemic therapies did not predict better outcomes overall, but it did correlate with improved survival for patients with brain metastases who were treated with systemic therapies. These factors may be used in guiding patient management and for stratifying patients in clinical trials. Cancer 2011. © 2010 American Cancer Society.

447 citations


Journal ArticleDOI
15 May 2011-Cancer
TL;DR: Psychosocial and behavioral interventions for young adult cancer patients and survivors often involve assisting these individuals in retaining or returning to function in significant social roles, such as spouse, parent, student, worker, or friend.
Abstract: Theories of human development suggest that, although all cancer patients experience a common set of life disruptions, they experience them differently, focus on different issues, and attach different levels of importance to different aspects of the experience depending on the time in life at which they were diagnosed. During the critical developmental transition from childhood to adulthood, older adolescents and young adults in particular have typical concerns with establishing identity, developing a positive body image and sexual identity, separating from parents, increasing involvement with peers and dating, and beginning to make decisions about careers or employment, higher education, and/or family. Accordingly, cancer-related issues such as premature confrontation with mortality, changes in physical appearance, increased dependence on parents, disruptions in social life and school/employment because of treatment, loss of reproductive capacity, and health-related concerns about the future may be particularly distressing for adolescents and young adults. Psychosocial and behavioral interventions for young adult cancer patients and survivors often involve assisting these individuals in retaining or returning to function in significant social roles, such as spouse, parent, student, worker, or friend. Successful interventions will enable these young people to overcome the detrimental impact of a health crisis and strengthen the internal and external coping resources available to them.

391 citations


Journal ArticleDOI
01 Aug 2011-Cancer
TL;DR: There is a disconnect between the nation’s discovery and delivery enterprises, suggesting that some Americans have not shared sufficiently in this progress as measured by higher mortality, lower survival, and 5-year cancer survival.
Abstract: In 1971 President Richard Nixon declared a war on cancer and signed the National Cancer Act. During the past several decades since this declaration, the nation has made extraordinary progress toward a far better understanding of the molecular, cellular, and genetic changes resulting in cancer. We have also seen significant declines in overall and site-specific cancer mortality1. This decline in mortality has been attributed to improved cancer prevention, screening, and detection measures as well as the application of more effective and more targeted cancer treatments. However, some Americans (such as the poor, uninsured, and underinsured) have not shared sufficiently in this progress as measured by higher mortality, lower survival, and 5-year cancer survival2, 3. These findings suggest that there is a disconnect between the nation’s discovery and delivery enterprises; a disconnect between what we know and what we do (Fig 1). Figure 1 Discovery-Delivery Disconnect Disparities occur when beneficial medical interventions are not shared by all. Moreover, health disparities arise from a complex interplay of economic, social, and cultural factors. The model presented in (Fig. 2) illustrates the overlapping factors of poverty, culture, and social injustice as principal causes of health disparities. These causal factors impact on all aspects of the healthcare continuum from prevention, detection, diagnosis, treatment, and survival to the end of life. Disparities occur principally in individuals or populations who experience one or more of the following circumstances: insufficient resources, risk-promoting lifestyle and behavior, and social inequities. Approaches to reducing or eliminating disparities must necessarily take these factors into consideration. Figure 2 Causes of Health Disparities

374 citations


Journal ArticleDOI
01 Aug 2011-Cancer
TL;DR: The unique role that patient navigation can play in improving health outcomes for racial and ethnic minorities, as well as other underserved populations, in the context of a changing healthcare environment is explored.
Abstract: Despite many important efforts to increase equity in the US health care system, not all Americans have equal access to health care—or similar health outcomes. With the goal of lowering costs and increasing accessibility to health care, the nation's new health care reform legislation includes certain provisions that expand health insurance coverage to uninsured and underinsured populations, promote medical homes, and support coordination of care. These provisions may help narrow existing health care disparities. Many of the most vulnerable patients, however, may continue to have difficulty accessing and navigating the complex US health care delivery system. This article explores the unique role that patient navigation can play in improving health outcomes for racial and ethnic minorities, as well as other underserved populations, in the context of a changing healthcare environment. Patient navigators can not only facilitate improved health care access and quality for underserved populations through advocacy and care coordination, but they can also address deep-rooted issues related to distrust in providers and the health system that often lead to avoidance of health problems and non-compliance with treatment recommendations. By addressing many of the disparities associated with language and cultural differences and barriers, patient navigators can foster trust and empowerment within the communities they serve. Specific patient navigator activities are discussed, and metrics to evaluate program efforts are presented. Cancer 2011;117(15 suppl):3541–50. © 2011 American Cancer Society.

352 citations


Journal ArticleDOI
15 Nov 2011-Cancer
TL;DR: The authors aimed to develop a similar postsurgical score with improved accuracy via incorporation of pathologic data to predict prostate cancer recurrence based on pretreatment clinical data.
Abstract: BACKGROUND: The authors previously developed and validated the Cancer of the Prostate Risk Assessment (CAPRA) score to predict prostate cancer recurrence based on pretreatment clinical data. They aimed to develop a similar postsurgical score with improved accuracy via incorporation of pathologic data. METHODS: A total of 3837 prostatectomy patients in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE™) national disease registry were analyzed. Cox regression was used to determine the predictive power of preoperative prostate-specific antigen (PSA), pathologic Gleason score (pGS), surgical margins (SM), extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node invasion (LNI). Points were assigned based on the relative weights of these variables in predicting recurrence. The new postsurgical score (CAPRA-S) was tested and compared with a commonly cited nomogram with proportional hazards analysis, concordance (c) index, calibration plots, and decision-curve analysis. RESULTS: Recurrence appeared in 16.8% of the men; actuarial progression-free probability at 5 years was 78.0%. The CAPRA-S was determined by adding up to 3 points for PSA, up to 3 points for pGS, 1 point each for ECE and LNI, and 2 points each for SM and SVI. The hazard ratio for each point increase in CAPRA-S score was 1.54 (95% confidence interval, 1.49-1.59), indicating a 2.4-fold increase in risk for each 2-point increase in score. The CAPRA-S c-index was 0.77, substantially higher than 0.66 for the pretreatment CAPRA score and comparable to 0.76 for the nomogram. The CAPRA-S score performed better in both calibration and decision curve analyses. CONCLUSIONS: The CAPRA-S offers good discriminatory accuracy, calibration, and ease of calculation for clinical and research settings. Cancer 2011;. © 2011 American Cancer Society.

350 citations


Journal ArticleDOI
01 Jul 2011-Cancer
TL;DR: The authors report the survival of patients who underwent complete metastasectomy for multiple RCC metastases and the utility of surgery in patients with multiple sites of disease.
Abstract: BACKGROUND: Although a role for resection of solitary metastases from renal cell carcinoma (RCC) has been described, the utility of surgery in patients with multiple sites of disease has been less well defined The authors report the survival of patients who underwent complete metastasectomy for multiple RCC metastases METHODS: The authors identified 887 patients who underwent nephrectomy for RCC between 1976 and 2006 who developed multiple metastatic lesions The impact of complete metastasectomy on survival was evaluated controlling for the timing, location, and number of metastases and for patient performance status RESULTS: Of 887 patients, 125 (14%) underwent complete surgical resection of all metastases Complete metastasectomy was associated with a significant prolongation of median cancer-specific survival (CSS) (48 years vs 13 years; P < 001) Patients who had lung-only metastases had a 5-year CSS rate of 736% with complete resection versus 19% without complete resection (P < 001) A survival advantage from complete metastasectomy also was observed among patients with multiple, nonlung-only metastases, who had a 5-year CSS rate of 325% with complete resection versus 124% without complete resection (P < 001) Complete resection remained predictive of improved CSS for patients who had ≥3 metastatic lesions (P < 001) and for patients who had synchronous (P < 001) and asynchronous (P = 002) multiple metastases Moreover, on multivariate analysis, the absence of complete metastasectomy was associated significantly with an increased risk of death from RCC (hazard ratio, 291; 95% confidence interval, 217-390; P < 001) CONCLUSIONS: The current results indicated that complete resection of multiple RCC metastases may be associated with long-term survival and should be considered when technically feasible in appropriate surgical candidates Cancer 2011 © 2011 American Cancer Society

338 citations


Journal ArticleDOI
01 Oct 2011-Cancer
TL;DR: The objective of this study was to further elucidate the clinical course and prognostic determinants of patients with hepatocellular carcinoma who have extrahepatic metastasis.
Abstract: BACKGROUND: Despite significant advances in the treatment of intrahepatic lesions, the prognosis for patients with hepatocellular carcinoma (HCC) who have extrahepatic metastasis remains poor. The objective of this study was to further elucidate the clinical course and prognostic determinants of patients with this disease. METHODS: In total, 342 patients who had HCC with extrahepatic metastasis were enrolled. The metastases were diagnosed at initial presentation with HCC in 28 patients and during follow-up in the remaining patients. The authors analyzed clinical features, prognoses, and treatments and established a scoring system to predict prognosis using a split-sample method with a testing set and a training set. RESULTS: The most frequent site of extrahepatic metastasis was the lung followed by lymph nodes, bone, and adrenal glands. These metastases were related directly to death in only 23 patients (7.6%). The median survival after diagnosis of extrahepatic metastasis was 8.1 months (range, 0.03-108.7 months). In univariate analysis of the training set (n = 171), performance status, Child-Pugh classification, the number and size of intrahepatic lesions, macroscopic vascular invasion, symptomatic extrahepatic metastases, α-fetoprotein levels, and complete responses to treatment were associated significantly with prognosis. On the basis of multivariate analysis, a scoring system was developed to predict prognosis that assessed uncontrollable intrahepatic lesions, extent of vascular invasion, and performance status. This scoring system was validated in the testing set (n = 171) and produced a concordance index of 0.73. CONCLUSIONS: The controllability of intrahepatic lesions and performance status were identified as important prognostic factors in patients with advanced HCC who had extrahepatic metastasis. Cancer 2011. © 2011 American Cancer Society.

329 citations


Journal ArticleDOI
15 Nov 2011-Cancer
TL;DR: There is a need to develop novel therapies for relapsed/refractory diffuse large B‐cell lymphoma (DLBCL) and to identify biomarkers predictive for therapeutic response and it is currently unknown if response rates differ between patients with different DLBCL subtypes.
Abstract: BACKGROUND: There is a need to develop novel therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and to identify biomarkers predictive for therapeutic response. Lenalidomide was previously shown to induce an overall response rate (ORR) of 28% in patients with relapsed/refractory DLBCL. It is currently unknown if response rates differ between patients with different DLBCL subtypes. METHODS: The authors retrospectively evaluated clinical outcomes of patients with germinal center B-cell–like versus nongerminal center B-cell–like DLBCL treated with salvage lenalidomide at 4 academic institutions. RESULTS: Forty patients with relapsed/refractory DLBCL were included (24 men; 16 women; median age, 66 years; median of 4 prior treatments, including rituximab chemotherapy). Patients were classified as germinal center B-cell–like (n = 23) or nongerminal center B-cell–like (n = 17) DLBCL according to the Hans algorithm. The subgroups were similar in terms of stage, international prognostic index score, prior number of treatments, and rituximab resistance. A significant difference in clinical response to lenalidomide was observed in nongerminal center B-cell–like versus germinal center B-cell–like patients. ORR was 52.9% versus 8.7% (P = .006); complete response rate was 23.5% versus 4.3%. Median progression-free survival was 6.2 versus 1.7 months (P = .004), although no difference in OS was observed between nongerminal center B-cell–like and germinal center B-cell–like DLBCL patients. CONCLUSIONS: The data suggest that the 2 major subgroups of patients with DLBCL (germinal center B cell and nongerminal center B cell) have different antitumor responsiveness to lenalidomide in the relapsed/refractory setting. A large international trial (NCT01197560) has been opened to enrollment in an attempt to prospectively validate these retrospective observations. Cancer 2011;. © 2011 American Cancer Society.

Journal ArticleDOI
01 Oct 2011-Cancer
TL;DR: Evaluated patterns of RAI use and elevated risk of secondary primary malignancies (SPM) in patients with low‐risk (T1N0) WDTC.
Abstract: The incidence of well differentiated thyroid cancers (WDTC) has increased substantially over the past 3 decades, and an estimated 37,200 cases were diagnosed in the United States in 2009. The majority of the increase is attributable to small (<2 cm) tumors (T1), a trend that has been ascribed mainly to improved detection of subclinical disease.1 The clinical relevance of these tumors is the subject of much debate, because a high prevalence of incidental microcarcinomas has been reported in autopsy series.2 Furthermore, the increased incidence in WDTC has not been associated with a concurrent increase in thyroid cancer mortality, suggesting that much of the disease being detected may be clinically insignificant. Despite the indolent nature of small WDTCs, few clinicians are willing to conservatively manage these malignancies. Treatment usually comprises thyroidectomy, and, when indicated, adjuvant radioactive iodine (RAI) therapy. Decision-making regarding the extent of surgery remains a subject of debate, reflecting a lack of high-quality data to support management decisions. Similar levels of controversy exist regarding the role of adjuvant RAI therapy. The administration of adjuvant RAI has 2 main objectives: first, to ablate occult microscopic foci of WDTC, reducing the risk of tumor recurrence, and, second, to ablate any remaining normal thyroid tissue, thereby facilitating surveillance with serum thyroglobulin or radioiodine whole-body scintigraphy.3 On the basis of these objectives, the decision to use RAI depends on the risk of the original thyroid cancer and the completeness of surgery in removing malignant and normal thyroid tissue. Most studies report little benefit from RAI in low-risk patients.4,5 Even in intermediate-risk patients, RAI administration confers only minor benefit in reducing the risk of recurrence or death.6 Existing guidelines from the American Thyroid Association (ATA) cite these factors.7 Notwithstanding available data and guidelines, there is widespread use of RAI in patients who have a low risk of recurrence. The decision to treat patients with RAI should be undertaken carefully. Although the side-effect profile is superior to those of other commonly used adjuvant modalities, such as external-beam radiation or cytotoxic chemotherapy, currently, there are ample data to suggest that RAI is not altogether benign.8,9 Complications range from relatively minor salivary gland dysfunction (short-term and long-term) to more serious but rare complications, such as myelosuppression and aplastic anemia.10 Furthermore, several studies have documented an increase in the incidence of second primary malignancies (SPM) in organs known to concentrate RAI.11-14 In 1 of those studies, the authors established a clear-cut dose-dependent effect, which implies causality.13 However, those analyses included patients with locally advanced and/or metastatic disease, who have few effective options apart from RAI therapy. In fact, there is no debate on the utility of RAI for patients who fall into the high-risk group, such as patients with gross extrathyroid extension or distant metastases, for whom the risk-benefit ratio favors RAI.7 However, the risk-benefit ratio may be far less favorable in low-risk patients. To our knowledge, there are no reports specifically focusing on the risk of SPM after RAI in patients with low-risk WDTC. Because this is the cohort of patients that now forms the majority of thyroid cancer cases, it is important to comprehensively define the risk of SPM caused by RAI in these patients. Therefore, the objectives of the current study were to report the use patterns of adjuvant RAI in patients with low-risk WDTC over time using a population-based registry, to determine the excess risk of SPM in the same cohort of patients, and to determine whether there is any correlation between SPM incidence and trends in RAI use.

Journal ArticleDOI
01 Aug 2011-Cancer
TL;DR: A recent proposal for a tumor‐node‐metastasis (TNM) classification and a grading system based on the proliferative fraction proved valid in NETs of foregut origin.
Abstract: BACKGROUND: Prognostic classification of neuroendocrine tumor (NET) patients is difficult due to the complexity of current classification systems. A recent proposal for a tumor-node-metastasis (TNM) classification and a grading system based on the proliferative fraction proved valid in NETs of foregut origin. The purpose of this study was to test the efficacy of a proposal for TNM staging and grading for midgut and hindgut NETs. METHODS: Two hundred seventy patients with histologically proven midgut and hindgut NETs were investigated. Epidemiological, clinicopathological, and tumor-specific data at initial diagnosis were recorded. Tumors were classified according to the World Health Organization (WHO) and the recent European Neuroendocrine Tumor Society-TNM staging and grading proposal. Survival analysis and statistical testing for independent prognostic factors were performed using log-rank tests and Cox regression. RESULTS: Of 270 NETs originating in the midgut or hindgut, 7% (5-year survival rate [YSR], 100%) were stage 1, 8% (5-YSR, 100%) were stage 2, 19% (5-YSR, 89.5%) were stage 3, and 66% (5-YSR, 83.3%) were stage 4 NETs; 62% (5-YSR 95.2%) were grade 1, 32% (5-YSR 82.0%) were grade 2, and 6% (5-YSR, 51.4%) were grade 3 NETs. WHO classification significantly separated poorly from well-differentiated NET or carcinomas but did not further discriminate. TNM staging significantly separated stages 1, 2, and 3 from stage 4 NETs, as did grading according to proliferative capacity for all grades. Multivariate analysis confirmed these results, particularly for Ki67 grading. CONCLUSIONS: The acquired data confirmed the prognostic relevance of the proposed TNM staging and grading system and demonstrated the applicability of these classification tools. The TNM system can therefore facilitate therapeutic stratification and comparison of data from different institutions. Cancer 2011. © 2011 American Cancer Society.

Journal ArticleDOI
01 Jul 2011-Cancer
TL;DR: The long‐term survival of patients with high‐risk prostate cancer was compared after radical prostatectomy and after external beam radiation therapy (EBRT) with or without adjuvant androgen‐deprivation therapy (ADT).
Abstract: BACKGROUND: The long-term survival of patients with high-risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen-deprivation therapy (ADT). METHODS: In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate-specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow-up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer-specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk-regression model. RESULTS: The 10-year cancer-specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51-1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68-1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all-cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25-2.05; P = .0002). CONCLUSIONS: RRP alone and EBRT plus ADT provided similar long-term cancer control for patients with high-risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality-of-life and noncancer mortality will be necessary to determine the optimal management approach for these patients. Cancer 2011. © 2011 American Cancer Society.

Journal ArticleDOI
01 Sep 2011-Cancer
TL;DR: This study was undertaken to determine outcomes of stereotactic body radiotherapy for colorectal liver metastases in a pooled patient cohort.
Abstract: BACKGROUND: This study was undertaken to determine outcomes of stereotactic body radiotherapy for colorectal liver metastases in a pooled patient cohort. METHODS: Patients with colorectal liver metastases from 3 institutions were included if they had 1 to 4 lesions, received 1 to 6 fractions of stereotactic body radiotherapy, and had radiologic imaging ≥3 months post-treatment. Sixty-five patients with 102 lesions treated from August 2003 to May 2009 were retrospectively analyzed. A tumor control probability (TCP) model was used to estimate the 3-fraction dose required for >90% local control after converting the schedule into biologically equivalent dose (BED), single-fraction equivalent dose, or linear quadratic model-based single-fraction dose. RESULTS: Forty-seven (72%) patients had ≥1 chemotherapy regimen before stereotactic body radiotherapy, and 27 (42%) patients had ≥2 regimens. The median follow-up was 1.2 years (range, 0.3-5.2 years). The median dose was 42 gray (Gy; range, 22-60 Gy). When evaluated separately by multivariate analysis, total dose (P = .0015), dose/fraction (P = .003), and BED (P = .004) all correlated with local control by lesion. On multivariate analysis, nonactive extrahepatic disease was associated with overall survival (OS; P = .046), and sustained local control was closely correlated (P = .06). By using single-fraction equivalent dose, BED, or linear quadratic model-based single-fraction dose in the TCP model, the estimated dose range needed for 1-year local control >90% is 46 to 52 Gy in 3 fractions. CONCLUSIONS: Liver stereotactic body radiotherapy is well tolerated and effective for colorectal liver metastases. The strong correlation between local control and OS supports controlling hepatic disease even for heavily pretreated patients. For a 3-fraction regimen of stereotactic body radiotherapy, a prescription dose of ≥48 Gy should be considered, if normal tissue constraints allow. Cancer 2011. © 2011 American Cancer Society.

Journal ArticleDOI
15 May 2011-Cancer
TL;DR: Critical elements of effective AYA psychosocial services should include access to AYA‐specific information and support resources, fertility and sexuality counseling, programs to maximize academic and vocational functioning, and financial support.
Abstract: To deliver developmentally appropriate psychosocial care, the key developmental tasks facing adolescents and young adults (AYA) need to be taken into consideration. These include establishing autonomy from parents; a personal set of values and identity; strong peer relationships, including intimate and sexual relationships; and obtaining adequate preparation to join the workforce. To minimize the amount of disruption caused by the cancer experience and to maximize the health-related quality of life of AYA patients, young individuals with cancer need opportunities to participate as much as possible in typical AYA activities and to master the developmental tasks of this life stage. Promoting a sense of normalcy is essential. To achieve this, the health care environment must be flexible and recognize the important role of peers. Informational and practical supports also are necessary for AYA to stay on track developmentally in the context of coping with cancer. Critical elements of effective AYA psychosocial services should include access to AYA-specific information and support resources, fertility and sexuality counseling, programs to maximize academic and vocational functioning, and financial support.

Journal ArticleDOI
01 Dec 2011-Cancer
TL;DR: Although spiritual care is associated with less aggressive medical care at the end of life (EOL), it remains infrequent and it is unclear if the omission of spiritual care impacts EOL costs.
Abstract: BACKGROUND: Although spiritual care is associated with less aggressive medical care at the end of life (EOL), it remains infrequent. It is unclear if the omission of spiritual care impacts EOL costs. METHODS: A prospective, multisite study of 339 advanced cancer patients accrued subjects from September 2002 to August 2007 from an outpatient setting and followed them until death. Spiritual care was measured by patients' reports that the health care team supported their religious/spiritual needs. EOL costs in the last week were compared among patients reporting that their spiritual needs were inadequately supported versus those who reported that their needs were well supported. Analyses were adjusted for confounders (eg, EOL discussions). RESULTS: Patients reporting that their religious/spiritual needs were inadequately supported by clinic staff were less likely to receive a week or more of hospice (54% vs 72.8%; P = .01) and more likely to die in an intensive care unit (ICU) (5.1% vs 1.0%, P = .03). Among minorities and high religious coping patients, those reporting poorly supported religious/spiritual needs received more ICU care (11.3% vs 1.2%, P = .03 and 13.1% vs 1.6%, P = .02, respectively), received less hospice (43.% vs 75.3% ≥1 week of hospice, P = .01 and 45.3% vs 73.1%, P = .007, respectively), and had increased ICU deaths (11.2% vs 1.2%, P = .03 and 7.7% vs 0.6%, P = .009, respectively). EOL costs were higher when patients reported that their spiritual needs were inadequately supported ($4947 vs $2833, P = .03), particularly among minorities ($6533 vs $2276, P = .02) and high religious copers ($6344 vs $2431, P = .005). CONCLUSIONS: Cancer patients reporting that their spiritual needs are not well supported by the health care team have higher EOL costs, particularly among minorities and high religious coping patients. Cancer 2011;. © 2011 American Cancer Society.

Journal ArticleDOI
15 Oct 2011-Cancer
TL;DR: This study evaluated the effect of temozolomide in PDEC patients who had progressed on first‐line treatment and found it to have a positive effect on survival.
Abstract: BACKGROUND: Patients with metastatic poorly differentiated endocrine carcinoma (PDEC) usually have a short survival. The chemotherapy combination of cisplatin and etoposide is frequently used as first-line palliative chemotherapy. There are, however, no published studies concerning second-line treatment of the disease. Temozolomide has shown clinical effect in well-differentiated endocrine carcinomas. This study was performed to evaluate the effect of temozolomide in PDEC patients who had progressed on first-line treatment. METHODS: Twenty-five patients with PDEC (mainly gastrointestinal) were treated with temozolomide alone or in combination with capecitabine. A subset of patient also received bevacizumab. MGMT methylation was analyzed in tissue specimens. Data were collected retrospectively. RESULTS: One patient had a complete response, and 7 patients had partial response (33% response rate). Median duration of response was 19 months. Another 9 (38%) patients had a stable disease, after progression at inclusion, with a median duration of 18 months. Median progression-free survival for all patients was 6 months, and median overall survival was 22 months. Only 1 patient had a MGMT methylation. CONCLUSIONS: Treatment with temozolomide alone or in combination with capecitabine and bevacizumab resulted in objective response or stabilization in 71% of PDEC patients who failed on first-line chemotherapy. These results indicated that temozolomide may be used as second-line treatment in PDEC. Cancer 2011;117:4617–22. V C 2011 American Cancer Society.

Journal ArticleDOI
01 May 2011-Cancer
TL;DR: The aim of this phase 2 study was to determine the long‐term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma treated with intensity‐modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy.
Abstract: BACKGROUND: The aim of this phase 2 study was to determine the long-term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy. METHODS: Eighty-one patients with pathologically diagnosed locally advanced NPC were enrolled in this study. IMRT was delivered with the SMART boost technique at prescribed doses of 68 grays (Gy)/30 fraction to the nasopharynx gross target volume. Concurrent cisplatin chemotherapy (80 mg/m2/d on Days 1 and 22) was administered. RESULTS: The mean actual physical dose delivered to the nasopharynx gross target volume was 73.8 Gy, and the mean biologically effective dose (BED) for the nasopharynx gross target volume was 84.8 Gy. With a median follow-up of 54 months, 4 (4.9%) patients experienced local recurrence. The 5-year local control rate was 94.9%. Eighteen patients died. Among them, 66.7% died of distant metastasis. The 5-year disease-free and overall survivals were 76.7% and 74.5%, respectively. The most common late toxicities among 68 patients with ≥4 years follow-up were grade 1-2 xerostomia, hearing loss, skin dystrophy, and subcutaneous fibrosis. No grade 4 late toxicities were noted. CONCLUSIONS: IMRT with SMART to enhance BED and concurrent chemotherapy is feasible in patients with locally advanced NPC. Long-term results showed excellent local control with fewer late toxicities, although no further improvement was noted in overall survival, and the major cause of death was distant metastasis. Exploration of more effective combined chemoradiation strategies is warranted. Cancer 2011. © 2010 American Cancer Society.

Journal ArticleDOI
15 Apr 2011-Cancer
TL;DR: Nutritional intervention with fish oil (FO)‐derived eicosapentaenoic acid (EPA) may prevent deterioration of body composition in newly referred patients with nonsmall cell lung cancer.
Abstract: BACKGROUND: Involuntary weight loss is a major contributor to mortality and morbidity in patients with advanced cancer. Nutritional intervention with fish oil (FO)-derived eicosapentaenoic acid (EPA) may prevent deterioration of body composition. This study compared intervention with FO with standard of care (SOC; no intervention) with regard to weight, skeletal muscle, and adipose tissue in newly referred patients with nonsmall cell lung cancer from the time of initiation to completion of first-line chemotherapy. METHODS: Forty patients completed the study; there were 16 in the FO group (dose of 2.2 g of EPA/day) and 24 patients in the SOC group. Skeletal muscle and adipose tissue were measured using computed tomography images. Blood was collected and weight was recorded at baseline and throughout chemotherapy. RESULTS: Patients in the SOC group experienced an average weight loss of 2.3 ± 0.9 kg whereas patients receiving FO maintained their weight (0.5 ± 1.0 kg) (P = .05). Patients with the greatest increase in plasma EPA concentration after FO supplementation were found to have the greatest gains in muscle (r2 = 0.55; P = .01). Approximately 69% of patients in the FO group gained or maintained muscle mass. Comparatively, only 29% of patients in the SOC group maintained muscle mass, and overall the SOC group lost 1 kg of muscle. No difference in total adipose tissue was observed between the 2 groups. CONCLUSIONS: Nutritional intervention with 2.2 g of FO per day appears to provide a benefit over SOC, resulting in the maintenance of weight and muscle mass during chemotherapy. Cancer 2011. © 2011 American Cancer Society.

Journal ArticleDOI
15 Feb 2011-Cancer
TL;DR: The effectiveness of mammography screening for women ages 40 to 49 years still is questioned, and few studies of the effectiveness of service screening for this age group have been conducted.
Abstract: BACKGROUND: The effectiveness of mammography screening for women ages 40 to 49 years still is questioned, and few studies of the effectiveness of service screening for this age group have been cond ...

Journal ArticleDOI
15 May 2011-Cancer
TL;DR: This study aimed to determine the prognostic relevance of PD‐L1 expression for the survival of melanoma patients.
Abstract: BACKGROUND: Cancers are known to elude the immune system, for example, by MHC loss, FAS up-regulation, or increased secretion of TGF-beta. Recently, ligands of coinhibitory receptors like programmed cell death ligand–1 (PD-L1, B7-H1) have come to attention for their role in tumor immune escape. Various tumors have been tested for PD-L1 expression, and conflicting results were obtained regarding its correlative impact on patient survival. This study aimed to determine the prognostic relevance of PD-L1 expression for the survival of melanoma patients. METHODS: Paraffin-embedded nevi, primary melanoma, and in-transit, lymph node, and distant organ metastases from a set of 63 stages III-IV melanoma patients referred to the Netherlands Cancer Institute between 2000 and 2004 for a sentinel-node procedure or systemic therapy were studied. A large effort was invested in validating specific PD-L1 staining. In addition to immunological factors such as T-cell infiltration (CD8, CD4, and regulatory T cells), TGF-beta and MHC-I expression were assessed. RESULTS: Longitudinal analysis revealed no relevant PD-L1 expression on primary melanoma compared with metastatic disease. No significant correlations with prognosis were found regarding immunological factors, whereas known prognostic markers such as Breslow thickness and sex could be confirmed. Analyses of the overall survival of our patient cohort did not reveal a negative association with PD-L1 expression. CONCLUSIONS: Correlation of overall survival with PD-L1 expression by melanoma cells remains controversial, and future clinical studies should focus on antibody validation and time of analysis in respect to disease progression. Cancer 2011. © 2010 American Cancer Society.

Journal ArticleDOI
01 Oct 2011-Cancer
TL;DR: Stereotactic body radiotherapy is a technique used to deliver high, ablative doses of radiation in a limited number of fractions to ≥1 extracranial target(s) and use among radiation oncologists in the United States is unknown.
Abstract: BACKGROUND Stereotactic body radiation therapy (SBRT) is a technique used to deliver high, ablative doses of radiation in a limited number of fractions to one or more extracranial target(s). The prevalence of SBRT use among radiation oncologists in the United States is unknown.

Journal ArticleDOI
01 Nov 2011-Cancer
TL;DR: The authors review the emerging role of the ICG fluorophore in the development of the authors' comprehension of the lymphatic system and its use in SLN mapping and biopsy in various cancers and introduces the novel role of ICG‐guided video angiography as a new intraoperative method of assessing microvascular circulation.
Abstract: Ever since Kitai first performed fluorescent navigation of sentinel lymph nodes (SLNs) using indocyanine green (ICG) dye with a charge-couple device and light emitting diodes, the intraoperative use of near infrared fluorescence has served a critical role in increasing our understanding in various fields of surgical oncology. Here the authors review the emerging role of the ICG fluorophore in the development of our comprehension of the lymphatic system and its use in SLN mapping and biopsy in various cancers. In addition, they introduce the novel role of ICG-guided video angiography as a new intraoperative method of assessing microvascular circulation. The authors attempt to discuss the promising potential in addition to assessing several challenges and limitations in the context of specific surgical procedures and ICG as a whole. PubMed and Medline literature databases were searched for ICG use in clinical surgical settings. Despite ICG's significant impact in various fields of surgical oncology, ICG is still in its nascent stages, and more in-depth studies need to be carried out to fully evaluate its potential and limitations.

Journal ArticleDOI
01 May 2011-Cancer
TL;DR: This study examines cancer‐related chronic pain and its impact on QOL in diverse cancer survivors and finds disparities in cancer survival and pain rates negatively impact quality of life (QOL).
Abstract: BACKGROUND: Disparities in cancer survival and pain rates negatively impact quality of life (QOL). This study examines cancer-related chronic pain (CP) and its impact on QOL in diverse cancer survivors. METHODS: This survey study focused on current and past pain, health, and QOL in black and white cancer survivors. Participants with breast, colorectal, lung, and prostate cancer and multiple myeloma were recruited through the Michigan State Cancer Registry. Analysis of variance was used to examine outcome differences by pain status, race, and sex. Hierarchical regressions explored predictors for experiencing pain. RESULTS: The subjects (N = 199) were 31% black, 49% female, and 57 to 79 years old; 19.5% experienced current pain, and 42.6% reported pain since diagnosis. Women experience more pain (P < .001) and greater pain severity (P = .04) than men. Blacks experienced more pain interference and disability (P < .05). Experiencing pain is related to greater depressive symptoms, poorer functioning, and more symptoms. In hierarchical regressions, female sex predicted pain since diagnosis; pain severity for pain since diagnosis was predicted by black race and female sex. CONCLUSIONS: The authors extend the literature by showing that 20% of diverse cancer survivors had cancer-related CP, and 43% had experienced pain since diagnosis, revealing racial and sex disparities in cancer-related CP's incidence and impact on QOL. Having pain was related to poorer QOL in several domains and was more frequently experienced by women. Although black race was not related to pain prevalence, it was related to greater severity. This study reveals an unaddressed cancer survivorship research, clinical, and policy issue. Cancer 2011. © 2010 American Cancer Society.

Journal ArticleDOI
01 Feb 2011-Cancer
TL;DR: The authors aimed to construct a framework of known clinical presentations, diagnostic features, disease complications, treatment, and outcomes to improve prognostication of primary cardiac lymphoma.
Abstract: BACKGROUND: Primary cardiac lymphoma (PCL) represents a rare subset of non-Hodgkin lymphoma, characterized by poor outcomes. The authors aimed to construct a framework of known clinical presentations, diagnostic features, disease complications, treatment, and outcomes to improve prognostication. METHODS: Individual patient data were obtained from defined cases of PCL (1949-2009) and systematically analyzed. RESULTS: The authors report results of a review of 197 cases of PCL, with half of all cases reported since 1995. Survival was affected by 4 factors: immune status, left ventricular involvement, presence of extra-cardiac disease, and arrhythmia. Median overall survival (OS) for immunocompromised and immunocompetent was 3.5 months (m) and not reached, respectively (HR 0.29, 95% CI, 0.13-0.68; P = .004). LV involvement was uncommon (26%) and associated with an OS of only 1m, whereas patients free of LV involvement had a median OS of 22m (HR 0.28, 95% CI, 0.12-0.64; P = .002). Patients with extracardiac disease had shorter median OS compared with those without (6m vs 22m, HR 0.49, 95% CI, 0.26-0.91; P = .02). Those patients with an arrhythmia of any type had a median OS that was not reached (n = 55), whereas those without rhythm disturbances (n = 41) had median OS of 6m (HR 0.51, 95% CI, 0.29-0.91; P = .024). Overall response rate to therapy was 84%, with long-term OS over 40%. CONCLUSIONS: The current study presents the largest analysis of PCL to date. The data demonstrate that PCL is now more frequently diagnosed premortem and appears to have reasonable response rates. Lack of LV involvement and the presence of arrhythmias are associated with improved survival. Cancer 2011. © 2010 American Cancer Society.

Journal ArticleDOI
01 Mar 2011-Cancer
TL;DR: The objective of this study was to determine whether the overall survival of patients with metastatic soft tissue sarcoma (STS) has improved over the last 20 years.
Abstract: BACKGROUND: The objective of this study was to determine whether the overall survival of patients with metastatic soft tissue sarcoma (STS) has improved over the last 20 years. METHODS: In total, 1024 patients who had synchronous metastatic (SM) STS or metachronous metastatic (MM) STS diagnosed between 1987 and 2006 were included prospectively in the French Sarcoma Group database after central histologic review. Four periods of diagnosis of metastatic disease were defined: P1, from 1987 to 1991 (n = 208); P2, from 1992 to 1996 (n = 287); P3, from 1997 to 2001 (n = 285); and P4, from 2002 to 2006 (n = 244). Patient characteristics were analyzed as prognostic factors by using a Cox model. RESULTS: The proportion of patients with SM, the interval between diagnosis and MM, and the clinical characteristics of the patients were similar across the 4 periods. Although there was no significant difference in the median overall survival (OS) from P1 through P2 (P1, 12.3 months; 95% confidence interval [CI], 9.9-14.7 months; P2, 11.4 months; 95% CI, 9-13.9 months), significant improvements were observed in the later periods (P3, 15 months; 95% CI, 11.8-18.2 months; P4, 18 months; 95% CI, 15.3-20.7 months; P = .029; log-rank test). The 2-year OS rate also increased throughout the study period from 28.1% during P1 to 38.7% during P4. On multivariate analysis, period of diagnosis, age, histologic subtype, time to metastatic recurrence, French Federation of Cancer Centers Sarcoma Group grade, and the number of metastatic sites were independent prognostic factors for OS. CONCLUSIONS: The current analysis revealed that the median OS of patients with metastatic STS had improved by 50% during the last 20 years. These data should be considered in the interpretation of results from ongoing and future STS trials. Cancer 2011. © 2010 American Cancer Society.

Journal ArticleDOI
01 Apr 2011-Cancer
TL;DR: The authors investigated long‐term tumor control and toxicity outcomes after high‐dose, intensity‐modulated radiation therapy (IMRT) in patients who had clinically localized prostate cancer.
Abstract: BACKGROUND. The authors investigated long-term tumor control and toxicity outcomes after high-dose, intensity-modulated radiation therapy (IMRT) in patients who had clinically localized prostate cancer. METHODS. Between April 1996 and January 1998, 170 patients received 81 gray (Gy) using a 5-field IMRT technique. Patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0. Freedom from biochemical relapse, distant metastases, and cause-specific survival outcomes were calculated. The median follow-up was 99 months. RESULTS. The 10-year actuarial prostate-specific antigen relapse-free survival rates were 81% for the low-risk group, 78% for the intermediate-risk group, and 62% for the high-risk group; the 10-year distant metastases–free rates were 100%, 94%, and 90%, respectively; and the 10-year cause-specific mortality rates were 0%, 3%, and 14%, respectively. The 10-year likelihood of developing grade 2 and 3 late genitourinary toxicity was 11% and 5%, respectively; and the 10-year likelihood of developing grade 2 and 3 late gastrointestinal toxicity was 2% and 1%, respectively. No grade 4 toxicities were observed. CONCLUSIONS. To the authors' knowledge, this report represents the longest followed cohort of patients who received high-dose radiation levels of 81 Gy using IMRT for localized prostate cancer. The findings indicated that high-dose IMRT is well tolerated and is associated with excellent long-term tumor-control outcomes in patients with localized prostate cancer Cancer 2011. © 2010 American Cancer Society.

Journal ArticleDOI
01 Nov 2011-Cancer
TL;DR: Hemangiopericytomas and malignant solitary fibrous tumors (HPC/SFT) are rare, closely related sarcomas with unpredictable behavior that respond infrequently to chemotherapy.
Abstract: BACKGROUND: Hemangiopericytomas and malignant solitary fibrous tumors (HPC/SFT) are rare, closely related sarcomas with unpredictable behavior that respond infrequently to chemotherapy. An optimal systemic treatment strategy for advanced HPC/SFT has not yet been identified. METHODS: We retrospectively analyzed the records of 14 patients with histopathologically confirmed HPC/SFT who were treated at The University of Texas MD Anderson Cancer Center between May 2005 and June 2007. All patients were treated with temozolomide 150 mg/m2 orally on days 1-7 and days 15-21 and bevacizumab 5 mg/kg intravenously on days 8 and 22, repeated at 28-day intervals. Computed tomography assessment of tumor size and density (Choi criteria) was used to determine the best response to therapy. The Kaplan–Meier method was used to estimate progression-free survival. RESULTS: The median follow-up period was 34 months. Eleven patients (79%) achieved a Choi partial response, with a median time to response of 2.5 months. Two patients (14%) had stable disease as the best response, and 1 patient (7%) had Choi progressive disease as the best response. The estimated median progression-free survival was 9.7 months, with a 6-month progression-free rate of 78.6%. The most frequently observed toxic effect was myelosuppression. CONCLUSION: Combination therapy with temozolomide and bevacizumab is a generally well-tolerated and clinically beneficial regimen for HPC/SFT patients. Additional investigation in a controlled, prospective trial is warranted. Cancer 2011;. © 2011 American Cancer Society.

Journal ArticleDOI
01 May 2011-Cancer
TL;DR: A prospective cohort study was undertaken to develop and validate a risk model for neutropenic complications in cancer patients receiving chemotherapy and found it to be a good fit for clinical practice.
Abstract: Myelosuppression represents a major toxicity of systemic cancer chemotherapy associated with considerable morbidity, mortality, and costs.1 Such complications also result in dose reductions or treatment delays, which may compromise clinical outcomes.2–6 Previous studies have demonstrated that the risk of an initial episode of febrile neutropenia is greatest during the first cycle of treatment when most patients are receiving full dose intensity often without prophylactic measures.7–9 The risk of febrile neutropenia in cancer patients who are receiving systemic chemotherapy is generally based on reported rates in randomized controlled clinical trials (RCTs).10 However, studies have suggested that the risk of chemotherapy-induced neutropenia and its complications are considerably underreported in RCTs.11 Reported rates vary greatly for the same chemotherapy regimen, making it difficult to estimate the actual risk for neutropenic complications for common chemotherapy regimens.11 Variation in reported rates may relate to differences in study populations as well as to the chemotherapy dose intensity delivered, which is also frequently underreported.11 In addition, the selected patient populations eligible for such trials may not be representative of the majority of cancer patients treated in the general cancer population. Recognized risk factors for chemotherapy-induced neutropenia and its complications can be classified on the basis of patient characteristics, cancer type, or type of treatment.12 Although older age has been identified as a risk factor for neutropenic complications potentially compromising cancer treatment in the elderly, age is less relevant than major in Wiley Online Library (wileyonlinelibrary.com) comorbidities that accompany increasing age.1–3,6,13,14 Low baseline white blood cell and neutrophil counts and hemoglobin levels appear to be predictors for febrile neutropenia.7,8 The intensity of the specific chemotherapy regimen used also represents a major determinant of the risk of chemotherapy-induced neutropenia.4 Risk assessment models for neutropenia developed to date have largely been based on retrospective data with several important methodologic limitations including small sample size, adjustment for different risk factors, and little, if any, validation.12 A prospective cohort study of cancer patients treated at oncology practices throughout the United States was undertaken to further study the incidence of and risk factors for neutropenic events in cancer patients who were receiving systemic chemotherapy. Preliminary observations with this population have confirmed that half to two-thirds of initial febrile neutropenia episodes occur during the first chemotherapy cycle across a broad range of malignancies.9 The primary goal of this investigation was to prospectively develop and validate a clinical risk model for the occurrence of severe or febrile neutropenia. The development of a valid risk model for neutropenic complications in patients receiving cancer chemotherapy should enable the identification of patients at greatest risk, facilitating more targeted application of available supportive care.