Showing papers in "Cancer in 2009"

Osteosarcoma incidence and survival rates from 1973 to 2004: Data from the Surveillance, Epidemiology, and End Results Program

Abstract: Background Osteosarcoma, the most common primary bone tumor, occurs most frequently in adolescents, but a second incidence peak among individuals over age 60 exists. Most osteosarcoma epidemiology studies have been embedded in large analyses of all bone tumors, or focused on cases occurring in adolescence. Detailed descriptions of osteosarcoma incidence and survival specifically, with direct comparisons among subjects of all ages and ethnicities, are not available.

Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO).

Abstract: BACKGROUND: Primary surgery followed by platinum-taxane based chemotherapy has been the standard therapy in advanced ovarian cancer. However, the prognostic role of complete and so-called optimal and suboptimal debulking and its interaction with biological factors has not been not fully defined. METHODS: Exploratory analysis was conducted of 3 prospective randomized trials (AGO-OVAR 3, 5, and 7) investigating platinum-taxane based chemotherapy regimens in advanced ovarian cancer conducted between 1995 and 2002. RESULTS: A total of 3126 patients were analyzed. Approximately one-third each fulfilled criteria for complete resection (group A), small residual tumor burden of 1-10 mm (group B), or macroscopic residual disease exceeding 1 cm in diameter (group C). Multivariate analysis showed improved progression-free and overall survival for group A with complete resection compared with groups B or C (P < .0001). The impact of so-called optimal debulking as in group B showed a smaller prognostic impact compared with group C. Further independent prognostic factors for overall survival were age, performance status, grade, FIGO stage, and histology, namely the mucinous subtype. An interaction between residual tumor and some biologic factors was demonstrated. CONCLUSIONS: The goal of primary surgery should be complete resection. The prognostic impact of tumor biology seemed to be partially overruled by residual tumor and further evaluation of biologic factors should stratify for residual tumor. Cancer 2009. © 2009 American Cancer Society.

Outcomes of radical nephroureterectomy: A series from the Upper Tract Urothelial Carcinoma Collaboration

Abstract: BACKGROUND: The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified. METHODS: Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were rereviewed by genitourinary pathologists according to strict criteria. RESULTS: Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high-grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) -positive. Over a mean follow-up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5-year recurrence-free and cancer-specific survival probabilities (� SD) were 69% � 1% and 73% � 1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P < .001), advancing pathologic T stage (P-for-trend <.001), LN metastases (HR: 1.8, P < .001), infiltrative growth pattern (HR: 1.5, P < .001), and LVI (HR: 1.2, P ¼ .041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P ¼ .001), high tumor grade (HR: 1.7, P ¼ .001), increasing pathologic T stage (P-for-trend <.001), LN metastases (HR: 1.7, P < .001), sessile architecture (HR: 1.5, P ¼ .002), and LVI (HR: 1.4, P ¼ .02) were independently associated with cancer-specific survival. CONCLUSIONS: Radical nephroureterectomy provided durable local control and cancer-specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with

Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005

Abstract: BACKGROUND: Studies have reported an increasing incidence of thyroid cancer since 1980. One possible explanation for this trend is increased detection through more widespread and aggressive use of ultrasound and image-guided biopsy. Increases resulting from increased detection are most likely to involve small primary tumors rather than larger tumors, which often present as palpable thyroid masses. The objective of the current study was to investigate the trends in increasing incidence of differentiated (papillary and follicular) thyroid cancer by size, age, race, and sex. METHODS: Cases of differentiated thyroid cancer (1988-2005) were analyzed using the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) dataset. Trends in incidence rates of papillary and follicular cancer, race, age, sex, primary tumor size ( 4 cm), and SEER stage (localized, regional, distant) were analyzed using joinpoint regression and reported as the annual percentage change (APC). RESULTS: Incidence rates increased for all sizes of tumors. Among men and women of all ages, the highest rate of increase was for primary tumors <1.0 cm among men (1997-2005: APC, 9.9) and women (1988-2005: APC, 8.6). Trends were similar between whites and blacks. Significant increases also were observed for tumors ≥4 cm among men (1988-2005: APC, 3.7) and women (1988-2005: APC, 5.70) and for distant SEER stage disease among men (APC, 3.7) and women (APC, 2.3). CONCLUSIONS: The incidence rates of differentiated thyroid cancers of all sizes increased between 1988 and 2005 in both men and women. The increased incidence across all tumor sizes suggested that increased diagnostic scrutiny is not the sole explanation. Other explanations, including environmental influences and molecular pathways, should be investigated. Cancer 2009. © 2009 American Cancer Society.

Perineural invasion in cancer: A review of the literature

Abstract: Perineural invasion (PNI) is the process of neoplastic invasion of nerves and is an under-recognized route of metastatic spread. It is emerging as an important pathologic feature of many malignancies, including those of the pancreas, colon and rectum, prostate, head and neck, biliary tract, and stomach. For many of these malignancies, PNI is a marker of poor outcome and a harbinger of decreased survival. PNI is a distinct pathologic entity that can be observed in the absence of lymphatic or vascular invasion. It can be a source of distant tumor spread well beyond the extent of any local invasion; and, for some tumors, PNI may be the sole route of metastatic spread. Despite increasing recognition of this metastatic process, there has been little progress in the understanding of molecular mechanisms behind PNI and, to date, no targeted treatment modalities aimed at this pathologic entity. The objectives of this review were to lay out a clear definition of PNI to highlight its significance in those malignancies in which it has been studied best. The authors also summarized current theories on the molecular mediators and pathogenesis of PNI and introduced current research models that are leading to advancements in the understanding of this metastatic process.

Depression as a predictor of disease progression and mortality in cancer patients: a meta-analysis.

Abstract: BACKGROUND: Cancer patients and oncologists believe that psychological variables influence the course of cancer, but the evidence remains inconclusive. This meta-analysis assessed the extent to which depressive symptoms and major depressive disorder predict disease progression and mortality in cancer patients. METHODS: Using the MEDLINE, PsycINFO, CINAHL, and EMBASE online databases, the authors identified prospective studies that examined the association between depressive symptoms or major/minor depression and risk of disease progression or mortality in cancer patients. Two raters independently extracted effect sizes using a random effects model. RESULTS: Based on 3 available studies, depressive symptoms were not shown to significantly predict cancer progression (risk ratio [RR] unadjusted = 1.23; 95% confidence interval [CI], 0.85-1.77; P = .28). Based on data from 25 independent studies, mortality rates were up to 25% higher in patients experiencing depressive symptoms (RR unadjusted = 1.25; 95% CI, 1.12-1.40; P < .001), and up to 39% higher in patients diagnosed with major or minor depression (RR unadjusted = 1.39; 95% CI, 1.10-1.89; P = .03). In support of a causal interpretation of results, there was no evidence that adjusting for known clinical prognostic factors diminished the effect of depression on mortality in cancer patients. CONCLUSIONS: This meta-analysis presented reasonable evidence that depression predicts mortality, but not progression, in cancer patients. The associated risk was statistically significant but relatively small. The effect of depression remains after adjustment for clinical prognosticators, suggesting that depression may play a causal role. Recommendations were made for future research to more clearly examine the effect of depression on cancer outcomes. Cancer 2009. © 2009 American Cancer Society.

Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with Sipuleucel-T in advanced prostate cancer

Abstract: BACKGROUND: Sipuleucel-T is an investigational active cellular immunotherapy product designed to stimu­ late an immune response against prostate cancer. The safety and efficacy of sipuleucel-T was evaluated in 2 identically designed, randomized, double-blind, placebo-controlled trials (D9901 and D9902A) conducted in men with advanced prostate cancer. METHODS: A total of 225 patients were randomized in D9901 or D9902A to sipuleucel-T (n ¼ 147) or placebo (n ¼ 78), given as 3 intravenous infusions approximately 2 weeks apart. Patients were followed for survival until death or a prespecified cutoff of 36 months after randomization. RESULTS: In the integrated analysis of D9901 and D9902A, patients randomized to sipuleu­ cel-T demonstrated a 33% reduction in the risk of death (hazard ratio, 1.50; 95% confidence interval, 1.10­ 2.05; P ¼ .011; log-rank). The treatment effect remained strong after performing adjustments for imbalances in baseline prognostic factors, poststudy treatment chemotherapy use, and non–prostate cancer-related deaths. Additional support for the activity of sipuleucel-T is provided by the correlation between a measure of the product’s potency, CD54 up-regulation, and overall survival. The most common adverse events asso­ ciated with treatment were chills, pyrexia, headache, asthenia, dyspnea, vomiting, and tremor. These events were primarily grade 1 and 2, with durations of 1 to 2 days. CONCLUSIONS: The integrated results of D9901 and D9902A demonstrate a survival benefit for patients treated with sipuleucel-T compared with those treated with placebo. The generally modest toxicity profile, coupled with the survival benefit, suggests a favorable risk-benefit ratio for sipuleucel-T in patients with advanced prostate cancer. Cancer 2009;115:3670–9. V 2009 American Cancer Society. C

The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS.

Abstract: BACKGROUND: The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene resulting from the chromosome inversion inv(2)(p21;p23) recently was identified in nonsmall cell lung cancer (NSCLC). The authors of this study investigated the frequency, genetic and clinicopathologic profiles of EML4-ALK in Chinese patients with NSCLC. METHODS: EML4-ALK was investigated in 266 resected primary NSCLC, including adenocarcinomas (AD), lymphoepithelioma-like carcinomas, squamous cell carcinomas, mucoepidermoid carcinomas, and adenosquamous carcinomas, by reverse transcriptase-polymerase chain reaction and was verified by sequencing. EML4-ALK protein expression was studied by immunohistochemistry. RESULTS: Thirteen tumors (4.9%) had EML4-ALK comprising 4 fusion transcript variants with fusion of the variable segments from 5′ EML4 to 3′ ALK and with preservation of the ALK kinase domain. The most common variant consisted of 8 tumors with variant 3 that involved EML4 exon 6. The others included 2 tumors with variant 1 (exon 13), 2 tumors with variant 2 (exon 20), and 1 tumor with the novel variant 5 (exon 18). There were 11 ADs and 2 unusual carcinomas with mixed squamous and glandular components. Immunohistochemistry demonstrated diffuse ALK fusion proteins in the tumor cell cytoplasm. EML4-ALK was associated with nonsmokers (P = .009). Tumors with the fusion gene had the wild-type epidermal growth factor receptor (EGFR) (P = .001) and v-Ki-ras2/Kirsten rat sarcoma viral oncogene homolog (KRAS) genes. Patients who had EML4-ALK-positive AD had a younger median age (P = .018) compared with patients who did not have the fusion gene. CONCLUSIONS: The EML4-ALK fusion gene was present in various histologic types of NSCLC. It occurred in mutual exclusion to EGFR and KRAS mutations and was associated with nonsmokers. The authors concluded that EML4-ALK may be useful for predicting the potential response to ALK inhibitors as a therapeutic option for patients with lung cancer. Cancer 2009. © 2009 American Cancer Society.

Real-time identification of liver cancers by using indocyanine green fluorescent imaging

Abstract: BACKGROUND: We have often encountered difficulties in identifying small liver cancers during surgery. Fluorescent imaging using indocyanine green (ICG) has the potential to detect liver cancers through the visualization of the disordered biliary excretion of ICG in cancer tissues and noncancerous liver tissues compressed by the tumor. METHODS: ICG had been intravenously injected for a routine liver function test in 37 patients with hepatocellular carcinoma (HCC) and 12 patients with metastasis of colorectal carcinoma (CRC) before liver resection. Surgical specimens were investigated using a near-infrared light camera system. Among the 49 subjects, the 26 patients examined during the latter period of the study (20 with HCC and 6 with metastasis) underwent ICG-fluorescent imaging of the liver surfaces before resection. RESULTS: ICG-fluorescent imaging identified all of the microscopically confirmed HCCs (n = 63) and CRC metastases (n = 28) in surgical specimens. Among the 63 HCCs, 8 tumors (13%, including 5 early HCCs) were not evident grossly unless observed by ICG-fluorescent imaging. Five false-positive nodules (4 large regenerative nodules and 1 bile duct proliferation) were identified among the fluorescent lesions. Well-differentiated HCCs appeared as uniformly fluorescing lesions with higher lesion-to-liver contrast than that of moderately or poorly differentiated HCCs (162.6 [71.1-218.2] per pixel vs 67.7 [-6.3-211.2] per pixel, P < .001), while CRC metastases were delineated as rim-fluorescing lesions. Fluorescent microscopy confirmed that fluorescence originated in the cytoplasm and pseudoglands of HCC cells and in the noncancerous liver parenchyma surrounding metastases. ICG-fluorescent imaging before resection identified 21 of the 41 HCCs (51%) and all of the 16 metastases that were examined. CONCLUSIONS: ICG-fluorescent imaging enables the highly sensitive identification of small and grossly unidentifiable liver cancers in real time, enhancing the accuracy of liver resection and operative staging. Cancer 2009. © 2009 American Cancer Society.

Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal for a Revised TNM Classification.

Abstract: BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy, and it was only in 2004 that the International Union Against Cancer (UICC) defined TNM criteria and published the first staging classification. However, to date, the prognostic value of the proposed classification has not been evaluated. METHODS: The German ACC Registry comprising 492 patients was searched for patients who were diagnosed between 1986 and 2007 with detailed information on primary diagnosis and a minimum follow-up of 6 months. Patients were assigned to UICC tumor stage, and disease-specific survival (DSS) was assessed. In addition, the contribution of potential risk factors for DSS was evaluated. RESULTS: In total, 416 patients with a mean follow-up of 36 months met the inclusion criteria (stage I, n = 23 patients; stage II, n = 176 patients; stage III, n = 67 patients; stage IV, n = 150 patients). Kaplan-Meier analysis revealed a stage-dependent DSS. However, DSS in patients with stage II ACC did not differ significantly from DSS in patients with stage III ACC (hazard ratio, 1.38; 95% confidence interval, 0.89-2.16). Furthermore, patients who had stage IV ACC without distant metastases had an improved DSS compared with patients who had metastatic disease (P = .004). An analysis of different potential risk factors for defining stage III ACC revealed important roles in DSS for tumor infiltration in surrounding tissue, venous tumor thrombus (VTT), and positive lymph nodes; whereas tumor invasion in adjacent organs carried a prognosis similar to that of infiltration in surrounding tissue only. CONCLUSIONS: The 2004 UICC staging classification for ACC has significant limitations. On the basis of the current analysis, a revised classification with superior prognostic accuracy is proposed (the European Network for the Study of Adrenal Tumors classification). In this system, stage III ACC is defined by the presence of positive lymph nodes, infiltration of surrounding tissue, or VTT; and stage IV ACC is restricted to patients with distant metastasis. Cancer 2009. © 2009 American Cancer Society.

Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma.

Abstract: BACKGROUND Yes-associated protein (YAP), a downstream target of the Hippo signaling pathway, was recently linked to hepatocarcinogenesis in a mouse hepatocellular carcinoma (HCC) model. The objective of the current study was to investigate the clinical significance of YAP in HCC and its prognostic values in predicting survival and tumor recurrence.

Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: are response evaluation criteria in solid tumors reliable?

Abstract: BACKGROUND: Evaluation of response to treatment is a key aspect in cancer therapy. Response Evaluation Criteria in Solid Tumors (RECIST) are used in most oncology trials, but those criteria evaluate only unidimensional tumor measurements and disregard the extent of necrosis, which is the target of all effective locoregional therapies. Therefore, the European Association for the Study of the Liver (EASL) guidelines recommended that assessment of tumor response should incorporate the reduction in viable tumor burden. The current report provides an assessment of the agreement/concordance between both RECIST and the EASL guidelines for the evaluation of response to therapy. METHODS: The authors evaluated a cohort of 55 patients within prospective studies, including 24 patients with hepatocellular carcinoma who underwent transarterial chemoembolization (TACE) with drug eluting beads (DEB-TACE) and 31 patients who underwent percutaneous ablation (percutaneous ethanol injection [PEI]/radiofrequency [RF]). Triphasic helical computed tomography scans were performed at baseline, at 1 month, and at 3 months after procedure, and 2 independent radiologists evaluated tumor response. RESULTS: Evaluating response according to RECIST criteria, no patients achieved a complete response (CR), 21.8% of patients achieved a partial response (PR) (none in the PEI/RF group), 47.3% of patients had stable disease (SD), and 30.9% of patients had progressive disease (PD). When response was evaluated according to the EASL guidelines, 54.5% of patients achieved a CR, 27.3% of patients achieved a PR, 3.6% of patients had SD, and 14.5% had PD. The κ coefficient was 0.193 (95% confidence interval, 0.0893-0.2967; P < .0001). CONCLUSIONS: RECIST missed all CRs and underestimated the extent of partial tumor response because of tissue necrosis, wrongly assessing the therapeutic efficacy of locoregional therapies. This evaluation should incorporate the reduction in viable tumor burden as recognized by nonenhanced areas on dynamic imaging studies. Cancer, 2009. © 2008 American Cancer Society.

Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975-2005

Abstract: BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents aged <20 years; its etiology remains largely unknown. It is believed that embryonal (ERMS) and alveolar rhabdomyosarcoma (ARMS), the most common subtypes, arise through distinct biologic mechanisms. The authors of this report evaluated incidence and survival trends by RMS demographic subgroups to inform future etiologic hypotheses. METHODS: Incidence and survival trends in RMS among children and adolescents aged <20 years were analyzed using data from the Surveillance, Epidemiology, and End Results Program. Frequencies, age-adjusted incidence and survival rates, and joinpoint regression results, including annual percentage change (APC) and 95% confidence interval (CI), were calculated. RESULTS: Between 1975 and 2005, the incidence of ERMS was stable, whereas a significant increase in the incidence of ARMS was observed (APC, 4.20%; 95%CI, 2.60%-5.82%). This trend may have been attributable in part to shifts in diagnosis, because a significant negative trend in RMS, not otherwise specified was observed concurrently. A bimodal age peak for ERMS was observed, with the second, smaller peak in adolescence noted for males only; ARMS incidence did not vary by age or sex. Five-year survival rates for RMS and ERMS increased during the period from 1976 to 1980 (52.7% and 60.9%, respectively) to the period from 1996 to 2000 (61.8% and 73.4%, respectively), whereas there was little improvement for ARMS (40.1% and 47.8%, respectively). CONCLUSIONS: Observed differences in incidence and survival for 2 major RMS subtypes across sex and age subgroups further supported the hypothesis that there are unique underlying etiologies for these tumors. Exploration of these differences presents an opportunity to increase current knowledge of RMS. Cancer 2009. © 2009 American Cancer Society.

Metabolic syndrome and hepatocellular carcinoma: two growing epidemics with a potential link.

Abstract: Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer death in the United States. Although many risk factors for HCC are well defined, including hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol, most series have indicated that 5% to 30% of patients with HCC lack a readily identifiable risk factor for their cancer. The majority of "cryptogenic" HCC in the United States is attributed to nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome. The metabolic syndrome is a constellation of problems that includes insulin resistance, obesity, hypertension, and hyperlipidemia. Increasingly, components of the metabolic syndrome are being linked to various forms of cancer with respect to both increased risk of disease and worsened outcome. In this review, the authors focused on the relation between metabolic syndrome and HCC. They investigated the increased risks of HCC among individuals with features of metabolic syndrome, potentially worsened cancer outcomes in these patients, possible pathogenic mechanisms to explain these relations, and treatment options for those with NAFLD and its progressive counterpart, nonalcoholic steatohepatitis. It is predicted that metabolic syndrome will lead to large increases in the incidence of HCC over the next decades. A better understanding of the relation between these 2 diseases ultimately should lead to improved screening and treatment options for patients with HCC.

Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial.

Abstract: Background Actinic keratoses (AKs) are established as direct precursors of squamous cell carcinoma (SCC), but there is significant controversy regarding the rate at which AKs progress to SCC. The authors of this report studied a high-risk population to estimate the risk of progression of AK to SCC and to basal cell carcinoma (BCC) and the risk of spontaneous regression of untreated AKs. Methods Data were obtained from participants in the Department of Veterans Affairs Topical Tretinoin Chemoprevention Trial. Participants were examined every 6 months for up to 6 years. At each examination, the locations on the face and ears of clinically diagnosed AKs and lesions scheduled for biopsy were marked, and high-resolution digital photographs were taken. These photographs were used later to map and track the presence, absence, or biopsy of each AK across visits. Results In total, 7784 AKs were identified on the face and ears of 169 participants. The risk of progression of AK to primary SCC (invasive or in situ) was 0.60% at 1 year and 2.57% at 4 years. Approximately 65% of all primary SCCs and 36% of all primary BCCs diagnosed in the study cohort arose in lesions that previously were diagnosed clinically as AKs. The majority of AKs (55%) that were followed clinically were not present at the 1-year follow-up, and the majority (70%) were not present at the 5-year follow-up. Conclusions In the current study, the authors quantified the malignant potential of clinically diagnosed AKs for both SCC and BCC, although many did not persist, and the results suggested that AKs may play a greater role in the overall burden of keratinocyte carcinomas than previously documented.

Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis.

Abstract: BACKGROUND: It was investigated whether the European Group for Blood and Marrow Transplantation risk score, previously established for chronic myeloid leukemia, could be used to predict outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for hematological disease in general. METHODS: Age of patient, disease stage, time interval from diagnosis to transplant, donor type, and donor-recipient sex combination were used to establish a score from 0 to 7 points. Its validity was tested in 56,505 patients, 33,113 (58%) male, 23,392 female, median age 33 years (range, 0.5-77 years), with an allogeneic HSCT for a hematological disorder between 1980 and 2005. RESULTS: Survival probability at 5 years decreased from 71% (95% confidence interval [CI], 69%-73%) for risk score 0 for the whole cohort (75%, 95% CI, 72%-78% for the most recent time cohort) to 24% (95% CI, 21%-27% for risk score 6 and 7; 25%, 95% CI, 22%-29% most recent cohort). Transplant-related mortality increased from 15% (95% CI, 14%-17%) for risk score 0 (11%, 95% CI, 9%-13%, most recent cohort) to 47% with risk score 6 and 7 (95% CI, 44%-50%) for the whole cohort (45%, 95% CI, 42%-48%, most recent cohort). The risk score was predictive in all disease categories, over all time periods, and was not altered by transplant techniques. CONCLUSIONS: Five well-defined pretransplant patient and donor characteristics give a reasonable risk estimate of allogeneic HSCT. This risk score can provide a basis for the decision between transplant and nontransplant strategies.

Supportive versus palliative care: What's in a name?

Abstract: BACKGROUND: Palliative care has been progressively adopted by American cancer centers; however, referrals to palliative care continue to occur late in the trajectory of illness. It was hypothesized that the perceived association between the name palliative care and hospice was a barrier to early patients' referral. The objectives of this study were to determine the perception of the impact of the name palliative care compared with supportive care on patient referral and to determine whether there was an association between demographic factors and the perceptions of the 2 names by medical oncologists and their midlevel providers (advance practice nurses and physician assistants) at a comprehensive cancer center. METHODS: A survey was conducted among a random sample of 100 medical oncologists and 100 midlevel providers from The University of Texas M. D. Anderson Cancer Center. Information was collected on demographics, previous experience in palliative care, and attitudes and beliefs toward the impact of the name palliative care compared with supportive care on patient referral. RESULTS: A total of 140 of 200 (70%) participants responded (74 midlevel providers and 66 medical oncologists). Median age was 43 years (range, 34.5-50 years), and there were 83 (60%) women. Midlevel providers and medical oncologists generally agreed in their responses to most of the items. More participants preferred the name supportive care (80, 57%) compared with palliative care (27, 19% P .99). CONCLUSIONS: The name palliative care was perceived by medical oncologists and midlevel providers as more distressing and reducing hope to patients and families. Medical oncologists and midlevel providers significantly prefer the name supportive care and stated more likelihood to refer patients on active primary and advanced cancer treatments to a service named supportive care. Cancer 2009. © 2009 American Cancer Society.

Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas.

Abstract: BACKGROUND: The authors report on the local control and toxicity of stereotactic body radiotherapy (SBRT) for patients with unresectable pancreatic adenocarcinoma. METHODS: Seventy-seven patients with unresectable adenocarcinoma of the pancreas received 25 gray (Gy) in 1 fraction. Forty-five patients (58%) had locally advanced disease, 11 patients (14%) had medically inoperable disease, 15 patients (19%) had metastatic disease, and 6 patients (8%) had locally recurrent disease. Nine patients (12%) had received prior chemoradiotherapy. Sixteen patients (21%) received between 45 to 54 Gy of fractionated radiotherapy and SBRT. Various gemcitabine-based chemotherapy regimens were received by 74 patients (96%), but 3 patients (4%) did not receive chemotherapy until they had distant failure. RESULTS: The median follow-up was 6 months (range, 3-31 months) and, among surviving patients, it was 12 months (range, 3-31 months). The overall rates of freedom from local progression (FFLP) at 6 months and 12 months were 91% and 84%, respectively. The 6- and 12-month isolated local recurrence rates were 5% and 5%, respectively. There was no difference in the 12-month FFLP rate based on tumor location (head/uncinate, 91% vs body/tail, 86%; P = .52). The progression-free survival (PFS) rates at 6 months and 12 months were 26% and 9%, respectively. The PFS rate at 6 months was superior for patients who had nonmetastatic disease versus patients who had metastatic disease (28% vs 15%; P = .05). The overall survival (OS) rates at 6 months and 12 months from SBRT were 56% and 21%, respectively. Four patients (5%) experienced grade ≥2 acute toxicity. Three patients (4%) experienced grade 2 late toxicity, and 7 patients (9%) experienced grade ≥3 late toxicity. At 6 months and 12 months, the rates of grade ≥2 late toxicity were 11% and 25%, respectively. CONCLUSIONS: SBRT for pancreatic adenocarcinoma was effective for local control with associated risk of toxicity and should be used with rigorous attention to quality assurance. Efforts to reduce complications are warranted. Distant metastases account for the vast majority of disease-related mortality. Cancer 2009. © 2008 American Cancer Society.

BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer.

Abstract: Background In women at increased risk for breast and ovarian cancer, the identification of a BRCA1/2 mutation has important implications for screening and prevention counseling. Uncertainty regarding the role of BRCA1/2 testing in high-risk women from diverse ancestral backgrounds exists due to variability in prevalence estimates of deleterious (disease-associated) mutations in non-White populations. We examined the prevalence of BRCA1/2 mutations in an ethnically diverse group of women referred for genetic testing.

Predictive value of tumor thickness for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity: a meta-analysis of reported studies.

Abstract: BACKGROUND: Tumor thickness (TT) appears to be a strong predictor for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity (OSCC), but a precise clinically optimal TT cutoff point has not been established To address this question, the authors conducted a meta-analysis METHODS: All relevant articles were identified from MEDLINE and EMBASE as well as from cross-referenced publications cited in relevant articles Lymph-node involvement was confirmed and identified as positive lymph-node declaration (PLND) by either pathologic positivity on immediate neck dissection or by neck recurrence identified after follow-up ≥2 years Odds ratios (OR) were calculated to quantify the predictive value of TT Negative predictive values (and the percentage of patients falsely predicted to not have PLND [FN-PLND]) were compared to determine the optimal TT cutoff point RESULTS: Sixteen studies were selected from 72 potential studies, yielding a pooled total of 1136 patients Data were examined for the following TT cutoff points: 3 mm (4 studies, 387 patients), 4 mm (9 studies, 778 patients), 5 mm (6 studies, 367 patients), and 6 mm (4 studies, 488 patients) The OR (95% CI) was 73 (53-101) for the overall group The proportion of FN-PLND was 53% (95% CI, 20-112), 45% (26-72), 166% (115-228), and 130% (97-169) for TT<3, <4, <5, and <6 mm, respectively There was a statistically significant difference between the 4-mm and 5-mm TT cutoff points (P = 007) CONCLUSIONS: TT was a strong predictor for cervical lymph-node involvement The optimal TT cutoff point was 4 mm Cancer 2009 © 2009 American Cancer Society

A retrospective review of 1349 cases of sebaceous carcinoma

Abstract: BACKGROUD: Sebaceous carcinoma is a rare and aggressive cutaneous carcinoma. It is believed that this malignancy predominates in the periocular region and occurs more frequently in Asian populations and in women. The objective of the current study was to analyze demographic characteristics and outcomes for patients with this malignancy from a large United States-based population registry. METHODS: An analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results database from 1973 through 2004 was performed. RESULTS: Of 1349 patients who were identified, 54% were men, 86.2% were white, and 5.5% were of Asian/Pacific Islander ancestry. The median age at diagnosis was 73 years. The most frequent site of disease was the eyelid (38.7%). The population-matched 5- and 10-year age-matched relative survival rate was 91.9% (standard error [SE], 1.9%) and 79.2% (SE, 3.7%), respectively. Cause of death was attributable to cancer in 31% of patients. Orbital involvement did not predict for worsened survival compared with nonorbital involvement (5-year overall survival, 75.2% vs 68%, respectively; P = .66). The overall population-matched rate of sebaceous carcinoma was highest in whites (2.03 cases per 1000,000; SE, 0.08) versus Asian/Pacific Islanders (1.07 per 1000,000; SE, 0.18; P = .0001) versus blacks (0.48 per 1000,000; SE, 0.11; P < .0001). CONCLUSIONS: The current results support the finding of a predominance of men among patients with sebaceous carcinoma, and no difference was observed in the prognosis for orbital and periorbital involvement. This retrospective analysis also corroborated previous case reports of a higher incidence among patients with advanced age and the highest incidence for sites in the eyelid and skin of the face. The results also established that Asian/Pacific Islander ancestry is not a risk factor for developing sebaceous carcinoma. Cancer 2009. © 2008 American Cancer Society.

Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer.

Abstract: Androgen-deprivation therapy (ADT) is a common treatment for men with prostate cancer. Although ADT is effective at suppressing prostate-specific antigen (PSA), stabilizing disease, alleviating symptoms in advanced disease, and potentially prolonging survival, it is not without serious side effects. However, to the authors' knowledge, there is lack of a systematic review of its major adverse effects to date. The authors of this report systematically reviewed and quantitatively assessed the literature on skeletal and cardiac side effects associated with ADT in men with prostate cancer. The PubMed database was searched for relevant published articles from 1966 to May 2008, and 683 articles were reviewed systematically from an original 20 different Medical Subject Heading search combinations. The focus of the review was on bone-related and cardiovascular-related outcomes. When appropriate, results were pooled from articles on specific adverse outcomes, summary risk estimates were calculated, and tests of heterogeneity were performed. Fourteen articles were identified that met inclusion criteria from the original 683 studies. Men who underwent ADT for prostate cancer had a significantly increased risk of overall fracture of 23% (summary relative risk, 1.23; 95% confidence interval [95% CI], 1.10-1.38) compared with men who had prostate cancer but who did not undergo ADT. Furthermore, men who underwent ADT had a 17% increase in cardiovascular-related mortality compared with men who did not undergo with ADT (summary hazards ratio, 1.17; 95% CI, 1.07-1.29). Significant elevations in the risk of diabetes also were observed from 2 large studies. ADT was associated with an increased risk of skeletal fracture, incident diabetes, and cardiovascular-related mortality, although the absolute risk of these events was low. Preventive measures against these adverse effects and careful assessment of patient's baseline health status should be considered. Cancer 2009. © 2009 American Cancer Society.

Radical versus partial nephrectomy: effect on overall and noncancer mortality.

Abstract: BACKGROUND: Relative to radical nephrectomy (RN), partial nephrectomy (PN) performed for renal cell carcinoma (RCC) may protect from non-cancer-related deaths. The authors tested this hypothesis in a cohort of PN and RN patients. METHODS: The Surveillance, Epidemiology, and End Results-9 database allowed identification of 2198 PN (22.4%) and 7611 RN (77.6%) patients treated for T1aN0M0 RCC between 1988 and 2004. Analyses matched for age, year of surgery, tumor size, and Fuhrman grade addressed the effect of nephrectomy type (RN vs PN) on overall mortality (Cox regression models) and on non-cancer-related mortality (competing-risks regression models). RESULTS: Relative to PN, RN was associated with 1.23-fold (P = .001) increased overall mortality rate, which translated into a 4.9% and 3.1% absolute increase in mortality at 5 and 10 years after surgery, respectively. Similarly, non-cancer-related death rate was significantly higher after RN in competing-risks regression models (P < .001), which translated into a 4.6% and 4.5% absolute increase in non-cancer-related mortality at 5 and 10 years after surgery, respectively. CONCLUSIONS: Relative to PN, RN predisposes to an increase in overall mortality and non-cancer-related death rate in patients with T1a RCC. In consequence, PN should be attempted whenever technically feasible. Selective referrals should be considered if PN expertise is unavailable Cancer 2009. © 2009 American Cancer Society.

Pancreatic Neuroendocrine Tumors : The Impact of Surgical Resection on Survival

Abstract: Joshua S. Hill, MD, James T. McPhee, MD, Theodore P. McDade, MD, Zheng Zhou, MD, PhD,Mary E. Sullivan, MS, Giles F. Whalen, MD, and Jennifer F. Tseng, MD, MPHBACKGROUND: Although surgical resection is generally recommended for patients with localized pancre-atic neuroendocrine tumors (PNETs), the impact of resection on overall survival is unknown. The authorsinvestigated the survival advantage of pancreatic resection using a national database. METHODS: This is aretrospective survival analysis of patients with PNETs from the Surveillance, Epidemiology, and End Resultsdatabase (1988-2002). RESULTS: A total of 728 patients with PNETs were identified with a median survivalof 43 months using Kaplan-Meier survival methods. Resection of tumor was associated with significantlyimproved survival compared with those patients who were recommended for but did not undergo resec-tion (114 months vs 35 months; P < .0001). This survival benefit was demonstrated for patients with local-ized, regional, and metastatic disease. A multivariable Cox proportional hazards model was constructed toassess the overall effect of surgical resection on survival, and demonstrated an adjusted odds ratio of 0.48(95% confidence interval, 0.35-0.66) compared with those who were recommended for surgery but did notproceed to surgery. CONCLUSIONS: The authors have demonstrated in a large national study that resectionof primary tumor in patients with PNETs is associated with improved survival across all disease stages. Patientswith localized, regional, and metastatic PNETs who are reasonable operative candidates should be consideredfor resection of their primary tumors. Cancer 2009;115:741–51. V

Sex and racial differences in bladder cancer presentation and mortality in the US

Abstract: BACKGROUD: Sex, race, and age at diagnosis have a significant impact on mortality from bladder cancer (BC). Women, African Americans of both sexes, and the elderly, all experience higher mortality rates. Tumor grade, stage, and histologic type at presentation also affect outcome. To determine whether age and tumor characteristics alone explain the excess hazard of death from BC observed in some demographic groups, the authors queried the Surveillance, Epidemiology, and End Results (SEER) limited-use database for the presentations of and outcomes from BC between 1990 and 2005. METHODS: Tumors were characterized by grade, stage, and histologic type. Hazards rates for BC-specific mortality were compared by race and sex using a piecewise Cox regression model, adjusting for factors (age, stage, grade, and histologic type) that differed significantly between the groups that were compared. RESULTS: Excess hazard of death from BC was present during the first 2 to 3 years of follow-up among women and during the first 4 years of follow-up among African Americans. Adjustment for age and tumor characteristics eliminated approximately 30% of this excess hazard in sex comparison among whites. In sex comparison among blacks and in racial comparisons within each sex, approximately 50% to 70% of excess hazard could be eliminated by adjustment. CONCLUSIONS: Significant differences in tumor characteristics and age at presentation did not fully account for the excess hazard of death from BC among women and African Americans. Other factors, such as choice and efficacy of therapies, differences within a given tumor characteristic group, and/or host factors, also may play important roles. Cancer 2009. © 2008 American Cancer Society.

Time costs associated with informal caregiving for cancer survivors

Abstract: BACKGROUND: To the authors' knowledge, little work has been done to estimate the time costs associated with informal caregiving for cancer survivors. METHODS: Data from a national survey of caregivers of cancer patients in 2003 to 2006 were used to estimate the time associated with informal caregiving in the 2 years after patient diagnosis with bladder, breast, colorectal, kidney, lung, melanoma of the skin, ovarian, prostate, or uterine cancer, or non-Hodgkins lymphoma (NHL). Caregivers reported the duration and daily intensity of caregiving as well as the types and frequency of support provided. The median wage rate in 2006 ($16.28) was used to value caregiver time, and other methods to value time were evaluated with sensitivity analyses. RESULTS: On average, caregivers provided care for 8.3 hours per day for 13.7 months. The number of months and daily hours spent caregiving were the highest for cancer survivors diagnosed with distant disease compared with survivors with regional or localized disease (P < .05). Approximately half of caregivers provided emotional, instrumental, tangible, or medical support, although the frequency varied dramatically. Informal caregiver time costs over the 2-year period after diagnosis were the highest for caregivers of patients diagnosed with lung ($72,702; 95% confidence interval [95% CI], $56,814-$88,590) and ovarian ($66,210; 95% CI, $40,750-$91,670) cancers and NHL ($59,613; 95% CI, $43,423-$75,803) and the lowest for caregivers of patients with breast cancer ($38,334; 95% CI, $31,442-$45,226). CONCLUSIONS: Time spent by informal caregivers was substantial and was an important component of the burden of cancer care. Incorporation of the value of informal caregiver time will be important when evaluating the costs and benefits of cancer control interventions. Cancer 2009;115(18 suppl):4362–73. © 2009 American Cancer Society.

Synovial sarcoma: Retrospective analysis of 250 patients treated at a single institution

Abstract: Background The optimal treatment for synovial sarcoma remains controversial. Treatment, outcome, and prognostic factors in patients treated in a single institution were examined. Methods Synovial sarcoma patients who underwent surgery at the Rizzoli Institute between 1976 and 2006 were identified and analyzed. Results Characteristics of the 250 patients (128 female; 122 male) included: median age, 37 years (range, 7-83 years); 177 (71%) with tumors in the lower extremity, 40 (16%) with tumors in the upper extremity, and 33 with tumors in the trunk (13%); primary lesion size >5 cm in 121 patients (55%); and 204 (82%) patients with localized disease and 46 (18%) with metastatic disease at the time of presentation. All patients with localized disease underwent surgery. Twenty-four percent of patients underwent amputation. Adequate surgical margins were achieved in 88% patients. In patients with localized disease, radiotherapy was administered to 103 (50%) patients, and chemotherapy to 98 (48%). With a median follow-up of 5.5 years (range, 1-30 years), the 5-year overall survival rate was 10% for patients with metastatic disease and 76% for patients with localized disease (P = .0001). The 5-year event-free survival was 58% in patients with localized disease. Multivariate analysis indicated that size, age, histologic subtype, and the use of radiotherapy were independent factors for event-free survival. Conclusions In those patients with localized disease, a good rate of cure can be achieved. Age, size, histology, and use of radiotherapy influence prognosis, whereas to the authors' knowledge, the role of adjuvant chemotherapy remains unproven.

Local recurrence after surgery for early stage lung cancer: an 11-year experience with 975 patients.

Abstract: BACKGROUND: The objective of the current study was to evaluate the actuarial risk of local failure (LF) after surgery for stage I to II nonsmall cell lung cancer (NSCLC) and assess surgical and pathologic factors affecting this risk. METHODS: The records, including pertinent radiologic studies, of all patients who underwent surgery for T1 to T2, N0 to N1 NSCLC at Duke University between 1995 and 2005 were reviewed. Risks of disease recurrence were estimated using the Kaplan-Meier method. A multivariate Cox regression analysis assessed factors associated with LF in the entire cohort and a subgroup undergoing optimal surgery for stage IB to II disease. RESULTS: For all 975 consecutive patients, the 5-year actuarial risk of local and/or distant disease recurrence was 36%. First sites of failure were local only (25%), local and distant (29%), and distant only (46%). The 5-year actuarial risk of LF was 23%. On multivariate analysis, squamous/large cell histology (hazards ratio [HR], 1.98), stage > IA (HR, 2.02), and sublobar resections (HR, 1.99) were found to be independently associated with a higher risk of LF. For the subset of patients (n = 445) undergoing at least a lobectomy with negative surgical margins and currently considered for adjuvant chemotherapy (stage IB-II disease), the 5-year actuarial risk of LF was 27%. Within this subgroup, squamous/large cell histology (HR, 2.5) and lymphovascular space invasion (HR, 1.74) were associated with a higher risk of LF. The 5-year rate of LF was 13%, 32%, and 47%, respectively, with 0, 1, or 2 risk factors. CONCLUSIONS: Greater than half of disease recurrences after surgery for early stage NSCLC involved local sites. Pathologic factors may help to distinguish those patients at highest risk. Cancer 2009. © 2009 American Cancer Society.

Candidemia in patients with hematologic malignancies in the era of new antifungal agents (2001-2007): stable incidence but changing epidemiology of a still frequently lethal infection.

Abstract: BACKGROUND: The incidence, epidemiology, Candida species distribution, resistance patterns, and outcome of candidemia in high-risk hematologic malignancy and/or stem cell transplantation patients have not been extensively described since the introduction of new antifungal agents. METHODS: In this retrospective study, the authors reviewed the medical records and microbiologic data of hematologic malignancy patients with candidemia at The University of Texas M. D. Anderson Cancer Center from March 2001 to February 2007. RESULTS: The authors analyzed 173 episodes of candidemia (170 patients), 125 (72%) of which were breakthrough cases after prior antifungal agents, mainly fluconazole (28 [22%]), caspofungin (25 [20%]), and voriconazole (18 [14%]). The incidence of candidemia (per 100,000 inpatient days) remained relatively stable, from 13.9 in 2001 to 19.2 in 2006. However, compared with the findings of previous studies at the authors' institution, the frequency of Candida glabrata and C. krusei infection decreased (to 5% and 17%, respectively) and C. parapsilosis (24%) and C. tropicalis (21%) increased. C. parapsilosis fungemia was associated with prior caspofungin use (P < .001). The overall 30-day crude mortality rate was 38%, and the attributable mortality rate was 19%, similar to previous findings at the authors' institution. The Candida species associated with the highest mortality rate was C. glabrata. CONCLUSIONS: Despite the widespread use of antifungal prophylaxis and the introduction of new antifungal agents, the incidence and associated mortality rates of candidemia remained stable in high-risk hematologic malignancy patients. However, its epidemiological characteristics have shifted, with C. parapsilosis and C. tropicalis becoming more common. Cancer 2009. © 2009 American Cancer Society.

Comparing children and adults with synovial sarcoma in the Surveillance, Epidemiology, and End Results program, 1983 to 2005: an analysis of 1268 patients.

Abstract: BACKGROUND: Synovial sarcoma (SS) is a typical soft tissue sarcoma subtype crosswise between the pediatric and the adult age groups. Less satisfactory overall outcome has been recorded in adult series. METHODS: This study compares clinical features and outcomes of SS across the different age groups, by analyzing 1268 cases, 213 children/adolescents (≤18 years) and 1055 adults, registered in the Surveillance, Epidemiology, and End Results (SEER) 17 database from 1983 to 2005. Cancer-specific survival estimates were compared with univariate and multivariate models. RESULTS: No major differences in stage distribution (localized, regional, and distant stage) were observed comparing the 2 age groups. The estimated 5-year cancer-specific survival was 83% for children/adolescents and 62% for adults (P < .001). Female sex, nonblack race, tumors located in the extremities, localized tumors, and tumors <5 cm in size were associated with better survival. In multivariate analysis, adult patients had significantly higher mortality rates than children after adjusting for other variables. CONCLUSIONS: Children and adults with SS have a similar clinical presentation but a dissimilar outcome, suggesting that factors other than unfavorable clinical features might be involved in the unsatisfactory outcome of adult SS patients. It remains to be ascertained whether this difference is related to biological variables or to historically different treatment approaches adopted in pediatric versus adult patients. Cancer 2009. © 2009 American Cancer Society.