Wednesday, January 20, 2010

Hot off the presses! Jan 20 Cancer

The Jan 20 issue of the Cancer is now up on Pubget (About Cancer): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

  • CancerScope
    - Cancer 116(2):261-262 (2010)
  • Tamoxifen use tied to aggressive second cancers
    - Cancer 116(2):262 (2010)
  • Winning the war against cancer, one battle at a time
    - Cancer 116(2):263 (2010)
  • Addressing cancer health disparities using a global biopsychosocial approach
    King D Miranda P Gor B Fuchs-Young R Chilton J Hajek R Torres-Vigil I Hernández-Valero MA Snipes SA Jones L - Cancer 116(2):264-269 (2009)
    The Center for Research on Minority Health has translated the biopsychosocial framework to address global cancer health disparities through the integration of biological (eg, endogenous steroids, genetic susceptibility, and pesticide levels) and behavioral (eg, dietary interventions) determinants, along with community-based research (eg, comprehensive involvement of community advisory boards) and educational approaches (eg, kindergarten through postgraduate training). Evidence of successful implementation of this framework includes health disparities training for >2000 individuals ranging from elementary to the postgraduate level, and conducting transdisciplinary projects that incorporate traditional and nontraditional health professionals to examine associations between biological and nonbiological determinants of health. Examples and recommendations for implementation of the biopsychosocial approach as it applies to cancer health disparities research are described. C! ancer 2010. © 2010 American Cancer Society.
  • We need better randomized comparison trials of prostate cancer
    Lee WR - Cancer 116(2):270-272 (2009)
    More than 50 years after the first randomized oncology trial, the number of randomized trials comparing differing primary treatments for prostate cancer is disappointing. One of these rare, randomized primary treatment comparisons appears in this edition of Cancer, and the investigators are to be congratulated for their efforts comparing cryotherapy with external beam radiotherapy.
  • Radiotherapy for patients with the human immunodeficiency virus: Are special precautions necessary?
    Housri N Yarchoan R Kaushal A - Cancer 116(2):273-283 (2009)
    Shortly after the onset of the acquired immunodeficiency syndrome (AIDS) epidemic in the 1980s, reports of radiation-associated toxicity in patients with the human immunodeficiency virus (HIV) and AIDS began to appear in the medical literature. Although the majority of reports have focused on AIDS-defining malignancies such as Kaposi sarcoma, greater-than-expected toxicity after a course of radiotherapy or chemoradiotherapy has also been documented in cancers not generally classified as being related to HIV. With improved antiretroviral therapies, HIV patients are living longer and have the potential to develop a variety of HIV-associated and nonassociated malignancies that require treatment, including radiotherapy. This review reports the published data regarding the interactions of HIV, AIDS, and antiretroviral therapy with radiotherapy and implications for the management of malignancies in patients with HIV. Cancer 2010. Published 2009 by the American Cancer Society.
  • A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D3 in breast cancer patients with bone metastases
    Amir E Simmons CE Freedman OC Dranitsaris G Cole DE Vieth R Ooi WS Clemons M - Cancer 116(2):284-291 (2009)
    BACKGROUND: Vitamin D deficiency has potential roles in breast cancer etiology and progression. Vitamin D deficiency has also been associated with increased toxicity from bisphosphonate therapy. The optimal dose of vitamin D supplementation is unknown, but daily sunlight exposure can generate the equivalent of a 10,000-IU oral dose of vitamin D3. This study therefore aimed to assess the effect of this dose of vitamin D3 in patients with bone metastases from breast cancer. METHODS: Patients with bone metastases treated with bisphosphonates were enrolled into this single-arm phase 2 study. Patients received 10,000 IU of vitamin D3 and 1000 mg of calcium supplementation each day for 4 months. The effect of this treatment on palliation, bone resorption markers, calcium metabolism, and toxicity were evaluated at baseline and monthly thereafter. RESULTS: Forty patients were enrolled. No significant changes in bone resorption markers were seen. Despite no change in global pain scales, there was a significant reduction in the number of sites of pain. A small but statistically significant increase in serum calcium was seen, as was a significant decrease in serum parathyroid hormone. Treatment unmasked 2 cases of primary hyperparathyroidism, but was not associated with direct toxicity. CONCLUSIONS: Daily doses of 10,000 IU vitamin D3 for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption. Cancer 2010. © 2010 American Cancer Society.
  • Results of the first phase 1 clinical trial of the HER-2/neu peptide (GP2) vaccine in disease-free breast cancer patients : United States Military Cancer Institute Clinical Trials Group Study I-04
    Carmichael MG Benavides LC Holmes JP Gates JD Mittendorf EA Ponniah S Peoples GE - Cancer 116(2):292-301 (2009)
    BACKGROUND: HER-2/neu, overexpressed in breast cancer, is a source of immunogenic peptides that include GP2 and E75. Phase 2 testing of E75 as an adjuvant vaccine has suggested a clinical benefit. GP2, derived from the transmembrane portion of HER-2/neu, has differing binding characteristics and may be more immunogenic than E75. Results of the first phase 1 trial of GP2 peptide vaccine are presented. METHODS: Disease-free, lymph node-negative, human leukocyte antigen (HLA)-A2+ breast cancer patients were enrolled. This dose escalation trial included 4 groups to determine safety and optimal GP2 peptide/granulocyte-macrophage colony-stimulating factor (GM-CSF) dose. Toxicities were monitored. Immunologic response was assessed ex vivo via the HLA-A2:immunoglobulin dimer assay to detect GP2-specific CD8+ T cells (and E75-specific CD8+ T cells to assess epitope spreading) and in vivo via delayed type hypersensitivity (DTH) reaction (medians/ranges). RESULTS: Eighteen patients were enrolled. All toxicities were grade 2. Eight (88.9%) of 9 patients in the first 3 dose groups required GM-CSF dose reductions for local reactions 100 mm or grade 2 systemic toxicity. GM-CSF dose was reduced to 125 g for the final dose group. All patients responded immunologically ex vivo (GP2-specific CD8+ T cells from prevaccination to maximum, 0.4% [0.0%-2.0%] to 1.1% [0.4%-3.6%], P < .001) and in vivo (GP2 pre- to postvaccination DTH, 0 mm [0.0-19.5 mm] to 27.5 mm [0.0-114.5 mm, P < .001). E75-specific CD8+ T cells also increased in response to GP2 from prevaccination to maximum (0.8% [0.0%-2.41%] to 1.6% [0.86%-3.72%], P < .001). CONCLUSIONS: The GP2 peptide vaccine appears safe and well tolerated with minimal local/systemic toxicity. GP2 elicited HER-2/neu-specific immune responses, including epitope spreading, in high-risk, lymph node-negative breast cancer patients. These findings support further investigation of the GP2 vaccine for the prevention of breast cancer recurrence. Cancer 2010. © 2010 American Cancer Society.
  • Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neu-positive breast cancer
    Yonemori K Tsuta K Ono M Shimizu C Hirakawa A Hasegawa T Hatanaka Y Narita Y Shibui S Fujiwara Y - Cancer 116(2):302-308 (2009)
    BACKGROUND: Generally, the blood-brain barrier (BBB) of brain metastasis was thought to be disrupted. METHODS: We retrospectively performed immunohistochemical staining for glucose transporter 1 (GLUT1) and breast cancer resistance protein (BCRP) to evaluate the status of the BBB in resected brain metastases. Associations between expression of GLUT1 and/or BCRP and the immunohistochemical profiles of breast cancers, such as the statuses of hormone receptors, human epidermal growth factor receptor 2 (HER2/neu), and a basal-type marker (cytokeratin 5/6, HER1), were also analyzed. RESULTS: The study included 29 breast cancer patients with brain metastasis who had undergone brain tumor resections. Among the 29 patients, there was no expression of GLUT1 and BCRP in the intratumor microvessels of 9 (32%) and 11 (38%) patients, respectively. There was no expression of both GLUT1 and BCRP in 8 patients (28%). The expression of GLUT1 was significantly associated with that of BCRP (P < .001). A positive correlation was observed between the expression of GLUT1 and/or BCRP and brain metastases of HER2/neu-positive breast cancer (P = .012), while a negative correlation was observed between the expression of GLUT1 and/or BCRP and brain metastases of triple negative or basal-type breast cancer (P = .014 and P = .003 for triple negative and basal-type, respectively). CONCLUSIONS: Brain metastases of triple negative or basal-type breast cancers may often disrupt the BBB, whereas brain metastases of HER2/neu-positive breast cancer tend to preserve the BBB. Cancer 2010. © 2009 American Cancer Society.
  • Extracapsular lymph node spread : A new prognostic factor in gastric cancer
    Alakus H Hölscher AH Grass G Hartmann E Schulte C Drebber U Baldus SE Bollschweiler E Metzger R Mönig SP - Cancer 116(2):309-315 (2009)
    BACKGROUND: Lymphatic spread is 1 of the most relevant prognostic factors for gastric carcinoma. The current International Union Against Cancer (UICC) pN staging system is based on the number of metastatic lymph nodes and does not take into consideration the characteristics of the metastatic lymph nodes itself. The aim of the current study was to examine the prognostic value of extracapsular lymph node involvement in gastric cancer and to find correlations with clinicopathological parameters. METHODS: Tissue samples were obtained from 159 gastric cancer patients who underwent gastrectomy with D2-lymphadenectomy in 142 (89.3%) cases and subtotal gastrectomy with D2-lymphadenectomy in 17 (10.7%) cases. The number of resected lymph nodes, number of metastatic lymph nodes, and number of metastatic lymph nodes with extracapsular lymph node involvement were determined. Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the metastatic lymph node. RESULTS: Ninety-six (60.4%) patients had lymph node metastasis. In 57 (35.8%) cases, extracapsular lymph node involvement was also detected. Extracapsular lymph node involvement was significantly associated with higher pN-category (P < .001), higher pM category (P = .048), and higher UICC stages (P = .001). According to the Kaplan-Meier log-rank statistical method, extracapsular lymph node involvement was significantly associated with poor survival (P = .001). In the multivariate analysis besides pT (P < .001) and R-category (P = .009), extracapsular lymph node involvement also remained as an independent prognostic factor (P = .003), whereas the UICC pN-category (P = .822) lost its prognostic value. CONCLUSIONS: Extracapsular lymph node involvement is associated with higher tumor stages and is an independent negative prognostic factor in gastric cancer. In future staging systems for gastric cancer, extracapsular lymph node involvement should be considered. Cancer 2010. © 2009 American Cancer Society.
  • Modern systemic chemotherapy in surgically unresectable neoplasms of appendiceal origin : A single-institution experience
    Shapiro JF Chase JL Wolff RA Lambert LA Mansfield PF Overman MJ Ohinata A Liu J Wang X Eng C - Cancer 116(2):316-322 (2009)
    BACKGROUND: Appendiceal neoplasms include tumors ranging from benign-appearing cells with widespread mucin deposits to aggressive poorly differentiated signet ring cell adenocarcinomas. Traditionally, these tumors are treated with cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy. For some patients, cytoreductive surgery is not an option, and minimal published data exist in the management and outcome of these patients. A retrospective analysis was conducted to determine the benefit of modern systemic chemotherapy in patients with disseminated appendiceal neoplasm who were not considered optimal candidates for cytoreductive surgery. METHODS: A retrospective review was conducted using The University of Texas M. D. Anderson Cancer Center tumor registry between January 2000 and July 2005. Response was determined by radiographic response and/or overall clinical benefit. RESULTS: Of 186 patients diagnosed with appendiceal neoplasm, 54 (29%) patients considered to be suboptimal surgical candidates received 2 cycles of systemic chemotherapy. Thirty (55.6%) patients had a disease control rate noted as a complete response, partial response, or stable disease. After a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival were determined to be 7.6 months (95% confidence interval [CI], 4-11) and 56 months (95% CI, 36-not applicable), respectively. CONCLUSIONS: Systemic chemotherapy has a role in appendiceal neoplasm patients who are suboptimal candidates for cytoreductive surgery. The intermediate PFS indicates the challenges that exist for appendiceal neoplasm patients in this setting. Prospective randomized trials including systemic chemotherapy are needed to provide further insight into this malignancy, for which no standard exists. Cancer 2010. © 2010 American Cancer Society.
  • A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer
    Donnelly BJ Saliken JC Brasher PM Ernst SD Rewcastle JC Lau H Robinson J Trpkov K - Cancer 116(2):323-330 (2009)
    BACKGROUND: Localized prostate cancer can be treated several different ways, but head-to-head comparisons of treatments are infrequent. The authors of this report conducted a randomized, unblinded, noninferiority trial to compare cryoablation with external beam radiotherapy in these patients. METHODS: From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were assigned randomly to receive either cryoablation or radiotherapy (122 men in each arm). All received neoadjuvant antiandrogen therapy. The primary endpoint was disease progression at 36 months based on a trifecta definition: 1) radiologic evidence of metastatic disease, or 2) initiation of further antineoplastic therapy, or 3) biochemical failure. Two definitions of biochemical failure were used: 1) 2 consecutive rises in prostate-specific antigen (PSA) with a final value >1.0 ng/mL, and 2) a rise above PSA nadir + 2 ng/mL. Secondary endpoints included overall survival, disease-specific survival, and prostate biopsy at 36 months. RESULTS: The median follow-up was 100 months. Disease progression at 36 months was observed in 23.9% (PSA nadir + 2 ng/mL, 17.1%) of men in the cryoablation arm and in 23.7% (PSA nadir + 2 ng/mL, 13.2%) of men in the radiotherapy arm. No difference in overall or disease-specific survival were observed. At 36 months, more patients in the radiotherapy arm had a cancer-positive biopsy (28.9%) compared with patients in the cryoablation arm (7.7%). CONCLUSIONS: The observed difference in disease progression at 36 months was small, 0.2%; however, because of the wide confidence interval, from -10.8% to 11.2%, it was not possible to rule out inferiority (defined a priori as a 10% difference). With longer term follow-up, the trend favors cryoablation. Significantly fewer positive biopsies were documented after cryoablation than after radiotherapy. Cancer 2010. © 2009 American Cancer Society.
  • Urinary diversion and morbidity after radical cystectomy for bladder cancer
    Gore JL Yu HY Setodji C Hanley JM Litwin MS Saigal CS the Urologic Diseases in America Project - Cancer 116(2):331-339 (2009)
    BACKGROUND: The rate of continent urinary diversion after radical cystectomy for bladder cancer varies by patient and provider characteristics. Demonstration of equivalent complication rates, independent of diversion type, may decrease provider reluctance to perform continent reconstructions. The authors sought to determine whether continent reconstructions confer increased complication rates after radical cystectomy. METHODS: From the Nationwide Inpatient Sample, the authors used International Classification of Disease (ICD-9) codes to identify subjects who underwent radical cystectomy for bladder cancer during 2001-2005. They determined acute postoperative medical and surgical complications from ICD-9 codes and compared complication rates by reconstruction type using the nearest neighbor propensity score matching method and multivariate logistic regression models. RESULTS: Adjusting for case-mix differences between reconstructive groups, continent diversions conferred a lower risk of medical, surgical, and disposition-related complications that was statistically significant for bowel (3.1% lower risk; 95% confidence interval [95% CI], -6.8% to -0.1%), urinary (1.2% lower risk; 95% CI, -2.3%, to -0.4%), and other surgical complications (3.0% lower risk; 95% CI, -6.2% to -0.4%), and discharge other than home (8.2% lower risk; 95% CI, -12.1% to -4.6%) compared with ileal conduit subjects. Older age and certain comorbid conditions, including congestive heart failure and preoperative weight loss, were associated with significantly increased odds of postoperative medical and surgical complications in all subjects. CONCLUSIONS: Mode of urinary diversion after radical cystectomy for bladder cancer is not associated with increased risk of immediate postoperative complications. These results may encourage broader consideration of continent urinary diversion without concern for increased complication rates. Cancer 2010. © 2010 American Cancer Society.
  • Cytoplasmic mislocalization of the orphan nuclear receptor Nurr1 is a prognostic factor in bladder cancer
    Inamoto T Czerniak BA Dinney CP Kamat AM - Cancer 116(2):340-346 (2009)
    BACKGROUND: Nurr1 belongs to a novel class of orphan nuclear receptors (the NR4A family). The authors have previously shown that Nurr1 is important in carcinogenesis. In the current study, they examined the clinicopathologic relevance of expression patterns of Nurr1 in bladder tumors. METHODS: Nurr1 expression was determined using immunohistochemical staining in a bladder cancer tissue array (145 tumors). Tumors were classified according to Nurr1 protein levels in both cytoplasm and nucleus. Disease-specific survival and recurrence-free survival were investigated by Kaplan-Meier analysis and Cox proportional hazards analysis in multivariate models and correlated with variables such as tumor stage, growth pattern, and clinical outcome (recurrence and survival). In vitro, Nurr1 was examined for its role in bladder cancer cell proliferation and migration using small interfering RNA silencing. RESULTS: Nurr1 expression in tumor cells correlated with increasing tumor stage and invasive growth pattern. Disease-specific survival was significantly shorter in patients whose tumors demonstrated a high level of cytoplasmic Nurr1 compared with those with lower levels of cytoplasmic Nurr1 expression. Furthermore, cytoplasmic Nurr1 expression level was found to be an independent predictor of disease-specific survival (odds ratio, 4.894; P < .001). In vitro, silencing of endogenous Nurr1 attenuated the migration of bladder cancer cells. CONCLUSIONS: The expression of Nurr1 in the cytoplasm correlates with adverse outcome and is an independent prognostic marker for tumor progression and survival in patients with bladder cancer. This might represent a novel target in bladder cancer therapy. Cancer 2010. © 2010 American Cancer Society.
  • Stage migration and increasing proportion of favorable-prognosis metastatic renal cell carcinoma patients : Implications for clinical trial design and interpretation
    Patil S Ishill N Deluca J Motzer RJ - Cancer 116(2):347-354 (2009)
    BACKGROUND: The Memorial Sloan-Kettering Cancer Center risk model classifies patients with metastatic renal cell carcinoma (RCC) by 5 pretreatment features as favorable, intermediate, and poor risk. The number of Memorial Sloan-Kettering Cancer Center patients in each risk group was examined by year of treatment to analyze stage migration. METHODS: The distribution of risk groups was examined retrospectively in 789 Memorial Sloan-Kettering Cancer Center patients with metastatic RCC treated in a first-line therapy clinical trial from 1975 to 2007. Date of treatment onset was divided into 6 cohorts between 1975 and 2007 (1975-1980, 1981-1985, 1986-1990, 1991-1995, 1996-2001, and 2001-2007). RESULTS: The median age of the first-line metastatic RCC clinical trial patients was 59 years (range, 20-82 years). Most patients received cytokine therapy (55%), 37% received chemotherapy/other, and 8% received vascular endothelial growth factor-targeted therapies. Overall survival increased with each consecutive cohort year group (P < .001). Median survival was 0.43 years (95% confidence interval [CI], 0.27-0.68) in the 1973-1980 cohort and 1.5 years in the 2001-2007 cohort (95% CI, 1.15-2.11). Memorial Sloan-Kettering Cancer Center risk-group distribution shifted between 1975 and 2007 (P < .0001). The poor-risk group proportion became smaller (from 44% in 1975-1980 to 13% in 2001-2007), whereas the favorable-risk group increased (from 0% in 1975-1980 to 49% in 2001-2007). The intermediate-risk group remained stable at 50%. After adjusting for type of therapy, the shifts continue to be significant (P < .0001). CONCLUSIONS: The risk-group distribution for metastatic RCC patients in clinical trials shifted from 1975 to 2007. These shifts have direct implications for data analysis, interpretation of metastatic RCC trends, and drug development. Cancer 2010. © 2010 American Cancer Society.
  • Chemotherapy intensity and toxicity among black and white women with advanced and recurrent endometrial cancer : A Gynecologic Oncology Group Study
    Farley JH Tian C Rose GS Brown CL Birrer M Risinger JI Thigpen JT Fleming GF Gallion HH Maxwell GL - Cancer 116(2):355-361 (2009)
    BACKGROUND: The purpose of this study was to confirm whether black and white women with endometrial cancer are equally tolerant of chemotherapy and identify factors that impact survival. METHODS: A retrospective review of 169 black women and 982 white women with the International Federation of Gynecologists and Obstetricians stage III, stage IV, or recurrent endometrial carcinoma was performed. All patients received doxorubicin combined with cisplatin. Chemotherapy parameters that were reviewed included relative dose, relative time, and relative dose intensity. Treatment cycles 7 were defined as treatment completion. RESULTS: Although black patients were more likely to experience grades 3-4 anemia (20% vs 14%) and genitourinary (5% vs 1%) toxicity, and less likely to experience severe gastrointestinal toxicity (10% vs 17%), the overall incidence of grades 3-4 treatment-related chemotoxicity was the same between the 2 groups (82% vs 82%). There were no differences in the number of cycles received, relative dose (0.57 vs 0.58), relative time (0.77 vs 0.78), or relative dose intensity (0.76 vs 0.76) for black and white patients. CONCLUSIONS: Black patients with advanced stage or recurrent endometrial cancer, treated on 4 Gynecologic Oncology Group (GOG) protocols, had similar dose intensity and severe chemotherapy-related toxicity compared with white patients, suggesting that previously described racial disparities in survival among patients in GOG trials may have an novel etiology. Cancer 2010. © 2010 American Cancer Society.
  • A phase 2 study of platinum and gemcitabine in patients with advanced salivary gland cancer : A Trial of the NCIC Clinical Trials Group
    Laurie SA Siu LL Winquist E Maksymiuk A Harnett EL Walsh W Tu D Parulekar WR - Cancer 116(2):362-368 (2009)
    BACKGROUND: Salivary gland cancers are rare, histologically diverse, and varied in their biologic behavior and responsiveness to systemic therapy. To the authors' knowledge, there currently is no standard chemotherapy for these tumors, but cisplatin-based regimens are often used. This phase 2 trial evaluated the combination of gemcitabine with cisplatin (carboplatin in those with protocol-defined contraindications to cisplatin). METHODS: Fit, consenting adult patients had advanced, metastatic, or locoregionally recurrent salivary gland cancer (any histologic subtype) that was not suitable for radiation or surgery. Therapy was comprised of gemcitabine at a dose of 1000 mg/m2 administered intravenously on Days 1 and 8, and cisplatin at a dose of 70 mg/m2 on Day 2, of a 21-day cycle. If carboplatin was substituted, it was administered on Day 1, targeted to an area under the concentration-time curve of 5 mg/mL/s. Response was assessed every 2 cycles according to Response Evaluation Criteria In Solid Tumors. Patients received up to 6 cycles. The primary endpoint was objective response. A 2-stage design was used, with a response rate of 45% required to declare the regimen active. RESULTS: Thirty-three eligible patients were enrolled, of whom 30 were response evaluable. Eight objective responses were observed (1 complete and 7 partial) for a response rate of 24% (95% confidence interval, 11-42%), with responses observed in all histologic subtypes. Toxicity was within that expected for this combination. CONCLUSIONS: This regimen did not meet the predefined criteria to be declared active in advanced salivary gland cancers. Enrollment of patients with these rare cancers into well-designed clinical trials remains an urgent priority. Cancer 2010. © 2010 American Cancer Society.
  • Rapid and reliable confirmation of acute promyelocytic leukemia by immunofluorescence staining with an antipromyelocytic leukemia antibody : The M. D. Anderson Cancer Center experience of 349 patients
    Dimov ND Medeiros LJ Kantarjian HM Cortes JE Chang KS Bueso-Ramos CE Ravandi F - Cancer 116(2):369-376 (2009)
    BACKGROUND: The authors evaluated the utility of immunofluorescence staining with an antipromyelocytic leukemia (anti-PML) antibody for patients with a suspected diagnosis of new or relapsed acute promyelocytic leukemia (APL) and correlated the findings with the results of other established diagnostic modalities. METHODS: Bone marrow (BM) and/or peripheral blood (PB) smears from 349 patients in whom the diagnosis of APL was considered were assessed with the anti-PML antibody using immunofluorescence. The study group included 199 patients with confirmed APL and 150 with other conditions. The results of conventional cytogenetics, reverse transcription polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH) performed on these patients were correlated with the PML results. RESULTS: Among patients with confirmed APL, anti-PML antibody was positive in 182 of 184 BM and 32 of 33 PB smears. Conventional cytogenetics demonstrated t(15;17)(q22;q12) in 166 of 182 (91%) patients; 10 had a normal karyotype, 4 had insufficient mitoses to grow in culture, 1 was inconclusive, and 1 was 48, XX, +8, +8. Anti-PML staining was positive in 9 of 10 with a normal karyotype and in all 4 cases with insufficient mitoses. RT-PCR and FISH were positive for PML-retinoic acid receptor- in 169 of 172 (98%) and 90 of 94 (96%) cases, respectively. Among the patients without APL, 148 of 150 (98.6%) were negative with anti-PML antibody. The sensitivity and specificity of the test were 98.9% and 98.7%, respectively. CONCLUSIONS: PML immunofluorescence staining is a rapid (<4 hours turnaround time) and reliable frontline diagnostic approach that can facilitate initiation of targeted therapy, particularly in clinical settings where cytogenetic and molecular testing are not readily available. Cancer 2010. © 2009 American Cancer Society.
  • Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion
    Porkka K Khoury HJ Paquette RL Matloub Y Sinha R Cortes JE - Cancer 116(2):377-386 (2009)
    BACKGROUND: Dasatinib, a highly potent BCR-ABL inhibitor, is an effective treatment for patients with chronic myeloid leukemia in chronic phase (CML CP) after resistance, suboptimal response, or intolerance to prior imatinib. In a phase 3 dose optimization trial in patients with CML CP (CA180-034), the occurrence of pleural effusion was significantly minimized with dasatinib 100 mg once daily (QD) compared with other treatment arms (70 mg twice daily [twice daily], 140 mg QD, or 50 mg twice daily). METHODS: To investigate the occurrence and management of pleural effusion during dasatinib treatment, and efficacy in patients with or without pleural effusion, data from CA180-034 were analyzed. RESULTS: With 24-month minimum follow-up, 14% of patients treated with dasatinib 100 mg QD incurred pleural effusion (grade 3: 2%; grade 4: 0%) compared with 23% to 26% in other study arms. The pleural effusion rate showed only a minimal increment from 12 to 24 months. In the 100 mg QD study arm, median time to pleural effusion (any grade) was 315 days, and after pleural effusion, 52% of patients had a transient dose interruption, 35% had a dose reduction, 57% received a diuretic, and 26% received a corticosteroid. Three patients in the 100 mg QD study arm discontinued treatment after pleural effusion. Across all study arms, patients with or without pleural effusion demonstrated similar progression-free and overall survival, and cytogenetic response rates were higher in patients with a pleural effusion. CONCLUSIONS: Pleural effusion is minimized with dasatinib 100 mg QD dosing and its occurrence does not affect short- or long-term efficacy. Cancer 2010. © 2010 American Cancer Society.
  • Expression of interleukin 15 in primary adult acute lymphoblastic leukemia
    Wu S Fischer L Gökbuget N Schwartz S Burmeister T Notter M Hoelzer D Fuchs H Blau IW Hofmann WK Thiel E - Cancer 116(2):387-392 (2009)
    BACKGROUND: Interleukin-15 (IL-15) has been associated with the growth, survival and biological behavior of leukemic cells and response to therapy. We determined the expression of IL-15 in lymphoblasts and evaluated its potential impact on the outcome in adult acute lymphoblastic leukemia (ALL). METHODS: Between June 1999 and June 2006, ALL samples were collected from 87 adult patients before initiation of antineoplastic therapy. These patients were enrolled in the German Multicenter Acute Lymphoblastic Leukemia June 1999 and July 2003 study trials. The expression of IL-15 in leukemic cells was analyzed by real-time polymerase chain reaction. RESULTS: The expression of IL-15 correlated with the immunophenotype: T-lineage ALL had a more than 4-fold higher IL-15 mRNA expression as compared with B-cell precursor (BCP)-ALL (P < .001). Patients with BCR-ABL+-BCP-ALL had lower IL-15 expression compared with BCR-ABL--BCP-ALL (P = .041). Furthermore, higher expression of IL-15 was associated with mediastinal (P = .001) and lymph node infiltration (P = .051), but not with hepatomegaly and splenomegaly. Notably, high IL-15 expression in BCP-ALL was associated with an inferior relapse-free survival (RFS) at 5 years (0.17 ± 0.13 vs 0.47 ± 0.13) (P = .008), but there was no impact on overall survival (P = .249). CONCLUSIONS: Differential expression of IL-15 in adult ALL at diagnosis was associated with clinical features and outcome, in particular, RFS. It remains to be evaluated whether IL-15 might be a relevant therapy target, or might be used for risk stratification. Cancer 2010. © 2010 American Cancer Society.
  • Excellent outcomes with angiographic subsegmentectomy in the treatment of typical hepatocellular carcinoma : A retrospective study of local recurrence and long-term survival rates in 120 patients with hepatocellular carcinoma
    Iwamoto S Yamaguchi T Hongo O Iwamoto H Sanefuji H - Cancer 116(2):393-399 (2009)
    BACKGROUND: The authors successfully adopted an interesting and effective treatment for hepatocellular carcinoma (HCC) referred to as angiographic subsegmentectomy (AS). This treatment involved simultaneous embolization of the peripheral feeding artery and the portal vein. The result was that almost all of the HCC and peripheral liver parenchyma developed complete anatomic necrosis. METHODS: To determine the effectiveness of this method, the authors retrospectively studied the local recurrence rates of 49 solitary HCCs and the long-term survival rates of 120 patients with HCC between 2000 and 2008. RESULTS: The results indicated that, in 31 small, solitary HCCs (<2.0 cm), the local recurrence rate was only 9.6%; and, in 10 slightly larger HCCs (<3.0 cm), the local recurrence rate was only 10%. The 5-year, 8-year, and 10-year survival rates for patients with stage I and stage I/Child-Pugh grade A HCC were 74.27% and 77.65%, 53.05% and 51.76%, and 53% and 51.76%, respectively; and the 5-year, 8-year, and 10-year survival rates for patients with stage II and stage II/Child-Pugh grade A HCC were 66.21% and 71.41%, 39.9% and 39.60%, and 29.92% and 25%), respectively. There were no severe complications. CONCLUSIONS: AS should be investigated further as potential first-line therapy for the treatment of patients with stage I and II HCC. Cancer 2010. © 2010 American Cancer Society.
  • Depth of invasion determines the postresectional prognosis for patients with T1 extrahepatic cholangiocarcinoma
    Nagahashi M Shirai Y Wakai T Sakata J Ajioka Y Nomura T Tsuchiya Y Hatakeyama K - Cancer 116(2):400-405 (2009)
    BACKGROUND: We tested the hypothesis that in patients with T1 extrahepatic cholangiocarcinoma (EHC), prognosis postresection is significantly different for those with tumors that are limited to the mucosa than for those with tumors that have invaded (but not penetrated) the fibromuscular layer. METHODS: A retrospective analysis was conducted of 33 consecutive patients with pathologic T1 (pT1) EHC tumors. According to the depth of invasion, the pT1 tumors were divided into 2 groups: Group 1, tumors that were limited to the mucosa (mucosal tumors); and Group 2, tumors that had invaded (but not penetrated) the fibromuscular layer (fibromuscular layer-invasive tumors). Long-term outcomes after resection were compared between the 2 groups for a median follow-up time of 175 months. RESULTS: Eighteen patients had mucosal tumors and 15 patients had tumors that had invaded the fibromuscular layer. None of the patients with mucosal tumors had lymphovascular invasion, whereas 3 of the patients with fibromuscular layer-invasive tumors had lymphovascular invasion (P = .083). Overall survival after resection was better in Group 1 than in Group 2 (cumulative 10-year survival rate, 100% vs 52%; P = .024). The rate of disease-free survival after resection was higher in Group 1 than in Group 2 (cumulative disease-free 10-year survival rate, 100% vs 56%; P = .022). CONCLUSIONS: The long-term outcome after resection for EHC is significantly better for patients with mucosal tumors than for patients with fibromuscular layer-invasive tumors. This suggests that the depth of tumor invasion affects the postresection prognosis for patients with pT1 EHC. Cancer 2010. © 2009 American Cancer Society.
  • Stage I nonsmall cell lung cancer in patients aged 75 years : Outcomes after stereotactic radiotherapy
    Haasbeek CJ Lagerwaard FJ Antonisse ME Slotman BJ Senan S - Cancer 116(2):406-414 (2009)
    BACKGROUND: The number of patients aged 75 years who present with a stage I nonsmall cell lung cancer (NSCLC) is increasing. Elderly patients often have significant comorbidity and may be unfit for surgery. Furthermore, surgery in the elderly is associated with increased mortality and morbidity. In this study, the authors evaluated the outcomes of stereotactic radiotherapy (SRT) in elderly patients. METHODS: Since 2003, 203 tumors in 193 patients aged 75 years were treated using SRT (118 T1 tumors, 85 T2 tumors). The median patient age was 79 years, 80% of patients were considered medically inoperable, and 20% of patients declined surgery. The median Charlson comorbidity score was 4, and severe chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease Class III or greater) was present in 25% of patients. Risk-adapted SRT schemes were used with the same total dose of 60 grays in 3 fractions (33%), 5 fractions (50%), or 8 fractions (17% of patients), depending on the patient's risk for toxicity. RESULTS: SRT was well tolerated, and all but 1 patient completed treatment. Survival rates at 1 year and 3 years were 86% and 45%, respectively. Survival was correlated with performance score (P = .001) and pre-SRT lung function (P = .04). The actuarial local control rate at 3 years was 89%. Acute toxicity was uncommon, and late Radiation Therapy Oncology Group grade 3 toxicity was observed in <10% of patients. CONCLUSIONS: SRT achieved high local control rates with minimal toxicity in patients aged 75 years despite their significant medical comorbidities. These results indicated that more active diagnostic and therapeutic approaches are justified in elderly patients and that SRT should be considered and discussed as a curative treatment alternative. Cancer 2010. © 2009 American Cancer Society.
  • Characteristics associated with early and late melanoma metastases
    Brauer JA Wriston CC Troxel AB Elenitsas R Shin DB Guerry D Ming ME - Cancer 116(2):415-423 (2009)
    BACKGROUND: Differences in risk factors for metastases at different time intervals after treatment have been described in several malignancies; however, to the authors' knowledge, no extensive study examining this issue in melanoma has been conducted to date. METHODS: The authors performed a nested case-control study of patients with melanoma who presented with only local disease. Patients in the case group included 549 patients who developed metastases 6 months after surgery. Of these, 320 patients developed metastasis within 3 years after undergoing definitive surgery (early metastases [EM]), and 70 patients developed metastasis 8 years after undergoing definitive surgery (late metastases [LM]). For each case, a control patient was chosen who had melanoma but who did not develop metastases in the same interval. Univariate and conditional multivariate logistic regression were used in the analysis of 34 clinical and tumor characteristics. RESULTS: Multivariate analysis confirmed previously established risk factors for metastases, such as increasing tumor thickness. In addition, the authors discovered that a personal history of nonmelanoma skin cancer (P = .006) and a history of cancer other than skin cancer (P = .020) also were associated with metastasis. In comparing the 320 EM patients with the 70 LM patients, EM patients were more likely to have thicker lesions (P < .001), ulcerated lesions (P = .016), and a history of nonmelanoma skin cancer (P = .024). CONCLUSIONS: In this study, 2 potentially novel risk factors for melanoma metastases were identified, and different profiles of risk factors were constructed for EM versus LM. These differences may be important in future risk identification and stratification for clinical trials and for the management and treatment of patients with melanoma. Cancer 2010. © 2010 American Cancer Society.
  • Phase 2 trial of combination thalidomide plus temozolomide in patients with metastatic malignant melanoma: Southwest Oncology Group S0508
    Clark JI Moon J Hutchins LF Sosman JA Kast WM Da Silva DM Liu PY Thompson JA Flaherty LE Sondak VK - Cancer 116(2):424-431 (2009)
    BACKGROUND: In limited institution phase 2 studies, thalidomide and temozolomide has yielded response rates (RRs) up to 32% for advanced melanoma, leading to the use of this combination as standard by some. We conducted a multicenter phase 2 trial to better define the clinical efficacy of thalidomide and temozolomide and the immune modulatory effects of thalidomide, when combined with temozolomide, in patients with metastatic melanoma. METHODS: Patients must have had stage IV cutaneous melanoma, no active brain metastases, Zubrod PS 0-1, up to 1 prior systemic therapy excluding thalidomide, temozolomide, or dacarbazine, adequate organ function, and given informed consent. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included overall survival (OS), RR, toxicities, and assessment of relationships between biomarkers and clinical outcomes. Patients received thalidomide (200 mg/d escalated to 400 mg/d for patients <70, or 100 mg/d escalated to 250 mg/d for patients 70) plus temozolomide (75 mg/m2/d × 6 weeks, and then 2 weeks rest). RESULTS: Sixty-four patients were enrolled; 2 refused treatment. The 6-month PFS was 15% (95% confidence interval [CI], 6%-23%), the 1-year OS was 35% (95% CI, 24%-47%), and the RR was 13% (95% CI, 5%-25%), all partial. One treatment-related death occurred from myocardial infarction; 3 other grade 4 events occurred, including pulmonary embolism, neutropenia, and central nervous system (CNS) ischemia. There was no significant correlation between biomarkers and PFS or OS. CONCLUSIONS: This combination of thalidomide and temozolomide does not appear to have a clinical benefit that exceeds dacarbazine alone. We would not recommend it further for phase 3 trials or for standard community use. Cancer 2010. © 2010 American Cancer Society.
  • The role of postoperative radiotherapy for the treatment of gangliogliomas
    Rades D Zwick L Leppert J Bonsanto MM Tronnier V Dunst J Schild SE - Cancer 116(2):432-442 (2009)
    BACKGROUND: Because of their rarity, no prospective studies have been performed regarding gangliogliomas. The optimal treatment regimen is unclear. In this study, the authors compared 4 therapies for local control (LC) and overall survival (OS) in patients with ganglioglioma. METHODS: In 402 patients with ganglioglioma, outcomes were compared for patients who underwent gross total resection alone (GTR) (n = 188), GTR plus radiotherapy (GTR + RT) (n = 21), subtotal resection alone (STR) (n = 113), and STR plus RT (STR + RT (n = 80). Age, sex, tumor site, and histologic grade also were investigated. Subgroup analyses were performed for both low-grade and high-grade tumors. RESULTS: The 10-year LC rates were 89% after GTR, 90% after GTR + RT, 52% after STR, and 65% after STR + RT (P < .001); and the 10-year OS rates were 95%, 95%, 62%, and 74%, respectively (P < .001). After STR, irradiation significantly improved LC (P = .004) but not OS (P = .22). After GTR, irradiation did not significantly improve LC (P = .23) or OS (P = .29). On multivariate analyses, LC and OS were associated with therapy and pathologic grade, and OS also was associated with tumor site. In low-grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .18); and, after GTR, LC (P = .28) and OS (P = 1.0) were not improved with postoperative radiotherapy. In high-grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .41); after GTR, LC (P = .56) and OS (P = .61) were not improved with irradiation. CONCLUSIONS: According to this review, GTR should be performed whenever safely possible and does not require postoperative irradiation. If only STR is achieved, then RT improves LC of both low-grade and high-grade tumors and, thus, should be considered seriously. Cancer 2010. © 2010 American Cancer Society.
  • The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES)
    Haeusler J Ranft A Boelling T Gosheger G Braun-Munzinger G Vieth V Burdach S van den Berg H Juergens H Dirksen U - Cancer 116(2):443-450 (2009)
    BACKGROUND: The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES) was investigated. METHODS: We analyzed 120 patients registered into the European Ewing Tumor Working Initiative of National Groups (EURO-E.W.I.N.G. 99) trial at the trial center of Muenster from 1998 to 2006. Median age was 16.2 years. Local treatment of the primary tumor was surgery in 26 of 120 patients, surgery and radiotherapy in 21 patients, and definitive radiotherapy in 40 patients. For treatment of metastases, 6 of 120 patients received surgery; 9 patients, surgery and radiotherapy; and 33 patients, definitive radiotherapy. Forty-seven (39%) patients had local treatment of both the primary tumor and metastases, 41 (34%) patients of either the primary tumor or metastases, and 32 (27%) received no local therapy. RESULTS: Event-free survival (EFS) at 3 years was 0.24 (95% CI, 0.16-0.33). Univariate analyses demonstrated the impact of local therapy given to the primary tumor: 3-year EFS was 0.25 with surgery, 0.47 with surgery and radiotherapy, 0.23 with radiotherapy, and 0.13 when no local therapy was administered (P < .001). Three-year EFS in PDMES was also influenced by the local treatment: surgery, 0.33; surgery and radiotherapy, 0.56; radiotherapy, 0.35; no local therapy, 0.16 (P = .003). Three-year EFS was 0.39 in patients who received local treatment of both primary tumor and PDMES, compared with 0.17 in patients with any local treatment of either primary tumor or PDMES and 0.14 in patients with no local therapy (P < .001). Multivariate analysis showed absence of local treatment to be the major risk factor (HR = 2.21; P = .027; n = 20). CONCLUSIONS: Local therapy of involved sites is important for patients with PDMES and should complement systemic treatment whenever possible. Cancer 2010. © 2010 American Cancer Society.
  • Quantitative F18-fluorodeoxyglucose positron emission tomography accurately characterizes peripheral nerve sheath tumors as malignant or benign
    Benz MR Czernin J Dry SM Tap WD Allen-Auerbach MS Elashoff D Phelps ME Weber WA Eilber FC - Cancer 116(2):451-458 (2009)
    BACKGROUND: Correct pretreatment classification is critical for optimizing diagnosis and treatment of patients with peripheral nerve sheath tumors (PNSTs). The aim of this study was to evaluate whether F18-fluorodeoxyglucose positron emission tomography (FDG PET) can differentiate malignant (MPNST) from benign PNSTs. METHODS: Thirty-four adult patients presenting with PNST who underwent a presurgical FDG PET/computed tomography (CT) scan between February 2005 and November 2008 were included in the study. Tumors were characterized histologically, by FDG maximum standardized uptake value (SUVmax [g/mL]), and by CT size (tumor maximal diameter [cm]). The accuracy of FDG PET for differentiating MPNSTs from benign PNSTs (neurofibroma and schwannoma) was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: SUVmax was measured in 34 patients with 40 tumors (MPNSTs: n = 17; neurofibromas: n = 9; schwannomas: n = 14). SUVmax was significantly higher in MPNST compared with benign PNST (12.0 ± 7.1 vs 3.4 ± 1.8; P < .001). An SUVmax cutoff point of 6.1 separated MPNSTs from BPSNTs with a sensitivity of 94% and a specificity of 91% (P < .001). By ROC curve analysis, SUVmax reliably differentiated between benign and malignant PNSTs (area under the ROC curve of 0.97). Interestingly, the difference between MPNSTs and schwannomas was less prominent than that between MPNSTs and neurofibromas. CONCLUSIONS: Quantitative FDG PET imaging distinguished between MPNSTs and neurofibromas with high accuracy. In contrast, MPNSTs and schwannomas were less reliably distinguished. Given the difficulties in clinically evaluating PNST and in distinguishing benign PNST from MPNST, FDG PET imaging should be used for diagnostic intervention planning and for optimizing treatment strategies. Cancer 2010. © 2010 American Cancer Society.
  • Isolated limb infusion with cytotoxic agents: A simplified approach for venous access
    Vyas A Avritscher R Ensor J Ross M Wallace MJ - Cancer 116(2):459-464 (2009)
    BACKGROUND: Isolated limb infusion (ILI) of cytotoxic agents is a regional therapy for cutaneous malignancies in a single extremity. Conventional ILI technique requires retrograde catheterization of the contralateral femoral vein. A novel modified ILI technique uses an ipsilateral popliteal venous approach. The purpose of this study was to compare the performance of ILI using the 2 different approaches. METHODS: Data from patients who underwent lower-extremity ILI at the authors' institution between October 2005 and June 2008 were retrospectively reviewed. The authors compared the 2 ILI approaches with regard to overall procedure time, fluoroscopy time, and the number of callbacks to the operating room (OR) for flow-related issues. The Student t test and Fisher exact test were used. Adverse events, including deep venous thrombosis (DVT) in the treated limb, were recorded. RESULTS: Between October 2005 and June 2008, 67 lower-extremity ILI procedures (15 using a contralateral venous access approach and 52 using an ipsilateral venous access approach) were performed in 62 patients (28 men and 34 women aged 31-82 years). The mean fluoroscopy times for the contralateral and ipsilateral groups were 17.9 and 8.3 minutes, respectively (P = .0019). No significant difference in the overall procedure time and number of callbacks to the OR for flow-related issues between the 2 groups was identified. CONCLUSIONS: The ipsilateral popliteal venous approach is a simplified and safe ILI technique with significantly lower overall fluoroscopy procedure times required for catheter placement and no difference in catheter-related adverse events, when compared with the conventional contralateral approach. Cancer 2010. © 2010 American Cancer Society.
  • Variations in gastric cancer care : A trend beyond racial disparities
    Al-Refaie WB Gay G Virnig BA Tseng JF Stewart A Vickers SM Tuttle TM Feig BW - Cancer 116(2):465-475 (2009)
    BACKGROUND: Race is associated with patterns of presentation and survival outcomes of gastric cancer in the United States. However, the impact of race on the receipt of guideline-recommended care is not well characterized. By using current recommendations, the authors examined the association between race and guideline-recommended treatments and identified factors that are predictive of variations in gastric cancer care. METHODS: By using the National Cancer Database for 1998 through 2005, 106,002 patients with gastric adenocarcinoma were identified. Multivariate analysis techniques were used to examine the association between race, the receipt of guideline-recommended care, and survival after adjusting for covariates. RESULTS: Although African-American and Hispanic patients were more likely to undergo adequate lymphadenectomy (15 lymph nodes) and to receive care at comprehensive cancer centers and high-volume facilities (for all, P .001), they were less likely to receive adjuvant multimodality therapy for American Joint Committee on Cancer stage IB through IV, lymph node-negative (M0) disease. Up to 60% of all patients who underwent gastrectomy failed to receive adequate lymphadenectomy and adjuvant multimodality therapy. The delivery of multimodality therapy varied significantly by stage and lymph node evaluation (P .001). These findings persisted on our multivariate analyses, indicating that African-American and Hispanic patients received adequate lymph node evaluation (P .001), whereas they were associated with receiving no adjuvant multimodality therapy (P .025). CONCLUSIONS: There were significant variations in treatment for gastric cancer among ethnic groups in the United States. It was noteworthy that, although nonwhite race was associated with improved surgical care, gastric cancer care remained suboptimal overall. Cancer programs need to identify procedures to maximize the delivery of adequate gastric cancer care to all patients. Cancer 2010. © 2010 American Cancer Society.
  • The impact of health insurance status on the survival of patients with head and neck cancer
    Kwok J Langevin SM Argiris A Grandis JR Gooding WE Taioli E - Cancer 116(2):476-485 (2009)
    BACKGROUND: In 2006, it was estimated that 47 million people in the United States are without insurance. Studies have shown that patients who are uninsured or are insured by Medicaid are more likely to present with more advanced cancer. The objective of this study was to examine whether cancer recurrence and mortality of patients diagnosed with squamous cell carcinoma of the head and neck are associated with insurance status, after adjusting for known cancer risk factors. The main outcome measures were overall survival and relapse-free survival. METHODS: Retrospective cohort of patients with a biopsy-proven primary squamous cell carcinoma of the oral cavity, pharynx, or larynx diagnosed or treated at the University of Pittsburgh Medical Center between 1998 and 2007. Patients were stratified by their insurance status, including private insurance, uninsured/Medicaid, Medicare disability (Medicare under age 65), and Medicare 65 years + . Covariates included age, gender, race, smoking status, alcohol consumption, anatomic tumor site, treatment, stage at diagnosis, and occupational prestige score. Cox proportional hazards regression was used to estimate the effect of insurance status on overall survival, relapse-free survival, tumor stage, and lymph node involvement. RESULTS: A total of 1231 patients were included in the analysis. Patients with Medicaid/uninsured (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.07-2.11) and Medicare disability (HR, 1.69; 95% CI, 1.16-2.48) had significantly lower overall survival compared with patients with private insurance; the result was independent of variables known to affect outcome, such as alcohol and tobacco use. For all squamous cell carcinoma of the head and neck (SCCHN) cancer sites, Medicaid and uninsured patients were significantly more likely to present with an advanced stage tumor at diagnosis (odds ratio [OR] = 2.94; 95% CI, 1.72-5.01) and to present with at least 1 positive lymph node (OR = 1.84; 95% CI, 1.16-2.90) compared with patients with private insurance. CONCLUSIONS: Patients with Medicaid/uninsured and Medicare disability were at increased risk of death after a diagnosis of SCCHN when compared with patients with private insurance, after adjustment for age, gender, race, smoking, alcohol use, site, socioeconomic status, treatment, and cancer stage. Cancer 2010. © 2009 American Cancer Society.
  • Gene expression signatures in breast cancer distinguish phenotype characteristics, histologic subtypes, and tumor invasiveness
    Pedraza V Gomez-Capilla JA Escaramis G Gomez C Torné P Rivera JM Gil A Araque P Olea N Estivill X Fárez-Vidal ME - Cancer 116(2):486-496 (2009)
    BACKGROUND: The development of reliable gene expression profiling technology is having an increasing impact on the understanding of breast cancer biology. METHODS: In this study, microarray analysis was performed to establish gene signatures for different breast cancer phenotypes, to determine differentially expressed gene sequences at different stages of the disease, and to identify sequences with biologic significance for tumor progression. Samples were taken from patients before their treatment. After microarray analysis, the expression level of 153 selected genes was studied by real-time quantitative polymerase chain reaction analysis. RESULTS: Several gene sequences were expressed differentially in tumor samples versus control samples and also were associated with different breast cancer phenotypes, estrogen receptor status, tumor histology, and grade of tumor differentiation. In lymph node-negative tumors were identified a set of genes related to tumor differentiation grade. CONCLUSIONS: Several differentially expressed gene sequences were identified at different stages of breast cancer. Cancer 2010. © 2010 American Cancer Society.
  • Health status of the oldest adult survivors of cancer during childhood
    Kenney LB Nancarrow CM Najita J Vrooman LM Rothwell M Recklitis C Li FP Diller L - Cancer 116(2):497-505 (2009)
    BACKGROUND: Young adult survivors of childhood cancer have an increased risk for treatment-related morbidity and mortality. In this study, the authors assessed how treatment for childhood cancer affects older-adult health and health practices. METHODS: One hundred seven adults treated for childhood cancer between 1947 and 1968, known to have survived past age 50 years, were identified from a single-institution cohort established in 1975. Updated vital status on eligible cases was obtained from public records. Survivors and a control group of their age-matched siblings and cousins completed a mailed survey to assess physical and social function, healthcare practices, and the prevalence of common adult illnesses. RESULTS: Of the 107 survivors known to be alive at age 50 years, 16 were deceased at follow-up; 7 deaths could be associated with prior treatment (second malignancy in radiation field [3], small bowel obstruction after abdominal radiation [2], and cardiac disease after chest irradiation [2]). The 55 survivors (median age, 56 years; range, 51-71 years), and 32 family controls (median age, 58 years; range, 48-70 years), reported similar health practices, health-related quality of life, and social function. However, survivors reported more frequent visits to healthcare providers (P < .05), more physical impairments (P < .05), fatigue (P = .02), hypertension (P = .001), and coronary artery disease (P = .01). An increased risk of hypertension was associated with nephrectomy during childhood (odds ratio, 18.9; 95% confidence interval, 3.0-118.8). CONCLUSIONS: The oldest adult survivors of childhood cancer continue to be at risk for treatment-related complications that potentially decrease their life expectancy and compromise their quality of life. Cancer 2010. © 2010 American Cancer Society.
  • A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL)
    Ladas EJ Kroll DJ Oberlies NH Cheng B Ndao DH Rheingold SR Kelly KM - Cancer 116(2):506-513 (2009)
    BACKGROUND: Despite limited preclinical and clinical investigations, milk thistle (MT) is often used for the treatment of chemotherapy-associated hepatotoxicity. Limited treatment options exist for chemotherapy-related hepatoxicity. Given the wide use of MT, the authors investigated MT in both the laboratory and a clinical setting. METHODS: In a double-blind study, children with acute lymphoblastic leukemia (ALL) and hepatic toxicity were randomized to MT or placebo orally for 28 days. Liver function tests were evaluated during the study period. To assess MT in vitro, the authors evaluated supratherapeutic concentrations in an ALL cell line. RESULTS: Fifty children were enrolled. No significant differences in frequency of side effects, incidence and severity of toxicities, or infections were observed between groups. There were no significant changes in mean amino alanine transferase (ALT), aspartate amino transferase (AST), or total bilirubin (TB) at Day 28. At Day 56, the MT group had a significantly lower AST (P = .05) and a trend toward a significantly lower ALT (P = .07). Although not significantly different, chemotherapy doses were reduced in 61% of the MT group compared with 72% of the placebo group. In vitro experiments revealed no antagonistic interactions between MT and vincristine or L-asparaginase in CCRF-CEM cells. A modest synergistic effect with vincristine was observed. CONCLUSIONS: In children with ALL and liver toxicity, MT was associated with a trend toward significant reductions in liver toxicity. MT did not antagonize the effects of chemotherapy agents used for the treatment of ALL. Future study is needed to determine the most effective dose and duration of MT and its effect on hepatotoxicity and leukemia-free survival. Cancer 2010. © 2009 American Cancer Society
  • Survey on human papillomavirus/p16 screening use in oropharyngeal carcinoma patients in the United States
    Shoushtari AN Rahimi NP Schlesinger DJ Read PW - Cancer 116(2):514-519 (2009)
    BACKGROUND: Patients with human papillomavirus (HPV)-positive oropharyngeal carcinoma (OC) have better prognosis than patients with HPV-negative OC. The objective of the current study was to assess how different practices across the United States treat patients with OC with respect to screening for HPV DNA or p16. METHODS: Five hundred forty-two randomly selected radiation oncologists were sent an 11-question survey by email regarding the use of HPV/p16 screening in OC. The questionnaire addressed demographics of the practice, intensity-modulated radiotherapy (IMRT) use, screening practices for HPV DNA or p16, which year this began, the use of HPV or p16 data to direct patient care, and future plans for its use if it had not already been instituted. RESULTS: One hundred ninety-two responses (39.6%) were received. Thirty-five percent of respondents (67 of 188) reported screening for HPV DNA routinely, whereas 4.8% of respondents (9 of 188) reported screening for p16. Of the physicians who did not use screening techniques, 37.2% (44 of 118 respondents) reported future plans to institute these screening techniques, 20% (9 of 45 respondents) stated plans to institute these techniques in the next 6 months, 55.5% (25 of 45 respondents) stated plans to institute these techniques within 6 months to 1 year, and 22.2% (10 of 45 respondents) stated plans to institute these techniques within 1 to 2 years. Academic physicians were more likely to use screening techniques (62.7%; P < .001) compared with private practitioners (31.4%). Only 12.4% of respondents reported using HPV or p16 data to direct care. CONCLUSIONS: Approximately 40.4% of radiation oncology practices that responded to a survey in the United States screened for HPV DNA or p16 in OC, whereas only 12.4% used it to further direct care. This number appears to be growing rapidly. Clinical trials to further elucidate how HPV or p16 status should direct care in OC are warranted. Cancer 2010. © 2009 American Cancer Society.
  • Methadone initiation and rotation in the outpatient setting for patients with cancer pain
    Parsons HA de la Cruz M El Osta B Li Z Calderon B Palmer JL Bruera E - Cancer 116(2):520-528 (2009)
    BACKGROUND: Methadone is an effective and inexpensive opioid for cancer pain treatment. It has been reported as difficult to use in the outpatient setting because of its variable relative potency and long half-life. The purpose of this study was to determine the outcome of methadone initiation or rotation for cancer pain treatment in outpatient settings. METHODS: Chart review was done of 189 consecutive patients who underwent methadone initiation or rotation at the authors' palliative care outpatient center. Data were collected regarding demographic and clinical characteristics, symptoms, and opioid side effects at baseline and for 2 follow-up visits (F1, F2). Failure was defined as methadone discontinuation by the palliative care physician or patient's hospitalization for uncontrolled pain or methadone-related side effects at F1. RESULTS: One hundred (53%) initiations and 89 (47%) rotations were conducted. Success rates for methadone initiation and rotation were 82 of 89 (92%) and 85 of 100 (84%), respectively. Mean (standard deviation) age was 60 (11) years. One hundred (53%) patients were women, 138 (73%) were white, and 182 (96%) had solid cancers. The main reason for rotation was pain (65 of 89 patients, 47%). Median (interquartile range, IQR) pain scores (Edmonton Symptom Assessment Scale/0-10) were 6 (5-8), 4 (3-6), and 3 (2-5) at baseline, F1, and F2, respectively (P < .0001). Median (IQR) daily methadone dose for initiation and rotation was 10 (5-15) mg and 15 (10-30) mg at F1 (P < .0001) and 10 (8-15) mg and 18 (10-30) mg at F2 (P < .0001), respectively. Constipation and nausea improved (P < .005) after initiation/rotation to methadone. Frequency of sedation, hallucinations, myoclonus, and delirium did not increase after initiation/rotation to methadone. CONCLUSIONS: Outpatient methadone initiation and rotation for cancer pain treatment were safe, with high success rates and low side effect profiles. Cancer 2010. © 2010 American Cancer Society.
  • A multidimensional examination of correlates of fatigue during radiotherapy
    Purcell A Fleming J Bennett S McGuane K Burmeister B Haines T - Cancer 116(2):529-537 (2009)
    BACKGROUND: Cancer-related fatigue can be measured as both a unidimensional and a multidimensional construct. Unidimensional fatigue and its symptom correlates have undergone some previous investigation; however, minimal research has considered the differential effect of correlates on individual dimensions of fatigue. The objective of the current study was to investigate cancer-related fatigue in a radiotherapy sample using a multidimensional conceptualization to determine whether correlates of fatigue are consistent across all dimensions or whether each fatigue dimension has its own unique pattern of correlates. METHODS: The study used a prospective cohort design with data collected from radiotherapy patients at 3 time points; before, after, and 6 weeks after radiotherapy treatment. RESULTS: A total of 210 participants were enrolled in the study. Results indicated the following relations. Increased general fatigue was found to be associated with lower performance status, being in a de facto relationship, depression, having treatment to the brain, and reduced vigorous physical activity. Increased physical fatigue was associated with lower performance status, depression, reduced physical activity, reduced productive hours, and nausea. Higher levels of reduced activity were associated with depression, decreased participation in activities of daily living, decreased number of productive hours, and lower performance status. Higher levels of reduced motivation were associated with radiotherapy to the brain, reduced moderate physical activity, and depression. Increased mental fatigue was associated with diagnosis of a brain tumor, anxiety, depression, and sleep problems. CONCLUSIONS: The results of the current study support the recognition of multiple dimensions of fatigue, because each dimension examined had various correlates. These findings further develop our understanding of fatigue and may help clinicians provide more targeted information to people with cancer-related fatigue. Furthermore, these results can guide the development of group or individually tailored interventions that ultimately may reduce the impact of this distressing symptom on people with cancer. Cancer 2010. © 2010 American Cancer Society.
  • Locoregional recurrence of triple-negative breast cancer after breast-conserving surgery and radiation
    Puglisi F - Cancer 116(2):538 (2009)
    No Abstract.
  • Reply to Locoregional recurrence of triple-negative breast cancer after breast-conserving surgery and radiation
    Freedman GM - Cancer 116(2):538-539 (2009)
    No Abstract.
  • Erratum
    - Cancer 116(2):540 (2009)
  • Erratum
    - Cancer 116(2):540 (2009)

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