Tuesday, April 6, 2010

Hot off the presses! Apr 06 Cancer

The Apr 06 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:

  • Community networks program hits 5-year mark
    - Cancer 116(8):1841-1843 (2010)
  • AANCART uses many routes to reach minority populations
    - Cancer 116(8):1842 (2010)
  • Declines in ductal hyperplasia may be linked to hormone therapy reduction
    - Cancer 116(8):1843 (2010)
  • Disrupting established tumor blood vessels : An emerging therapeutic strategy for cancer
    McKeage MJ Baguley BC - Cancer 116(8):1859-1871 (2010)
    The unique characteristics of tumor vasculature represent an attractive target that may be exploited by vascular-targeting anticancer agents. A promising strategy involves the selective disruption of established tumor blood vessels by tumor-vascular disrupting agents (tumor-VDAs), which exhibit antivascular activity, resulting in inhibition of tumor blood flow and extensive necrosis within the tumor core. The tumor-VDA class can be subdivided into flavonoid compounds, which are related to flavone acetic acid, and tubulin-binding compounds. ASA404, of the flavonoid class, is the most advanced tumor-VDA in clinical development and has been evaluated preclinically and in several phase 1 and phase 2 studies. Preclinical studies have demonstrated the selective apoptosis of tumor endothelial cells and the inhibition of tumor blood flow. Synergistic activity was observed with ASA404 and with several chemotherapeutic agents, particularly taxanes. In clinical trials, compared w! ith chemotherapy alone, ASA404 was tolerated well and produced improved activity in patients with nonsmall cell lung cancer when combined with paclitaxel and carboplatin. Phase 3 clinical trials are ongoing. Selectively targeting established tumor vasculature with tumor-VDAs represents a promising and innovative approach to improving the efficacy of standard anticancer therapies. Cancer 2010. © 2010 American Cancer Society.
  • Angiosarcoma after breast-conserving therapy : Long-term outcomes with hyperfractionated radiotherapy
    Palta M Morris CG Grobmyer SR Copeland EM Mendenhall NP - Cancer 116(8):1872-1878 (2010)
    BACKGROUND: With breast-conserving therapy (BCT) as the standard of care for patients with noninvasive and early stage invasive breast cancer, a small incidence of post-BCT angiosarcoma has emerged. The majority of therapeutic interventions have been unsuccessful. To the authors' knowledge, there is no consensus in the medical literature to date regarding the treatment of this malignancy. The current study was conducted to report the long-term outcomes of a novel approach using hyperfractionated and accelerated radiotherapy (HART) for angiosarcoma developing after BCT. METHODS: The authors retrospectively reviewed the outcomes of 14 patients treated with HART with or without surgery at the University of Florida between November 1997 and March 2006 for angiosarcoma that developed after BCT. RESULTS: At the time of last follow-up, 9 patients had remained continuously without evidence of disease for a median of 61 months after HART (range, 36-127 months). Five patients had further manifestations of angiosarcoma after HART at a median of 1 month (range, 1-28 months): 3 with progressive pulmonary and/or mediastinal disease that was likely present before HART and 2 with local or regional disease extension. Progression-free survival rates for the 14 patients at 2 years and 5 years were 71% and 64%, respectively. The overall and cause-specific survival rates were both 86% at 2 years and 5 years. CONCLUSIONS: To the best of the authors' knowledge, HART with or without subsequent surgery, as documented in the current series, is the first approach to provide a high rate of local control, disease-free survival, and overall survival after the development of post-BCT angiosarcoma. The authors believe the success noted with this approach is related to both the hyperfractionation and acceleration of the RT. Cancer 2010. © 2010 American Cancer Society.
  • Patient-reported acute gastrointestinal symptoms during concurrent chemoradiation treatment for rectal cancer
    Chen RC Mamon HJ Chen YH Gelman RS Suh WW Talcott JA Clark JW Hong TS - Cancer 116(8):1879-1886 (2010)
    BACKGROUND: Although it is known that standard 5-fluorouracil-based chemoradiation therapy for rectal cancer causes significant acute gastrointestinal (GI) toxicity, research on patient-reported outcomes (PROs) is limited. The authors undertook the current study to assess the feasibility of incorporating PRO measurement into routine clinical practice and to describe the trajectory of symptom development during treatment. METHODS: Seventy-seven consecutive patients who were treated between 2006 and 2008 were eligible. Patients completed the 7-item Bowel Problems Scale immediately before weekly physician visits. RESULTS: The questionnaire completion rate was 95%. Individual GI symptoms had different trajectories of development. By Week 5, approximately 40% of all patients developed clinically meaningful pain, bowel urgency, or tenesmus that was not present during Week 1; 30% developed diarrhea, abdominal cramping, and passing mucus. However, overall symptom burden was moderate. Seventy-five percent of patients who presented with rectal bleeding at Week 1 improved by Week 3 of treatment. Within each physician-assessed grade of diarrhea, patient experience varied widely. For example, of the 50 patients who developed grade 2 diarrhea on the Radiation Therapy Oncology Group Acute Morbidity Scale, the numbers of patients reporting only occasional symptoms versus those reporting frequent or very frequent symptoms were similar. CONCLUSIONS: PROs provided information on patient symptoms during chemoradiation treatment for rectal cancer that was not captured otherwise, and it was feasible to incorporate PROs into routine clinical practice. The current results may be used by physicians to counsel their patients before treatment initiation and to provide a benchmark against which trials that use new therapies may be compared. Cancer 2010; 116:1879-86. © 2010 American Cancer Society.
  • Impact of postoperative prostate-specific antigen disease recurrence and the use of salvage therapy on the risk of death
    Choueiri TK Chen MH D'Amico AV Sun L Nguyen PL Hayes JH Robertson CN Walther PJ Polascik TJ Albala DM Moul JW - Cancer 116(8):1887-1892 (2010)
    BACKGROUND: This report evaluated whether biochemical recurrence (BCR) as a time-dependent covariate (t) after radical prostatectomy (RP) for prostate cancer was associated with the risk of death and whether salvage therapy with radiotherapy (RT) and/or hormonal therapy (HT) can lessen this risk METHODS: This was a retrospective cohort study of 3071 men who underwent RP at Duke University between 1988 and 2008 and had complete follow-up data. A Cox regression multivariable analysis was used to determine whether BCR (t) was associated with the risk of death in men after adjusting for age, prostatectomy findings, and the use of salvage RT and/or HT. RESULTS: After a median follow-up of 7.4 years, 546 (17.8%) men experienced BCR and 454 (14.8%) died. The median follow-up after prostate-specific antigen (PSA) failure was 11.2 years (interquartile range, 5.8-16.0 years). BCR (t) was associated with an increased risk of death (adjusted hazards ratio [AHR], 1.03; 95% confidence interval [95% CI], 1.004-1.06 [P = .025]). In men who experienced BCR, a PSA doubling time <6 months was associated with an increased risk of death (AHR, 1.55; 95% CI, 1.15-2.1 [P = .004]); whereas a decrease in the risk of death was observed in men who received RT (AHR, 0.58; 95% CI, 0.40-0.58 [P = .002]) or HT (AHR, 0.56; 95% CI, 0.37-0.84 [P = .005]) after BCR. CONCLUSIONS: The occurrence of BCR was found to increase the risk of death in men undergoing RP for prostate cancer, and this risk appeared to increase as the time to BCR shortened. However, the addition of RT and/or HT in men with BCR significantly lowered this risk. Cancer 2010. © 2010 American Cancer Society.
  • Gemcitabine versus bacille Calmette-Guérin after initial bacille Calmette-Guérin failure in non-muscle-invasive bladder cancer : A multicenter prospective randomized trial
    Di Lorenzo G Perdonà S Damiano R Faiella A Cantiello F Pignata S Ascierto P Simeone E De Sio M Autorino R - Cancer 116(8):1893-1900 (2010)
    BACKGROUND: The efficacy of intravesical gemcitabine was evaluated compared with repeated administration of bacille Calmette-Guérin (BCG) after BCG failure in high-risk, non-muscle-invasive bladder cancer (BC). METHODS: In this multicenter, prospective, randomized, phase 2 trial, eligible patients were those with high-risk non-muscle-invasive BC, failing 1 course of BCG therapy. All patients were randomly allocated to Group A, receiving intravesical gemcitabine (at a dose of 2000 mg/50 mL) twice weekly for 6 consecutive weeks and then weekly for 3 consecutive weeks at 3, 6, and 12 months, or Group B, receiving intravesical BCG (Connaught strain, 81 mg/50 mL) over a 6-week induction course and each week for 3 weeks at 3, 6, and 12 months. Outcome measures were recurrence rate, time to first recurrence, and progression rate. Treatment-related complications were also evaluated. RESULTS: Eighty participants were enrolled, 40 for each group 52.5% in Group A developed disease recurrence versus 87.5% of those in Group B (P = .002). There was no statistically significant difference in mean time to the first recurrence (Group A, 3.9 months; Group B, 3.1 months; P = .09). Kaplan-Meier analysis of 2-year recurrence-free survival showed significant differences between Group A and B (19% and 3%, respectively, P < .008). Seven of 21 (33%) patients in Group A and 13 of 35 (37.5%) patients in Group B had disease progression and underwent radical cystectomy (P = .12). Both intravesical administrations were generally well tolerated. CONCLUSIONS: Gemcitabine might represent a second-line treatment option after BCG failure in high-risk non-muscle-invasive BC patients. Cancer 2010. © 2010 American Cancer Society.
  • Effect of a minimum lymph node policy in radical cystectomy and pelvic lymphadenectomy on lymph node yields, lymph node positivity rates, lymph node density, and survivorship in patients with bladder cancer
    Fang AC Ahmad AE Whitson JM Ferrell LD Carroll PR Konety BR - Cancer 116(8):1901-1908 (2010)
    BACKGROUND: Extended pelvic lymphadenectomy (PLND) during radical cystectomy (RC) reportedly improves bladder cancer-specific survival. Lymph node counts are often a proxy for the extensiveness of a dissection. In the current study, the impact of an institutional policy requiring a minimum number of lymph nodes was assessed. METHODS: Patients undergoing RC and PLND for invasive bladder cancer between March 2000 and February 2008 were retrospectively reviewed at the study institution. Beginning March 1, 2004, a policy was established that at least 16 lymph nodes had to be examined. Specimens with <16 lymph nodes were resubmitted (including any fat) to detect additional lymph nodes. Lymph node yields, lymph node positivity, lymph node density (LND), and survivorship before and after policy implementation were compared. RESULTS: A total of 147 patients underwent surgery 4 years before policy implementation and 202 underwent surgery 4 years after. The median number of lymph nodes increased from 15 to 20. Percentage of cases with 16 lymph nodes increased from 42.9% to 69.3% (P <.01). The lymph node positivity rates did not change significantly, but the proportion of patients with LND <20% increased from 43.9% to 65.5% (P = .04). Overall survival increased from 41.5% to 72.3% (P <.01). Univariate and multivariate regression demonstrated that policy implementation, and subsequent increase in median lymph node yield, decreased mortality risk by 30% (hazards ratio [HR], 0.70; P = .04) and 48% (HR, 0.52; P = .01), respectively. CONCLUSIONS: Thorough evaluation of PLND specimens obtained at RC can be influenced by an institutional policy mandating a minimum number of lymph nodes. This could lead to greater confidence in pathologic staging and reliability of LND as a predictor of prognosis. Survival can improve due to increased awareness to perform a more thorough PLND. Cancer 2010. © 2010 American Cancer Society.
  • Sex or survival : Short-term versus long-term androgen deprivation in patients with locally advanced prostate cancer treated with radiotherapy
    Wilke DR Krahn M Tomlinson G Bezjak A Rutledge R Warde P - Cancer 116(8):1909-1917 (2010)
    BACKGROUND: Combined long-term androgen deprivation (LTAD) and radiation conveys a prostate cancer-specific survival advantage over combined short-term androgen deprivation (STAD) and radiation. The seminal question is whether or not the gains are worth the adverse effects of LTAD with respect to patient preferences. METHODS: Preferences for LTAD compared with STAD were elicited by direct patient interview using the probability trade-off method. Time trade-off utilities (TTOu) for erectile dysfunction and osteoporosis were elicited using the time trade-off method. Participants' current prostate cancer-specific health state was assessed using the Patient-Oriented Prostate Utility Scale-Psychometric. Participants' current sexual function was assessed using the International Index of Erectile Function (IIEF). RESULTS: All participants were willing to trade survival rather than undergo LTAD compared with STAD. The mean minimally required increment in prostate cancer-specific survival (MRIS) was 8.2%. The mean TTOu for impotence was 0.78, and the mean TTOu for osteoporosis was 0.71. The MRIS was correlated with the Sexual Desire domain score of the IIEF (Spearman rank-correlation coefficient, r = 0.50; P<.0001). CONCLUSIONS: Patients desired more prostate cancer-specific survival than what was afforded by LTAD and radiotherapy compared with STAD and radiotherapy. Cancer 2010. © 2010 American Cancer Society.
  • Plasma cell-free DNA in ovarian cancer : An independent prognostic biomarker
    Kamat AA Baldwin M Urbauer D Dang D Han LY Godwin A Karlan BY Simpson JL Gershenson DM Coleman RL Bischoff FZ Sood AK - Cancer 116(8):1918-1925 (2010)
    BACKGROUND: Cell-free DNA reflects both normal and tumor-derived DNA released into the circulation through cellular necrosis and apoptosis. The authors sought to determine the role of preoperative total plasma cell-free DNA levels in predicting clinical outcome in patients with ovarian cancer. METHODS: After institutional review board consent, DNA was extracted from plasma of 164 women with invasive epithelial ovarian carcinoma (EOC), 49 with benign ovarian neoplasms, and 75 age-matched controls. The samples were randomly divided into training (n = 144) and validation (n = 144) sets. Quantification of cell-free DNA was performed using real-time polymerase chain reaction for -globin, and the number of genome equivalents (GE) per milliliter of plasma was determined. Cell-free DNA was correlated with clinicopathologic parameters. RESULTS: The training and validation sets were similar in terms of demographic features. In the training set, EOC patients had a median preoperative cell-free DNA level of 10,113 GE/mL, compared with patients with benign ovarian neoplasms (median, 2365 GE/mL; P < .0001) and controls (median, 1912 GE/mL, P < .0001). Cell-free DNA >22,000 GE/mL was significantly associated with decreased patient survival (P < .001). After adjusting for other clinical variables, preoperative cell-free DNA >22,000 GE/mL was an independent predictor (P = .02) for disease-specific survival. Analysis of the validation set confirmed significantly higher cell-free DNA levels in EOC (median, 13,672 GE/mL) and that cell-free DNA >22,000 GE/mL was associated with a 2.83-fold increased risk of death from disease (P < .001). CONCLUSIONS: Preoperative plasma total cell-free DNA levels are significantly elevated in patients with EOC. Elevated plasma cell-free DNA is an independent predictor for death from disease in ovarian cancer. Cancer 2010. © 2010 American Cancer Society.
  • Circulating endothelial cells in patients with chronic lymphocytic leukemia : Clinical-prognostic and biologic significance
    Rigolin GM Maffei R Rizzotto L Ciccone M Sofritti O Daghia G Cibien F Cavazzini F Marasca R Cuneo A - Cancer 116(8):1926-1937 (2010)
    BACKGROUND: In patients with cancer, circulating endothelial cells (CECs) are increased and are correlated with an aggressive disease course. However, the clinical and biologic significance of CECs in chronic lymphocytic leukemia (CLL) remains uncertain. METHODS: In 170 patients with CLL, CEC levels were quantified by flow cytometry and were correlated with clinical and biologic data. In addition, CECs were characterized by immunophenotypic, fluorescence in situ hybridization (FISH), and gene expression profile analyses. RESULTS: In patients with CLL, CECs were increased compared with controls. A higher level of CECs (>20/L) identified a subset of patients with a more aggressive disease course characterized by a shorter time to first treatment both in univariate and multivariate analyses. In FISH analysis, 7 patients had a significant proportion of CECs and presented with the same cytogenetic lesion of neoplastic lymphocytes and immunophenotypic features of endothelial progenitor cells. The gene expression profile of sorted CECs revealed a molecular pattern, suggesting a derivation from CLL leukemic cells with increased cell survival and proliferation, diminished cell adhesion to extracellular matrix, and enhanced proangiogenic function compared with their normal counterparts. CONCLUSIONS: The current data suggest that, in CLL, CECs may represent a biologic marker of aggressiveness and disease progression to be considered for new, targeted antiangiogenic treatments. Cancer 2010. © 2010 American Cancer Society.
  • Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma
    Hassan MM Curley SA Li D Kaseb A Davila M Abdalla EK Javle M Moghazy DM Lozano RD Abbruzzese JL Vauthey JN - Cancer 116(8):1938-1946 (2010)
    BACKGROUND: Despite the observed association between diabetes mellitus and hepatocellular carcinoma (HCC), little is known about the effect of diabetes duration before HCC diagnosis and whether some diabetes medications reduced the risk of HCC development. This objective of the current study was to determine the association between HCC risk and diabetes duration and type of diabetes treatment. METHODS: A total of 420 patients with HCC and 1104 healthy controls were enrolled in an ongoing hospital-based case-control study. Multivariate logistic regression models were used to adjust for HCC risk factors. RESULTS: The prevalence of diabetes mellitus was 33.3% in patients with HCC and 10.4% in the control group, yielding an adjusted odds ratio (AOR) of 4.2 (95% confidence interval [95% CI], 3.0-5.9). In 87% of cases, diabetes was present before the diagnosis of HCC, yielding an AOR of 4.4 (95% CI, 3.0-6.3). Compared with patients with a diabetes duration of 2 to 5 years, the estimated AORs for those with a diabetes duration of 6 to 10 years and those with a diabetes duration >10 years were 1.8 (95% CI, 0.8-4.1) and 2.2 (95% CI, 1.2-4.8), respectively. With respect to diabetes treatment, the AORs were 0.3 (95% CI, 0.2-0.6), 0.3 (95% CI, 0.1-0.7), 7.1 (95% CI, 2.9-16.9), 1.9 (95% CI, 0.8-4.6), and 7.8 (95% CI, 1.5-40.0) for those treated with biguanides, thiazolidinediones, sulfonylureas, insulin, and dietary control, respectively. CONCLUSIONS: Diabetes appears to increase the risk of HCC, and such risk is correlated with a long duration of diabetes. Relying on dietary control and treatment with sulfonylureas or insulin were found to confer the highest magnitude of HCC risk, whereas treatment with biguanides or thiazolidinediones was associated with a 70% HCC risk reduction among diabetics. Cancer 2010. © 2010 American Cancer Society.
  • Route of intracerebrospinal fluid chemotherapy administration and efficacy of therapy in neoplastic meningitis
    Glantz MJ Van Horn A Fisher R Chamberlain MC - Cancer 116(8):1947-1952 (2010)
    BACKGROUND: A study was undertaken to determine whether route (intraventricular vs intralumbar) of intracerebrospinal fluid (intra-CSF) drug administration influences progression-free survival in the treatment of patients with neoplastic meningitis, which occurs in 1% to 5% of patients with known cancer. Currently available treatment options result in modest responses, which is in part a reflection of obstacles to drug delivery into the leptomeningeal space. METHODS: One hundred patients with clinically and cytologically or radiographically documented neoplastic meningitis because of solid cancers received intra-CSF liposomal cytarabine or methotrexate as specified in a randomized phase 4 trial. The 2 treatment arms were well balanced for demographic and tumor-related characteristics of known prognostic importance, including age, performance status, tumor type, extent of systemic and other central nervous system (CNS) disease, prior CNS therapy, and concurrent systemic chemotherapy. RESULTS: One hundred patients were randomized and treated (52 with sustained-release cytarabine, and 48 with methotrexate). Progression-free survival (the primary study endpoint) was identical between the sustained-release cytarabine and methotrexate treatment arms for all 100 patients (35 vs 37.5 days, P = .79). When progression-free survival was examined as a function of route of chemotherapy administration (lumbar vs ventricular), there was no difference for patients treated with sustained-release cytarabine (29 vs 43 days, P = .35). For patients treated with methotrexate, however, there was a statistically significant difference favoring patients receiving intraventricular therapy (19 vs 43 days, P = .048). CONCLUSIONS: Site of intra-CSF chemotherapy drug administration is clinically relevant with short half-life drugs such as methotrexate. Cancer 2010. © 2010 American Cancer Society.
  • Accuracy and sensitivity of computed tomography-guided percutaneous needle biopsy of pulmonary hilar lymph nodes
    Avritscher R Krishnamurthy S Ensor J Gupta S Tam A Madoff DC Murthy R Hicks ME Wallace MJ - Cancer 116(8):1974-1980 (2010)
    BACKGROUND: Because of their proximity to the pulmonary artery or vein, hilar lymph nodes are routinely biopsied with endobronchial or endoscopic ultrasonography (EUS)-guided fine-needle aspiration biopsy (FNAB). Computed tomography (CT)-guided percutaneous needle biopsy (PNB) allows the operator to acquire a larger core needle biopsy (CNB) when initial samples are inconclusive, when the suspected disease is not optimally diagnosed with FNAB, or when biomarkers are required. The purpose of this study was to retrospectively evaluate the sensitivity and accuracy of CT-guided PNB in patients with hilar adenopathy. METHODS: The authors identified 80 patients who underwent 81 CT-guided PNBs of pulmonary hilar lesions from October 2002 through December 2006 and retrospectively reviewed their medical and imaging records. The PNB sensitivity and accuracy were calculated in each case, and each case was reviewed for complications, including pneumothorax and subsequent thoracostomy tube insertion. RESULTS: PNB included FNAB and CNB in 81 (100%) and 14 (17%) procedures, respectively. Data on 69 PNB specimens (67 FNAB specimens and 13 CNB specimens) were available for statistical analysis. Overall, PNB had a sensitivity of 91.4% (95% confidence interval [CI], 81.0%-97.1%) and an accuracy rate of 92.8% (95% CI, 83.9%-97.1%). Pneumothoraxes occurred in 39 patients (48%), 26 (32%) of whom required thoracostomy tube insertion. CONCLUSIONS: CT-guided PNB of pulmonary hilar lesions has high sensitivity and accuracy and represents a viable alternative for endobronchial ultrasound- or EUS-guided FNAB when larger biopsy samples are required for diagnosis or biomarker analysis. However, the procedure can result in high rates of pneumothorax. Cancer 2010. © 2010 American Cancer Society.
  • Number of lymph nodes removed in sentinel lymph node-negative breast cancer patients is significantly related to patient age and tumor size : A new source of bias in morbidity assessment?
    Port ER Patil S Stempel M Morrow M Cody HS - Cancer 116(8):1987-1991 (2010)
    BACKGROUND: Sentinel lymph node (SLN) biopsy has been well-established for axillary lymph node staging for patients with breast cancer. For lymph node-negative patients, planned backup axillary lymph node dissection (ALND) is rarely indicated. Among patients with negative SLNs, the authors observed variation by tumor size and patient age in the total number of lymph nodes removed (SLNs plus non-SLNs). They hypothesized that this variation is an unrecognized source of bias for studies examining the morbidity of SLN biopsy. METHODS: Retrospective review of this institution's SLN database identified 4103 SLN biopsy procedures between 1997 and 2004 in which SLN biopsy was performed for prophylactic mastectomy, ductal carcinoma in situ, or T1 to T2 invasive cancers, and the SLNs were benign. RESULTS: The mean number of SLNs, non-SLNs, and total lymph nodes for all tumor sizes was 2.8, 1.5, and 4.3, respectively, and increased with tumor size (more lymph nodes were removed for T2 than for T1 tumors: 6.3 vs 4.3; P < .0001). This trend remained significant even in the later years of these investigators' experience with SLN biopsy, and was observed for 5 of 9 (56%) surgeons. More total lymph nodes were also removed in patients aged 50 years than in those aged >50 years (4.6 lymph nodes vs 4.2 lymph nodes; P = .006). In approximately 8% of patients (322 of 4103 patients), 10 lymph nodes were removed. CONCLUSIONS: The morbidity of SLN biopsy is less than that of ALND, but for pN0 patients, the total number of lymph nodes removed increased with tumor size and younger patient age. This variation is a previously unrecognized source of bias for studies that examine the morbidity of SLN biopsy. Cancer 2010. © 2010 American Cancer Society.
  • Women's experiences with genomic testing for breast cancer recurrence risk
    Tzeng JP Mayer D Richman AR Lipkus I Han PK Valle CG Carey LA Brewer NT - Cancer 116(8):1992-2000 (2010)
    BACKGROUND: Few studies have examined how patients understand and use genomic test results when deciding about treatment. This study examined how women receive and incorporate results of Oncotype DX, a genomic test that offers recurrence risk estimates, into decisions about adjuvant treatment for early stage breast cancer. METHODS: Participants in the cross-sectional study were 77 women with early stage, estrogen receptor-positive breast cancer with 0 to 3 positive lymph nodes who received Oncotype DX between 2004 and 2009. Mailed surveys, supplemented by medical chart review, assessed how women received and understood recurrence risk information based on the test. RESULTS: The most common test results were low (50%, 34 of 68) or intermediate (37%, 25 of 68) breast cancer recurrence risk. Most women accurately recalled their recurrence risk based on the test (71%) and felt they understood much of what they were told about it (67%). Approximately 25% of women recalled experiencing test-related distress. Women's perceived recurrence risk was associated with their actual genomic-based recurrence risks, having had a previous cancer diagnosis, and worry about recurrence. Women with high recurrence risk typically had chemotherapy (78%, 7 of 9), whereas only 2 with a low recurrence risk did (7%, 2 of 30). CONCLUSIONS: This is among the first studies to describe patients' experiences with genomic testing for recurrence risk. Although many women understood discussions about their genomic test results, a third reported not fully understanding these discussions, suggesting a need to aid and improve risk communication and treatment decision making. Cancer 2010. © 2010 American Cancer Society.
  • Nuclear grading of primary pulmonary adenocarcinomas : Correlation between nuclear size and prognosis
    Nakazato Y Minami Y Kobayashi H Satomi K Anami Y Tsuta K Tanaka R Okada M Goya T Noguchi M - Cancer 116(8):2011-2019 (2010)
    BACKGROUND: According to the World Health Organization Classification of Tumors, the prognostic value of morphometric cytologic atypia has not been assessed in pulmonary adenocarcinoma. METHODS: Primary tumors of 133 pulmonary adenocarcinomas 2 cm were analyzed using an image processor for analytical pathology. The results were evaluated using receiver operator characteristic curve analysis, and survival curves were drawn by the Kaplan-Meier method. Furthermore, the results were applied to routine histological diagnosis. Four pathologists evaluated the nuclear factors relative to the size of small lymphocytes as a standard. RESULTS: By using the nuclear area and nuclear major axis dimension, lung adenocarcinomas were divisible into 2 groups showing extremely favorable prognosis and fairly favorable prognosis, without considering histological features or classification. A nuclear area level of <67 m2 was correlated with longer survival (P < .0001), and the 5-year survival rate was 90.4%. Similarly, a nuclear diameter level of <0.7 m was correlated with longer survival (P = .0002), and the 5-year survival rate was 88.6%. The mean (±standard deviation [SD]) value of the kappa statistic for the 4 pathologists who evaluated the cases using the size of small lymphocytes as a standard was 0.58 ± 0.10, and the mean (±SD) value of the accuracy metric was 0.66 ± 0.10. CONCLUSIONS: Nuclear area and nuclear major dimension are 2 useful independent markers for evaluating the prognosis of lung adenocarcinoma. Cancer 2010. © 2010 American Cancer Society.
  • Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients : A randomized double-blind study
    Lundholm K Gunnebo L Körner U Iresjö BM Engström C Hyltander A Smedh U Bosaeus I - Cancer 116(8):2044-2052 (2010)
    BACKGROUND: The short-term provision of ghrelin to patients with cancer indicates that there may be benefits from long-term provision of ghrelin for the palliative treatment of weight-losing cancer patients. This hypothesis was evaluated in a randomized, double-blind, phase 2 study. METHODS: Weight-losing cancer patients with solid gastrointestinal tumors were randomized to receive either high-dose ghrelin treatment (13 g/kg daily; n = 17 patients) or low-dose ghrelin treatment (0.7 g/kg daily; n = 14 patients) for 8 weeks as a once-daily, subcutaneous injections. Appetite was scored on a visual analog scale; and food intake, resting energy expenditure, and body composition (dual x-ray absorpitometry) were measured before the start of treatment and during follow-up. Serum levels of ghrelin, insulin, insulin-like growth factor 1, growth hormone (GH), triglycerides, free fatty acids, and glucose were measured. Health-related quality of life, anxiety, and depression were assessed by using standardized methods (the 36-item Short Form Health Survey and the Hospital Anxiety and Depression Scale). Physical activity, rest, and sleep were measured by using a multisensor body monitor. RESULTS: Treatment groups were comparable at inclusion. Appetite scores were increased significantly by high-dose ghrelin analyzed both on an intent-to-treat basis and according to the protocol. High-dose ghrelin reduced the loss of whole body fat (P < .04) and serum GH (P < .05). There was a trend for high-dose ghrelin to improve energy balance (P < .07; per protocol). Otherwise, no statistically significant differences in outcome variables were observed between the high-dose and low-dose groups. Adverse effects were not observed by high-dose ghrelin, such as serum levels of tumor markers (cancer antigen 125 [CA 125], carcinoembryonic antigen, and CA 19-9). CONCLUSIONS: The current results suggested that daily, long-term provision of ghrelin to weight-losing cancer patients with solid tumors supports host metabolism, improves appetite, and attenuates catabolism. Cancer 2010. © 2010 American Cancer Society.
  • Validation and application of a module of the M. D. Anderson Symptom Inventory for measuring multiple symptoms in patients with gastrointestinal cancer (the MDASI-GI)
    Wang XS Williams LA Eng C Mendoza TR Shah NA Kirkendoll KJ Shah PK Trask PC Palos GR Cleeland CS - Cancer 116(8):2053-2063 (2010)
    BACKGROUND: The M. D. Anderson Symptom Inventory (MDASI) was developed as a brief yet comprehensive tool to assess patient-reported symptom severity and interference in patients with cancer. The authors report the development of an MDASI module for use in patients with gastrointestinal (GI) cancer (the MDASI-GI). METHODS: Patients with GI cancer (N = 184) participated in module development and validation. The process included: 1) generating GI-specific candidate items with input from GI oncologists and from qualitative interviews with patients and adding those items to the core MDASI for testing; 2) dropping candidate GI items that lacked sensitivity; 3) validating the psychometric properties (validity, reliability, sensitivity) of the resulting MDASI-GI; and 4) conducting cognitive debriefing interviews with patients to confirm the questionnaire's ease of comprehension, relevance, and acceptability. RESULTS: Five GI-specific symptom items (constipation, diarrhea, difficulty swallowing, change in taste, and feeling bloated) were added to the original 19 MDASI symptom and interference items to form the MDASI-GI. Sixty-one percent of the sample had 1 or more moderate-to-severe symptom(s) (5 on a severity scale from 0 to 10). Cronbach values were .80 and .87 for symptom severity items and interference items, respectively. Known-group validity (sensitivity) was supported by the ability of the MDASI-GI to detect significant differences in symptom and interference levels according to performance status (P < .001). Cognitive debriefing demonstrated that, for patients, the MDASI-GI was an easy-to-use and understandable tool. CONCLUSIONS: The current results indicated that the MDASI-GI is a valid, reliable, and concise tool for measuring symptom severity and interference with function in patients with GI cancer. Cancer 2010.
  • Correction
    - Cancer 116(8):2064 (2010)

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