Latest Articles Include:
- Micro research with big impact
- Cancer 116(3):541-542 (2010)
- Detection and treatment key topics at annual breast cancer symposium
- Cancer 116(3):543 (2010)
- Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates
Edwards BK Ward E Kohler BA Eheman C Zauber AG Anderson RN Jemal A Schymura MJ Lansdorp-Vogelaar I Seeff LC van Ballegooijen M Goede SL Ries LA - Cancer 116(3):544-573 (2009)
BACKGROUND. The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information regarding cancer occurrence and trends in the United States. This year's report includes trends in colorectal cancer (CRC) incidence and death rates and highlights the use of microsimulation modeling as a tool for interpreting past trends and projecting future trends to assist in cancer control planning and policy decisions. METHODS. Information regarding invasive cancers was obtained from the NCI, CDC, and NAACCR; and information on deaths was obtained from the CDC's National Center for Health Statistics. Annual percentage changes in the age-standardized incidence and death rates (based on the year 2000 US population standard) for all cancers combined and for the top 15 cancers were estimated by joinpoint analysis of long-term trends (1975-2006) and for short-term fixed-interval trends (1997-2006). All statistical tests were 2-sided. RESULTS. Both incidence and death rates from all cancers combined significantly declined (P < .05) in the most recent time period for men and women overall and for most racial and ethnic populations. These decreases were driven largely by declines in both incidence and death rates for the 3 most common cancers in men (ie, lung and prostate cancers and CRC) and for 2 of the 3 leading cancers in women (ie, breast cancer and CRC). The long-term trends for lung cancer mortality in women had smaller and smaller increases until 2003, when there was a change to a nonsignificant decline. Microsimulation modeling demonstrates that declines in CRC death rates are consistent with a relatively large contribution from screening and with a smaller but demonstrable impact of risk factor reductions and improved treatments. These declines are projected to continue if risk factor modification, screening, and treatment remain at current rates, but they could be accelerated further with favorable trends! in risk factors and higher utilization of screening and optimal treatment. CONCLUSIONS. Although the decrease in overall cancer incidence and death rates is encouraging, rising incidence and mortality for some cancers are of concern. Cancer 2010. © 2009 American Cancer Society. - Paired specimens : An opportunity to answer some important questions
Haas NB - Cancer 116(3):574-576 (2009)
This editorial in response to Histologic Evaluation of Metastases in Renal Cell Carcinoma With Sarcomatoid Transformation and Its Implications for Systemic Therapy concludes that a molecular analysis of paired specimens is critical in determining whether sarcomatoid features will play a role in future therapy for this poor prognosis cancer. - Complex care systems in developing countries : Breast cancer patient navigation in Ethiopia
Dye TD Bogale S Hobden C Tilahun Y Hechter V Deressa T Bizé M Reeler A - Cancer 116(3):577-585 (2009)
BACKGROUND: As the global visibility and importance of breast cancer increases, especially in developing countries, ensuring that countries strengthen and develop health systems that support prevention, diagnosis, and treatment of a complex chronic disease is a priority. Understanding how breast cancer patients navigate health systems to reach appropriate levels of care is critical in assessing and improving the health system response in countries to an increasing breast cancer burden in their populations. Ethiopia has accelerated attention to breast cancer, expanding clinical and public health efforts at diagnosing and treating breast cancer earlier and more efficiently. METHODS: This project used a mixed-method approach to assessing patient navigation of the healthcare system that resulted in care at the cancer referral hospital for Ethiopia (Tikur Anbessa Hospital [TAH]). In total, 69 patients representative of the entire breast cancer clinical population at TAH were interviewed. RESULTS: Navigation chains are widely divergent and typically involve 3 or more care nodes until they reach the referral hospital. Patients who consult traditional healers have significantly more care nodes to reach the referral hospital than others, and patients who have direct access to local and regional hospitals have the smallest number of care nodes. Patients report moving laterally from 1 health institution to another or regressing to lower levels of care, sometimes complicated by reinvolving traditional healers. CONCLUSIONS: The care system can be streamlined for breast cancer patients in Ethiopia to facilitate patient access to available and clinically effective diagnostic and treatment services in the country, largely through improving local primary care and hospital capacity to provide basic breast cancer services and improve detection and referral. Cancer 2010. © 2009 American Cancer Society. - Life expectancy of screen-detected invasive breast cancer patients compared with women invited to the Nijmegen screening program
Otten JD Broeders MJ Den Heeten GJ Holland R Fracheboud J De Koning HJ Verbeek AL - Cancer 116(3):586-591 (2009)
BACKGROUND: Screening can lead to earlier detection of breast cancer and thus to an improvement in survival. The authors studied the life expectancy of women with screen-detected invasive breast cancer (patients) compared with women invited to the breast cancer screening program in Nijmegen, the Netherlands (comparison group). METHODS: Each patient diagnosed between 1975 and 2006 was randomly age-matched with a woman invited in the same calendar year and free from breast cancer at the time of diagnosis of the patient. Survival analyses were performed to study differences in life expectancy. RESULTS: The life expectancy for 858 patients was 6 years shorter than for the comparison group. However, for 360 patients with small (<15 mm) invasive breast cancer, life expectancy was similar to that of the comparison group. In contrast, for patients detected with larger tumors (15 mm) the life expectancy was 6 to 12 years shorter, depending on tumor size. Furthermore, life expectancy was modified by screening history. For patients who had a negative screening examination 2 years before the detection of their breast cancer, the difference in life expectancy from the comparison group became smaller for the larger tumor sizes (15 mm). CONCLUSIONS: In conclusion, about 40% (360 of 858) of all women with invasive screen-detected breast cancer have the same life expectancy as women from the comparison group (reflecting the general population). For women diagnosed with larger tumors at diagnosis, life expectancy diminishes with increasing tumor size and is modified by screening history. Cancer 2010. © 2009 American Cancer Society. - Antimullerian hormone and inhibin B are hormone measures of ovarian function in late reproductive-aged breast cancer survivors
Su HI Sammel MD Green J Velders L Stankiewicz C Matro J Freeman EW Gracia CR Demichele A - Cancer 116(3):592-599 (2009)
BACKGROUND: In late reproductive-aged breast cancer survivors, there is a need for real-time biomarkers of postchemotherapy ovarian function. The objective was to determine whether antimullerian hormone (AMH) and inhibin B are such biomarkers. The authors tested whether AMH and inhibin B were impacted by breast cancer treatment by comparing cancer survivors to age-matched control women and determined the association between these hormones and postchemotherapy menstrual pattern. METHODS: Breast cancer patients (n = 127) with American Joint Committee on Cancer stage I to III disease who were premenopausal at diagnosis were enrolled postchemotherapy and observed. The primary endpoint was chemotherapy-related amenorrhea (CRA) (12 months of amenorrhea after chemotherapy). Matched pair analyses compared AMH, inhibin B, and follicle-stimulating hormone (FSH) levels between cancer and age-matched control subjects. Associations between hormones, CRA status, and change in CRA status over time were assessed. RESULTS: The median age of the patients at chemotherapy was 43.2 years (range, 26.7-57.8 years). At enrollment, median follow-up since chemotherapy was 2.1 years, and 55% of subjects had CRA. Compared with age-matched controls, cancer subjects had significantly lower AMH (P = .004) and inhibin B (P < .001) and higher FSH (P < .001). AMH (P = .002) and inhibin B (P = .001) were found to be significantly associated with risk of CRA, even after controlling for FSH. AMH was significantly lower (P = .03) and FSH was significantly higher (P = .04) in menstruating subjects who developed subsequent CRA. CONCLUSIONS: AMH and inhibin B are 2 additional measures of postchemotherapy ovarian function in late reproductive-aged breast cancer survivors. With further research and validation, these hormones may supplement limited current tools for assessing and predicting postchemotherapy ovarian function. Cancer 2010. © 2009 American Cancer Society. - Reactive antibodies against bacillus Calmette-Guerin heat-shock protein-65 potentially predict the outcome of immunotherapy for high-grade transitional cell carcinoma of the bladder
Ardelt PU Kneitz B Adam P Reiss C Kocot A Fensterle J Chen L Pasqualini R Arap W Gerharz EW Riedmiller H - Cancer 116(3):600-609 (2009)
BACKGROUND: Intravesical immunotherapy with Mycobacteriumbovis (M. bovis) bacillus Calmette-Guerin (BCG) is the current standard of care against superficial, high-grade transitional cell carcinoma (TCC) of the urinary bladder (carcinoma in situ and pathologic T1, grade 3 disease). However, individual patient outcome is barely predictable because of the lack of serum markers. Consequently, progression to muscle-invasive bladder cancer and critical delay of treatments (such as neoadjuvant combination chemotherapy and/or radical cystectomy) often occur. The objectives of this study were to identify a marker for measuring the BCG-induced immune response and to predict the outcomes and potential improvements of BCG immunotherapy. METHODS: Because host immunoresponse mediates BCG activity, the authors screened a combinatorial random peptide library on the circulating pool of immunoglobulins (Igs) purified from an index patient after successful BCG immunotherapy to identify the corresponding target antigen(s). RESULTS: An immunogenic peptide motif was selected, isolated, and validated from M. bovis BCG heat-shock protein 65 (HSP-65) as a dominant epitope of the humoral response to treatment. Increasing IgA and IgG anti-HSP-65 titers specifically predicted a positive patient outcome in a cohort of patients with bladder cancer relative to several cohorts of control patients. CONCLUSIONS: The current results indicated that antibody production against M. bovis BCG HSP-65 can serve as a serologic marker for the predictive outcome of BCG immunotherapy. Subsequent studies will determine the value of this candidate marker to modify BCG-based treatment for individual patients with bladder cancer. Cancer 2010. © 2009 American Cancer Society. - Comorbidity, body mass index, and age and the risk of nonprostate-cancer-specific mortality after a postradiation prostate-specific antigen recurrence
Nguyen PL Chen MH Beard CJ Suh WW Choueiri TK Efstathiou JA Hoffman KE Loffredo M Kantoff PW D'Amico AV - Cancer 116(3):610-615 (2009)
BACKGROUND: Some men with a postradiation therapy (RT) prostate-specific antigen (PSA) recurrence will die of noncancer causes before developing metastases. Therefore, our ability to determine who would benefit from salvage hormonotherapy (HT) would be enhanced if an individual's risk of nonprostate-cancer-specific mortality were known. METHODS: Among 206 men with unfavorable-risk localized prostate cancer initially randomized to RT+/-HT, 87 men who experienced PSA recurrence were studied. Fine and Gray's competing risks regression was used to assess whether body mass index (BMI) and the Adult Comorbidity Evaluation-27 comorbidity level at randomization were associated with the risk of nonprostate-cancer-specific mortality after PSA recurrence, adjusting for age at recurrence. RESULTS: After a median postrecurrence follow-up of 4.4 years, moderate/severe comorbidity (adjusted hazard ratio [HR] = 3.15; P = .02), BMI median (27.4 kg/m2; adjusted HR=2.98; p=.04), and increasing age at recurrence (adjusted HR = 1.17; P = .03) were significantly associated with an increased risk of nonprostate-cancer-specific mortality. Five-year cumulative incidence estimates of nonprostate-cancer-specific mortality were as follows: 0% (95% confidence interval [CI] [0,0]) for low-risk patients (mild/no comorbidity and age- Histologic evaluation of metastases in renal cell carcinoma with sarcomatoid transformation and its implications for systemic therapy
Shuch B Said J Larochelle JC Zhou Y Li G Klatte T Pouliot F Kabbinavar FF Belldegrun AS Pantuck AJ - Cancer 116(3):616-624 (2009)
BACKGROUND: Sarcomatoid features in renal cell carcinoma may represent an aggressive subclone arising from the primary tumor. The patterns of metastases for these tumors were evaluated to determine if sarcomatoid features were retained at metastasis and whether the percentage of sarcomatoid features in the primary tumor influenced spread. METHODS: All patients with sarcomatoid features found at nephrectomy with synchronous or metachronous resection of metastases were evaluated. The histology, grade, and percentage of sarcomatoid features in the primary and metastatic site were recorded. The association between percentage of sarcomatoid features, grade, histology, and pattern of metastases was evaluated. RESULTS: Thirty-two patients were identified with sarcomatoid features and resected metastases. Fifty-two metastatic sites were evaluated. A single histologic appearance (sarcomatoid or carcinomatoid) was present in 50 of 52 sites (96%). Thirty sites (58%) demonstrated only a sarcomatoid pattern, whereas 20 (38%) contained only a carcinoma pattern. Histology and carcinoma grade did not influence metastatic pattern; however, greater percentage of sarcomatoid features was associated with the presence of distant sarcomatoid histology. A cutoff of 30% sarcomatoid features in the primary tumor was useful in predicting systemic sarcomatoid histology. CONCLUSIONS: Sarcomatoid elements are frequently observed in the metastases of primary tumors with sarcomatoid features, and these metastases generally contain a solitary pattern supporting the subclone hypothesis. However, both components can metastasize in the same patient. The percentage of sarcomatoid features influences the pattern of spread, and patients with >30% sarcomatoid features in the primary tumor frequently have distant sarcomatoid histology. This cutpoint may be helpful for inclusion criteria for future clinical trials. Cancer 2010. © 2009 American Cancer Society.- Pelvic fractures after radiotherapy for cervical cancer : Implications for Survivors
Schmeler KM Jhingran A Iyer RB Sun CC Eifel PJ Soliman PT Ramirez PT Frumovitz M Bodurka DC Sood AK - Cancer 116(3):625-630 (2010)
BACKGROUND: The incidence of pelvic fractures and associated risk factors was determined in women treated with curative-intent radiotherapy for cervical cancer. METHODS: The records of 516 women treated with curative-intent radiotherapy for cervical cancer between 2001 and 2006 at the University of Texas M. D. Anderson Cancer Center were reviewed. Among these, 300 patients had at least 1 post-treatment computed tomography scan or magnetic resonance imaging study available for review, and they comprised our study population. All imaging studies were re-reviewed by a single radiologist to evaluate for fractures. RESULTS: Pelvic fractures were noted in 29 of 300 patients (9.7%). Fracture sites included sacrum (n = 24; 83%), sacrum and pubis (n = 3; 10%), iliac crest (n = 1; 3%), and sacrum and acetabulum (n = 1; 3%). Thirteen patients (45%) were symptomatic, with pain being the most common presenting symptom. The median time from the completion of radiotherapy to the detection of fractures on imaging studies was 14.1 months (range, 2.1-63.1 months), with 38% of patients diagnosed within 1 year and 83% diagnosed within 2 years of completing therapy. The median age of the patients at diagnosis was higher in the women who developed a fracture compared with the women who did not (56.5 years vs 46.7 years; P = .04). A higher number of women with a fracture were postmenopausal (62% vs 37%; P = .03). The median body mass index was lower in the women who had a fracture (26.0 kg/m2 vs 28.0 kg/m2; P = .03). CONCLUSIONS: Pelvic fractures were detected in a substantial proportion of women after radiotherapy for cervical cancer. Bone mineral density screening and pharmacologic intervention should be considered in these women. Cancer 2010. © 2010 American Cancer Society.- Nodular, lymphocyte-predominant Hodgkin lymphoma : A long-term study and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the Adult Lymphoma Study Group
Biasoli I Stamatoullas A Meignin V Delmer A Reman O Morschhauser F Coiffier B Bosly A Diviné M Brice P - Cancer 116(3):631-639 (2009)
BACKGROUND: Nodular, lymphocyte-predominant Hodgkin lymphoma (NLPHL) represents a rare entity. METHODS: A clinical registry was launched from 1973 to 2003 in France. To determine the histologic transformation (HT) rate to diffuse large B-cell lymphoma (DLBCL) and long-term outcomes, 164 patients were selected after histologic review. RESULTS: The median follow-up was 9.5 years. The high biopsy rate (85%) at each recurrence enabled the analysis of HT. The median patient age was 30 years (range, 6-69 years), 80% of patients were men, 83% had Ann Arbor stage I/II disease, 65% had supradiaphragmatic-disease; 27% received radiotherapy, 9% received chemotherapy, 29% received combined-modality therapy, and 35% were followed with a watch-and-wait strategy. All 106 treated patients achieved complete remission and 66 patients developed disease recurrence at a median of 3.3 years (range, 0.4-18.3 years after diagnosis). The majority of recurrences were NLPHL, but 19 patients progressed to DLBCL at a median of 4.7 years (range, 0.4-18 years after diagnosis). The 10-year cumulative HT rate was 12% and was found to be associated significantly with a poor prognosis. The 10-year overall survival rate was 91%. Fourteen patients died (7 died of progressive disease, 3 died of secondary cancers, and 4 died from other causes). HT was! diagnosed at a median of 4.7 years (range, 0.4-18 years after diagnosis). The 19 patients who had HT were treated with curative intent: Nine patients received high-dose therapy with subsequent autologous stem cell transplantation (ASCT), and 10 patients received different chemotherapy regimens. The overall survival rate after HT did not differ between patients who underwent ASCT and the others. CONCLUSIONS: This long-term follow-up study confirmed that NLPHL is a separate entity that has a favorable clinical presentation and outcome despite frequent recurrences. The current findings also emphasize the importance of biopsies at the time patients develop recurrent disease to evaluate HT. Cancer 2010. © 2009 American Cancer Society.- Residual serum monoclonal protein predicts progression-free survival in patients with previously untreated multiple myeloma
Schaefer EW Kumar S Dispenzieri A Allred JB Gertz MA Lacy MQ Rajkumar SV Mandrekar SJ - Cancer 116(3):640-646 (2009)
BACKGROUND: Currently used treatment response criteria in multiple myeloma (MM) are based in part on serum monoclonal protein (M-protein) measurements. A drawback of these criteria is that response is determined solely by the best level of M-protein reduction, without considering the serial trend. The authors hypothesized that metrics incorporating the serial trend of M-protein would be better predictors of progression-free survival (PFS). METHODS: Fifty-five patients with measurable disease at baseline (M-protein 1 g/dL) who received 4 cycles of treatment from 2 clinical trials in previously untreated MM were included. Three metrics based on the percentage of M-protein remaining relative to baseline (residual M-protein) were considered: metrics based on the number of times residual M-protein fell within prespecified thresholds, metrics based on area under the residual M-protein curve, and metrics based on the average residual M-protein reduction between Cycles 1 and 4. The predictive value of these metrics was assessed in Cox models using landmark analysis. RESULTS: The average residual M-protein reduction was found to be significantly predictive of PFS (P = .02; hazard ratio, 0.37), in which a patient with a 10% lower average residual M-protein reduction from Cycle 1 to 4 was estimated to be at least 2.7× more likely to develop disease progression or die early. None of the other metrics was predictive of PFS. The concordance index for the average residual M-protein reduction was 0.63, compared with 0.56 for best response. CONCLUSIONS: The average residual M-protein reduction metric is promising and needs further validation. This exploratory analysis is the first step in the search for treatment-based trend metrics predictive of outcomes in MM. Cancer 2010. © 2009 American Cancer Society.- Long-term outcomes after hepatic resection for colorectal metastases in young patients
de Haas RJ Wicherts DA Salloum C Andreani P Sotirov D Adam R Castaing D Azoulay D - Cancer 116(3):647-658 (2009)
BACKGROUND: Long-term outcomes after hepatectomy for colorectal liver metastases in relatively young patients are still unknown. The aim of the current study was to evaluate long-term outcomes in patients 40 years old, and to compare them with patients >40 years old. METHODS: All consecutive patients who underwent hepatectomy for colorectal liver metastases at the authors' hospital between 1990 and 2006 were included in the study. Patients 40 years old were compared with all other patients treated during the same period. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) rates were determined, and prognostic factors were identified. RESULTS: In total, 806 patients underwent hepatectomy for colorectal liver metastases, of whom 56 (7%) were aged 40 years. Among the young patients, more colorectal liver metastases were present at diagnosis, and they were more often diagnosed synchronous with the primary tumor. Five-year OS was 33% in young patients, compared with 51% in older patients (P = .12). Five-year PFS was 2% in young patients, compared with 16% in older patients (P < .001). DFS rates were comparable between the groups (17% vs 23%, P = .10). At multivariate analysis, age 40 years was identified as an independent predictor of poor PFS. CONCLUSIONS: In young patients, colorectal liver metastases seem to be more aggressive, with a trend toward lower OS, more disease recurrences, and a significantly shorter PFS after hepatectomy. However, DFS rates were comparable between young and older patients, owing to an aggressive multimodality treatment approach, consisting of chemotherapy and repeat surgery. Therefore, physicians should recognize the poor outcome of colorectal liver metastases in young patients and should consider an aggressive approach to diagnosis and early treatment. Cancer 2010. © 2009 American Cancer Society.- Prognostic significance of grading in lung adenocarcinoma
Barletta JA Yeap BY Chirieac LR - Cancer 116(3):659-669 (2009)
BACKGROUND: Although grading has prognostic significance for many tumor types, a prognostically significant grading system for lung adenocarcinoma has not yet been established. The aim of this study was to evaluate histologic characteristics included in tumor grading systems, establish optimal cutoff values that have the strongest association with overall survival, and develop a grading system incorporating the histopathologic characteristics that the authors found to have prognostic significance in patients with lung adenocarcinoma. METHODS: The authors studied lung adenocarcinomas from 85 consecutive patients, and evaluated the percentage of solid pattern (as a reflection of tumor architecture), the degree of cytologic atypia, and the mitotic count. RESULTS: In univariate analysis, overall survival was associated significantly with sex (P = .045), age (P = .0008), tumor status (P < .0001), lymph node status (P = .02), solid pattern (P = .046), and cytologic atypia (P = .01), but not with mitotic count (P = .26). On the basis of optimal cutoff values, the authors found that a solid pattern 90% and severe cytologic atypia were the best discriminators of worse outcome. A grading score, computed as the sum of the architecture score and cytologic atypia score (2 = well differentiated, 3 = moderately differentiated, 4 = poorly differentiated), was a significant predictor of overall survival in univariate analysis (median overall survival times, 72.4, 39.5, and 8.7 months for well, moderately, and poorly differentiated adenocarcinoma, respectively; P = .0001). Moreover, grading was an independent predictor of survival in multivariate analysis (P = .002). CONCLUSIONS: The authors describe a grading system that incorporates the percentage of solid pattern and degree of the cytologic atypia that is an independent predictor of survival in patients with lung adenocarcinoma. Cancer 2010. © 2009 American Cancer Society.- Pack-years of cigarette smoking as a prognostic factor in patients with stage IIIB/IV nonsmall cell lung cancer
Janjigian YY McDonnell K Kris MG Shen R Sima CS Bach PB Rizvi NA Riely GJ - Cancer 116(3):670-675 (2009)
BACKGROUND: This study was undertaken to characterize the relation between the survival of patients with stage IIIB/IV nonsmall cell lung cancer (NSCLC) and pack-years of cigarette smoking (graded according to the American Joint Committee on Cancer staging system). METHODS: Data were analyzed from patients with stage IIIB/IV NSCLC who had completed a prospective smoking questionnaire. The impact of pack-years of cigarette smoking, age, sex, Karnofsky performance status (KPS), and the presence of weight loss >5% was evaluated on overall survival using univariate and multivariate analyses. RESULTS: Smoking history and clinical data were available for 2010 patients with stage IIIB/IV NSCLC (1004 women and 1006 men). Approximately 70% of patients (1409 patients) had smoked >15 pack-years, 13% (270) were former and current smokers who had smoked 15 pack-years, and 16% (331) were never-smokers (<100 lifetime cigarettes). Never-smokers had a longer median survival compared with former or current smokers (17.8 months vs 11.3 months; log-rank P < .001). Among smokers, patients with a 15 pack-year history of smoking had a longer median survival than patients who had smoked >15 pack-years (14.6 months vs 10.8 months; log-rank P = .03). As the number of pack-years increased, the median overall survival decreased (log-rank P < .001). Multivariate analysis indicated that a history of smoking was an independent prognostic factor (hazard ratio, 1.36; P < .001). CONCLUSIONS: More cigarette smoking, measured in pack-years, was associated with decreased survival after a diagnosis of stage IIIB/IV NSCLC. Trials assessing survival in patients with stage IIIB/IV NSCLC should report a detailed cigarette smoking history for all patients. Cancer 2010. © 2009 American Cancer Society.- Clinical impact of phosphorylated signal transducer and activator of transcription 3, epidermal growth factor receptor, p53, and vascular endothelial growth factor receptor 1 expression in resected adenocarcinoma of lung by using tissue microarray
Kim HS Park YH Lee J Ahn JS Kim J Shim YM Kim JH Park K Han J Ahn MJ - Cancer 116(3):676-685 (2010)
BACKGROUND: The signal transducer and activator of transcription 3 (STAT3) play a key role in the downstream pathway of the epidermal growth factor receptor (EGFR) in nonsmall cell lung cancer and promote cell proliferation, invasion, and angiogenesis. The clinical significance of phosphorylated STAT3 (pSTAT3), EGFR, p53, and vascular endothelial growth factor receptor 1 (VEGFR-1) expression in patients with completely resected lung adenocarcinoma was evaluated to determine the effects of pSTAT3 in tumor angiogenesis and proliferation. METHODS: The expressions of pSTAT3, EGFR, p53, and VEGFR-1 were evaluated by immunohistochemical staining of tissue microarrays from 162 samples of resected lung adenocarcinoma. RESULTS: The median age of the 162 patients was 62 years, the median disease-free survival was 41.7 months, and the median OS (OS) was 80.2 months. Expression of pSTAT3, EGFR, p53, and VEGFR-1 was detected in 51.2%, 71%, 35.2%, and 35.2% of the samples, respectively. pSTAT3 expression was correlated significantly with VEGFR-1 expression (P = .025). The coexpression of pSTAT3 and VEGFR-1 was correlated with increased lymph node involvement (P = .021) and a trend toward a short OS (P = .085). In multivariate analysis, the expression levels of p53 and VEGFR-1 were identified as independent prognostic factors that affected OS. CONCLUSIONS: The results of this study suggested that pSTAT3 and VEGFR-1 expression may play roles in the tumor progression and angiogenesis of lung adenocarcinoma. Further studies are needed, however, to uncover the detailed mechanisms that underlie the roles of these proteins in lung adenocarcinoma. Cancer 2010. © 2010 American Cancer Society.- Underutilization of radiotherapy for lung cancer in New South Wales, Australia
Vinod SK Simonella L Goldsbury D Delaney GP Armstrong B O'Connell DL - Cancer 116(3):686-694 (2009)
BACKGROUND: Lung cancer is the leading cause of cancer death in most developed countries. Radiotherapy is important in its treatment, with an estimated optimal utilization rate between 45% and 68% at initial diagnosis. The objective of this study was to describe radiotherapy practice for lung cancer in New South Wales (NSW), Australia. METHODS: Patients with lung cancer were identified prospectively from the NSW Central Cancer Registry (CCR) from November 1, 2001 to December 31, 2002. Questionnaires were mailed to diagnosing and treating clinicians to obtain detailed information on diagnosis, staging, referrals, and treatment. The authors describe referral for and receipt of radiotherapy treatment. RESULTS: Of 1812 patients with lung cancer patients who were identified, 943 patients (52%) were referred for radiotherapy, 846 patients (47%) received a radiotherapy questionnaire, and 727 patients (40%) received radiotherapy. Compared with optimal radiotherapy, there was less curative radiotherapy to the primary site (20% actual vs 50% optimal), and there was more palliative radiotherapy to metastatic sites (36% actual vs 11% optimal). The greatest shortfall in radiotherapy use was observed in patients who had limited stage small cell lung cancer (46% actual vs 94% optimal). The use of combined-modality treatment for stage III nonsmall cell lung cancer and for limited stage small cell lung cancer was uncommon. CONCLUSIONS: There is underutilization of radiotherapy for lung cancer in NSW, especially in small cell lung cancer. The use of combined-modality treatment for potentially curable lung cancers is suboptimal. These issues have to be addressed to improve survival and quality of life for patients with lung cancer. Cancer 2010. © 2009 American Cancer Society.- Quantitative assessment of cardiorespiratory fitness, skeletal muscle function, and body composition in adults with primary malignant glioma
Jones LW Friedman AH West MJ Mabe SK Fraser J Kraus WE Friedman HS Tresch MI Major N Reardon DA - Cancer 116(3):695-704 (2009)
BACKGROUND: The study was undertaken to evaluate cardiorespiratory fitness, skeletal muscle function, and body composition of patients with newly diagnosed and untreated, postsurgical primary malignant glioma. METHODS: By using a cross-sectional design, patients with clinically stable (10 ± 7 days postsurgery) high-grade glioma (HGG; n = 25) or low-grade glioma (LGG; n = 10) were studied. Participants performed a cardiopulmonary exercise test (CPET) with expired gas analysis to assess cardiorespiratory fitness (peak oxygen consumption, VO2peak). Other physiological outcomes included skeletal muscle cross-sectional area (CSA; magnetic resonance imaging), isokinetic muscle strength (isokinetic dynamometer), and body composition (air displacement plethysmography). Quality of life was assessed with the Functional Assessment of Cancer Therapy-Brain scale. RESULTS: CPET was a feasible and safe procedure to assess VO2peak, with no serious adverse events. VO2peak indexed to total body weight and lean body mass (LBM) for both groups was 13.0 mL · weight · min-1 and 19 mL · LBM · min-1, the equivalent to 59% and 38% below age- and sex-predicted normative values, respectively. Skeletal muscle strength and mid-thigh CSA were lower in HGG relative to LGG patients (83 vs 125 Nm, P = .025; 94 vs 119 cm2, P = .171, respectively). Skeletal muscle isokinetic strength, CSA, and body composition outcomes predicted VO2peak (r = -0.59 to 0.68, P < .05). CONCLUSIONS: Postsurgical glioma patients have markedly reduced cardiorespiratory fitness, isokinetic strength, and CSA. Prospective studies are now required to determine whether such abnormalities influence treatment toxicity and clinical outcome as well as to test the effect of appropriately selected interventions to prevent and/or mitigate dysfunction. Cancer 2010. © 2009 American Cancer Society.- Intensive chemotherapy improves survival in pediatric high-grade glioma after gross total resection: results of the HIT-GBM-C protocol
Wolff JE Driever PH Erdlenbruch B Kortmann RD Rutkowski S Pietsch T Parker C Metz MW Gnekow A Kramm CM - Cancer 116(3):705-712 (2009)
BACKGROUND: The authors hypothesized that intensified chemotherapy in protocol HIT-GBM-C would increase survival of pediatric patients with high-grade glioma (HGG) and diffuse intrinsic pontine glioma (DIPG). METHODS: Pediatric patients with newly diagnosed HGG and DIPG were treated with standard fractionated radiation and simultaneous chemotherapy (cisplatin 20 mg/m2 × 5 days, etoposide 100 mg/m2 × 3 days, and vincristine, and 1 cycle of cisplatin + etoposide + ifosfamide 1.5 g/m × 5 days [PEI] during the last week of radiation). Subsequent maintenance chemotherapy included further cycles of PEI in Weeks 10, 14, 18, 22, 26, and 30, followed by oral valproic acid. RESULTS: Ninety-seven (pons, 37; nonpons, 60) patients (median age, 10 years; grade IV histology, 35) were treated. Resection was complete in 21 patients, partial in 29, biopsy only in 26, and not performed in 21. Overall survival rates were 91% (standard error of the mean [SE] ± 3%), 56%, and 19% at 6, 12, and 60 months after diagnosis, respectively. When compared with previous protocols, there was no significant benefit for patients with residual tumor, but the 5-year overall survival rate for patients with complete resection treated on HIT-GBM-C was 63% ± 12% SE, compared with 17% ± 10% SE for the historical control group (P = .003, log-rank test). CONCLUSIONS: HIT-GBM-C chemotherapy after complete tumor resection was superior to previous protocols. Cancer 2010. © 2009 American Cancer Society.- A black-white comparison of the quality of stage-specific colon cancer treatment
Berry J Caplan L Davis S Minor P Counts-Spriggs M Glover R Ogunlade V Bumpers K Kauh J Brawley OW Flowers C - Cancer 116(3):713-722 (2009)
BACKGROUND: Several studies have attributed racial disparities in cancer incidence and mortality to variances in socioeconomic status and health insurance coverage. However, an Institute of Medicine report found that blacks received lower quality care than whites after controlling for health insurance, income, and disease severity. METHODS: To examine the effects of race on colorectal cancer outcomes within a single setting, the authors performed a retrospective cohort study that analyzed the cancer registry, billing, and medical records of 365 university hospital patients (175 blacks and 190 whites) diagnosed with stage II-IV colon cancer between 2000 and 2005. Racial differences in the quality (effectiveness and timeliness) of stage-specific colon cancer treatment (colectomy and chemotherapy) were examined after adjusting for socioeconomic status, health insurance coverage, sex, age, and marital status. RESULTS: Blacks and whites had similar sociodemographic characteristics, tumor stage and site, quality of care, and health outcomes. Age and diagnostic stage were predictors of quality of care and mortality. Although few patients (5.8%) were uninsured, they were more likely to present at advanced stages (61.9% at stage IV) and die (76.2%) than privately insured and publicly insured patients (p = .002). CONCLUSIONS: In a population without racial differences in socioeconomic status or insurance coverage, patients receive the same quality of care, regardless of racial distinction, and have similar health outcomes. Age, diagnostic stage, and health insurance coverage remained independently associated with mortality. Future studies of disparities in colon cancer treatment should examine sociocultural barriers to accessing appropriate care in various healthcare settings. Cancer 2010. © 2009 American Cancer Society.- Are patients of low socioeconomic status receiving suboptimal management for pancreatic adenocarcinoma?
Cheung MC Yang R Byrne MM Solorzano CC Nakeeb A Koniaris LG - Cancer 116(3):723-733 (2009)
BACKGROUND: The objective of this study was to define the effects of socioeconomic status (SES) and other demographic variables on outcomes for patients with pancreatic adenocarcinoma. METHODS: Florida cancer registry and inpatient hospital data were queried for pancreatic adenocarcinoma diagnosed from 1998 to 2002. RESULTS: In total, 16,104 patients were identified. Low SES (LSES) patients were younger at diagnosis (P < .001) but presented with similar disease stage and tumor grade. LSES patients were less likely to receive surgical extirpation (16.5% vs 19.8%; P < .001), chemotherapy (30.7% vs 36.4%; P < .001), or radiotherapy (14.3% vs 16.9%; P = .003). Among surgical patients, 30-day mortality was significantly higher (5.1% vs 3.7%; P < .001) and overall median survival was significantly worse (5.0 months vs 6.2 months; P < .001) in the LSES cohorts. Although surgical patients who were treated at teaching facilities (TF) did significantly better; an increased 30-day surgical mortality (2.2% vs 1.3%; P < .001) and decreased median survival (5 months for poverty level >15% vs 6.2 months for poverty level <5%; P < .001) also were observed for patients of LSES. In a multivariate analysis that corrected for patient comorbidities, significant independent predictors of a poorer prognosis included L! SES (hazard ratio [HR], 1.09); treatment at a non-TF (HR, 1.09); and failure to receive surgical extirpation (HR, 1.92), chemotherapy (HR 1.41), or radiation (HR 1.25). CONCLUSIONS: Patients of LSES were less likely to receive surgical extirpation, chemotherapy, or radiation and had significantly higher perioperative and long-term mortality rates. A greater understanding of the barriers to providing optimal care and identifying means for improving successful delivery of therapies to the poor with pancreatic cancer are needed. Cancer 2010. © 2009 American Cancer Society.- Racial disparities in the use of radiotherapy after breast-conserving surgery: A national Medicare study
Smith GL Shih YC Xu Y Giordano SH Smith BD Perkins GH Tereffe W Woodward WA Buchholz TA - Cancer 116(3):734-741 (2009)
BACKGROUND: In prior studies, the use of standard breast cancer treatments has varied by race, but previous analyses were not nationally representative. Therefore, in a comprehensive, national cohort of Medicare patients, racial disparities in the use of radiotherapy (RT) after breast-conserving surgery (BCS) for invasive breast cancer were quantified. METHODS: A national Medicare database was used to identify all beneficiaries (age >65 years) treated with BCS for incident invasive breast cancer in 2003. Claims codes identified RT use, and Medicare demographic data indicated race. Logistic regression modeled RT use in white, black, and other-race patients, adjusted for demographic, clinical, and socioeconomic covariates. RESULTS: Of 34,080 women, 91% were white, 6% were black, and 3% were another race. The mean age of the patients was 76 ± 7 years. Approximately 74% of whites, 65% of blacks, and 66% of other-race patients received RT (P < .001). After covariate adjustment, whites were found to be significantly more likely to receive RT than blacks (odds ratio, 1.48; 95% confidence interval, 1.34-1.63 [P < .001]). Disparities between white and black patients varied by geographic region, with blacks in areas of the northeastern and southern United States demonstrating the lowest rates of RT use (57% in these regions). In patients age <70 years, racial disparities persisted. Specifically, 83% of whites, 73% of blacks, and 78% of other races in this younger group received RT (P < .001). CONCLUSIONS: In this comprehensive national sample of older breast cancer patients, substantial racial disparities were identified in RT use after BCS across much of the United States. Efforts to improve breast cancer care require overcoming these disparities, which exist on a national scale. Cancer 2010. © 2009 American Cancer Society.- Evaluation of direct medical costs of hospitalization for febrile neutropenia
Lathia N Mittmann N Deangelis C Knowles S Cheung M Piliotis E Shear N Walker S - Cancer 116(3):742-748 (2009)
BACKGROUND: Treatment of febrile neutropenia (FN) is costly, because it typically involves hospitalization. As cancer rates continue to increase, the number of patients suffering from FN will also increase, making it important to quantify the costs of treating this condition accurately and comprehensively. METHODS: A consecutive sample of patients admitted to an inpatient hematology/oncology ward at a tertiary care hospital for the treatment of chemotherapy-induced FN was enrolled in this study. Patients were followed prospectively during hospitalization, and information on medical resource utilization including length of stay, medications, and laboratory and diagnostic tests was collected. Costs, extracted from hospital and provincial databases, were used to calculate the overall cost per FN episode, from the hospital perspective. RESULTS: Fifty-one episodes of FN that occurred in 46 patients were included in the study. Approximately 52% of these episodes occurred in women, and 65% of these episodes occurred in patients with hematologic malignancies. The mean ± standard deviation age of patients was 60.3 ± 13.4 years. The mean length of stay per episode was 6.8 ± 4.9 days. The mean overall cost per episode was 6324 ± 4783 in 2007 Canadian dollars. CONCLUSIONS: Hospitalization for the treatment of FN is expensive. The results of this study could be used in future economic evaluations of preventive measures and treatments for FN, including primary prophylactic administration of hematopoietic growth factors and outpatient treatment of this condition. Cancer 2010. © 2009 American Cancer Society.- Angiogenesis and vascular targeting in Ewing sarcoma : A review of preclinical and clinical data
Dubois SG Marina N Glade-Bender J - Cancer 116(3):749-757 (2009)
Ewing sarcoma is the second most common type of bone cancer in children and young adults. In recent years, the mechanisms by which these tumors develop and maintain their vascular supply have been elucidated. Additional work has demonstrated that inhibition of angiogenic pathways or disruption of established vasculature can attenuate the growth of Ewing sarcoma mouse xenografts. Early clinical data suggest that these results also may extend to patients with Ewing sarcoma who are treated with antiangiogenic or antivascular therapies. For the current review, the authors summarized the available data supporting this approach. Cancer 2010. © 2009 American Cancer Society.- Distinct features of colorectal cancer in children and adolescents : A population-based study of 159 cases
Sultan I Rodriguez-Galindo C El-Taani H Pastore G Casanova M Gallino G Ferrari A - Cancer 116(3):758-765 (2009)
BACKGROUND: Colorectal cancer is exceedingly rare in children and adolescents. Reports from small series indicate that poor prognostic factors are more common in children than in adults, resulting in worse outcome for the pediatric population. METHODS: The Surveillance, Epidemiology, and End Results database was searched for records of children/adolescents with colorectal cancer, and the features and outcomes were compared with those of adults. RESULTS: From January 1973 through December 2005, only 159 children/adolescents (ages 4-20 years) were reported with a diagnosis of colorectal cancer. The most common sites of involvement were the rectum (27%) and the transverse colon (26%). Adenocarcinoma was the most common histiotype in both adults and pediatric patients; however, children/adolescents had more unfavorable histiotypes (ie, mucinous adenocarcinoma [22%] and signet ring cell carcinoma [18%]) when compared with adults (10% and 1%, respectively; P < .001). Poorly differentiated and undifferentiated tumors (grades III and IV, respectively) and distant stage were more common in children/adolescents (P < .001). The 5-year relative survival estimates in children/adolescents and adults were 40% ± 4.2% and 60% ± 0.10%, respectively, confirming a worse outcome in the pediatric age group (P < .001). CONCLUSIONS: Children/adolescents represent a minority of patients with colorectal cancer and have high-risk features and worse outcome than adults. The small number of patients in this age group was an impediment to the development of meaningful clinical trials. Thus, the principles of management for adult colorectal cancer should be used in the treatment of children and adolescents. Cancer 2010. © 2009 American Cancer Society.- Placebo and nocebo effects in randomized double-blind clinical trials of agents for the therapy for fatigue in patients with advanced cancer
de la Cruz M Hui D Parsons HA Bruera E - Cancer 116(3):766-774 (2009)
BACKGROUND: A significant response to placebo in randomized controlled trials of treatments for cancer-related fatigue (CRF) had been reported. A retrospective study was conducted to determine the frequency and predictors of response to placebo effect and nocebo effects in patients with CRF treated in those trials. METHODS: The records of 105 patients who received placebo in 2 previous randomized clinical trials conducted by this group were reviewed. The proportion of patients who demonstrated clinical response to fatigue, defined as an increase in Functional Assessment of Chronic Illness Therapy-Fatigue score of 7 from baseline to Day 8, and the proportion of patients with a nocebo effect, defined as those reporting >2 side effects, were determined. Baseline patient characteristics and symptoms recorded using the Edmonton Symptom Assessment Scale (ESAS) were analyzed to determine their association with placebo and nocebo effects. RESULTS: Fifty-nine (56%) patients had a placebo response. Worse baseline anxiety and well-being subscale score (univariate) and well-being (multivariate) were significantly associated with placebo response. Commonly reported side effects were insomnia (79%), anorexia (53%), nausea (38%), and restlessness (34%). Multivariate analysis indicated that worse baseline (ESAS) sleep, appetite, and nausea were associated with increased reporting of the corresponding side effects. CONCLUSIONS: Greater than half of advanced cancer patients enrolled in CRF trials had a placebo response. Worse baseline physical well-being score was associated with placebo response. Patients experiencing specific symptoms at baseline were more likely to report these as side effects of the medication. These findings should be considered in the design of future CRF trials. Cancer 2010. © 2009 American Cancer Society.- Erratum
- Cancer 116(3):775 (2009)
- Histologic evaluation of metastases in renal cell carcinoma with sarcomatoid transformation and its implications for systemic therapy
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