| Radiosensitivity translates into excellent local control in extremity myxoid liposarcoma
May 26, 2009 at 6:51 pm
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| | Myxoid liposarcoma has been reported to be more radiosensitive compared with other soft tissue sarcomas (STS). The authors report the results of multidisciplinary treatment of extremity myxoid liposarcoma compared with a contemporary cohort of other STS subtypes with an emphasis on the role of radiotherapy (RT) in improving local control.Between 1989 and 2004, 691 patients were identified from a prospective STS database who underwent combined management for localized extremity STS and were followed for a minimum of 12 months or until death. All patients underwent surgery together with pre or postoperative RT, depending on their presenting characteristics and resection margins. Demographics and outcomes were compared between patients with myxoid liposarcoma and other STS subtypes (other-STS).Of 691 patients, 88 patients had myxoid liposarcoma and 603 had other STS subtypes (other-STS). Median age was 48 and 60 years for the myxoid liposarcoma and other-STS groups, respectively. Median follow-up was 86 and 61 months, respectively. For myxoid liposarcoma and other-STS groups, preoperative RT was used in 57% versus 61% of patients and postoperative RT in 43% versus 39%, respectively. The 5-year local recurrence-free survival was 97.7% for patients with myxoid liposarcoma compared with 89.6% for patients with other-STS tumors (P = .008). High-grade tumors were present in 7% and 59% of myxoid liposarcoma and other-STS patients, respectively (P = .0003). Two myxoid liposarcoma patients with local recurrence had positive resection margins, whereas only 33% of patients in the other-STS group who developed a local recurrence had positive resection margins. No patients with myxoid liposarcoma required amputation as primary management, whereas 8 (1.3%) required amputation as primary management in the other-STS group. Systemic disease control was superior in myxoid liposarcoma compared with other-STS patients, with 5-year overall and metastasis-free survival rates of 93.9% versus 76.4% (P = .0008) and 89.1% versus 66.0% (P = .0001) respectively. Of 12 myxoid liposarcoma patients with distant metastases, 7 appeared in nonpulmonary sites. In comparison, 205 (34%) patients with other-STS tumors developed systemic disease but 78% had pulmonary metastases.Multidisciplinary management of extremity STS achieves high rates of local control. Myxoid liposarcoma is associated with higher rates of local control compared with other STS subtypes, after combined surgery and radiation, suggesting a particular radiosensitivity that can be exploited to improve oncologic outcome in appropriate cases. Cancer 2009. © 2009 American Cancer Society. |
| The presence of aberrant DNA methylation in noncancerous esophageal mucosae in association with smoking history
May 26, 2009 at 6:51 pm
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| | Esophageal squamous cell carcinomas (ESCCs) tend to have multiple primary lesions, and it is believed that they arise from background mucosae with accumulation of genetic/epigenetic alterations. In this study, the objective was to elucidate the effects of smoking and drinking on the accumulation of epigenetic alterations in background mucosae.Genes that are silenced in human ESCCs were searched for by treating 3 ESCC cell lines with the demethylating agent, 5-aza-2[prime]-deoxycytidine and performing oligonucleotide microarrays. Methylation levels were analyzed by quantitative methylation-specific polymerase chain reaction analysis of 60 ESCCs and their corresponding background mucosae.Forty-seven genes were identified as methylation-silenced in at least 1 of the 3 ESCC cell lines, and 14 of those genes (claudin 6 [CLDN6]; G protein-coupled receptor 158 [GPR158]; homeobox A9 [HOXA9]; metallothionein 1M [MT1M]; neurofilament, heavy polypeptide 200 kDa [NEFH]; plakophilin 1 [PKP1]; protein phosphatase 1, regulatory [inhibitor] subunit 14A [PPP1R14A]; pyrin domain and caspase recruitment domain containing [PYCARD]; R-spondin family, member 4 [RSPO4]; testis-specific protein, Y-encoded-like 5 [TSPYL5]; ubiquitin carboxyl-terminal esterase L1 [UCHL1]; zinc-finger protein 42 homolog [ZFP42]; zinc-finger protein interacting with K protein 1 homolog [ZIK1]; and zinc-finger and SCAN domain containing 18 [ZSCAN18]) were used as markers. In the background mucosae, methylation levels of 5 genes (HOXA9, MT1M, NEFH, RSPO4, and UCHL1) had significant correlations with smoking duration ([rho] = .268; P = .044; [rho] = .405; P = .002; [rho] = .285; P = .032; [rho] = .300; P = .024; and [rho] = .437; P = .001, respectively). In contrast, an inverse correlation between PYCARD methylation levels and alcohol intake was observed ([rho] = -.334, P = .025) among individuals with the inactive aldehyde dehydrogenase 2 (ALDH2) genotype.The current results suggested that ESCCs developed from an epigenetic field for cancerization, which was induced by exposure to carcinogenic factors, such as tobacco smoking. The epigenetic field defect will be a novel target for risk diagnosis and prevention of ESCCs. Cancer 2009. © 2009 American Cancer Society. |
| Making a link between childhood physical abuse and cancer
May 26, 2009 at 6:51 pm
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| | Abuse in childhood is associated with many negative adult health outcomes. Only 1 study to date has found an association between childhood abuse and cancer. By using a regionally representative community sample, this preliminary study sought to investigate the association between childhood physical abuse and cancer while controlling for 3 clusters of risk factors: childhood stressors, adult health behaviors, and adult socioeconomic status.Regional data from the Canadian provinces of Manitoba and Saskatchewan were selected from the 2005 Canadian Community Health Survey. Of the 13,092 respondents, 7.4% (n = 1025) reported that they had been physically abused as a child by someone close to them, and 5.7% (95% confidence interval [CI], 4.9-6.6) reported that they had been diagnosed with cancer by a health professional. The regional level response rate was 84%.Childhood physical abuse was associated with 49% higher odds (95% CI, 1.10-2.01) of cancer when adjusting for age, sex, and race only. The odds ratio decreased only slightly to 47% higher odds (95% CI, 1.05-1.99) when the model was adjusted for all 3 clusters of risk factors.A significant and highly stable association between childhood physical abuse and cancer was found even when adjusting for 3 clusters of risk factors. Further research focusing on the potential mechanisms linking childhood abuse and cancer is needed. Cancer 2009. © 2009 American Cancer Society. |
| Gemcitabine and oxaliplatin combination chemotherapy for metastatic well-differentiated neuroendocrine carcinomas
May 26, 2009 at 6:51 pm
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| | Beyond the usual regimens based on streptozocin and doxorubicin or 5-fluorouracil, no second-line therapy of metastatic neuroendocrine tumor has gained wide acceptance. Gemcitabine and oxaliplatin are generally well tolerated and have shown activity against a wide range of malignancies. The authors assessed the efficacy of gemcitabine-oxaliplatin combination (GEMOX) in the treatment of patients with metastatic neuroendocrine tumors.Twenty consecutive patients with progressive disease were treated with GEMOX, in most cases after failure of other chemotherapy regimens (median = 2). Patients were followed for evidence of toxicity, response, and survival. Two patients were chemotherapy-naive at treatment initiation and were excluded from the efficacy analysis.Toxicity was manageable overall; however, 6 (30%) patients had to discontinue treatment because of oxaliplatin-induced neurotoxicity (grade 2). Three (17%) of 18 patients had a partial response, median progression-free survival was 7.0 months, and median overall survival was 23.4 months.Gemcitabine-oxaliplatin combination shows interesting activity and is well tolerated in pretreated patients with neuroendocrine tumors. Cancer 2009. © 2009 American Cancer Society. |
| Is sex associated with the outcome of patients treated with radiation for nonsmall cell lung cancer?
May 26, 2009 at 6:51 pm
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| | Lung cancer is the leading cause of cancer death for both men and women, but the disease course differs between the sexes. To the authors' knowledge, sex-based differences in outcomes among the population of nonsmall cell lung cancer (NSCLC) patients receiving radiation have not been well defined.Data for 831 patients (319 women and 512 men) with stage I to III NSCLC and treated with [ge]45 Gray of radiation between March 1985 and November 2003 were retrospectively analyzed (grading determined according to the 1997 American Joint Committee on Cancer grading system).Women were more likely to have earlier stage disease, to have smoked <50 pack-years, and to have adenocarcinoma or large-cell carcinoma (all P [le] .001). For each stage, treatment did not differ between women and men. Five-year survival rates were significantly better for women than for men: overall survival (OS), 28.6% versus 16.1% (P < .001); disease-free survival, 31.2% versus 20.1% (P = .02); and distant metastasis-free survival, 48.8% versus 37.6% (P < .02). Among patients with medically inoperable stage I NSCLC, women had improved 5-year OS compared with men (30.0% vs 13.1%; P = .004). On multivariate analysis, male sex, weight loss, age [ge]65 years, and stage III disease were found to be associated with poorer OS (all P < 0.02).Although women are more likely to have earlier stage disease, among patients with medically inoperable stage I NSCLC, women still have a better OS. Along with known prognostic factors, including age, weight loss, and stage, sex remained significant on multivariate analysis of OS, suggesting that sex is a determinant of outcome in NSCLC patients receiving radiation. Cancer 2009. © 2009 American Cancer Society. |
| Erratum
May 26, 2009 at 6:51 pm
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| | No abstract. |
| The 2008 World Health Organization classification system for myeloproliferative neoplasms
May 26, 2009 at 6:50 pm
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| | The first formal classification of chronic myeloid neoplasms is credited to William Dameshek, who in 1951 described the concept of "myeloproliferative disorders (MPD)" by grouping together chronic myelogenous leukemia, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2001 World Health Organization (WHO) classification of myeloid malignancies included these MPDs under the broader category of chronic myeloproliferative diseases (CMPD), which also included chronic neutrophilic leukemia, chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES), and "CMPD, unclassifiable." The revised 2008 WHO classification system featured the following changes: 1) the term "CMPD" was replaced by "myeloproliferative neoplasm (MPN)," 2) mast cell disease was formally included under the category of MPN, and 3) the subcategory of CEL/HES was reorganized into "CEL not otherwise specified (CEL-NOS)" and "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, and FGFR1"; CEL-NOS remained a subcategory of "MPN," whereas the latter neoplasms were now assigned a new category of their own. Furthermore, diagnostic criteria for PV, ET, and PMF were revised by incorporating recently described molecular markers (eg, JAK2 and MPL mutations) as well as underscoring the role of histology in differentiating reactive from clonal myeloproliferations. As a result, red cell mass measurement is no longer necessary for the diagnosis of PV, and ET can now be diagnosed at a lower platelet count threshold. The revised WHO document continues to promote the recognition of histologic categories as a necessary first step toward the genetic characterization of myeloid malignancies. Cancer 2009. © 2009 American Cancer Society. |
| NV-128, a novel isoflavone derivative, induces caspase-independent cell death through the Akt/mammalian target of rapamycin pathway
May 26, 2009 at 6:50 pm
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| | Resistance to apoptosis is 1 of the key events that confer chemoresistance and is mediated by the overexpression of antiapoptotic proteins, which inhibit caspase activation. The objective of this study was to evaluate whether the activation of an alternative, caspase-independent cell death pathway could promote death in chemoresistant ovarian cancer cells. The authors report the characterization of NV-128 as an inducer of cell death through a caspase-independent pathway.Primary cultures of epithelial ovarian cancer (EOC) cells were treated with increasing concentration of NV-128, and the concentration that caused 50% growth inhibition (GI50) was determined using a proprietary assay. Apoptotic proteins were characterized by Western blot analyses, assays that measured caspase activity, immunohistochemistry, and flow cytometry. Protein-protein interactions were determined using immunoprecipitation. In vivo activity was measured in a xenograft mice model.NV-128 was able to induce significant cell death in both paclitaxel-resistant and carboplatin-resistant EOC cells with a GI50 between 1 [mu]g/mL and 5 [mu]g/mL. Cell death was characterized by chromatin condensation but was caspase-independent. The activated pathway involved the down-regulation of phosphorylated AKT, phosphorylated mammalian target of rapamycin (mTOR), and phosphorylated ribosomal p70 S6 kinase, and the mitochondrial translocation of beclin-1 followed by nuclear translocation of endonuclease G.The authors characterized a novel compound, NV-128, which inhibits mTOR and promotes caspase-independent cell death. The current results indicated that inhibition of mTOR may represent a relevant pathway for the induction of cell death in cells resistant to the classic caspase-dependent apoptosis. These findings demonstrate the possibility of using therapeutic drugs, such as NV-128, which may have beneficial effects in patients with chemoresistant ovarian cancer. Cancer 2009. © 2009 American Cancer Society. |
| The cancer Support Person's Unmet Needs Survey
May 26, 2009 at 6:50 pm
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| | A rigorous psychometric methodology was used to develop a measure of unmet needs for cancer survivors' principal support persons. Principal support person was defined as "someone you can count on and who helps you with your needs."Development of the domains and the items followed an extensive literature review, iterative input from support persons, and consultation with health professionals and front-line staff working with cancer survivors and their supports. Cognitive interviews helped clarify item wording, and the draft questionnaire was reappraised by a group of support persons. The questionnaire was reduced to 90 items and sent to a stratified, random sample of cancer survivors selected from a provincial population-based cancer registry. They were asked to give the survey to their support person.The resulting 78-item Support Person Unmet Needs Survey has high acceptability, item test-retest reliability, internal consistency (Chronbach alpha = .990), and face, content, and construct validity. It captures 6 domains of unmet needs and accounts for 73.5% of total variance: Information and Relationship Needs (27 items, 22.1% of variance), Emotional Needs (16 items, 15.2%), Personal Needs (14 items, 14.0%), Work and Finance (8 items, 8.8%), Health Care Access and Continuity (9 items, 8.6%), and Worries About Future (4 items, 4.8%).This instrument will be of use where there is an interest in examining the impact of cancer not only on cancer survivors but also on their identified principal support persons. Cancer 2009. © 2009 American Cancer Society. |
| Cervical cancer histology and tumor differentiation affect 18F-fluorodeoxyglucose uptake
May 26, 2009 at 6:50 pm
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| | This study aimed to evaluate the variation in cervical cancer glucose metabolism for different tumor histologies and levels of differentiation, as measured by the uptake of 18F-fluorodeoxyglucose (FDG) by positron emission tomography (PET).The study population consisted of 240 patients with International Federation of Gynecology and Obstetrics stages Ib1 through IVb cervical cancer, who underwent a pretreatment FDG-PET. Tumor histology included 221 squamous cell (SC), 4 adenosquamous (AS), and 15 adenocarcinoma (AC) tumors. There were 14 well, 145 moderately, and 81 poorly differentiated tumors. The stage distribution was as follows: 70 stage I tumors (9 AC, 2 AS, and 59 SC), 102 stage II tumors (3 AC, 1 AS, and 98 SC), 64 stage III tumors (3 AC, 1 AS, and 60 SC), and 4 stage IV tumors (4 SC). From the FDG-PET, maximal standardized uptake value (SUVmax) was determined. The variation in SUVmax was analyzed for differences based on tumor histology and differentiation.For all patients, the mean SUVmax was 11.62 (range, 2.50-50.39). The mean SUVmax by histology was as follows: SC, 11.91 (range, 2.50-50.39); AS, 8.85 (range, 6.53-11.26); and AC, 8.05 (range, 2.83-13.92). Squamous versus nonsquamous tumors demonstrated a significant difference in SUVmax (P = .0153). SUVmax and tumor volume were not found to be correlated (R2 = 0.013). The mean SUVmax was 8.58 for well-differentiated, 11.56 for moderately differentiated, and 12.23 for poorly differentiated tumors. The mean SUVmax was significantly different for well-differentiated versus poorly differentiated cervical tumors (P = .0474).Cervical tumor FDG uptake varied by histology and differentiation. SC tumors demonstrated a significantly higher SUVmax compared with nonsquamous cell tumors, and poorly differentiated tumors also had a higher SUVmax. Cancer 2009. © 2009 American Cancer Society. |
| The clinical application of 18F-fluorodeoxyglucose positron emission tomography to predict survival in patients with operable esophageal cancer
May 26, 2009 at 6:50 pm
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| | Metabolic tumor activity using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was believed to have a predictive value for patient outcome in malignancies. The objective of the current study was to assess the prognostic effectiveness of the highest standardized uptake value (SUV) in the primary or regional area (peak SUV) and the number of PET-positive lymph nodes in esophageal cancer.The authors retrospectively reviewed their experience with 184 consecutive esophageal cancer patients imaged preoperatively using FDG-PET scanning.The median peak SUV was 4.5 (range, 1.4-21.9). The survival curve was analyzed using the median peak SUV as the cutoff value. Comparison of each group and clinicopathologic characteristics revealed significant associations between peak SUV and each of the following factors: tumor status (P < .001), lymph node status (P < .001), metastatic status (P < .05), stage of disease (P < .001), number of PET-positive lymph nodes (P < .001), and the number of histologically positive lymph nodes (P < .001). The 5-year overall survival (OS) rate for patients having FDG uptake with a peak SUV [ge]4.5 was 47% and that for patients with a peak SUV <4.5 was 76% (P < .0001). On multivariate survival analysis using the Cox proportional hazards model, peak SUV and the number of PET-positive lymph nodes were found to be independent predictive factors for OS. The number of PET-positive lymph nodes was a single prognostic factor predicting both disease-free survival and OS.Pretreatment PET cannot only potentially diagnose the extent of disease, but also may be predictive of patient survival after esophageal cancer resection. Cancer 2009. © 2009 American Cancer Society. | | | 
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