Showing papers in "Cancer in 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

Abstract: 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.

Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors.

Abstract: BACKGROUND: A phase 3 trial demonstrated superiority at interim analysis for everolimus over placebo in patients with metastatic renal cell carcinoma (mRCC) progressing on vascular endothelial growth factor receptor–tyrosine kinase inhibitors. Final results and analysis of prognostic factors are reported. METHODS: Patients with mRCC (N ¼ 416) were randomized (2:1) to everolimus 10 mg/d (n ¼ 277) or placebo (n ¼ 139) plus best supportive care. Progression-free survival (PFS) and safety were assessed to the end of double-blind treatment. Mature overall survival (OS) data were analyzed, and prognostic factors for survival were investigated by multivariate analyses. A rank-preserving structural failure time model estimated the effect on OS, correcting for crossover from placebo to everolimus. RESULTS: The median PFS was 4.9 months (everolimus) versus 1.9 months (placebo) (hazard ratio [HR], 0.33; P < .001) by independent central review and 5.5 months (everolimus) versus 1.9 months (placebo) (HR, 0.32; P < .001) by investigators. Serious adverse events with everolimus, independent of causality, in � 5% of patients included infections (all types, 10%), dyspnea (7%), and fatigue (5%). The median OS was 14.8 months (everolimus) versus 14.4 months (placebo) (HR, 0.87; P ¼ .162), with 80% of patients in the placebo arm crossed over to everolimus. By the rank-preserving structural failure time model, the survival corrected for crossover was 1.9-fold longer (95% confidence interval, 0.5-8.5) with everolimus compared with placebo only. Independent prognostic factors for shorter OS in the study included low performance status, high corrected calcium, low hemoglobin, and prior sunitinib (P < .01). CONCLUSIONS: These results established the efficacy and safety of everolimus in patients with mRCC after progression on sunitinib and/or sorafenib. Cancer 2010;116:4256–65. V C 2010 American Cancer Society.

Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma†

Abstract: BACKGROUND: Melanoma tends to be refractory to various immunotherapies because of tumor-induced immunosuppression. To investigate the mechanism underlining the immunosuppression of melanoma patients, the authors focused on programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) interaction between tumor cells and T cells. METHODS: Melanoma specimens were collected from 59 primary tumors, 16 lymph nodes, and 4 lesions of in-transit metastasis. Specimens stained with anti-PD-L1 monoclonal antibodies were digitalized to jpg files. To evaluate the intensity of PD-L1 expression, histograms were used, and the red density (RD) was measured. PD-1 expression on T cells was analyzed in blood samples from 10 patients who had stage IV melanoma and in 4 samples of in-transit metastases. RESULTS: Twenty-five patients comprised the ‘‘low’’ PD-L1 expression group (RD value, <90), and 34 patients comprised the ‘‘high’’ group (RD value, � 90). Breslow tumor thickness in the high-expression group was significantly higher than in the low-expression group. Univariate and multivariate analyses revealed that the overall survival rate of the high-expression group was significantly lower than that of the low-expression group. In all patients with stage IV disease who were examined, both CD8-positive and CD4-positive T cells had significantly higher PD-1 expression levels in the peripheral blood. Tumor-infiltrating T cells expressed high levels of PD-1, and its expression was elevated further during the clinical course. CONCLUSIONS: The current results indicated that there is a correlation between the degree of PD-L1 expression and the vertical growth of primary tumors in melanoma. Multivariate analysis demonstrated that PD-L1 expression is an independent prognostic factor for melanoma. Cancer 2010;116:1757–66. V C 2010 American Cancer Society.

Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy

Abstract: BACKGROUND: Peritoneal carcinomatosis (PC) from nonovarian malignancies long has been regarded as a terminal disease. Over the past decade, new locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved that have demonstrated improved survival. METHODS: A retrospective, multicenter cohort study was performed in French-speaking institutions to evaluate toxicity and principal prognostic factors after cytoreductive surgery and PIC (hyperthermic intraperitoneal chemotherapy [HIPEC] and/or early postoperative intraperitoneal chemotherapy [EPIC]) for PC from nongynecologic malignancies. RESULTS: The study included 1290 patients from 25 institutions who underwent 1344 procedures between February 1989 and December 2007. HIPEC was performed in 1154 procedures. The principal origins of PC were colorectal adenocarcinoma (N = 523), pseudomyxoma peritonei (N = 301), gastric adenocarcinoma (N = 159), peritoneal mesothelioma (N = 88), and appendiceal adenocarcinoma (N = 50). The overall morbidity and mortality rates were 33.6% and 4.1%, respectively. In multivariate analysis, patient age, the extent of PC, and institutional experience had a significant influence on toxicity. The overall median survival was 34 months; and the median survival was 30 months for patients with colorectal PC, not reached for patients with pseudomyxoma peritonei, 9 months for patients with gastric PC, 41 months for patients with peritoneal mesothelioma, and 77 months for patients with PC from appendiceal adenocarcinoma. Independent prognostic indicators in multivariate analysis were institution, origin of PC, completeness of cytoreductive surgery, extent of carcinomatosis, and lymph node involvement. CONCLUSIONS: A therapeutic approach that combined cytoreductive surgery with PIC was able to achieve long-term survival in a selected group of patients who had PC of nonovarian origin and had acceptable morbidity and mortality. The current results indicated that this treatment should be centralized to institutions with expertise in the management of PC. Cancer 2010. © 2010 American Cancer Society.

TNM seventh edition: What's new, what's changed

Abstract: The seventh edition of the TNM Classification of Malignant Tumors (TNM-7) contains several new and modified component classifications. The purpose of this communication was to briefly summarize these changes, which became effective in January 2010. Among the new classifications are adrenal cortical carcinoma, appendiceal carcinoma, extrahepatic bile duct carcinoma, esophagogastric junction carcinoma, gastrointestinal stromal tumors (GISTs), intrahepatic cholangiocarcinoma, melanoma of the upper aerodigestive tract, Merkel cell carcinoma, neuroendocrine tumors of the lung and gastrointestinal tract, and uterine sarcomas. Among the classifications with major alterations are carcinomas of the esophagus, stomach, lung, skin, vulva, and prostate. In addition, there are several general rules that have been modified or established.

Cancer of the esophagus and esophagogastric junction: data-driven staging for the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer Cancer Staging Manuals.

Abstract: BACKGROUND: Previous American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) stage groupings for esophageal cancer have not been data driven or harmonized with stomach cancer. At the request of the AJCC, worldwide data from 3 continents were assembled to develop data-driven, harmonized esophageal staging for the seventh edition of the AJCC/UICC cancer staging manuals. METHODS: All-cause mortality among 4627 patients with esophageal and esophagogastric junction cancer who underwent surgery alone (no preoperative or postoperative adjuvant therapy) was analyzed by using novel random forest methodology to produce stage groups for which survival was monotonically decreasing, distinctive, and homogeneous. RESULTS: For lymph node-negative pN0M0 cancers, risk-adjusted 5-year survival was dominated by pathologic tumor classification (pT) but was modulated by histopathologic cell type, histologic grade, and location. For lymph node-positive, pN+M0 cancers, the number of cancer-positive lymph nodes (a new pN classification) dominated survival. Resulting stage groupings departed from a simple, logical arrangement of TNM. Stage groupings for stage I and II adenocarcinoma were based on pT, pN, and histologic grade; and groupings for squamous cell carcinoma were based on pT, pN, histologic grade, and location. Stage III was similar for histopathologic cell types and was based only on pT and pN. Stage 0 and stage IV, by definition, were categorized as tumor in situ (Tis) (high-grade dysplasia) and pM1, respectively. CONCLUSIONS: The prognosis for patients with esophageal and esophagogastric junction cancer depends on the complex interplay of TNM classifications as well as nonanatomic factors, including histopathologic cell type, histologic grade, and cancer location. These features were incorporated into a data-driven staging of these cancers for the seventh edition of the AJCC/UICC cancer staging manuals. Cancer 2010. © 2010 American Cancer Society.

Comparison of human papillomavirus in situ hybridization and p16 immunohistochemistry in the detection of human papillomavirus-associated head and neck cancer based on a prospective clinical experience.

Abstract: BACKGROUND: Human papillomavirus (HPV) is a causative agent in a subset of head and neck squamous cell carcinomas (HNSCCs). These HPV-related cancers have a clinicopathologic profile that diverges from HPV-negative HNSCCs. Accordingly, HPV testing may soon become integrated into standard pathologic assessment of HNSCCs. METHODS: Data were prospectively collected for all patients with head and neck carcinomas who had undergone HPV testing at the Johns Hopkins Hospital as part of clinical care during a 57-month period. HPV testing consisted of concurrent HPV16 in situ hybridization (ISH) and p16 immunohistochemistry (IHC). Wide spectrum HPV ISH was reserved for p16-positive cases that were HPV-16 negative. RESULTS: HPV analysis was performed on 256 head and neck carcinomas in an effort to predict clinical outcomes (56%), localize primary tumor origin (21%), establish tumor classification (9%), determine patient eligibility for vaccine trials (8%), or satisfy patient curiosity (5%). A total of 182 (71%) tumors were HPV positive. HPV positivity correlated with oropharyngeal site (82% vs 9%) and male sex (77% vs 48%). p16 positivity was present in all 176 HPV16-positive cases, and in 19 of 80 (24%) cases that were HPV-16 negative. In 6 (32%) discordant cases, p16 expression was because of the presence of another HPV type. CONCLUSIONS A feasible strategy that incorporates p16 IHC and HPV ISH is able to detect HPV in a high percentage of oropharyngeal carcinomas. HPV status is frequently requested by the oncologist to estimate clinical outcome, and used by pathologists to establish tumor classification and determine site of tumor origin. Cancer 2010. © 2010 American Cancer Society.

Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting lymphocyte count after 2 doses correlates with survival

Abstract: Melanoma is 1 of several cancers whose incidence has increased in the past several decades.1 In the metastatic setting, therapy is toxic and relatively ineffective.2–4 Most trials have reported objective responses in <15% of patients, which tend to be short-lived. In fact, a clear survival benefit for chemotherapy has yet to be demonstrated. The notable exception is treatment with high-dose interleukin-2 (IL-2), which has a similarly low response rate and serious toxicity but does lead to durable complete responses in a small subset of patients. As such, more effective therapy is urgently needed. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a coinhibitory molecule expressed by activated T cells and a subset of regulatory T cells.5–7 CTLA-4 is of primary importance in maintaining immune homeostasis by down-regulating T-cell signaling to inhibit the CD28-B7 costimulatory pathway, limiting T-cell responses, and contributing to tolerance to self-antigens.8, 9 Therefore, blockade of CTLA-4 is thought to prevent down-regulation of T cells and can potentiate immune responses against antigens expressed on tumor cells.10–13 Ipilimumab is a fully human immunoglobulin G1 monoclonal antibody that blocks CTLA-4. In several phase 1 and 2 trials, it has been found to produce objective and durable tumor responses in several tumor types, notably melanoma.14, 15 A group of mechanism-based side effects, termed immune-related adverse events, occur in patients treated with CTLA-4–blocking antibodies. The induction of this organ-specific inflammation underscores the importance of CTLA-4 in restraining the immune system under normal circumstances. The immune-related adverse events can be controlled using corticosteroids, according to simple algorithms. Interestingly, the frequency of clinical benefit has been observed to be higher in patients having immune-related adverse events, and the use of corticosteroids and other immunosuppressive medications does not interfere with sustained tumor immunity.16 In this article, we report on 51 evaluable patients with advanced melanoma treated in a compassionate use trial of ipilimumab at Memorial Sloan-Kettering Cancer Center (MSKCC). These were heavily pretreated patients who did not qualify for other clinical trials and were expected to have a poor prognosis. In addition to communicating a large single-institution experience with ipilimumab, which largely corroborates findings of multi-institutional trials, we also propose that the absolute lymphocyte count (ALC) after the first 2 treatments may be a useful biomarker to identify patients who are unlikely to benefit from ipilimumab therapy. Given the occurrence of immune-related adverse events in a significant number of patients and the sometimes long time interval required to obtain clinical benefit, a simple biomarker for identification of patients with low chance for benefit represents an important goal.

Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer

Abstract: BACKGROUND: Growing evidence supports cognitive dysfunction associated with standard dose chemotherapy in breast cancer survivors. We determined the incidence, nature, and chronicity of cognitive dysfunction in a prospective longitudinal randomized phase 3 treatment trial for patients with T1-3, N0-1, M0 breast cancer receiving 5-fluorouracil, doxorubicin, and cyclophosphamide with or without paclitaxel. METHODS: Forty-two patients underwent a neuropsychological evaluation including measures of cognition, mood, and quality of life. Patients were scheduled to be assessed before chemotherapy, during and shortly after chemotherapy, and 1 year after completion of chemotherapy. RESULTS: Before chemotherapy, 21% (9 of 42) evidenced cognitive dysfunction. In the acute interval, 65% (24 of 37) demonstrated cognitive decline. At the long-term evaluation, 61% (17 of 28) evidenced cognitive decline after cessation of treatment. Within this group of patients, 71% (12 of 17) evidenced continuous decline from the acute interval, and, notably, 29% (5 of 17) evidenced new delayed cognitive decline. Cognitive decline was most common in the domains of learning and memory, executive function, and processing speed. Cognitive decline was not associated with mood or other measured clinical or demographic characteristics, but late decline may be associated with baseline level of performance. CONCLUSIONS: Standard dose systemic chemotherapy is associated with decline in cognitive function during and shortly after completion of chemotherapy. In addition, delayed cognitive dysfunction occurred in a large proportion of patients. These findings are consistent with a developing body of translational animal research demonstrating both acute and delayed structural brain changes as well as functional changes associated with common chemotherapeutic agents such as 5-flouorouracil. Cancer 2010. © 2010 American Cancer Society.

Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study.

Abstract: BACKGROUND: Recurrence is a major cause of treatment failure after allogeneic transplantation for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), and treatment options are very limited. Azacitidine is a DNA methyltransferase inhibitor with activity in myeloid disease. The authors hypothesized that low-dose azacitidine administered after transplant would reduce recurrence rates, and conducted a study to determine a safe dose/schedule combination. METHODS: Forty-five high-risk patients were treated. Median age was 60 years; median number of comorbidities was 3; 67% were not in remission. By using a Bayesian adaptive method to determine the best dose/schedule combination based on time to toxicity, the authors investigated combinations of 5 daily azacitidine doses, 8, 16, 24, 32, and 40 mg/m2, and 4 schedules: 1, 2, 3, or 4 cycles, each with 5 days of drug and 25 days of rest. Cycle 1 started on Day +40. RESULTS: Reversible thrombocytopenia was the dose-limiting toxicity. The optimal combination was 32 mg/m2 given for 4 cycles. Median follow-up was 20.5 months. One-year event-free and overall survival were 58% and 77%, justifying further studies to estimate long-term clinical benefit. No dose significantly affected DNA global methylation. CONCLUSIONS: Azacitidine at 32 mg/m2 given for 5 days is safe and can be administered after allogeneic transplant for at least 4 cycles to heavily pretreated AML/MDS patients. The trial also suggested that this treatment may prolong event-free and overall survival, and that more cycles may be associated with greater benefit. Cancer 2010. © 2010 American Cancer Society.

Lymphedema beyond breast cancer

Abstract: BACKGROUND: Secondary lymphedema is a debilitating, chronic, progressive condition that commonly occurs after the treatment of breast cancer. The purpose of the current study was to perform a systematic review and meta-analysis of the oncology-related literature excluding breast cancer to derive estimates of lymphedema incidence and to identify potential risk factors among various malignancies. METHODS: The authors systematically reviewed 3 major medical indices (MEDLINE, Cochrane Library databases, and Scopus) to identify studies (1972-2008) that included a prospective assessment of lymphedema after cancer treatment. Studies were categorized according to malignancy, and data included treatment, complications, lymphedema measurement criteria, lymphedema incidence, and follow-up interval. A quality assessment of individual studies was performed using established criteria for systematic reviews. Bayesian meta-analytic techniques were applied to derive summary estimates when sufficient data were available. RESULTS: A total of 47 studies (7779 cancer survivors) met inclusion criteria: melanoma (n = 15), gynecologic malignancies (n = 22), genitourinary cancers (n = 8), head/neck cancers (n = 1), and sarcomas (n = 1). The overall incidence of lymphedema was 15.5% and varied by malignancy (P < .001): melanoma, 16% (upper extremity, 5%; lower extremity, 28%); gynecologic, 20%; genitourinary, 10%; head/neck, 4%; and sarcoma, 30%. Increased lymphedema risk was also noted for patients undergoing pelvic dissections (22%) and radiation therapy (31%). Objective measurement methods and longer follow-up were both associated with increased lymphedema incidence. CONCLUSIONS: Lymphedema is a common condition affecting cancer survivors with various malignancies. The incidence of lymphedema is related to the type and extent of treatment, anatomic location, heterogeneity of assessment methods, and length of follow-up. Cancer 2010. © 2010 American Cancer Society.

Physician factors associated with discussions about end‐of‐life care

Abstract: BACKGROUND: Guidelines recommend advanced care planning for terminally ill patients with <1 year to live. Few data are available regarding when physicians and their terminally ill patients typically discuss endof-life issues. METHODS: A national survey was conducted of physicians caring for cancer patients about timing of discussions regarding prognosis, do not resuscitate (DNR) status, hospice, and preferred site of death with their terminally ill patients. Logistic regression was used to identify physician and practice characteristics associated with earlier discussions. RESULTS: Among 4074 respondents, 65% would discuss prognosis ‘‘now’’ (defined as patient has 4 months to 6 months to live, asymptomatic). Fewer would discuss DNR status (44%), hospice (26%), or preferred site of death (21%) immediately, with most physicians waiting for patient symptoms or until there are no more treatments to offer. In multivariate analyses, younger physicians more often discussed prognosis, DNR status, hospice, and site of death ‘‘now’’ (all P < .05). Surgeons and oncologists were more likely than noncancer specialists to discuss prognosis ‘‘now’’ (P ¼ .008), but noncancer specialists were more likely than cancer specialists to discuss DNR status, hospice, and preferred site of death ‘‘now’’ (all P < .001). CONCLUSIONS: Most physicians report they would not discuss end-of-life options with terminally ill patients who are feeling well, instead waiting for symptoms or until there are no more treatments to offer. More research is needed to understand physicians’ reasons for timing of discussions and how their propensity to aggressively treat metastatic disease influences timing, as well as how the timing of discussions influences patient and family experiences at the end of life. Cancer 2010;116:000–000. V C 2010 American Cancer Society.

Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma

Abstract: 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.

Ovarian cancer: Age contrasts in incidence, histology, disease stage at diagnosis, and mortality

Abstract: Background. Age comparisons for incidence, histology, disease stage at initial diagnosis, and mortality of more than 20,000 ovarian cancer patients diagnosed between 1973-1987 are the focus of this descriptive epidemiologic study. This paper highlights key issues and concerns regarding ovarian cancer in women 65 years and older as a frame of reference for the proceedings of the working conference, «Perspectives on Ovarian Cancer in Older-Aged Women,» co-sponsored by the National Institute on Aging, National Cancer Institute, and American Cancer Society held at the National Institutes of Health, November, 1991

Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer.

Abstract: Purpose No adequate randomized trials comparing active treatment modalities for localized prostate cancer have been reported. We analyzed risk-adjusted cancer-specific mortality outcomes among men undergoing radical prostatectomy, external-beam radiation therapy, or primary androgen deprivation therapy.

Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis

Abstract: BACKGROUND: Survival benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion was demonstrated by a prospective randomized trial for colorectal peritoneal carcinomatosis. Because of a recent substantial improvement in chemotherapy, the authors analyzed treatment options of colorectal carcinomatosis in the current era. METHODS: Consecutive patients with colorectal carcinomatosis treated by cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion from 2001 to 2007 were included. The control group patients with carcinomatosis received contemporary chemotherapy alone. Overall survival was the primary endpoint. RESULTS: All patients underwent systemic chemotherapy. The cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion group (n=67) was similar to the control group (n=38) in sex, tumor grade, site of tumor origin, T status, and N status. The control group was, however, older (59 vs 51 years; P<.001). Median survival measured from the diagnosis of peritoneal disease was longer with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion (34.7 months vs 16.8 months; P<.001). Presence of liver metastasis was a significant negative predictor of survival (hazard ratio, 2.13). CONCLUSIONS: The authors concluded that 1) contemporary chemotherapy is associated with prolonged survival among patients with carcinomatosis as compared with historical controls, and 2) addition of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion to modern chemotherapy regimens may significantly prolong survival. Cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion and systemic chemotherapy are not competitive therapies, and they both have a role in a multidisciplinary approach to patients with carcinomatosis.

Coronary artery disease mortality in patients treated for Hodgkin's disease.

Abstract: The authors conducted a follow-up study of the association between mediastinal irradiation, chemotherapy, and mortality from coronary artery disease in 4665 patients treated for Hodgkin's disease. Study subjects were followed after the diagnosis of Hodgkin's disease until death or the closing date of the study. The average duration of follow-up was 7 years; 2415 patients died, and 124 cases of coronary artery disease were identified from death certificates, including 68 cases of acute myocardial infarction. The age-adjusted relative risks (RR) of death with any coronary artery disease after mediastinal irradiation and after chemotherapy were 1.87 (95% confidence interval [CI], 0.92 to 3.80) and 1.28 (CI, 0.77 to 2.15), respectively. A significantly increased risk of death in the subcategory myocardial infarction was observed after mediastinal irradiation (RR, 2.56; CI, 1.11 to 5.93) but not after chemotherapy (RR, 0. 97; CI, 0.53 to 1.77). These results support the hypothesis that radiation therapy to the mediastinum increases the risk of coronary artery disease.

Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization.

Abstract: BACKGROUND: To improve the efficacy of radiofrequency ablation (RFA) for the treatment of intermediate-sized hepatocellular carcinomas (HCCs), the authors compared RFA combined with transcatheter arterial chemoembolization (TACE) to RFA alone. METHODS: The authors randomly assigned 37 patients with solitary HCCs (diameter, 3.1-5.0 cm in the greatest dimension) to 2 groups: the TACE-RFA group, in which the patients received TACE followed by RFA on the same day, and the RFA group, in which the patients received only RFA. RESULTS: Technical success was achieved after 1.4 ± 0.5 RFA sessions in the RFA group and after 1.1 ± 0.2 RFA sessions in the TACE-RFA group (P < .01). The mean diameters of the longer and shorter axes of the RFA-induced ablated areas were 50 ± 8.0 mm and 41 ± 7.1 mm, respectively, in the RFA group and 58 ± 13.2 mm and 50 ± 11.3 mm, respectively, in the TACE-RFA group; the mean diameters of the shorter axes were significantly different (P = .012). The rates of local tumor progression at the end of the third year in the RFA and TACE-RFA groups were 39% and 6%, respectively (P = .012). The 3-year survival rates of the patients in the RFA and TACE-RFA groups were 80% and 93%, respectively (P = .369). CONCLUSIONS: In patients with intermediate-sized HCCs, RFA combined with TACE is more effective than RFA alone for extending the ablated area in fewer treatment sessions and for decreasing the local tumor progression rate. Cancer 2010. © 2010 American Cancer Society.

Percutaneous radiofrequency ablation of painful osseous metastases: a multicenter American College of Radiology Imaging Network trial.

Abstract: Background To determine if radiofrequency ablation (RFA) can safely reduce pain from osseous metastatic disease.

Cervical cancer prevention: new tools and old barriers

Abstract: Cervical cancer is the second most common female tumor worldwide, and its incidence is disproportionately high (>80%) in the developing world In the United States, in which Papanicolaou (Pap) tests have reduced the annual incidence to approximately 11,000 cervical cancers, >60% of cases are reported to occur in medically underserved populations as part of a complex of diseases linked to poverty, race/ethnicity, and/or health disparities Because carcinogenic human papillomavirus (HPV) infections cause virtually all cervical cancer, 2 new approaches for cervical cancer prevention have emerged: 1) HPV vaccination to prevent infections in younger women (aged or =30 years) Together, HPV vaccination and testing, if used in an age-appropriate manner, have the potential to transform cervical cancer prevention, particularly among underserved populations Nevertheless, significant barriers of access, acceptability, and adoption to any cervical cancer prevention strategy remain Without understanding and addressing these obstacles, these promising new tools for cervical cancer prevention may be futile In the current study, the delivery of cervical cancer prevention strategies to these US populations that experience a high cervical cancer burden (African-American women in South Carolina, Alabama, and Mississippi; Haitian immigrant women in Miami; Hispanic women in the US-Mexico Border; Sioux/Native American women in the Northern Plains; white women in the Appalachia; and Vietnamese-American women in Pennsylvania and New Jersey) is reviewed The goal was to inform future research and outreach efforts to reduce the burden of cervical cancer in underserved populations

MicroRNA‐205–directed transcriptional activation of tumor suppressor genes in prostate cancer

Abstract: BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of approximately 60% of all human genes. They play important roles in numerous cellular processes, including development, proliferation, and apoptosis. Currently, it is believed that miRNAs elicit their effect by silencing the expression of target genes. In this study, the authors demonstrated that miRNA-205 (miR-205) induced the expression the interleukin (IL) tumor suppressor genes IL24 and IL32 by targeting specific sites in their promoters. METHODS: The methods used in this study included transfection of small RNAs; quantitative real-time polymerase chain reaction; in situ hybridization; fluorescence-labeled in situ hybridization; cell cycle, apoptosis, cell viability, migratory, clonability, and invasion assays; immunoblotting; and luciferase reporter, nuclear run-on, and chromatin immunoprecipitation assays. RESULTS: The results revealed that miR-205 was silenced in prostate cancer. Its re-expression induced apoptosis and cell cycle arrest. It also impaired cell growth, migration, clonability, and invasiveness of prostate cancer cells. Micro-RNA-205 induced the expression of tumor suppressor genes IL24 and IL32 at both the messenger RNA and protein levels. The induction of in vitro transcription and enrichment of markers for transcriptionally active promoters in the IL24 and IL32 genes was observed in response to miR-205. CONCLUSIONS: In this study, a new function for miR-205 was identified that specifically activated tumor suppressor genes by targeting specific sites in their promoters. These results corroborate a newly identified function that miRNAs have in regulating gene expression at the transcriptional level. The specific activation of tumor suppressor genes (eg, IL24, IL32) or other dysregulated genes by miRNA may contribute to a novel therapeutic approach for the treatment of prostate cancer. Cancer 2010. © 2010 American Cancer Society.

Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America

Abstract: BACKGROUND: The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program made sorafenib available to patients with advanced renal cell carcinoma (RCC) before regulatory approval. METHODS: In this nonrandomized, open-label expanded access program, 2504 patients from the United States and Canada were treated with oral sorafenib 400 mg twice daily. Safety and efficacy were explored overall and in subgroups of patients including those with no prior therapy, nonclear cell (nonclear cell) RCC, brain metastases, prior bevacizumab treatment, and elderly patients. Sorafenib was approved for RCC 6 months after study initiation, at which time patients with no prior therapy or with nonclear cell RCC could enroll in an extension protocol for continued assessment for a period of 6 months. RESULTS: The most common grade ≥2 drug-related adverse events were hand-foot skin reaction (18%), rash (14%), hypertension (12%), and fatigue (11%). In the 1891 patients evaluable for response, complete response was observed in 1 patient, partial response in 67 patients (4%), and stable disease for at least 8 weeks in 1511 patients (80%). Median progression-free survival in the extension population was 36 weeks (95% confidence interval [CI], 33-45 weeks; censorship rate, 56%); median overall survival in the entire population was 50 weeks (95% CI, 46-52 weeks; censorship rate, 63%). The efficacy and safety results were similar across the subgroups. CONCLUSIONS: Sorafenib 400 mg twice daily demonstrated activity and a clinically acceptable toxicity profile in all patient subsets enrolled in the ARCCS expanded access program (clinicaltrials.gov identifier: NCT00111020). Cancer 2010. © 2010 American Cancer Society.

A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma

Abstract: BACKGROUND: Dysregulation of phosphatase and tensin homolog (PTEN) and the gene that encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), PIK3CA, are the most common mutations in endometrial carcinoma (EC). Loss of PTEN or activation of PIK3CA results in constitutive activation of AKT, which leads to up-regulation of mammalian target of rapamycin (mTOR). Everolimus is an oral rapamycin analog that acts by selectively inhibiting mTOR. METHODS: A single-institution, open-labeled, phase 2 study of everolimus in patients with measurable recurrent EC who had failed at least 1 and no more than 2 prior chemotherapeutic regimens was performed. Everolimus was administered at a dose of 10 mg orally daily for 28-day cycles. Patients were treated until disease progression or toxicity. The primary endpoint was clinical benefit response (CBR), defined as a confirmed complete or partial response or prolonged stable disease (SD) (≥8 weeks). Inclusion was limited to patients with endometrioid histology. RESULTS: A total of 35 patients were enrolled (median age, 58 years; range, 38-81 years). A total of 81 cycles were administered. Twelve of 28 (43%) evaluable patients had not developed disease progression at the time of the first objective evaluation (8 weeks). All these patients had SD (median, 4.5 cycles; range, 2-10 cycles). Six of the 28 (21%) patients had a confirmed CBR at 20 weeks of therapy. Patients with CBR discontinued treatment because of toxicity (6 patients), disease progression (5 patients), and noncompliance (1 patient). Seven patients were unevaluable after receiving ≤1 cycle because of toxicity (5 patients) or noncompliance (2 patients). The most common drug-related toxicities were fatigue, anemia, pain, lymphopenia, and nausea. CONCLUSIONS: Everolimus demonstrated encouraging single-agent CBR in pretreated patients with recurrent endometrioid EC. Future studies will evaluate this agent in combination with hormonal and/or cytotoxic therapy. Cancer 2010. © 2010 American Cancer Society.

The impact of socioeconomic status on stage of cancer at diagnosis and survival: a population-based study in Ontario, Canada.

Abstract: at Ontario’s 8 Regional Cancer Centers (RCCs). The Ontario population was divided into quintiles (Q1-Q5) based on community median household income reported in the 2001 census; Q1 represents the poorest communities. Overall survival (OS) and cancer-specific survival (CSS) were determined with Kaplan-Meier methodology. A Cox model was used to evaluate the association between survival and SES, stage, and age. RESULTS: Stage at diagnosis was available for 38,431 of 44,802 (85%) of cases seen at RCCs. The authors observed only very small differences in stage distribution by SES. Across all cases in Ontario, the authors found substantial gradients in 5-year OS and 3-year CSS across Q1 and Q5 for breast (7% absolute difference in OS, P < .001; 4% CSS, P < .001), colon (8% OS, P < .001; 3% CSS, P ¼ .002), rectal (9% OS, P < .001; 4% CSS, P ¼ .096), nonsmall cell lung (3% OS, P ¼ .002; 2% CSS, P ¼ .317), cervical (16% OS, P < .001; 10% CSS, P ¼ .118), and laryngeal cancers (1% OS, P ¼ .045; 3% CSS, P ¼ .011). Adjustments for stage and age slightly diminished the survival gradient only among patients with breast cancer. CONCLUSIONS: Despite universal healthcare, SES remains associated with survival among patients with cancer in Ontario, Canada. Disparities in outcome were not explained by differences in stage of cancer at time of diagnosis. Cancer 2010;116:4160–7. V C 2010 American Cancer Society.

Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy

Abstract: BACKGROUND: The prognosis of patients with myelodysplastic syndrome (MDS) after decitabine failure is not known. METHODS: Data from 87 patients with MDS (n = 67) and chronic myelomonocytic leukemia (n = .20) after failure of decitabine regimens were reviewed. RESULTS: After a median follow-up of 21 months from decitabine failure, 13 (15%) patients remained alive; the median survival was 4.3 months, and the estimated 12-month survival rate was 28%. The estimated 12-month survival rates were 27%, 33%, and 33%, respectively, for patients with high-risk, intermediate-2-risk, and intermediate-1-risk disease (P = .99) by the International Prognostic Scoring System. The estimated 12-month survival rates were 100%, 54%, 41%, and 18%, respectively, for patients with low-risk, intermediate-1-risk, intermediate-2-risk, and high-risk disease according to The University of Texas M. D. Anderson Cancer Center risk model (P = .01). CONCLUSIONS: The outcome of patients after decitabine failure is poor and appears to be predictable after decitabine failure. Cancer 2010. © 2010 American Cancer Society.

Adult Acute Lymphoblastic Leukemia: Concepts and Strategies

Abstract: Acute lymphoblastic leukemia (ALL), a clonal expansion of hematopoietic blasts, is a highly heterogeneous disease comprising many entities for which distinct treatment strategies are pursued. Although ALL is a success story in pediatric oncology, results in adults lag behind those in children. An expansion of new drugs, more reliable immunologic and molecular techniques for the assessment of minimal residual disease, and efforts at more precise risk stratification are generating new aspects of adult ALL therapy. For this review, the authors summarized pertinent and recent literature on ALL biology and therapy, and they discuss current strategies and potential implications of novel approaches to the management of adult ALL. Cancer 2010. (c) 2010 American Cancer Society.

hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer

Abstract: BACKGROUND: Hypoxia is an important mechanism of treatment resistance in head and neck squamous cell carcinoma (HNSCC). MicroRNAs are short noncoding RNAs that regulate multiple mRNAs and are frequently dysregulated in cancer. The authors have investigated the role of 3 microRNAs, including the hypoxia-induced hsa-miR-210, as potential markers of hypoxia or prognosis. METHODS: Three hypoxia-related microRNAs, hsa-miR-210, hsa-miR-21, and hsa-miR-10b, were measured in 46 samples from patients with HNSCC. Expression levels were correlated with clinicopathological variables and other markers of hypoxia: a published 99-gene hypoxia metagene, individual hypoxia-related genes such as TWIST1, and immunohistochemical expression of hypoxia-inducible factor 1 and its target gene carbonic anhydrase 9. We then performed survival analyses to investigate the prognostic significance of these microRNAs. RESULTS: Only the level of hsa-miR-210 was significantly correlated with other markers of hypoxia, including the 99-gene hypoxia metagene (rho = 0.67, P < .001). We found no association between hsa-miR-210, hsa-miR-21, or hsa-miR-10b and clinicopathological variables such as tumor size, differentiation, and stage. However, high levels of hsa-miR-210 were associated with locoregional disease recurrence (P = .001) and short overall survival (P = .008). hsa-miR-21 and hsa-miR-10b had no prognostic significance. CONCLUSIONS: Expression of hsa-miR-210 in head and neck cancer correlates with other approaches for assessing hypoxia and is associated with prognosis. This warrants further study as a classification marker of patients for therapies involving modulation of hypoxia. Cancer 2010. © 2010 American Cancer Society.

Active Treatment of Localized Renal Tumors May Not Impact Overall Survival in Patients Aged 75 Years or Older

Abstract: BACKGROUND: Although nephrectomy cures most localized renal cancers, this oncologic benefit may be outweighed by the renal functional costs of such an approach. In this study, the authors examined overall survival in 537 patients who had localized renal tumors ≤7 cm detected at age ≥75 years to investigate whether surgical intervention improved survival compared with active surveillance. METHODS: Clinical T1 renal tumors were managed with surveillance (20%), nephron-sparing interventions (53%), or nephrectomy (27%). Cox regression models were constructed based on age, comorbidity, management type, renal function, and other variables. RESULTS: The median follow-up was 3.9 years, and death from any cause occurred in 148 patients (28%). The most common cause of death was cardiovascular (29%), and cancer progression was responsible in only 4% of deaths. Kaplan-Meier analysis revealed decreased overall survival for patients who underwent surveillance and nephrectomy relative to nephron-sparing intervention (P = .01); however, surveilled patients were older and had greater comorbidity. In multivariate analysis, significant predictors of overall survival included age (P = .0004) and comorbidity (P < .0001) but not management type (P = .3). Preoperative renal function (P = .006) and comorbidity (P = .005) were predictors of cardiovascular mortality, and nephrectomy was associated with greatest loss of renal function. CONCLUSIONS: In patients aged ≥75 years, surgical management of clinically localized renal cortical tumors was not associated with increased survival. Patients died mostly of cardiovascular causes, similar to the general elderly population. Nephrectomy accelerated renal dysfunction, which was associated with cardiovascular mortality. Current paradigms suggest that there is over treatment of localized renal tumors, and further study will be required to evaluate the advisability of various options in patients with limited life expectancy. Cancer 2010. © 2010 American Cancer Society.

Forgoing medical care because of cost: assessing disparities in healthcare access among cancer survivors living in the United States.

Abstract: BACKGROUND: Many US cancer survivors live years after diagnosis, which emphasizes the importance of healthcare access for survivors. It is not known whether having cancer has an impact on disparities in healthcare access that are present in the general population. The objective of this study was to examine the prevalence of forgoing care because of financial concerns in a representative sample of US adults to determine whether cancer history and race/ethnicity are associated with the likelihood of forgoing medical care. METHODS: Data from the US National Health Interview Survey (NHIS) from 2003 to 2006 were used to identify 6602 adult cancer survivors and 104,364 individuals who had no history of cancer. Self-reports of forgoing medical care services because of cost were analyzed according to cancer history and race/ethnicity using multivariate logistic regression. RESULTS: The prevalence of forgoing care because of cost among cancer survivors was 7.8% for medical care, 9.9% for prescription medications, 11.3% for dental care, and 2.7% for mental healthcare. Cancer survivors aged <65 years were more likely to delay or forgo all types of medical care compared with adults who did not have a history of cancer. Hispanic and black cancer survivors were more likely to forgo prescription medications and dental care than white survivors. Disparities among cancer survivors largely were reflective of those in the general adult population. CONCLUSIONS: More than 2 million US cancer survivors did not get 1 or more needed medical services because of financial concerns during the studied period. Future research needs to examine the impact of forgoing care on survivors' quality of life and survival. Cancer 2010. Published 2010 by the American Cancer Society.