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PubMed2005

Predictors of prostate cancer tissue acquisition by an undirected core bone marrow biopsy in metastatic castration-resistant prostate cancer--a Cancer and Leukemia Group B study.

PURPOSE: Analyzing metastatic prostate cancer tissue is of considerable importance in evaluating new targeted agents, yet acquiring such tissue presents a challenge due to the predominance of bone metastases. We assessed factors predicting a successful tumor harvest from bone marrow biopsies (BMBx) in castration-resistant metastatic prostate cancer patients. MATERIAL AND METHODS: Data from Cancer and Leukemia Group B study 9663 were reviewed. Bone marrow biopsies were obtained from 184 patients who underwent an office-based, unguided bone marrow biopsy of the posterior iliac crest. RESULTS: Forty-seven of the 184 patients (25.5%) had a positive bone marrow biopsy. When considered in a multivariate logistic regression analysis, lower hemoglobin levels, higher alkaline phosphatase, and higher lactate dehydrogenase levels were associated with a higher likelihood of a positive BMBx. The median survival time was 11 months (95% confidence interval, 8.0-14) among patients with a positive BMBx compared with 23 months (95% confidence interval, 19-27) with a negative BMBx. The median time to progression and time to prostate-specific antigen progression-free survival were also significantly decreased among positive BMBx patients. No patients with a positive BMBx survived beyond 3 years, whereas 11 of the 137 patients with a negative BMBx survived beyond 5 years. DISCUSSION: Using common laboratory values, a specific patient cohort can be defined from whom the yield of a nonguided BMBx would be high enough to justify this approach. For studies that require broader entry criteria, a more directed approach with image guidance is recommended.

Aged↗

PubMed2004

An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort.

PURPOSE: Studies suggest eicosapentaenoic acid (EPA), an omega-3 fatty acid, augments weight, appetite, and survival in cancer-associated wasting. This study determined whether an EPA supplement-administered alone or with megestrol acetate (MA)-was more effective than MA. PATIENTS AND METHODS: Four hundred twenty-one assessable patients with cancer-associated wasting were randomly assigned to an EPA supplement 1.09 g administered bid plus placebo; MA liquid suspension 600 mg/d plus an isocaloric, isonitrogenous supplement administered twice a day; or both. Eligible patients reported a 5-lb, 2-month weight loss and/or intake of less than 20 calories/kg/d. RESULTS: A smaller percentage taking the EPA supplement gained >or= 10% of baseline weight compared with those taking MA: 6% v 18%, respectively (P =.004). Combination therapy resulted in weight gain of >or= 10% in 11% of patients (P =.17 across all arms). The percentage of patients with appetite improvement (North Central Cancer Treatment Group Questionnaire) was not statistically different: 63%, 69%, and 66%, in EPA-, MA-, and combination-treated arms, respectively (P =.69). In contrast, 4-week Functional Assessment of Anorexia/Cachexia Therapy scores suggested MA-containing arms experienced superior appetite stimulation compared with the EPA arm, with scores of 40, 55, and 55 in EPA-, MA-, and combination-treated arms, respectively (P =.004). Survival was not significantly different among arms. Global quality of life was not significantly different among groups. With the exception of increased impotence in MA-treated patients, toxicity was comparable. CONCLUSION: This EPA supplement, either alone or in combination with MA, does not improve weight or appetite better than MA alone.

Aged↗

PubMed2006

Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group.

PURPOSE: Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients. PATIENTS AND METHODS: This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) +/- zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin +/- zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months. RESULTS: Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, -14.4% after 36 months; mean T score reduction, -1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, -17.3%; mean T score reduction, -2.6) compared with patients receiving tamoxifen/goserelin (BMD, -11.6%; mean T score reduction, -1.1). In contrast, BMD remained stable in zoledronic acid-treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted. CONCLUSION: Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.

Adult↗

PubMed2005

Meeting the public's cancer information needs: characteristics of callers to the National Cancer Information Center of the American Cancer Society.

BACKGROUND: In this study, we describe the characteristics of the callers of the American Cancer Society's National Cancer Information Center (NCIC), why they called, how they learned about NCIC, and their satisfaction. METHODS: A random sample of callers (N = 19,487) completed a telephone survey. RESULTS: The majority were female, White, 45 to 74 years old, had incomes greater than 35,001 dollars, and were college educated. They learned about the NCIC through TV advertisements and requested information about specific cancers, local programs, or making donations. CONCLUSIONS: These findings validate the usefulness of the NCIC and are helpful in identifying and targeting persons who do not routinely use this service.

Adolescent↗

PubMed1994

Racial differences in survival from breast cancer. Results of the National Cancer Institute Black/White Cancer Survival Study.

OBJECTIVE: To examine the ability of recognized prognostic factors for breast cancer to account for the observed poorer survival in blacks compared with their white counterparts. DESIGN AND PARTICIPANTS: Subjects included 1130 women (612 blacks and 518 whites) aged 20 to 79 years residing in metropolitan Atlanta, Ga, New Orleans, La, or San Francisco/Oakland, Calif, who were diagnosed with primary invasive breast cancer. Information on stage, tumor characteristics, treatment, comorbid conditions, and sociodemographic factors was obtained from personal interview, physician and hospital records, and a pathology review of biopsy and surgical specimens. MAIN OUTCOME MEASURE: Multivariable survival models were used to estimate the hazard ratio (relative risk of mortality) for blacks compared with whites, adjusting for various combinations of potential explanatory factors. RESULTS: After controlling for geographic site and age, the risk of dying was 2.2 times (95% confidence interval [CI], 1.8 to 2.8) greater for blacks than whites. Adjustment for stage reduced the risk from 2.2 to 1.7; further adjustment for sociodemographic variables had no effect. Treatment was not a contributing factor once stage and tumor pathology were in the model. After adjusting for stage, treatment, comorbid illness, and pathologic and sociodemographic variables, blacks continued to demonstrate a slightly increased, but not statistically significant, risk of death (hazard ratio = 1.3; 95% CI, 1.0 to 1.8). Results were similar for all-cause mortality and breast cancer-specific mortality. CONCLUSIONS: Approximately 75% of the racial difference in survival was explained by the prognostic factors studied. Sociodemographic variables appeared to act largely through racial differences in stage at diagnosis, which may be amenable to change through improved access to and use of screening for black women.

Adult↗

PubMed1993

Children and cancer. A perspective from the Cancer Therapy Evaluation Program, National Cancer Institute.

The Cancer Therapy Evaluation Program, National Cancer Institute (CTEP, NCI) strongly supports the role of controlled clinical trials in improving the care of children with cancer, and particularly the central role that the pediatric Cooperative Groups play in this process. Trends that threaten the ability to perform these trials include the increasingly limited financial resources available for clinical investigations and the sentiment within some circles that controlled clinical trials may be inappropriate for ethical reasons. The inherent risks of accepting a new therapy without rigorous comparison to existing therapy strongly support the need for randomized trials with adequate accrual to answer important therapeutic questions in a timely and reliable fashion. Retrospective analysis of multiple clinical trials is one method for identifying compelling hypotheses to be tested prospectively. Using this method, we have demonstrated the association between doxorubicin dose intensity and positive response and outcome for patients with Ewing sarcoma and osteosarcoma, thereby providing direction for the selection of important therapeutic questions to be addressed in future clinical trials for these malignancies.

Antineoplastic Agents↗

PubMed1993

Endoscopic evaluation of the depth of invasion of the depressed type early gastric cancer and apparently early advanced cancer in cases of a peptic ulcer within the cancer lesion.

Depressed-type early and apparently early advanced cancers were divided into two groups according to whether or not an associated peptic ulcer was present within the cancer lesion, and the accuracy of preoperative endoscopic diagnosis was reviewed. As a result it was found that evaluation of depth of invasion was more difficult in the ulcer [UL(+)] group than in the group without an ulcer [UL(-)]. In the UL(+) group it was difficult to identify endoscopic findings which indicate depth of invasion at the tip of the folds, the volume of cancer invasion of the deeper layers was small, and there many cases of invasion of deeper layers in a portion of the margins of the peptic ulcers.

Adenocarcinoma↗

PubMed1992

The effect of family history of cancer, religion, parity and migrant status on survival in colorectal cancer. The Melbourne Colorectal Cancer Study.

The association between 5-year survival and several risk factors was investigated in 705 histologically confirmed, new cases of colorectal adenocarcinoma as one aspect of a comprehensive population-based study of large bowel cancer incidence, aetiology and survival--the Melbourne Colorectal Cancer Study. 5-year survival was not influenced by the previously determined risk of a family history of colorectal cancer in near-relatives. Similarly, other previously determined risk factors of religion, number of children, age at birth of first child and migrant status did not influence survival.

Adenocarcinoma↗

PubMed1998

Long-term follow-up of an EORTC randomized prospective trial comparing intravesical bacille Calmette-Guérin-RIVM and mitomycin C in superficial bladder cancer. EORTC GU Group and the Dutch South East Cooperative Urological Group. European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group.

OBJECTIVES: To determine long-term efficacy of intravesical mitomycin C (MMC) versus bacille Calmette-Guérin (BCG) in patients with superficial bladder cancer with regard to recurrences and progression. METHODS: Patients with superficial bladder cancer (pTa, pT1, pTis) were treated with intravesical MMC (30 mg, weekly for 4 weeks, and thereafter monthly for 5 months) or BCG (weekly for 6 weeks). RESULTS: Three hundred forty-four patients were eligible (171 in the BCG group, 173 in the MMC group). The median follow-up was 7.2 years. Toxicity was not significantly different between the two treatment groups. Efficacy of the two treatment policies was similar with regard to tumor recurrence. With regard to progression to invasive disease, MMC was more effective than BCG in patients without carcinoma in situ (CIS) (P = 0.006). CONCLUSIONS: We can confirm the conclusions of other studies that intravesical treatment with 30 mg of MMC remains an effective treatment option that can also be used in high-risk patients. Like others, we could not confirm that a 6-week course of BCG is more effective in the prevention of tumor progression. Of the 33 patients with tumor progression after intravesical therapy, 20 died of bladder cancer, confirming that tumor progression after intravesical therapy carries a poor prognosis. In this study the difference in toxicity between BCG and MMC was not significant. When comparing studies with MMC and BCG, differences in treatment schedule and/or patient selection should be kept in mind.

Adjuvants, Immunologic↗

PubMed2004

Differentially expressed genes in nonsmall cell lung cancer: expression profiling of cancer-related genes in squamous cell lung cancer.

The expression patterns of cancer-related genes in 13 cases of squamous cell lung cancer (SCC) were characterized and compared with those in normal lung tissue and 13 adenocarcinomas (AC), the other major type of nonsmall cell lung cancer (NSCLC). cDNA array was used to screen the gene expression levels and the array results were verified using a real-time reverse-transcriptase-polymerase chain reaction (RT-PCR). Thirty-nine percent of the 25 most upregulated and the 25 most downregulated genes were common to SCC and AC. Of these genes, DSP, HMGA1 (alias HMGIY), TIMP1, MIF, CCNB1, TN, MMP11, and MMP12 were upregulated and COPEB (alias CPBP), TYROBP, BENE, BMPR2, SOCS3, TIMP3, CAV1, and CAV2 were downregulated. The expression levels of several genes from distinct protein families (cytokeratins and hemidesmosomal proteins) were markedly increased in SCC compared with AC and normal lung. In addition, several genes, overexpressed in SCC, such as HMGA1, CDK4, IGFBP3, MMP9, MMP11, MMP12, and MMP14, fell into distinct chromosomal loci, which we have detected as gained regions on the basis of comparative genomic hybridization data. Our study revealed new candidate genes involved in NSCLC.

Adult↗

PubMed1998

Entry into clinical trials in breast cancer: the importance of specialist teams. Scottish Breast Cancer Focus Group and Scottish Cancer Therapy Network.

The aim of this study was to identify the factors influencing entry of women with invasive breast cancer into clinical trials in Scotland. Women diagnosed during 1987 and 1993 were identified from cancer registry data records and their case notes reviewed. Entry into clinical trials was recorded, along with clinical and demographic data for 4688 patients. In 1987, the proportion of women entering clinical trials was 12.3% and, allowing for shorter follow-up, this appeared unchanged in 1993. Patients seen by surgeons with a high case load and those referred to an oncologist were approximately seven times and three times, respectively, more likely to enter a clinical trial (P < 0.0001). The area of Scotland (Health Board) where the woman was first treated also influenced study entry (P < 0.0001), whereas social deprivation had no effect (P = 0.93). Older women, especially those over 80 years of age, were less likely to enter studies (P = 0.05). Extending the management of patients by specialist multidisciplinary teams should increase recruitment into clinical trials and help to identify better treatments for women with breast cancer.

Adult↗

PubMed1989

Combination versus sequential single agent chemotherapy in advanced breast cancer: associations with metastatic sites and long-term survival. The Western Cancer Study Group and The Southeastern Cancer Study Group.

Two hundred and twenty-two patients with advanced breast cancer were randomised in two separate trials of similar design to either concomitant combination treatment or sequential use of the same drugs given as single agents changed only at disease progression. Both trials used cyclophosphamide, methotrexate, 5-fluorouracil and prednisone; the WCSG using triiodothyronine and the SECSG using vincristine as the remaining agent. A common data base was generated for these trials and combined for analysis. Considering all patients, combination treatment was associated with a significantly increased response (46 versus 25%, P less than 0.05) but not survival improvement. For the 141 patients without liver involvement, survival was closely comparable in both treatment arms. Combination therapy did result in significant survival benefit for patients with liver involvement (P less than 0.05). These studies demonstrate: (1) in the majority of breast cancer patients, sequential single agent therapy can result in survival comparable to combination treatment; and (2) sole consideration of response frequency does not represent the optimal criterion to compare therapeutic approaches in advanced breast cancer.

Adenocarcinoma↗

PubMed1990

An overview of prognostic factors in small cell lung cancer. A report from the Subcommittee for the Management of Lung Cancer of the United Kingdom Coordinating Committee on Cancer Research.

Several studies of small cell lung cancer (SCLC) treatments have been performed in the United Kingdom. In some, prognostic factor analyses were carried out but the results were not entirely consistent. The Lung Cancer Subcommittee of the United Kingdom Coordinating Committee on Cancer Research (UKCCCR) consequently initiated an overview of these studies with the aim of identifying the important prognostic factors using a large number of patients. Information on almost 4,000 patients was available, but it was necessary to perform analyses on smaller subsets because the variables recorded in individual studies were inconsistent. A number of variables contributed significantly to the prediction of likely survival over the 6 months after starting treatment, but performance status (PS), alkaline phosphatase (AlkP) and disease stage were shown to be the most important; aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) may also be useful. A prognostic index was devised for this initial period and validated using independent data. For patients who survived the first 6 months, the pre-treatment variables important for prognosis in the 6-24 month period were stage, PS and plasma sodium (Na). The Subcommittee recommends that performance status, disease stage, AlkP, Na, AST and LDH should be measured in all future SCLC studies to assist comparisons between studies and possibly the selection of patients for different treatment strategies. The additional recording of five other variables would allow a more definitive overview to be performed at some future date.

Adult↗

PubMed1998

Consensus standards for the process of cancer care: a modified expert panel method applied to head and neck cancer. South and West Expert Tumour Panel for Head and Neck Cancer.

There are many pressures to improve the standard of care delivered to cancer patients, including the reforms subsequent to the Calman-Hine report. The establishment of standards is a prerequisite for audit, benchmarking and certification of cancer centres and units. Randomized trials of head and neck cancer are uncommon, and other forms of evidence often conflicting. In the south and west of England, a multidisciplinary expert panel consensus method has been applied to the development of standards. A panel representative of specialties involved in the process of care at all three levels, plus social medicine and lay members, was constructed. A model for the process of care was developed consisting of activity areas. For each activity, a near exhaustive list of tasks and standards was established. A three-iteration method with statistical group response was then used to refine the standards. The same method was also applied to the production of a minimum data set for registration, recording and audit. The resulting standards will be regularly reviewed. We have developed a model of the care process, and an expert panel methodology that is applicable to a wide range of problems in clinical oncology.

Head and Neck Neoplasms↗

PubMed2005

The potential of proton beam radiation therapy in prostate cancer, other urological cancers and gynaecological cancers.

A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In prostate cancer it is estimated that annually about 300 patients and in gynaecological cancer about 50 patients, are candidates for proton beam therapy. Owing to major uncertainties, it has not been possible to give an estimate of the number of potential patients with urinary bladder cancer.

Cost-Benefit Analysis↗

PubMed1996

How to prepare cancer patients for potentially threatening medical procedures: consensus guidelines. NSW Cancer Council Cancer Education Research Program.

BACKGROUND: Cancer patients face a frightening array of potentially threatening medical interventions. While the need to prepare patients for such procedures is widely acknowledged, there have been few attempts to clearly specify in detail what adequate preparation entails. METHODS: This study sought to develop a set of guidelines on how to prepare cancer patients for potentially threatening medical procedures. These guidelines were extensively reviewed and modified by a consensus panel of experts. The guidelines were then rated by 101 cancer patients. RESULTS AND CONCLUSIONS: These ratings led to further modification of the guidelines, the final version of which was developed into a training module for junior medical officers in New South Wales.

Adaptation, Psychological↗

PubMed1992

Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. IV. The pathogenesis of epithelial ovarian cancer. Collaborative Ovarian Cancer Group.

Two hypotheses have been proposed to explain the reduced risk of epithelial ovarian cancer associated with pregnancy and oral contraceptive use. The first states that some sequelae of ovulation increase the likelihood of malignancy and that pregnancies and oral contraceptives protect by suppressing ovulation. The second hypothesis states that circulating levels of pituitary gonadotropins increase the risk of malignancy and that pregnancies and oral contraceptives protect by suppressing secretion of these hormones. The authors evaluate the two hypotheses in light of combined data from 12 United States case-control studies of epithelial ovarian cancer in white women conducted from 1956 to 1986. While a number of observations support both hypotheses, there are exceptions. Differential risk reduction associated with pregnancy and oral contraceptive use (pregnancy being the more effective in young women and the less effective in older women) conflicts with the first "ovulation" hypothesis, while reduced risk associated with breast feeding and absence of altered risk associated with estrogen replacement therapy conflicts with the second "gonadotropin" hypothesis. Several findings would not have been predicted by either hypothesis, e.g., only weak trends relate cancer risk to age at menarche, and, among older women, no clear trends relate risk to age at menopause. Odds ratio attenuation due to errors in reporting personal characteristics may be responsible for some of these inconsistencies. Multidisciplinary research is needed to clarify the etiologic roles of ovulation and gonadotropin stimulation, both of which may enhance carcinogenesis in the ovarian epithelium.

Adult↗

PubMed2005

CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors: Australian Breast Cancer Family Study.

INTRODUCTION: Because CYP17 can influence the degree of exposure of breast tissues to oestrogen, the interaction between polymorphisms in this gene and hormonal risk factors is of particular interest. We attempted to replicate the findings of studies assessing such interactions with the -34T-->C polymorphism. METHODS: Risk factor and CYP17 genotyping data were derived from a large Australian population-based case-control-family study of 1,284 breast cancer cases and 679 controls. Crude and adjusted odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analyses. RESULTS: We found no associations between the CYP17 genotype and breast cancer overall. Premenopausal controls with A2/A2 genotype had a later age at menarche (P < 0.01). The only associations near statistical significance were that postmenopausal women with A1/A1 (wild-type) genotype had an increased risk of breast cancer if they had ever used hormone replacement therapy (OR 2.40, 95% CI 1.0 to 5.7; P = 0.05) and if they had menopause after age 47 years (OR 2.59, 95% CI 1.0 to 7.0; P = 0.06). We found no associations in common with any other studies, and no evidence for interactions. CONCLUSION: We observed no evidence of effect modification of reproductive risk factors by CYP17 genotype, although the experiment did not have sufficient statistical power to detect small main effects and modest effects in subgroups. Associations found only in subgroup analyses based on relatively small numbers require cautious interpretation without confirmation by other studies. This emphasizes the need for replication in multiple and large population-based studies to provide convincing evidence for gene-environment interactions.

Adult↗