Cancer

Adjuvant therapy for patients with melanoma using interferon α remains controversial despite numerous randomized clinical trials. In the current study, Kirkwood et al. present the results of a biologic companion trial to Intergroup Trial E1690, which compared high-dose and low-dose interferon α2b with observation after surgery. The implications for current practice and future clinical trials are discussed.

See also pages 1102-12.

Long-term estrogen use was associated with a statistically significant increased risk of breast carcinoma among both Hispanic and non-Hispanic white women. The risk estimate was much higher in Hispanics than that in non-Hispanic women.

Benign mammary epithelial cells and cells of in situ and invasive breast carcinomas express both erythropoietin (Epo) and Epo receptor (EpoR). Increased EpoR immunostaining in breast carcinomas is correlated with clinicohistopathologic features suggestive of an adverse prognosis. Increased autocrine Epo signaling may represent a novel mechanism by which hypoxia promotes breast carcinoma and induces a malignant phenotype.

Ultrasound (US)-guided fine-needle aspiration of nonpalpable, indeterminate and suspicious axillary lymph nodes is a simple, minimally invasive and reliable technique for the initial determination of axillary lymph node status in patients with breast carcinoma. The discrepancy between the initial and final axillary lymph node status may be related to the failure to visualize all lymph nodes during US examination, small-sized metastases, and preoperative neoadjuvant chemotherapy.

Physicians viewed the barriers to accruing older patients with breast carcinoma to clinical trials as multidimensional. Because the most important perceived barriers included protocol requirements, treatment specific issues, and older patients' medical and cognitive condition, a variety of interventions would be needed to improve accrual. Possible interventions may include increasing physicians' knowledge concerning the medical treatment of older patients, simplifying protocol requirements, reducing treatment toxicity, and reducing ageist attitudes.

Spinal cord tumors, of which ependymomas are the most frequent, are uncommon neoplasms of the central nervous system and scant information is available in the literature regarding chemotherapy treatment. The current study presents a pilot study of 10 patients with recurrent spinal cord ependymoma who were treated with oral etoposide, a therapy that demonstrated activity with modest toxicity.

Contrary to results reported for tumor models of rodent xenografts or for cells in culture, our results do not provide any evidence of a potential role for metallothioneins as a radioprotector in rectal tumors in humans undergoing preoperative irradiation. It is therefore difficult to extrapolate experimental results to humans.

Patients with carcinoma of the urinary bladder who received paclitaxel-based chemotherapy and who had tumors that were positive for HER2/neu expression had a significant decrease in the risk of death.

A validated, biopsy-based algorithm for the preoperative prediction of lymph node metastases in patients with clinically localized prostate carcinoma that has a 94% specificity and a 2.47% false negative rate is presented. This validated algorithm provides important selection basis regarding the appropriateness of a therapy that does not routinely include lymph node staging.

Chemotherapy options for patients with advanced urothelial carcinoma and renal dysfunction are limited. E2896, a Phase II trial of paclitaxel and carboplatin in these patients, is the first cooperative group study for this patient population and will serve as a reference for future trials.

There is little information regarding the pathology of metastatic prostate carcinoma to bone, or the significance of pathologic features regarding patient outcome. The results of the current study demonstrate that tumor differentiation, as assessed by the Gleason score of metastatic prostate carcinoma, and immunohistochemical chromogranin A positivity are associated significantly with the duration of cancer-specific survival after surgery for the metastatic lesion.

Awareness about prostate carcinoma (PCa) has not been associated with increased knowledge about the potential limitations of PCa screening. Study results suggest the importance of developing informed consent procedures and educational programs for the asymptomatic men who participate in the annual free prostate screening programs, as the decision to be screened is being made without the benefit of a full understanding of the current state of medical knowledge about PCa screening.

The authors demonstrate long-term benefits from subcutaneous interferon α and interleukin 2 (IL-2)-based home therapy in a subset of patients with metastatic, progressive renal cell carcinoma who were selected on the basis of their good or excellent performance status. The demonstration of augmented benefits from the addition of intravenous 5-fluorouracil and oral 13-cis retinoic acid will require further evaluation.

Salvage combination chemotherapy with 5-fluorouracil and actinomycin D was effective in the treatment of patients with refractory, high-risk gestational trophoblastic tumors. The extremely low toxicity level was manageable.

The hypoxia-inducible factor 1α (HIF-1α), a transcription factor that is induced in response to hypoxic stimuli, stimulates angiogenesis through activation of the vascular endothelial growth factor pathway and confers a poor prognosis in patients with endometrial carcinoma.

Medicare and third-party payers often are reluctant to pay for investigational (protocol) therapy for cancer patients based on the premise that such treatment is more expensive than standard therapy. In the current study, the authors conducted a retrospective review of the financial charges associated with the use of protocol versus nonprotocol therapy in patients with acute myelogenous leukemia.

Our findings suggest that high levels of plasma interleukin-6 correlated with worse clinical outcome in patients in the advanced stage of chronic lymphocytic leukemia.

The most relevant finding of this study is the high prevalence of endocrine dysfunction in recipients of allogeneic bone marrow transplantation who had not been irradiated. Ovarian failure was found in 95% of women and spermatogenesis damage was likely in 47% of men. Thyroid, adrenal, or insulin-like growth factor I (IGF-I) impairment occurred in 47.5%, 10%, and 27% of all patients, respectively. Endocrine disorders were significantly more frequent in patients with chronic graft versus host disease compared with those without this complication (69% vs. 28.6%, P = 0.048). These data suggest a relevant role of immune system derangement and immunosuppressive treatment in the development of endocrine dysfunction after allografting.

This study found that 15% of patients with unresectable lung carcinoma had some degree of suicidal ideation 6 months after the cancer diagnosis and that pain before the start of cancer therapy and the development of a depressive disorder were significant predictors. Suicidal ideation among unresectable lung carcinoma patients should not be neglected and comprehensive care consisting of at least earlier pain management and appropriate psychiatric intervention is indispensable to prevent subsequent suicidal ideation.

In the clinicopathologic evaluation of melanocytic skin lesions, a diagnostic discrepancy among dermoscopists seems to be predictive for a diagnostic disagreement among histopathologists. The presence of regression structures is strongly predictive for a histopathologic disagreement.

Laboratory immunologic corollary studies have not yet identified intermediate endpoints of value for interferon α2 therapy in patients with melanoma. This study is the first Intergroup clinical-laboratory evaluation of the phenotypic and functional aspects of blood lymphocytes and tumor tissue and identifies significant differences between the effects of high-dose and low-dose interferon. See also pages 947–9.

Acidosis may be an important determinant of glioma cell responses to adjuvant radiochemotherapy. The superior activity of nitrosoureas, compared with other agents, in glioblastoma may result from prolonged drug stability in an acidotic microenvironment.

In this retrospective study, neoadjuvant chemotherapy for soft tissue sarcoma resulted in tumor shrinkage sufficient to impact surgical therapy in only a few patients. However, radiographic response predicted improved local control and overall survival.

The presence of telomerase activity is correlated with local recurrence and distant metastasis as well as malignancy in soft tissue tumors. Telomerase activity and human telomerase reverse transcriptase mRNA expression may be useful markers for evaluating clinical aggressiveness in patients with soft tissue tumors.

This article summarizes the results of a workshop that reviewed existing knowledge of the role of physical activity across the cancer continuum. Innovative designs for future research from the basic to the population-based level are discussed.

In patients with recurrent rectal carcinoma, high doses of irradiation can be delivered with acceptable risks without long-term side effects. Surgical salvage and long-term survival of patients are possible.

Radiation enteritis and other radiation-induced, long-term complications of radiotherapy are characterized by excessive stimulation of transforming growth factor β1 (TGF-β1), which leads to increased fibrosis and, ultimately, organ failure. The authors conducted a literature search to identify the common denominator between many radiation-induced fibrotic conditions and other sclerotic diseases, and they also evaluated possible therapeutic interventions. Preliminary studies suggest that, because interferon γ (IFN-γ) inhibits the effects of TGF-β1 in the nucleus, IFN-γ should be considered in Phase I–II studies to assess its toxicity and efficacy in the treatment of patients with radiation enteritis.

Dextromethorphan (60 mg and 90 mg) given to patients who were undergoing surgery for bone and soft tissue malignancies was effective in reducing postoperative pain intensity, sparing morphine and oral analgesic consumption, and maintaining alertness. The incidence of side effects, cardiorespiratory parameters, and time to ambulation and home discharge were unaffected.

The replication-conditional herpes simplex virus 1 designated rRp450 combines direct viral oncolysis with p450 transgene bioactivation of the prodrug cyclophosphamide to effectively destroy colon carcinoma metastases.