Wilson C. Mertens

Longitudinal patterns of weight gain after breast cancer diagnosis: observations beyond the first year.

Abstract:  Many, but not all patients experience weight gain 1 year after a breast cancer diagnosis; clearly defined, clinically relevant groups at risk of weight gain have yet to be described. We set out to determine the factors associated with weight gain over time in patients with invasive breast cancer during a period of predominantly anthracycline‐based adjuvant chemotherapy and to identify groups with differing weight gain risks. Breast cancer patients (stage I–IIIB) were identified in a retrospective chart review. Evaluated parameters included weight at diagnosis and 1, 2, and 3 years later, height, body mass index (BMI), age, menopausal and change in menopausal status, as well as therapy and pathologic stage. Regression models identified significant independent predictors of weight change. Recursive partitioning analysis (RPA) was employed to divide the dataset into relevant and significant groups. In 185 identified patients, regression models and RPA demonstrated that weight gain at 1 year was associated with younger age, adjuvant chemotherapy, and lower BMI. Weight gain at 2 years (n = 176) was greater than at year 1, and in addition to weight gain at year 1, was associated with younger age and adjuvant chemotherapy in regression analysis; RPA found that anthracycline therapy, age, and BMI were important. Weights at 3 years were similar to those seen at 2 years. Early‐stage breast cancer patients treated with chemotherapy continue to gain weight 2 years after diagnosis, and this weight gain appears to be persistent at year 3. Observation beyond 1 year is needed to adequately evaluate weight gain in early‐stage breast cancer patients, particularly for those receiving contemporary adjuvant chemotherapy.

Improving the care of patients with regard to chemotherapy-induced nausea and emesis: the effect of feedback to clinicians on adherence to antiemetic prescribing guidelines.

PURPOSE To evaluate the effect of performance and outcomes feedback on adherence to clinical practice guidelines regarding chemotherapy-induced nausea and emesis (CINE). METHODS Institutional CINE clinical practice guidelines were developed based on American Society of Clinical Oncology guidelines. Consecutive administrations of moderately/highly emetogenic chemotherapy were assessed for errors. Baseline statistical process control (SPC) charts were created and mean errors per administration were calculated. Prospective SPC charts were used to measure the effect of guideline development and distribution, a visiting lecturer, and ongoing feedback regarding compliance with guidelines employing SPC charts. Patients were surveyed regarding the extent and severity of CINE for 5 days postadministration. These outcomes were then shared with physicians. RESULTS Baseline compliance was poor (mean, 0.87 omissions per chemotherapy administration), largely because of inadequate adherence to recommendations for delayed CINE management. Most patients experienced delayed nausea, particularly on day 3 postchemotherapy. Physician prescribing performance did not undergo sustained improvement despite guideline development or distribution, a lecture by a visiting expert, or sharing of adherence data with clinicians. Once patient outcomes were shared, physicians accepted the need for compliance and instituted nurse practitioner antiemetic prescribing, with almost complete compliance and concurrent measurable reduction in day 3 nausea. SPC charts documented improvements in both outcomes. CONCLUSIONS SPC charts effectively monitor ongoing compliance and patient symptoms and represent appropriate outcome measurement and change facilitation tools. However, physician participation in guideline development and evidence of poor compliance alone did not improve prescribing performance. Only evidence of patient CINE experience coupled with noncompliance improved results.

Metastatic melanoma from intraocular primary tumors: The Southwest Oncology Group experience in phase II advanced melanoma clinical trials

Ocular melanoma is an uncommon malignancy that, in the presence of metastatic disease, has a poor prognosis for response to treatment and survival. Patients with ocular melanoma are often excluded from clinical trials because of the impression that these patients have a poorer response rate to treatment with anticancer agents and poorer survival, possibly related to the predominance of the liver as a site of metastasis. Sixty-four eligible patients with advanced melanoma arising from ocular primary tumors were entered into seven phase II clinical trials of anticancer therapy activated by the Southwest Oncology Group (SWOG) during the 1980s. Eligible patients with nonocular primaries entered into these trials (420 patients) served as a comparison group for survival, pretreatment characteristics, and response rates. Multivariate Cox model analysis of survival data (with survival from the time of study registration as the primary end-point) was conducted. Among the 484 patients observed, patients with ocular melanoma were older than those with nonocular primary tumors and were more likely to have visceral metastasis, metastasis to the liver, and only one metastatic site at registration, primarily to viscera and liver. The median overall survival after registration to study for both groups was 5 months. There was no significant difference in overall survival between patients with ocular melanoma and those with nonocular melanoma after adjusting for a number of prognostic factor (p = 0.43). Furthermore, the overall objective response rate of patients with ocular melanoma in these studies was not significantly different from that achieved in the nonocular group (9% vs. 11%; p = 1.00). Patients with advanced ocular or nonocular melanoma have similar response rates and survival in this series of cooperative group phase II trials. Patients with ocular primaries should not be excluded from investigational studies in advanced melanoma.

Strontium 89 therapy and relief of pain in patients with prostatic carcinoma metastatic to bone: a dose response relationship?

Reports published in the English literature of clinical trials utilizing intravenous strontium 89 (89Sr) in the treatment of patients with prostatic adenocarcinoma metastatic to bone were reviewed. Correlation coefficients were calculated for increasing dose of 89Sr and complete pain relief and complete and partial pain relief. Statistically significant positive correlations were obtained for complete relief of pain. Positive correlations were also found between those patients who had at least partial pain relief (denned as at least a 50% reduction in analgesia requirement), but these did not reach significance. This analysis suggests that a dose response relationship may exist between the dosage of 89Sr administered, and complete relief of pain due to skeletal metastases. The optimal dosage of 89Sr in this clinical situation has not been established, and prospective, carefully executed and analyzed randomized trials will be required to test whether and to what extent dose intensity of 89Sr determines outcome independently of other factors.

Chronic diarrhea associated with persistent norovirus excretion in patients with chronic lymphocytic leukemia: report of two cases

BackgroundChronic diarrhea in patients treated with immunosuppressive agents or suffering from immunosuppressive disease can represent a diagnostic and therapeutic challenge to the clinician. Norovirus infection, a major cause of acute epidemic diarrhea, has been described as a cause of chronic diarrhea in patients who are immunosuppressed, including transplant recipients and the very young.Case presentationsWe describe two patients, a 64 year-old man and a 59 year-old woman, both suffering from chronic lymphocytic leukemia and hypogammaglobulinemia, who developed chronic diarrhea resistant to therapy. In both cases, after months of symptoms, persistent norovirus infection--documented by repeatedly-positive high-sensitivity stool enzyme immunoassay--was found to be the cause. Both patients died with active diarrheal symptoms.ConclusionsWe describe the first cases of advanced chronic lymphocytic leukemia to suffer from chronic symptomatic norovirus infection. Clinicians caring for such patients, particularly those with concomitant hypogammaglobulinema, who have chronic unexplained diarrhea, should consider norovirus infection in the differential diagnosis.

Weight gain following breast cancer diagnosis: Implication and proposed mechanisms.

Weight gain occurs in the majority of women following breast cancer treatment. An overview of studies describing weight gain amongst women treated with early to modern chemotherapy regimens is included. Populations at higher risk include women who are younger, closer to ideal body weight and who have been treated with chemotherapy. Weight gain ranges between 1 to 5 kg, and may be associated with change in body composition with gain in fat mass and loss in lean body mass. Women are unlikely to return to pre-diagnosis weight. Possible mechanisms including inactivity and metabolic changes are explored. Potential interventions are reviewed including exercise, dietary changes and pharmacologic agents. Although breast cancer prognosis does not appear to be significantly impacted, weight gain has negative consequences on quality of life and overall health. Future studies should explore change in body composition, metabolism and insulin resistance. Avoiding weight gain in breast cancer survivors following initial diagnosis and treatment should be encouraged.

Soft tissue sarcoma in adults

Over the past year, improved delineation of prognostic factors and other aspects of staging of localized sarcomas have been reported. Although little progress has been made in terms of improvement in adjuvant therapy, new efforts to enhance therapy for advanced disease, particularly through use of dose-intensive chemotherapy regimens with colony-stimulating factor support, have resulted in improved response rates and may herald the development of new chemotherapy regimens, which may be employed in future randomized studies in the early disease setting.

Neoadjuvant estramustine and etoposide followed by concurrent estramustine and definitive radiotherapy for locally advanced prostate cancer: feasibility and preliminary results.

PURPOSE Current therapy for locally advanced prostate cancer is suboptimal. A treatment regimen was designed to improve systemic control by neoadjuvant targeting of hormone-sensitive and -insensitive micrometastatic disease and to improve local control by escalating the biologic effective dose to the prostate using estramustine (EMP) concurrently with radiotherapy. PATIENTS AND METHODS Eighteen patients with locally advanced prostate cancer (Stages T3/T4 or T1c/T2b/T2c with a Gleason score of > or =7 and a serum PSA >15 ng/ml) were entered onto this trial. Therapy consisted of two 21-day cycles of oral estramustine (10 mg/kg/day) in three divided doses and oral etoposide (50 mg/m(2)/day, in two divided doses), followed by concurrent estramustine (10 mg/kg/day, PO) and three-dimensional conformal radiotherapy. RESULTS Two patients required discontinuation of chemotherapy due to development of Grade 3 and 4 toxicity. All others completed both components of therapy per protocol guidelines. Minor toxicities included alopecia (100% of patients), anemia (69%), leukopenia (37%), thrombocytopenia (19%), and nausea (6%) but did not require dose modifications. There were no fatalities. Actuarial 3-year overall survival and disease-free survival (DFS) were 88% and 73%, respectively. Local control rate, assessed by repeated prostate biopsies at 18 months post completion of therapy, was 71%. CONCLUSION The described regimen is well tolerated, and preliminary efficacy data are encouraging. The underlying concepts of early targeting of both hormone-sensitive and -insensitive micrometastatic clones, in combination with aggressive local therapy, warrant further investigation.

Malignant paraganglioma with skeletal metastases and spinal cord compression: Response and palliation with chemotherapy

Paragangliomas (carotid body tumours, chemodectomas) may arise in any area of the body where sympathetic ganglia are present, including chemoreceptors, the adrenal medulla and retroperitoneal ganglia. Increasing numbers of patients are being reported with vertebral metastases and spinal cord compression for which either decompression laminectomy or external beam radiotherapy, or both, are required. Patients with vertebral metastases may develop progression of disease after radiation therapy. There is little published information on the use of chemotherapy in this clinical situation. We report a case of metastatic paraganglioma complicated by spinal cord compression showing evidence of clinical benefit from chemotherapy after progressive disease and symptoms developed in a region previously treated by radiation therapy.

Effect of indomethacin plus ranitidine in advanced melanoma patients on high-dose interleukin-2

Preclinical models of advanced melanoma have shown that chronic indomethacin therapy combined with interleukin 2 (IL-2) can eradicate experimental metastases. A phase II trial was done in patients with advanced melanoma. Indomethacin and ranitidine were begun at least one week before IL-2. Of the objective responses in 3 patients, 2 were achieved on ranitidine and indomethacin alone, before start of IL-2. Indomethacin and ranitidine may be responsible for some responses in melanoma patients previously attributed to IL-2.