Perceptions of the ethical conduct of cancer trials by oncology nurses.

Informed consent and subject protection are internationally mandated requirements for the ethical conduct of research; however, the monitoring of the day-to-day conduct of research may be insufficient for ensuring consistent compliance with required ethical ideals. Oncology nurses were surveyed about their perceptions of ethical issues relevant to cancer trials research. Utilising an investigator-developed instrument, multi-item scales assessed six ethical domains. Of 192 respondents, 95% or more held definite views in 12 of 15 items about patient understanding of cancer trials, informed consent and the welfare of participants. Approximately 95% perceived that patients consented freely and knew how to withdraw from a trial, and 81% perceived better monitoring of trial than non-trial patients. However, more than 80% of respondents perceived that at times patients had unrealistic expectations of participation, and more than 50% perceived that participants sometimes did not understand the nature and risk of cancer trials. Although the conative attributes of patients place limits on the goals of bioethics, the results of this study show first that oncology nurses have opinions about ethical constructs directly linked to the daily conduct of cancer clinical trials, and second that this link warrants further investigation in order to benchmark trial conduct against the ideals of ethical research.

Acute myeloid leukemia after breast cancer: a population-based comparison with hematological malignancies and other cancers.

BACKGROUND: Clinical trials frequently report acute myeloid leukemia (AML) as a complication of adjuvant chemotherapy for breast cancer (BC). PATIENTS AND METHODS: This retrospective population-based study investigated AML risk after a prior BC diagnosis and compared the results with women after a prior diagnosis of hematological malignancies (HM), other cancers combined (OCC), and the age-matched Australian female population. RESULTS: Women with a prior BC diagnosis had 2.56 times the risk of developing AML compared with the Australian female population (P<0.001). AML risk was also elevated after prior HM and OCC diagnoses (4.73, P<0.001, and 1.70, P<0.001, respectively). Although the incidence of AML rose sharply with age in all cohorts, the age-specific relative risk was highest in the 30- to 49-age-group and decreased with increasing age. AML risk increased with the duration of follow-up but there was no change of risk during the 23 years of this study. CONCLUSION: AML risk was elevated after a prior diagnosis of BC but there was no evidence of an increasing risk of AML after a BC diagnosis or, in any of the other cancer cohorts, during this era of expansion of the evidence base for more intensive treatments.

Origin of corn: pollen evidence.

The origin of Indian corn remains controversial. Its closest wild relative is teosinte, with which it hybridizes freely to produce fertile progeny. Teosinte ears are smaller and simpler than those of corn. Searches for a more likely living ancestor have failed, but nine of its assumed pollen grains have been recovered in deep drillcore samples obtained from a stratum of soil under Mexico City, which is believed to antedate man in the Western Hemisphere. These nine largest grains are indistinguishable from pollen of modern corn. It has been assumed to be that of a postulated wild corn other than that of teosinte, but this does not account for the possibility that the pollen grains are those of a tetraploid teosinte-producing pollen with two sets of chromosomes. This likelihood has been examined by treating modern teosinte plants with colchicine, which induces tetraploidy. The result has been many teosinte pollen grains indistinguishable in size from modern corn. In interpreting thrs outcome it is important also to know that heat treatment of corn and other plants induces polyploidy, and that the deep drill-core pollen was recovered in a stratum of volcanic clay indicating the high temperature known to favor doubling of corn pollen volumes.

Prognostic value of quality of life scores in a trial of chemotherapy with or without interferon in patients with metastatic malignant melanoma.

In a multi-centre randomised clinical trial comparing dacarbazine (DTIC) plus recombinant interferon-alfa2a (IFN) versus DTIC alone for patients with metastatic malignant melanoma, aspects of quality of life (QL) were measured prospectively by patients using linear analogue self assessment (LASA) scales including the GLQ-8 and by doctors using Spitzer's QL Index. QL scores and performance status at the time of randomisation were available for 152 of 170 eligible patients. These scores carried significant prognostic information. In univariate analyses, Spitzer QL Index assessed by the doctor and LASA scores for physical wellbeing (PWB), mood, pain, appetite, nausea and vomiting, GLQ-8 total and overall QL were significant (P < 0.01) predictors of subsequent survival. QL Index and LASA scales for mood, appetite, and overall QL remained independently significant (all P < 0.05) in multivariate models allowing for significant prognostic factors other than QL (liver metastases and performance status). These findings closely parallel those in patients with metastatic breast cancer. They add further validity to the QL Index and LASA scores, provide the first evidence of the prognostic significance of the GLQ-8, and argue strongly for the routine assessment of QL in future therapy trials.

The effect of adjuvant chemotherapy on the cosmetic results after primary radiation treatment for early stage breast cancer.

Breast cancer patients treated by primary radiation therapy who have positive axillary lymph nodes now typically receive adjuvant chemotherapy. In order to evaluate the effect of adjuvant chemotherapy on the response of the breast to radiation treatment, we compared the cosmetic results of 49 patients treated with adjuvant chemotherapy and 206 patients not treated with adjuvant chemotherapy. A variety of chemotherapy regimens were employed, most commonly a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). The median follow-up time for all patients was 33 months. Cosmetic results were scored by the physician at each follow-up evaluation as excellent, good, and fair or poor, depending on the presence and extent of radiation-related changes in the treated breast. Patients who received adjuvant chemotherapy were less likely to have an excellent overall cosmetic result than patients who did not receive adjuvant chemotherapy. At 24 months 24% of these patients had an excellent cosmetic result compared with 64% of patients who did not receive adjuvant chemotherapy (p = 0.0002). This difference was due primarily to a shift in chemotherapy-treated patients from an excellent to a good overall cosmetic result. Breast retraction was noted to be the most frequent determinant of a fair or poor cosmetic result and was more common in patients treated with adjuvant chemotherapy. At 24 months, 62% of these patients had evidence of breast retraction compared with 44% of patients who did not receive adjuvant chemotherapy (p = 0.06). We conclude from this preliminary analysis that adjuvant chemotherapy modifies the response of the breast to radiation, most notably by increasing the development of retraction.

Clinical significance of solitary rib lesions in patients with extraskeletal malignancy.

A retrospective review of 2,851 bone scans done at a cancer center over a period of 4 yr revealed 41 patients having a single abnormality in a rib as their first abnormal scintigraphic finding. The scan findings in these cases were correlated with clinical, scintigraphic, and radiographic follow-up to ascertain their etiology and course. Four lesions (9.8%) were due to malignant disease, 16 (39%) were associated with benign fractures demonstrated on x-ray, 11 (27%) were associated with primary or postoperative radiation therapy. The remaining ten patients (24.2%) with normal x-rays and no association with radiation therapy or subsequent development of metastasis were assigned to benign etiology. This experience suggests that solitary rib lesions in cancer patients are uncommon and are most frequently (90%) associated with benign etiology.

Interferon-alpha 2a does not improve response or survival when combined with dacarbazine in metastatic malignant melanoma: results of a multi-institutional Australian randomized trial.

Following extensive phase II trials of the combination of dacarbazine and interferon-alpha 2a we performed a prospective, randomized, controlled trial of this combination versus dacarbazine alone as systemic therapy for symptomatic, measurable metastatic malignant melanoma. The two treatment arms were well matched for age, sex, performance, status, relapse-free survival, prior therapy and sites of disease. Therapy consisted of dacarbazine given in combination in escalating doses of 200 mg/m2, 400 mg/m2 and 800 mg/m2 i.v. every 3 weeks, or alone at 800 mg/m2 i.v. every 3 weeks. Interferon was administered subcutaneously starting at 3 mU daily on days 1-3, 9 mU daily on days 4-70, then 9 mU three times per week. Therapy was continued for at least 6 months unless overt progressive disease was observed. Eighty seven patients were randomized to the combination and 83 patients to dacarbazine alone. Response rates were respectively, complete 7% and 2%, and partial 14% and 15%, for a total response rate of 21% (95% confidence limits 13-31%) and 17% (95% confidence limits 10-27%). Median duration of response was 258 and 286 days, and survival of the whole groups 229 and 269 days respectively. Toxicity was worse in the combination arm, with more patients experiencing fatigue, nausea and anorexia, flu-like symptoms and neutropenia. However quality of life was not significantly different in either group, except that fatigue, as measured at week 12 by LASA scales, and activity, as measured by the functional living index, were both improved in the combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Reaginic antibody in cattle hypersensitised by foot-and-mouth disease vaccine.

The passive cutaneous anaphylaxis test (PCAT) in calves and goats was used to demonstrate reaginic antibody in the sera of cattle which had shown anaphylaxis following injection with foot-and-mouth disease vaccine. A period of two or three days between the intracutaneous injection of test sera and the intracutaneous or intravenous challenge with components of vaccine was found to be satisfactory. Positive reactions were obtained in calves for up to 49 days but many goats failed to react after eight days. The PCAT had a high degree of reproducibility within any one test animal, but a marked variation was found between individual test animals.

Acute ileotyphlitis as a complication of cytotoxic drug treatment of a non-seminomatous germ cell tumor of the testis.

A case of acute ileotyphlitis is reported in a man treated with cytotoxic drugs for metastatic non-seminomatous germ cell tumor of the testis. This case illustrates the variable features of acute ileotyphlitis and highlights the importance of clinical awareness in order to establish the diagnosis and commence treatment immediately.

Treatment of advanced malignant hemangiopericytoma with combination adriamycin and DTIC: a report of four cases.

One patient with a large inoperable malignant hemangiopericytoma and three patients with local recurrence and/or metastases were treated with combination adriamycin, 50 mg/m2, and DTIC, 600-700 mg/m2, intravenously every 4 weeks. Two achieved palliation, one with measureable shrinkage of tumor, and the other with loss of incapacitating lower limb edema secondary to vascular and lymphatic obstruction. The third patient objectively had a less than partial response. The fourth patient did not respond to adriamycin and DTIC or to a subsequent trial of cis-platinum, 60 mg/m2, intravenously every 3 weeks. However, radiotherapy produced an objective response at the site of the local recurrence and relief of painful bone metastases. Two patients died of progressive disease; the third patient has stable disease and is continuing chemotherapy; and the fourth patient died, probably from adriamycin-induced cardiac failure in the presence of rapidly advancing intraabdominal metastases. The combination of adriamycin and DTIC is active in malignant hemangiopericytoma, and palliation of advanced disease can be achieved. However, prolonged survival is uncommon in the presence of a large tumor burden.

The role of post-operative radiotherapy in the treatment of operable breast cancer.

In current practice, the management of early stage breast cancer involves a multidisciplinary cooperation among surgeons, radiation therapists, and medical oncologists. The goals of local treatment in this setting are to secure tumor control and to identify patients who are to be treated with adjuvant systemic therapy. For patients treated by mastectomy, the value of post-operative radiotherapy in primary treatment remains controversial. In this review, we examine the evolution of treatment philosophies for operable breast cancer and the results from recent clinical studies in an attempt to assess the current role of post-operative radiotherapy.

Clinical studies on the use of radiation therapy as primary treatment of early breast cancer.

The treatment of operable breast cancer by primary radiation therapy instead of mastectomy is undergoing evaluation in the United States and Europe. Retrospective studies of patients treated by primary radiation therapy show that local control and survival rates are comparable to those obtained by mastectomy. Detailed analysis of local failure following primary radiation therapy indicates the importance of excisional biopsy of the primary tumor, moderate doses of radiation to the breast and draining lymph node areas, and the use of a boost to the primary tumor area in maximizing local control. Further, the judicious use of local excision combined with meticulous radiotherapy technique yields highly satisfactory results for the majority of treated patients. Preliminary results from prospective trials also indicate that primary radiation therapy provides both local control and survival rates equivalent to mastectomy. Primary radiation therapy is becoming an increasingly important alternative to mastectomy where surgical and radiotherapeutic expertise are available to optimize both local tumor control and the final cosmetic outcome.

Psychosocial support, treatment of metastatic disease and palliative care.

This article deals with four linked but distinct aspects of care for women with breast cancer, with an emphasis on the pivotal role of the general practitioner: 1. Modern medicine is fast recognising the need for psychosocial support of patients; in fact, for an integrated approach to caring for the whole person at all stages of illness. 2. Oncological treatment of metastatic disease needs to be individualised and based on realistic expectations of outcome balanced against side effects. 3. An open dialogue about the role and appropriateness of so-called "alternative" or "complementary" therapies is needed. 4. Despite significant improvements in palliative care quality and access in Australia in the last decade, many practitioners still require support and advice in this demanding area of care (particularly about difficult symptom control).

Hypersensitivity in cattle after foot-and-mouth disease vaccination: response to hydroxpropylmethylcellulose.

Intravenous provocation (IVP) tests demonstrated that hydroxypropylmethylcellulose (MC) was able to elicit anaphylactic signs in cattle vaccinated with foot-and-mouth disease (FMD) vaccine produced at one centre but not with similar vaccine produced at another. The former vaccine also provoked serum reagins which were demonstrated by passive cutaneous anaphylaxis (PCA) tests in goats. Reaginic sera which reacted specifically with MC were used in PCA tests to screen samples taken serially from the vaccine production lines. The reactions observed suggested that a substance with MC or similar specificity was present in the antifoaming agent routinely added to vaccines.

Cosmetic results following primary radiation therapy for early breast cancer.

In order to assess the cosmetic results of treatment, the results in 239 patients with early breast cancer treated by primary radiation treatment without adjuvant chemotherapy were reviewed. Four patients had bilateral cancers, making a total of 243 breasts available for analysis. Follow-up ranged from 24 to 78 months with a median of 33 months. The parameters measured were breast edema, retraction, telangiectasia, arm edema, and the overall cosmetic appearance. The cosmetic results declined over the first 3 years after treatment, but then stabilized. At 5 years, the overall cosmetic results were judged by physicians as excellent in 77%, good in 9%, fair in 9%, and poor in 5%. A fair or poor cosmetic result was highly correlated with the development of moderate or severe breast retraction. Telangiectasia was uncommonly the only cause of a fair or poor cosmetic result. Breast and arm edema were rarely noted to be significant, but were more common in patients who underwent axillary dissection. In 210 cases, a supplementary boost dose of radiation was delivered to the primary tumor area, and in 33 cases a boost was not used. This boost consisted of an interstitial iridium-192 implant in 204 cases and either high-energy photons or electrons in the remainder. At 4 years, no patient treated without a boost had a fair or poor result compared with 22% who received a boost (P = 0.13). The conclusion is that, in general, primary radiation treatment provides highly satisfactory cosmetic results for patients with early breast cancer.

Werner's syndrome: a model of premature aging?

A 34 year-old woman with Werner's syndrome has been studied in the light of the current concept that this disorder is a model of premature aging. Endocrine function assays revealed an abnormal glucose tolerance and in vivo insulin insensitivity after prednisolone, and ovarian failure. Immune function assays revealed hypo-responsiveness in skin tests for delayed hypersensitivity, a poorly sustained IgG anti-body response after immunization with flagellin, and a low count of colony-forming T lymphocytes in blood. Cultured fibroblasts had a very limited capacity to replicate in vitro, in comparison with donors of similar age and, moreover, 85% of glucose-6-phosphate dehydrogenase in the patient's cultured fibroblasts was heat-stable at 60 degrees C compared with 100% for a healthy control. Cell receptors (for insulin) were examined by insulin binding to isolated fat-cells, with the finding that fat-cells were abnormally large for the patient's size, and their receptor density was low. The findings from the study point to a genetic defect in Werner's syndrome which, in its effect on particular tissues, may simulate features of aging, but the disease is not a true model of premature aging.

Illusions in advanced cancer: the effect of belief systems and attitudes on quality of life.

Patients with advanced cancer frequently express positive attitudes and can be unduly optimistic about the potential benefits of treatment. In order to evaluate an illusory domain in the context of advanced cancer, we developed a scale of will to live and characterized the beliefs that patients held about the curability of their cancer, and how committed they were to using alternative treatments. A measure of quality of life was used as the dependent variable in order to assess the association between these attributes. After a preliminary exploration confirmed the presence of an illusory domain, these concepts were prospectively tested in 149 ambulant patients with advanced cancer who attended for palliative systemic treatment, radiation treatment or supportive care. The scale of global quality of life was reliable (Cronbach's alpha coefficient 0.72). The distribution of the scores of will to live was skewed, with no respondent scoring poorly, and the scale was reliable (Cronbach's alpha coefficient 0.82). The scale of belief in curability showed diverse beliefs. In some cases, there was a discrepancy between respondents' beliefs in curability and what they believed to be the report by their doctors. There was also an association between a committed use of alternative treatments and a belief in the curability of the cancer (p<0.001). In a multiple regression analysis, both will to live and performance status remained associated with better quality of life scores after adjustment for other relevant variables (p<0.05 and <0.001, respectively). These results suggest that positive illusory beliefs can be measured and are an important component of adaption for some patients with advanced cancer. Furthermore, this illusory domain may influence the perception and measurement of quality of life.

Beliefs and practices of patients with advanced cancer: implications for communication.

The aim of this study was to investigate the beliefs that patients with advanced cancer held about the curability of their cancer, their use of alternatives to conventional medical treatment, and their need to have control over decisions about treatment. Of 149 patients who fulfilled the criteria for participation and completed a self-administered questionnaire, 45 patients (31%) believed their cancer was incurable, 61 (42%) were uncertain and 39 (27%) believed their cancer was curable. The index of need for control over treatment decisions was low in 53 patients (35.6%) and high in only 17 patients (11.4%). Committed users of alternatives to conventional medical treatments were more likely to believe that their cancer was curable (P<0.001) and to have a higher need for control over decisions about treatment (P<0.004). The mean need for control scores were highest in patients who believed that their cancer was curable, or who were uncertain about the curability of their cancer, but who acknowledged that their oncologist had reported that the cancer was incurable. The diverse beliefs, attitudes and actions of these patients were consistent with a range of psychological adaptations to a life-threatening illness, some realistic and others illusory. Illusory responses influence what communication can achieve in daily oncology practice.

Pathologic findings on re-excision of the primary site in breast cancer patients considered for treatment by primary radiation therapy.

Gross excision of the tumor followed by radiotherapy is used for treatment of early breast cancer. Local recurrence after this form of treatment is uncommon except in patients with infiltrating ductal carcinoma whose excision specimens reveal an extensive intraductal component (EIC). It is unclear whether this observation is due to a qualitative difference in the response of tumors with EIC to radiation or to a quantitative difference in the tumor burden remaining after gross excision in patients with EIC. To address this question, the authors examined pathologic material in 71 patients with infiltrating ductal carcinoma treated with gross excision of the tumor and then selected for re-excision of the tumor site prior to radiotherapy because of the presence of either EIC in the primary excision specimen or microscopic tumor at or close to margins in the initial excision. Residual carcinoma was seen in 62% of all patients but was more frequent among the 25 patients with EIC than the 46 without (88% vs. 48%, P = 0.002). The nature of the residual tumor differed for patients with and without EIC in the primary excision specimen. Residual carcinoma in patients with EIC was often widespread and composed predominantly of intraductal carcinoma. In contrast, residual tumor in patients without EIC usually consisted of only scattered microscopic foci of infiltrating and/or intraductal carcinoma. The authors conclude that patients with EIC treated with gross excision of the tumor frequently have considerable residual intraductal carcinoma near the primary site. This finding may account for the increased risk of local recurrence observed in patients with EIC treated without re-excision of the tumor site before radiation therapy.

Mantel irradiation for stage I and stage II Hodgkin's disease--results of a 10 year experience.

One hundred and thirty patients with Stage I and II supradiaphragmatic Hodgkin's disease treated with mantle irradiation alone at the Peter MacCallum Hospital, Melbourne between 1968-1977 were analysed retrospectively. The median followup was 7.4 years with a minimum of three years. There were 64 clinically staged (CS) and 66 pathologically staged (PS) patients. The major difference between the two groups was the transdiaphragmatic relapse which occurred in 33% of CS patients, and 7.5% in PS patients. The actuarial five year relapse free survival (RFS) was 48% for CS patients and 67% for PS patients, but the five year overall survival was 90% for both groups, reflecting the impact of salvage treatment. Avid attention must be given to radiotherapy techniques to minimise local treatment failures. High grade nodular sclerosis Hodgkin's disease is associated with poor RFS even after adjustment has been made for stage and constitutional symptoms (p less than 0.003). Further studies will be made on this group of patients who may benefit from combined modality treatment. For PS I and II patients mantle irradiation gives a five year RFS of 67%, thus offering potential for cure in these patients.