Screening Elderly Women for Urogenital Cancers: When Should We Stop Giving Older Women Pap Tests?

Marie-Hélène Mayrand, MD, MSc, FRCSC, Departments of Oncology and Epidemiology, McGill University, Montreal, PQ.
Eduardo L. Franco, PhD, Professor of Epidemiology and Oncology, Director, Division of Cancer Epidemiology, McGill University, Montreal, PQ.

Introduction
The Canadian population is growing older, and women represent an ever higher proportion among the elderly: 57% of Canadians over 65 years of age are female, and in the "over 85" age group, this proportion reaches 70%.¹ We can expect that specific health care issues that pertain to this segment of the population will receive renewed attention. Understandably, there has been a special interest in identifying preventive health care measures that can effectively prevent disability or premature death in women over age 65.

With the sole exception of cervical cancer, there is no evidence that screening women for urogenital neoplasms, such as endometrial, ovarian and bladder cancers, reduces mortality from these cancers, regardless of age.² Therefore, the focus of this article will be on reviewing the basis for practice recommendations concerning screening for cervical cancer. Although essentially preventable, cancer of the uterine cervix continues to be a significant health problem, particularly in older women. In Canada, older women have the highest incidence and mortality rates from cervical cancer when compared to younger age groups.

New Therapy for Non-Hodgkin’s Lymphoma

Rituximab, a chimeric monoclonal antibody against the B-cell CD20 antigen, has previously been shown to be effective for the treatment of relapsed or refractory indolent lymphomas and has activity in relapsed or refractory diffuse large-B-cell lymphoma. Currently, the standard treatment for large-B-cell lymphoma is cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), which is effective in younger patients, but induces complete responses in only 40-50% of elderly patients, with three-year event-free and overall survival rates of 30% and 35-40%, respectively. A recent study has examined the benefits of adding rituximab to the CHOP regimen, to see how this treatment compares to CHOP alone.

The researchers randomized previously untreated patients with diffuse large-B-cell lymphoma, 60-80 years old, to receive either eight cycles of CHOP every three weeks, or eight cycles of CHOP plus rituximab given on day one of each cycle. They found that the rate of complete response was significantly higher in the group that received CHOP + rituximab and with a median follow-up of two years, event-free and overall survival times were significantly higher in this group. In addition, this treatment significantly reduced the risk of treatment failure and death and there was no significant increase in treatment-related toxicity.

Non-Hodgkin's lymphoma is the fifth most common cancer in Canada, and there are expected to be 6,200 new cases diagnosed this year.

Source

1. Coiffier B, Lepage E, Briere J et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. NEJM 2002;346:235-242.

Raloxifene and Breast Cancer: The Influence of Estradiol

A recent study has suggested that Raloxifene may be more effective in preventing breast cancer in women with higher levels of estradiol. It has previously been shown that the risk for breast cancer increases with increased levels of endogenous estradiol. Scientists hypothesized that raloxifene, which competes with estradiol for binding to estrogen receptors in breast tissue, might have a greater effect on breast cancer risk in women with relatively high estradiol levels. They analyzed data from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, conducted in 7,290 women (80 or younger) with osteoporosis. Serum estradiol concentrations were measured by a central lab. They found that in the placebo group, women with estradiol levels greater than 10 pmol/L (2.7 pg/mL) had a 6.8-fold higher rate of breast cancer than did women with undetectable estradiol levels. Women with estradiol levels greater than 10 pmol/L in the raloxifene group had a rate of breast cancer that was 76% lower when compared to that of women in the placebo group with similar levels of estradiol. In contrast, women with undetectable levels of estradiol had similar breast cancer risk whether or not they were treated with raloxifene. If confirmed, this suggests that measuring estradiol and treating women with high estradiol levels could substantially reduce the rate of breast cancer among postmenopausal women.

Source

1. Cummings SR, Duong T, Kenyon E, et al. Serum estradiol level and risk of breast cancer during treatment with raloxifene. JAMA. 2002;287:216-20.

Chronic Non-Cancer Pain--An Organizational Approach to Best Practice

Donna Spevakow, RN, MSN
Lisa Hamilton, RN,MSc

Chronic Non-Cancer Pain (CNP) is a clinically complex and common phenomenon in the older adult. Data suggest that CNP is undertreated in older adults who are likely to suffer from arthritis, back problems and joint disorders. Left untreated, CNP in the older adult can lead to depression, sleep disturbances and decreased socialization.

Recently, the problem of untreated CNP was investigated at the Toronto Rehabilitation Institute, a tertiary rehabilitation centre and a teaching hospital of the University of Toronto. A survey to determine pain prevalence and severity was conducted in a patient population consisting of complex continuing care, geriatric, acquired brain injury and stroke rehabilitation. One hundred and ten patients were able to verbally respond to the survey questions, and results showed that 47% of the patient population experienced CNP and 39% of those with pain rated it as severe. At that time, no structures were in place within the organization for the assessment and management of CNP.

This evidence led to the creation of a clinical interprofessional CNP task force which had the goals of establishing a patient-centred, interprofessional approach to CNP rehabilitation using "best practice" evidence, preventing unnecessary suffering and improving outcomes in rehabilitation.

Clinical practice guidelines included information on cultural consideration in pain assessment and management, an initial pain assessment form, and a pain flow sheet to evaluate effectiveness of interventions. Pain assessment scales were made available in 14 languages. Three categories of therapeutic approaches were identified within the guidelines: pharmacological, physical and psychoeducational. These guidelines were then developed into policies.

In order to achieve consistent use in the clinical practice setting, all clinical staff needed to be knowledgeable about the guidelines and policies. To this end, the CNP task force developed an innovative teaching tool--a colourful poster that serves as a quick reference guide for both physicians and patients.

In addition, an educational program was developed for front-line staff. Staff attended a one half-day workshop where, using a case study, they reviewed the pain assessment forms. A second half-day workshop on specific physical modalities was offered to the Registered Nurses who had attended the previous workshop, and to physiotherapists. A full-day workshop was offered by an expert in guided imagery.

Patient and family education is also a crucial component in management of CNP. Recognizing this need, the task force developed an educational booklet entitled "Chronic Pain and You," available in four languages: Chinese, Portuguese, Italian and English.

Other outcomes of the initiative are that links have been established with the Comprehensive Pain Program at Toronto Western Hospital, University of Toronto Centre for the Study of Pain, and that a medical pain specialist is now available on-site for consultation.

We hope that this issue of Geriatrics & Aging will update our readers on the management of pain in the elderly. We have a series of excellent articles including an overview of the biology of pain, a summary of pain management and assessment in the elderly, the principles of palliative care and the management of pain in patients with dementia. We also have a summary of the Toronto Western Hospital's Chronic Pain Program. Topics for our regular columns include 'Syncope in the elderly' (Cardiology column) and chronic lymphocytic leukemia (Cancer column). Enjoy!

Donna Spevakow is a CNS at Toronto Rehabilitation Institute and Lisa Hamilton is a CNS at York Central Hospital. They were Co-Chairs of this Initiative. Toronto Rehab received the Health Care Papers National Best Practice Award at the Ontario Hospital Association Convention, November 2000 for this interprofessional Non-Cancer Pain initiative.

Chronic Lymphocytic Leukemia

Diagnosis and Management in the Elderly

Deirdre A. Jenkins, MD
Richard C. Woodman, MD
Division of Hematology and Hematological Malignancies,
University of Calgary and Tom Baker Cancer Centre, Calgary, AB.

Introduction
Chronic lymphocytic leukemia (CLL) is a monoclonal disorder of long-lived, mature lymphocytes. It is the most common leukemia in North America with an incidence of 2.7 cases per 100,000. CLL is primarily a disease of the elderly, with a median age of 70 at diagnosis and a slight male predominance. In patients older than 85 years, the incidence rises to 30.6 per 100,000.¹ There are no clear hereditary patterns; however, increased incidence is noted in families with other lymphoproliferative disorders. The etiology is unknown, and typical risk factors for other cancers (like viruses, radiation and chemicals) have no clear role in CLL. The importance of understanding the diagnosis and treatment of this disorder lies in the chronic nature of the disease, as patients may live years to decades after diagnosis. Knowing your treatment goals, and anticipating complications are fundamental for managing patients with CLL.

Diagnosis
While there has been a growing number of patients serendipitously diagnosed on routine blood tests, the majority of patients will present with symptoms referable to their disease (Table 1).

Management of Complications of Hematologic Malignancies in the Elderly

Jeffrey Zonder, MD
Ulka Vaishampayan, MD
Division of Hematology/Oncology,
Department of Medicine
Wayne State University School of Medicine/Barbara Ann Karmanos Cancer Institute
Detroit, MI, USA.

Introduction
The incidence of hematologic malignancies, especially lymphoma, is steadily rising in the elderly. These diseases and their complications pose specific problems for older patients. Factors that contribute to increased toxicity in the elderly include diminished marrow reserve, impaired renal and hepatic metabolism and, perhaps most importantly, poor performance status as a result of comorbidities.¹ This article will focus on the management of common complications of hematologic malignancies, particularly as they pertain to older patients.

Febrile Neutropenia

Risk of Neutropenia in the Elderly
The incidence of life-threatening neutropenia (absolute neutrophil count, ANC, <0.5x 10⁹/L) in elderly patients following chemotherapy for hematologic malignancies is 40% or higher.² The risk of infection is affected by the duration and severity of neutropenia with a steep rise in infection incidence at a neutrophil count of less than 0.5x 10⁹/L.

A New Icon in Cancer Research

Researchers at Yale University have come up with a new take on an old problem: how to cut off blood supply to a tumour. Previously, it was believed that we might be able to eradicate cancer by preventing tumour angiogenesis--a theory that worked well in animal models, but had disappointing results in humans. The new twist on the method developed by Hu and Garen is to destroy tumours by killing the blood vessels that supply them, rather than trying to prevent their development in the first place.

The researchers developed an immunoconjugate molecule (icon), composed of a mutated mouse factor VII (mfVII) targeting domain and the Fc effector domain of an IgG1 Ig (mfVII/Fc icon), and tested its efficacy in mouse models of human and mouse prostate cancer, and human melanoma. Mice were injected subcutaneously with a human prostatic tumour line, forming a skin tumour that produces a high blood titer of prostate-specific antigen and metastasizes to bone. The icon was encoded in a viral vector that was injected directly into the tumour. Tumour cells infected with the vector synthesize more of the icon molecule and secrete it into the blood where it binds to mouse tissue factor expressed on endothelial cells lining the lumen of the tumour vasculature and to human tissue factor on the tumour cells. One part of the icon then activates an immune attack against any cell that is capable of binding it--which means that the immune attack is only directed against cells that show 'tumour' characteristics. Injection with icon resulted in long-term regression of the injected human prostatic tumour, and also of the uninjected tumour (a model for a metastasis), without any toxicity to the mouse. The same results were obtained for the mouse model of human melanoma.

The researchers are hoping to begin clinical trials in humans next spring, although they caution that it is far too early to predict how well the technique will work in humans.

Source

1. Hu Z and Garen A. Targeting tissue factor on tumor vascular endothelial cells and tumor cells for immunotherapy in mouse models of prostatic cancer. Proc. Natl. Acad. Sci. USA, 10.1073/pnas.201420298.

The Diagnosis of Cancer: Psychological Impact in the Elderly

Jennifer M. Jones, PhD
Research Scientist,
Psychosocial Oncology Program,
Princess Margaret Hospital, University Health Network,
Toronto, ON.

Gary Rodin, MD, FRCP(C)
Head, Psychosocial Oncology,
Princess Margaret Hospital & Psychiatrist-in-Chief,
University Health Network,
Toronto, ON.

Psychological Response to Illness: Coping with a Diagnosis of Cancer
The diagnosis of cancer is inevitably experienced as a traumatic event, although the individual response to it depends upon the nature and stage of the disease, the associated disability, the life stage of the individual affected, its personal meaning and the sociocultural context in which the individual is situated. In the elderly, who commonly experience concerns about self-sufficiency, the onset of a serious medical illness such as cancer may trigger intolerable feelings of helplessness and dependence.

Most patients experience shock when they first learn of their diagnosis of cancer. In some cases, there may be profound anxiety with symptoms of hyperarousal and vigilance arousal, and an oscillation between intrusive thoughts of the cancer and avoidance of the frightening reality. These symptoms represent a stress response syndrome, which may be reactivated following a recurrence of the cancer, which can be even more traumatic than the original diagnosis.

Chronic Myelogenous Leukemia November 2001

Ahmed Galal, MD, MSc, FRCPC
Fellow in Allogeneic Bone Marrow Transplant,
University Health Network
Princess Margaret Hospital,
Toronto, ON.

Jeffrey Lipton, PhD, MD, FRCPC
Chief, Allogeneic Bone Marrow Transplant Program,
Princess Margaret Hospital,
Head, Chronic Myeloid Leukemia Group,
Associate Professor of Medicine,
University of Toronto,
Toronto, ON.

Introduction
Chronic myelogenous leukemia (CML), in addition to polycythemia rubra vera and essential thrombocytosis, are the most commonly diagnosed forms of the myeloproliferative disorders.^1-5 These diseases share several distinct features:

• They are clonal disorders of hema-topoiesis that arise in a hematopoietic stem or early progenitor cell;
• They are characterized by the dysregulated production of a particular lineage of mature myeloid cells with fairly normal differentiation;
• They exhibit a variable tendency to progress to acute leukemia.

Cytogenetic studies of bone marrow and peripheral blood in the benign myeloproliferative disorders are usually normal. However, CML is invariably associated with an abnormal chromosome known as the Philadelphia chromosome.⁶ CML accounts for 15-20% of adult leukemias. It has an annual incidence of 1 to 2 cases per 100,000, with a slight male predominance.

More on Helicobacter Pylori and Gastric Cancer

Another study has contributed to the growing body of evidence linking Helicobacter pylori, to the development of gastric cancers. Uemura et al., prospectively studied 1,526 Japanese patients who had duodenal ulcers, gastric ulcers, gastric hyperplasia or non-ulcer dyspepsia at the time of study enrollment. Of these, 1,246 had H. pylori infection, and 280 did not.

The researchers found that gastric cancers developed in 2.9% of the H. pylori infected individuals and none of the uninfected patients. Among the H. pylori infected patients, those with severe gastric atrophy, corpuscle-predominant gastritis and intestinal metaplasia, were at significantly higher risk for developing gastric cancer.

Source

1. Uemura, N, Okamoto, S, Yamamoto, S et al. Helicobacter pylori infection and the development of gastric cancer. New England Journal of Medicine. 2001; 345:784-789.