National Cancer Center Network Research Articles

A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours

Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day−1 of imatinib mesylate, 50 mg day−1 of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day−1 of imatinib had the highest MC (±s.d.) of treatment at $35 225.61 USD (±1253.65 USD); while sunitinib incurred a median MC of $17 805.87 USD (±694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (±472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients.

Evidence Based Clinical Practice: A Primer for Urologists

Evidence based clinical practice has been defined as the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients. It refers to a broad set of principles and methods intended to ensure that medical decisions, guidelines and health policy are based on well designed studies of therapeutic effectiveness and benefit. We review the principles and practice of evidence based clinical practice using examples from the urology literature. We further provide a guide to currently available web based evidence based clinical practice resources and guidelines for urologists. Evidence based clinical practice integrates a hierarchy of evidence and patient values with practitioner judgment to guide decision making for the individual patient. Important steps in the evidence based clinical practice process include the formulation of an answerable question and a systematic search of the literature. In the absence of pre-appraised evidence or disease specific guidelines, the practice of evidence based clinical practice relies heavily on the evaluation of the primary literature by the individual urologist. Depending on the question domain (therapy/prevention, etiology/cause/harm, diagnosis or prognosis) and study design, a given study is critically appraised for validity, impact and applicability. Evidence is then integrated with clinical judgment, and patient circumstances and preferences. Finally, the practice of evidence based clinical practice includes a self-assessment of provider performance. Knowledge, practice and documentation of evidence based clinical practice are of increasing importance to every urologist. Urologists should embrace evidence based clinical practice principles by acquiring the necessary skills to critically appraise the literature for the best evidence applicable to patient care.

Evidence-based medicine in prostate cancer: where do we stand in 2006?

A majority of medical decisions relating to the diagnosis, prognosis, and therapy of prostate cancer are based on low levels of evidence. This article reviews the recommendations of currently available evidence-based practice guidelines that relate to the management of patients with newly diagnosed prostate cancer. The article further introduces a selection of recent studies that are relevant to the evidence-based patient care. Updated clinical practice guidelines on the management of prostate-cancer patients provide an evidence-based summary of the literature and have recently been made available through the National Cancer Center Network and the European Urological Association. In addition, several recent high-quality studies have made major contributions to our knowledge of the natural history and therapy of prostate cancer. The efforts of professional associations to generate evidence-based guidelines are reflective of an increased awareness that the care of prostate cancer should--to the greatest possible extent--be evidence-based. Practicing urologists should seek to become involved in the evidence-based medicine process by supporting the accrual to high-quality clinical trials, demanding the highest standards to the timely and unbiased dissemination of research findings and ultimately, strive to apply the best available evidence to the care of individual patients.

Guidelines for the Management of the Older Cancer Patient

Evaluation of: Balducci L, Cohen HJ, Enstrom PF et al.: Senior adult oncology clinical practice guidelines in oncology. J. Natl Compr. Cancer Center Netw. 3, 572–590 (2005). The management of older cancer patients with cytotoxic chemotherapy involves a new balance of benefits and risks, given the limited life expectancy and increased susceptibility to therapeutic complications of older individuals. The National Cancer Center Network has been issuing guidelines for the management of older cancer patients since 1999. This article reviews the basis of the most recent set of guidelines, issued in 2005. These include: some form of geriatric assessment for individuals aged 70 years and older to estimate their life expectancy and treatment tolerance; adjustment of the first dose of chemotherapy to glomerular filtration rate for individuals aged 65 years and older; prophylactic use of myelopoietic growth factors (e.g., filgrastim or pegfilgrastim) in patients aged 65 years and older treated with moderately toxic chemotherapy (of which cyclophosphamide, doxorubicin, vincristine and prednisone is the paradigm); maintainance of hemoglobin levels at approximately 12 gm/dl; and preferential use of drugs of low toxicity (e.g., capecitabine, pegylated liposomal doxorubicin, weekly taxanes, gemcitabine or navelbine).

Cancer in the older person

Cancer in the older person is an increasingly common problem, due to the progressive prolongation of the life-expectancy of the Western population. This article reviews the mechanisms associating aging and cancer, age-related changes in cancer biology, assessment of the older person to estimate life-expectancy, treatment tolerance, and medical and social conditions that may interfere with cancer treatment, effectiveness of cancer prevention and cancer treatment in older individuals. A comprehensive geriatric assessment (CGA) is commonly used to predict life-expectancy and functional reserve and to unearth conditions that may jeopardize cancer prevention and treatment. In the interest of cost and time, shortened forms of CGA are being explored. Chemoprevention of cancer is a promising form of prevention that at present has no conclusive clinical indications. Early diagnosis of breast and colon cancer through screening of asymptomatic patients at risk may be beneficial for individuals with a life-expectancy of 5 years or longer. Early detection of lung cancer in ex-smokers is undergoing clinical trials, as this disease is becoming more and more common. Age should not prevent appropriate treatment of cancer in older individuals, especially in those with adequate life-expectancy and functional reserve. The National Cancer Center Network (NCCN) has issued a series of guidelines to minimize the toxicity and promote the effectiveness of cancer in older patients. Important interventions include prevention of neutropaenic infections with filgrastim and peg-filgrastim, prevention of anaemia with epoietin or darbepoietin, and prevention and early management of mucositis.

Utility of chest computed tomography for staging in patients with T1 extremity soft tissue sarcomas.

National Cancer Center Network (NCCN) and Society of Surgical Oncology (SSO) practice guidelines recommend chest computed tomography (CT) as part of the staging evaluation of patients with extremity soft tissue sarcoma (STS). In the current study, the authors evaluated the use and yield of chest roentgenography (CXR) and selective chest CT to screen for pulmonary metastases in patients with T1 STS. The utility of these staging studies was evaluated retrospectively in a cohort of 125 consecutive patients who presented to a tertiary care cancer center with T1 primary (nonrecurrent) extremity STS. Two diagnostic strategies (CXR alone vs. CXR plus chest CT) were evaluated using an incremental cost-effectiveness ratio. The majority of tumors (70%) were high grade. The median sarcoma size was 3.0 cm; 64 of the tumors (51%) were located deep to the investing fascia of the extremity. All patients underwent staging CXR; 1 CXR (< 1%) was suspicious for metastatic disease. Fifty-one patients (41%) also underwent chest CT; 1 chest CT, performed in the patient with a suspicious CXR, revealed metastatic disease. With a median follow-up of 76 months, 19 patients (15%) developed metachronous pulmonary metastases. The relatively low yield resulted in an incremental cost-effectiveness ratio of $59,772 per case of synchronous pulmonary metastasis detected by CXR plus chest CT. Less than 1% of patients with T1 primary extremity STS were found to have pulmonary metastases that were detectable using a staging algorithm that employs routine CXR with the selective use of chest CT. The findings of the current study do not support current NCCN or SSO practice guidelines for patients with high-grade T1 STS.

Using recombinant human TSH in the management of well-differentiated thyroid cancer: current strategies and future directions.

Mortality rates from thyroid cancer have fallen significantly in recent decades, almost certainly as the result of earlier diagnosis and improved treatment of differentiated (papillary and follicular) thyroid cancer. Enhanced survival is likely a result of early diagnosis and therapy applied at a disease stage when treatment is most effective. In the United States and Europe, most patients at high risk for relapse and death from thyroid cancer are treated with total or near-total thyroidectomy and receive radioiodine ablation of residual normal or malignant thyroid tissue, followed by treatment with thyroid hormone, a strategy that cures more than 80% of patients. Still, some die of the disease and nearly 15% have local recurrences, while another 5% to 10% develop distant metastases. Over 50% of recurrences appear in the first five years, but distant metastases may surface years, and sometimes decades, after initial therapy. Much has been learned about risk stratification to predict recurrence and death from thyroid cancer but individual patients continue to have adverse outcomes not always foreseen by a low tumor stage. Follow-up must accordingly be meticulous and prolonged. The National Cancer Center Network (NCCN) has recently established consensus practice guidelines that give explicit advice about the diagnosis and management of benign and malignant thyroid tumors, including paradigms for long-term follow-up and the treatment of recurrent disease. The guidelines confirm that diagnostic scanning with 131I and measurement of serum thyroglobulin (Tg) levels are the mainstay of follow-up, offering the opportunity to detect recurrent or persistent cancer at very early stages. These guidelines advocate TSH-stimulated serum Tg measurements, done either during thyroid hormone withdrawal or stimulation with recombinant human TSH (rhTSH, Thyrogen), that often identify the presence of cancer well before diagnostic whole-body scanning or other imaging studies can spot the tumor, which offers the opportunity to treat recurrent disease at an early stage. The use of rhTSH adds a new dimension to long-term follow-up that avoids putting patients through the symptoms of hypothyroidism, and offers the opportunity to follow some patients with rhTSH-stimulated serum Tg levels without performing 131I whole-body scans. A multicenter international study has shown that serum Tg measurements alone are not as sensitive in the identification of patients with persistent or recurrent tumor as are rhTSH-stimulated serum Tg determinations. Although not yet approved for preparation of patients for 131I therapy, rhTSH has been used successfully in a compassionate use program for this purpose in a relatively large number of patients. Formal clinical investigations now planned to provide guidelines for the use of rhTSH for therapeutic 131I portend a new set of effective therapeutic paradigms for the management of differentiated thyroid cancer.