The practice of palliative radiotherapy is founded on the same ethical principles as any other sphere of medicine. The principles of beneficence and non-maleficence define the goals of palliative therapy. The principle of rationality demands that treatment decisions should be guided by scientific knowledge. The principles of veracity, loyalty, and respect for autonomy define the conditions of the doctor-patient relationship. The principle of distributive justice reminds us that, in conditions of scarcity, resources used to treat one patient will not be available to treat others. Ten rules for the practice of palliative radiotherapy were derived from these principles.
BACKGROUND:Age is known to have an important influence on survival in non-Hodgkin's lymphoma (NHL). This observation and the relationship of age to other prognostic factors are of interest in designing treatment programs for these patients. This study was conducted to investigate the relationship of age to other known prognostic variables and survival in NHL. PATIENTS AND METHODS:Data on clinical features, treatment, response, survival and cause of death from 547 patients with NHL diagnosed between 1980 and 1989 were collected and analyzed by age group. Multivariate analysis of prognostic factors and a survival comparison to an age and sex matched control population were performed. RESULTS:Survival curves for 5-year age groups up to and including age 60-64 years were similar, after which a major effect of age upon survival was apparent. When groups aged < 65 years and > and = 65 years were compared, there were similar proportions of most known prognostic factors, except for a higher proportion with increased lactate dehydrogenase (LDH) levels and extranodal disease in older patients. When analyzed by age group, older patients had a lower response rate to initial therapy and salvage treatments. In younger patients, several recognized prognostic variables were found to lack significance. CONCLUSIONS:Prognostic variables differ between younger and older patients with NHL. Age, histology, LDH elevation and gender are less important in younger patients; only bulky disease is more important than in older patients. A lower response rate, poor response to salvage therapy and excess mortality, often due to concurrent diseases, were apparent in older patients. Age is a significant prognostic factor only in patients age > and = 65 years.
Demographics, treatment patterns, treatment efficacy and clinical predictors of survival were studied in 76 consecutive patients with malignant ascites. Sixty-four percent of patients were female, and mean age was 63 years. The most common primary malignancies were ovarian cancer, carcinoma of unknown primary, breast cancer, colorectal carcinoma and lymphoma. Ascites was present at the time of diagnosis of malignancy in 39%. Diuretics were administered in 22% of patients with a 22% response in ascites; all responding patients had hepatic metastases. Systemic anticancer therapy was administered in 38%, with a 38% objective response in ascites. Five peritoneovenous shunts were placed, with one shunt functional at 2 weeks. Paracentesis was performed in 71% of patients with complications potentially due to paracentesis occurring in 24% of these patients. Median survival was 78 days from the clinical diagnosis of ascites. Multivariate analysis revealed significantly shortened survival in patients with liver metastases and elevated serum bilirubin, while ovarian cancer was a significant independent predictor of prolonged survival.
Anthracyclines are among the most effective and commonly-prescribed antitumor agents but have dose-limiting cumulative cardiotoxicity. We performed a pharmacoeconomic evaluation of the ability of dexrazoxane to prevent cardiac-related adverse events in patients with Stage IIIB or IV metastatic breast cancer who were treated with a median of 10 cycles of intravenous FAC (5-fluorouracil, doxorubicin and cyclophosphamide) at doses of 500/50/500 mg/m2 respectively. Dexrazoxane was given at 500 mg/m2 commencing at the seventh cycle of treatment. We determined the cost of each cardiac event prevented and the cost of each additional life-year saved by dexrazoxane use. The cost per cardiac event prevented was CDN $5745 and the cost per additional life-year saved was CDN $2856. With the increasing use of anthracyclines in Stages I and II breast cancer, these favorable clinical and economic results may broaden the range of therapeutic possibilities for anthracyclines in adjuvant and metastatic therapy of breast cancer.
There is a dearth of knowledge on the radiobiology of palliative radiotherapy, but some of the principles relevant to radical radiation treatments can be applied to the palliative situation. Nevertheless with minimal animal or human data available, it would appear that this area can be a fertile one for future study, although many of the difficulties and problems inherent in this type of research must be acknowledged and addressed.
We have prospectively gathered information contained in the Ontario Cancer Foundation computerized clinical data base to provide a quantitative description of palliative radiotherapy workload and fractionation practices in the management of non-small cell lung cancer over a ten-year period. We found that the proportion of radiotherapy fractionations used in palliation has declined steadily between 1984 and 1991. In the palliation of non-small cell lung cancer there has been a steady decline in the number of fractions given per course of treatment in the management of chest disease, bone metastases, and brain metastases with significant variation both between and within individual cancer treatment centres.
A simple mathematical model based on queueing theory is introduced, and used to obtain a sensitive measure of the capacity of a radiation therapy centre to provide service. The model illustrates the relationships among the relevant variables: the patient waiting time, the number on the waiting list, the rate at which requests for radiation therapy are received and the rate at which courses of treatment are commenced. In particular, the rate at which the waiting time increases is equal to the difference between the request rate and the start rate, expressed as a fraction of the start rate, and is therefore a measure of the deficiency in service capacity of a facility. A study of the records of patients treated on the linear accelerators of the Tom Baker Cancer Centre from January 1991 to June 1994 shows that this relationship holds to a high degree of accuracy for average values of the various parameters in spite of the considerable variation in these values, and particularly variation in the individual waiting times. This finding suggests that such an approach would be useful in assessing and comparing the performance of radiation therapy facilities.
The role of radiotherapy in the palliation of patients with advanced cancer of the head and neck is not clear. Several distinctive characteristics of advanced head and neck cancer contribute to the complexities in the choice of appropriate palliative management strategies. Palliative treatment may be the appropriate management for a proportion of patients with advanced disease, but the current stage groupings of head and neck cancer are not sufficient for use in the reliable identification of such a patient group. Controversy arises because of the difficulties in distinguishing patients who should be offered conventional treatment with curative intent from those appropriate for treatment with palliative intent. A structured review of the cancer and quality of life literature identified 298 references pertaining to palliative radiotherapy in head and neck cancer, 26 of which met the criteria for inclusion in this review. An expert panel discussed the literature, and concluded that insufficient information precluded estimations of the frequency, degree of, or duration of symptomatic relief that radiation offered to those patients not cured of their disease. Moreover, the currently available literature does not address the toxicity or appropriate dose and fractionation of palliative radiotherapy in this setting. Further studies are necessary to evaluate clinical endpoints appropriate to the use of radiotherapy in the palliative management of patients with advanced head and neck cancer. Studies are also needed to refine the current clinical classification of patients, allowing the identification of patients suitable for palliative management.
Economic evaluations can be useful in decision making regarding allocation of scarce health care resources such as radiation therapy. However, assessment of treatment efficacy must be performed in addition to economic evaluations if proper resource allocation decisions are to be made. Economic evaluations cannot and should not relapse properly conducted clinical trials-particularly in the area of palliative care.
Brain metastases (BRM) are common complications of malignancy, frequently associated with disability and death. Clinical trials have addressed a few of the issues arising from treatment options for BRM. Phase III trials have shown superior survival for patients with solitary resectable BRM (SRBRM) when palliative radiation treatment (RT) to the brain is preceded by resection compared to brain RT alone, but no trial has explored resection plus brain RT compared to resection alone. One Phase III trial in patients with solitary unresected BRM comparing lower to higher doses of RT has shown a small survival advantage with higher-dose radiotherapy. All other trials, however, comparing different radiation doses and fractionation schedules have failed to indicate improved outcomes from treatment more intense than 2000 cGy in 5 fractions over 1 week (in any subset of patients with unresected BRM). A panel of radiation oncologists and medical oncologists discussed a literature review and results of Phase III trials of therapy for BRM. The panel was instructed to identify from these trials any evidence for the efficacy, indications, toxicity and fractionation of palliative RT for BRM. The panel concluded that unresected BRM is a possible indication for brain RT. The panel concluded that the benefits and toxicities of brain RT for unresected BRM are not characterized adequately to allow a stronger recommendation. The panel concluded that there is no evidence for superiority for any dose or schedule of brain RT for BRM more protracted or intense than 2000 cGy in 5 fractions over one week. The panel recommended further study in order to characterize the benefits and toxicities of brain RT for unresectable BRM. The panel considered the potential value of conducting a Phase III trial comparing palliative care and strategies that included brain RT to the same strategies excluding brain RT; the panel did not, however, reach consensus on the feasibility of such a trial.
A significant number of cancer patients undergoing palliative radiotherapy experience treatment-related nausea and vomiting. A number of factors are known to influence the incidence and severity of radiation-induced sickness including the site, field size and dose per fraction. The age of the patient and the level of patient anxiety may also play a role. Furthermore, there is some evidence that high alcohol consumption has a protective effect against radiation-induced illness. It is generally accepted that there is a high risk of nausea and vomiting associated with high doses of radiotherapy; however, this effect has never been adequately quantified. Nonetheless, as a consequence of radiation-induced nausea and vomiting, patients may experience a decrease in their quality of life and may choose to delay or even refuse further treatment. Thus, controlling the adverse side effects associated with radiation therapy is critical to optimal patient care.
In fact that radiation therapy is often the most effective means of palliating symptoms caused by cancer is well recognized in the United States. Estimates of the proportion of patients treated in the US with radiation therapy who are treated for palliative rather than curative intent range from 15% to 50% and depend on the geographic location, cancer incidence, referral patterns, etc. All radiation oncologists in the United States have had significant experience with the use of palliative radiation therapy during their residency and in their practice. Estimates from patterns of care studies indicate that over 250,000 patients were treated with palliative radiation therapy at a cost of between $1.0 and $1.8 billion in 1994. The scope of this presentation will cover four aspects of palliative radiation therapy in the United States: 1. existing practice patterns; 2. factors affecting treatment patterns; 3. the cost of palliative radiation therapy; and 4. present research and guidelines developments efforts.
Unresectable pelvic recurrence from carcinoma of the rectum becomes invariably symptomatic. While radiotherapy remains the most common antineoplastic modality used for palliation of symptoms, the optimal radiation dose and fractionation remains undefined. A systematic review of the literature was performed to determine the most effective dose fractionation schedule for the relief of symptoms in patients with pelvic recurrence. An expert panel reviewed and interpreted the data, with a special focus on indications, effectiveness, optimal dose fractionation, and toxicity of radiotherapy in this context. Only retrospective data (level V evidence) were available on this issue and were reviewed. Pain relief was the major indication for treatment, although bleeding and mucous discharge were also seen as indications for radiotherapy. Initial pain relief appeared to be achievable in 70-90% of patients. The median duration of pain relief was approximately three months, 23-50% of patients had symptom control at six months. The value of "local control" as a meaningful additional endpoint was discussed. There were no significant differences observable in initial symptom response and the proportion maintaining a response at six months, within the range of doses employed, comparing "lower" versus "higher" doses (using 45-50 Gy as the dividing dose). Toxicity was usually evaluated qualitatively and was deemed acceptable. The expert panel agreed that pelvic radiotherapy has a definite value in the relief of symptoms in patients with pelvic recurrence from rectal carcinoma. The optimal dose fractionation in this context could not be determined in view of the quality of the data available. Well designed, randomized studies with clinically relevant study arms and endpoints are necessary to define an optimal dose fractionation against which alternative strategies can be compared.
Docetaxel (Rhône-Poulenc Rorer Pharmaceuticals Inc.), a new and novel taxoid, is a potent antitumor agent that promotes microtubule polymerization and inhibits tubulin depolymerization, resulting in the inability of cells to replicate. Docetaxel exhibits a broad spectrum of antitumor activity in vitro and in vivo. Phase II trials indicate a high degree of activity against advanced breast cancer, including anthracycline-resistant disease, and significant activity in advanced non-small cell lung, ovarian, head and neck, and pancreatic carcinomas and potential activity against other tumors as well. The recommended dosing regimens is 100 mg/m2 administered intravenously over one hour, with cycles repeated every three weeks. The most frequent hematologic side effect is neutropenia. Most nonhematologic side effects are generally mild to moderate in severity. Dermatologic side effects occur frequently, and fluid retention occurs with cumulative dosing. Premedication regimens with corticosteroids prevent significant hypersensitivity reactions and appear to be of value in ameliorating skin reactions and fluid retention. Docetaxel is currently being intensively evaluated in a phase II/III clinical program both as a single agent and as part of combination chemotherapy regimens and should prove to be clinically useful for a number of tumors.
A number of different palliative radiotherapy techniques and fractionation schedules have been used in the UK over the past several years. In an attempt to standardize treatment practices, a handful of studies have been conducted in recent years compiling basic demographic data on the use of palliative radiotherapy as well as response data for the various techniques currently in use. In one study conducted at Mount Vernon Hospital, just outside of London, Maher and colleagues collected data on 425 consecutive patients given radiotherapy during a six-week period in 1988. Of those, 211 (49.6%) patients received radical treatment for long-term tumor control, and the remaining 214 (50.4%) patients received palliative treatment for symptom relief in the case of incurable cancer. Of the 214 patients treated with palliative radiotherapy, 90 (42%) patients were treated for bone secondaries, 63 (29%) patients for primary carcinoma of the bronchus, 12 (6%) patients for brain secondaries and 49 (23%) patients for other miscellaneous reasons. There is evidence that in the last few years British practice in palliative radiotherapy has changed substantially, largely as a result of the findings of recent clinical trials. This review will summarize the data relating to the radiotherapeutic management of bone secondaries, advanced lung cancer and cerebral metastases.
Some of the issues to be considered when designing trials of palliative treatments, and specifically palliative radiation therapy, are discussed. In particular the concepts of entry criteria, endpoints, measurement of response variables and follow-up, and how they might be applied in these situations are considered.
Non-small cell lung cancer is the most common cause of cancer death in both males and females. Despite this high incidence and mortality, comparatively little research has addressed the palliative treatment of thoracic symptoms. Until recently, information regarding the indications and effectiveness of radiation in this setting was obtained from retrospective reviews of single institutional experiences. More recently, three major randomized trials from the UK Medical Research Council (1991, 1992, 1994) have addressed the use of external beam radiation in randomized comparisons of different dose and fractionation strategies for patients with non-small cell lung cancer and symptoms due to intra-thoracic tumor. These studies show that shorter fractionation schemes provide equivalent palliation and essentially equivalent survival in the patient groups studied. Moreover, they provide estimates of the probability of successful palliation of common symptoms, and estimates of the toxicity of each regimen. A panel of oncologists with expertise in radiation oncology, medical oncology and epidemiology discussed the above trial results and a literature review. The panel concluded that radiation was indicated in the palliation of hemoptysis, chest pain, dysphagia, and dyspnea, and that the results of the MRC studies provided reasonable estimations of the efficacy and toxicity of radiation in this setting. These studies show that symptoms are more often than not improved with palliative radiotherapy (symptom improvement rates ranged from about 50 to 85%) and that palliation lasted for a substantial portion of the patients' remaining survival. The panel could not reach uniform consensus on the appropriate fractionation for radiation given with palliative intent. The panel agreed that favourable patients with stage IIIB NSCLC should be offered combined modality therapy with the intent of prolonging survival, and that patient preferences regarding the risks and benefits of this therapy should be considered. Further study was recommended, namely, a randomized trial evaluating five fractions of radiation vs a single fraction, using patient-based evaluation of palliation. The panel also recommended phase II development of a combined chemotherapy and low-dose radiation protocol appropriate for future study.
The relationship between oncology and palliative care is an evolving one. As one debates the processes of palliative radiotherapy, it is important to realize that "palliation" and "palliative care" are not synonymous. We need to explore the definition of palliative care, the myths surrounding palliative care and dying, the need for optimizing pain management and, finally, access to palliative radiotherapy and palliative care.
Historically, the goal of treatment in most cancer studies has been to improve survival, accepting variable levels of toxicity if survival can be improved. However, with palliative treatment, the goal is seldom to prolong survival but rather to alleviate symptoms and maintain quality of life and functional level while minimizing toxicity and patient inconvenience for those whose life expectancy is often short. Outcome measures for studies comparing palliative treatments are therefore often different and less objective than the more easily measured survival endpoint of curative studies. There are usually multiple outcomes of interest, many of them ideally requiring assessment by the patients themselves, repeatedly, over time. This can cause methodologic, statistical, and administrative difficulties which must be recognized and addressed when planning and conducting such studies. The following paper reviews some of these difficulties that challenge us when we attempt to accurately measure and compare the benefit and toxicity of palliative treatment. Despite these difficulties, the need for such studies is great, given their relative rarity in the published literature thus far and the magnitude of the clinical problem of palliative care.
Because lung cancer is a major health care problem in Canada, it would be useful to identify the direct health care costs of diagnosing and treating this disease and to create an analytic framework within which diagnostic and therapeutic options can be assessed. This paper describes a method of modelling the costs of care for lung cancer. The perspective of the costing model is that of the government as payer in a universal health care system. Clinical algorithms were developed to describe the management of non-small cell (NSCLC) and small cell (SCLC) lung cancer. Patients were allocated to the treatment algorithms in the model, based on a knowledge of the stage distribution of cases within provincial cancer registries and an estimate of the use of therapeutic modalities, according to lung cancer experts. A microsimulation model (POHEM) developed at Statistics Canada was used to integrate data on risk factors, disease onset and progression, health care resource utilization and direct medical care costs. The model incorporates survival data on patients, according to cell type and stage, based on published studies. Relapse and terminal care costs were assigned during the year of death, in order to determine the cost of continuing care and the cumulative cost of lung cancer management over time. Patients surviving five years were assumed to be cured. The model estimates that the total five year cost to provide care to the 15,624 cases of lung cancer diagnosed in Canada in 1988 was in excess of $328 million. Over 82% of this total was spent in the first year for diagnostic tests, therapy (surgery, chemotherapy, radiation therapy, or combinations of these), hospitalization and follow-up costs. The average five year cost per case was $21,000, and ranged from a high of $29,860 for limited disease SCLC, to a low of $16,500 for Stage IV NSCLC. The actual cost of providing care, including the management of complications, is unknown and our estimates should be regarded as an idealized estimate of the cost of lung cancer management. However, the POHEM model has a level of sophistication which, we believe, reasonably reflects the cost per case and total costs of treating lung cancer by stage and therapeutic modality in Canada.
