The Canadian journal of oncology最新文献

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.