Stephen Lutz

Palliative radiotherapy for bone metastases: An ASTRO evidence-based guideline

PURPOSE To present guidance for patients and physicians regarding the use of radiotherapy in the treatment of bone metastases according to current published evidence and complemented by expert opinion. METHODS AND MATERIALS A systematic search of the National Library of Medicines PubMed database between 1998 and 2009 yielded 4,287 candidate original research articles potentially applicable to radiotherapy for bone metastases. A Task Force composed of all authors synthesized the published evidence and reached a consensus regarding the recommendations contained herein. RESULTS The Task Force concluded that external beam radiotherapy continues to be the mainstay for the treatment of pain and/or prevention of the morbidity caused by bone metastases. Various fractionation schedules can provide significant palliation of symptoms and/or prevent the morbidity of bone metastases. The evidence for the safety and efficacy of repeat treatment to previously irradiated areas of peripheral bone metastases for pain was derived from both prospective studies and retrospective data, and it can be safe and effective. The use of stereotactic body radiotherapy holds theoretical promise in the treatment of new or recurrent spine lesions, although the Task Force recommended that its use be limited to highly selected patients and preferably within a prospective trial. Surgical decompression and postoperative radiotherapy is recommended for spinal cord compression or spinal instability in highly selected patients with sufficient performance status and life expectancy. The use of bisphosphonates, radionuclides, vertebroplasty, and kyphoplasty for the treatment or prevention of cancer-related symptoms does not obviate the need for external beam radiotherapy in appropriate patients. CONCLUSIONS Radiotherapy is a successful and time efficient method by which to palliate pain and/or prevent the morbidity of bone metastases. This Guideline reviews the available data to define its proper use and provide consensus views concerning contemporary controversies or unanswered questions that warrant prospective trial evaluation.

Update on the Systematic Review of Palliative Radiotherapy Trials for Bone Metastases

AIMS To update previous meta-analyses of randomised palliative radiotherapy trials comparing single fractions versus multiple fractions. MATERIALS AND METHODS All published randomised controlled trials comparing single fraction versus multiple fraction schedules for the palliation of uncomplicated bone metastases were included in this analysis. Odds ratios and 95% confidence intervals were calculated for each trial. Forest plots were created using a random effects model and the Mantel-Haenszel statistic. RESULTS In total, 25 randomised controlled trials were identified. For intention-to-treat patients, the overall response rate was similar in patients receiving single fractions (1696 of 2818; 60%) and multiple fractions (1711 of 2799; 61%). Complete response rates were 620 of 2641 (23%) in the single fraction arm and 634 of 2622 (24%) in the multiple fraction arm. No significant difference was seen in overall or complete response rates. Pathological fracture did not favour either arm, but spinal cord compression trended towards favouring multiple fractions; however, neither was statistically significant (P = 0.72 and P = 0.13, respectively). Retreatment rates favoured patients in the multiple fraction arm, where the likelihood of requiring re-irradiation was 2.6-fold greater in the single fraction arm (95% confidence interval: 1.92-3.47; P < 0.00001). Repeated analyses excluding drop-out patients did not alter these findings. In general, no significant differences in acute toxicities were seen. CONCLUSION Overall and complete response rates were similar in both intention-to-treat and assessable patients. Single and multiple fraction regimens provided equal pain relief; however, significantly higher retreatment rates occurred in those receiving single fractions.

Palliative Thoracic Radiotherapy for Lung Cancer: A Systematic Review

PURPOSE The optimal dose of radiotherapy (RT) to palliate symptomatic advanced lung cancer is unclear. We systematically reviewed randomized controlled trials (RCTs) of palliative thoracic RT. METHODS RCTs comparing two or more dose fractionation schedules were reviewed using the random-effects model of a freely available information management system. The relative risk and 95% CI for each outcome were presented in Forrest plots. Exploratory analysis comparing dose schedules after conversion to the time-adjusted biologically equivalent dose (BED) was performed to investigate for a dose-response relationship. RESULTS A total of 13 RCTs involving 3,473 randomly assigned patients were identified. Outcomes included symptom palliation, overall survival, toxicity, and reirradiation rate. For symptom control in assessable patients, lower-dose (LD) RT was comparable with higher-dose (HD), except for the total symptom score (TSS): 65.4% of LD and 77.1% of HD patients had improved TSS (P = .003). Greater likelihood of symptom improvement was seen with schedules of 35 Gy(10) versus lower BED. At 1 year after HD and LD RT, 26.5% versus 21.7% of patients were alive, respectively (P = .002). Sensitivity analysis suggests this survival improvement was seen with 35 Gy(10) BED schedules compared with LDs. Physician-assessed dysphagia was significantly greater in the HD arm (20.5% v 14.9%; P = .01), and the likelihood of reirradiation was 1.2-fold higher after LD RT. CONCLUSION No significant differences were observed for specific symptom-control end points, although improvement in survival favored HD RT. Consideration of palliative thoracic RT of at least 35 Gy(10) BED may therefore be warranted, but must be weighed against increased toxicity and greater time investment.

Update of the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone Metastases

PURPOSE To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the 2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time. METHODS AND MATERIALS A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey. RESULTS Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments. CONCLUSION An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: A retrospective multivariate analysis

PURPOSE To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beams eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.

Symptom Frequency and Severity in Patients with Metastatic or Locally Recurrent Lung Cancer: A Prospective Study Using the Lung Cancer Symptom Scale in a Community Hospital

PURPOSE To define symptoms and therapeutic requirements for patients with metastatic or locally recurrent lung cancer. METHODS AND MATERIALS Data were collected from 69 consecutive patients with locally advanced lung cancer seen in consultation at a radiation oncology facility serving a community hospital in Virginia. The Lung Cancer Symptom Scale, a validated quality of life instrument, measured the incidence of symptoms in this group. RESULTS Average survival for the entire group was 7 months. Fifty-seven patients received 81 courses of radiation therapy, 33 directed at thoracic disease and 48 delivered to sites of metastasis. Thirty-three percent of those who received radiation therapy required treatment to more than one anatomic site. Every patient was symptomatic at the time of consultation, with the number (p = 0.001) and severity (p = 0.001) of symptoms they suffered worse in the patient group seen 0 to 3 months prior to death rather than 4 to 6 months prior to death. With the exception of cough, symptoms were marked in their severity. CONCLUSIONS Patients with advanced lung cancer suffer frequent and severe symptoms that worsen in the final months of life. The appropriate timing and combination of radiotherapy and chemotherapy are yet to be resolved. Future studies will require use of validated quality of life instruments to better catalogue palliation and treatment toxicity.

Survey on Use of Palliative Radiotherapy in Hospice Care

PURPOSE Radiation oncologists and hospice professionals both provide end-of-life care for oncology patients, and little has been written about the interface between these two groups of specialists. Hospice professionals were surveyed to assess the perceived need for palliative radiotherapy in the hospice setting, to investigate factors that limit the access of hospice patients to radiotherapy, and to suggest areas of future collaboration on education, research, and patient advocacy. PATIENTS AND METHODS Members of the National Hospice and Palliative Care Organization (NHPCO) and American Society for Therapeutic Radiology and Oncology jointly authored a questionnaire to investigate the beliefs of hospice professionals toward the use of radiotherapy for oncology patients in hospice. The questionnaire was distributed to all NHPCO member institutions, and the results were compiled and statistically analyzed. RESULTS Four hundred eighty of more than 1,800 surveyed facilities responded to the questionnaire. The findings suggest that the majority of hospice professionals feel that radiotherapy is important in palliative oncology and that radiotherapy is widely available in the United States. Yet less than 3% on average of hospice patients served by hospices responding to the survey actually received radiotherapy in 2002. The most common barriers to radiotherapy in hospice care include radiotherapy expense, transportation difficulties, short life expectancy, and educational deficiencies between the specialties. CONCLUSION Multiple barriers act to limit the use of palliative radiotherapy in hospice care. Finding ways to surmount these obstacles will provide opportunity for improvement in the end-of-life care of cancer patients.

A review of hypofractionated palliative radiotherapy

Radiotherapy commonly is employed to address symptoms in patients with symptoms caused by cancer. For this article, the authors reviewed data supporting the use of hypofractionated palliative radiotherapy. In addition to single‐fraction treatment for painful bony metastasis, the available literature suggested that courses of 2 to 14 external‐beam fractions may provide equivalent relief to longer course treatment in patients with a poor prognosis who have primary cancers of the lung, rectum, bladder, prostate, head and neck, spleen, and gynecologic system. Hypofractionated treatment delivers palliation that is time efficient, cost effective, and minimally toxic. Evidence suggests that the reluctance of radiation oncologists to provide single‐fraction treatment acts as a barrier to referrals from palliative care professionals. Collaboration in education, research, and patient advocacy will advance the common objectives of the 2 specialties and lead to an appropriate increase in the use of palliative hypofractionated radiotherapy. Cancer 2007.

Role of Radiation Therapy in Palliative Care of the Patient With Cancer

Radiotherapy is a successful, time-efficient, well-tolerated, and cost-effective intervention that is crucial for the appropriate delivery of palliative oncology care. The distinction between curative and palliative goals is blurred in many patients with cancer, requiring that treatments be chosen on the basis of factors related to the patient (ie, poor performance status, advanced age, significant weight loss, severe comorbid disease), the cancer (ie, metastatic disease, aggressive histology), or the treatment (ie, poor response to systemic therapy, previous radiotherapy). Goals may include symptom relief at the site of primary tumor or from metastatic lesions. Attention to a patients discomfort and transportation limitations requires hypofractionated courses, when feasible. Innovative approaches include rapid response palliative care clinics as well as the formation of palliative radiotherapy specialty services in academic centers. Guidelines are providing better definitions of appropriate palliative radiotherapy interventions, and bone metastases fractionation has become the first radiotherapy quality measure accepted by the National Quality Forum. Further advances in the palliative radiation oncology subspecialty will require integration of education and training between the radiotherapy and palliative care specialties.

Palliative radiation therapy for bone metastases: Update of an ASTRO Evidence-Based Guideline.

PURPOSE The purpose is to provide an update the Bone Metastases Guideline published in 2011 based on evidence complemented by expert opinion. The update will discuss new high-quality literature for the 8 key questions from the original guideline and implications for practice. METHODS AND MATERIALS A systematic PubMed search from the last date included in the original Guideline yielded 414 relevant articles. Ultimately, 20 randomized controlled trials, 32 prospective nonrandomized studies, and 4 meta-analyses/pooled analyses were selected and abstracted into evidence tables. The authors synthesized the evidence and reached consensus on the included recommendations. RESULTS Available literature continues to support pain relief equivalency between single and multiple fraction regimens for bone metastases. High-quality data confirm single fraction radiation therapy may be delivered to spine lesions with acceptable late toxicity. One prospective, randomized trial confirms both peripheral and spine-based painful metastases can be successfully and safely palliated with retreatment for recurrence pain with adherence to published dosing constraints. Advanced radiation therapy techniques such as stereotactic body radiation therapy lack high-quality data, leading the panel to favor its use on a clinical trial or when results will be collected in a registry. The panels conclusion remains that surgery, radionuclides, bisphosphonates, and kyphoplasty/vertebroplasty do not obviate the need for external beam radiation therapy. CONCLUSION Updated data analysis confirms that radiation therapy provides excellent palliation for painful bone metastases and that retreatment is safe and effective. Although adherence to evidence-based medicine is critical, thorough expert radiation oncology physician judgment and discretion regarding number of fractions and advanced techniques are also essential to optimize outcomes when considering the patients overall health, life expectancy, comorbidities, tumor biology, anatomy, previous treatment including prior radiation at or near current site of treatment, tumor and normal tissue response history to local and systemic therapies, and other factors related to the patient, tumor characteristics, or treatment.