Palliative radiotherapy: history, recent advances, and future directions.

Radiotherapy has been used to palliate cancer symptoms since shortly after the time that X rays were discovered late in the 1800's. The 20th century witnessed improvements in treatment planning and delivery that permitted radiotherapy to serve as a successful, timely, and cost-efficient palliative intervention. Palliative radiation oncology has risen to the level of its own subspecialty, as evidenced by the formation of palliative radiation oncology clinical services and dedicated palliative radiotherapy guidelines, while additional changes have begun to alter the very definition and goals of palliative radiotherapy. Local treatment may now be offered with dual goals of symptom relief and the potential for increased disease-free or overall survival. While these new directions show great promise, novel strategies must be formulated to manage the increased complexity, workload, and cost of these approaches.

Utility of the ACE Inhibitor Captopril in Mitigating Radiation-associated Pulmonary Toxicity in Lung Cancer: Results From NRG Oncology RTOG 0123.

OBJECTIVES: The primary objective of NRG Oncology Radiation Therapy Oncology Group 0123 was to test the ability of the angiotensin-converting enzyme inhibitor captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. MATERIALS AND METHODS: Eligible patients included stage II-IIIB non-small cell lung cancer, stage I central non-small cell lung cancer, or limited-stage small cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for 1 year. The captopril was to be escalated to 50 mg three times a day. Primary endpoint was incidence of grade 2+ radiation-induced pulmonary toxicity in the first year. RESULTS: Eighty-one patients were accrued between June 2003 and August 2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent before randomization and 40 patients were not randomized postradiation. Major reasons for nonrandomization included patients' refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. CONCLUSIONS: Despite significant resources and multiple amendments, NRG Oncology Radiation Therapy Oncology Group 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer angiotensin-converting enzyme inhibitors started during radiotherapy may solve the accrual problems.

Does Graded Prognostic Assessment outperform Recursive Partitioning Analysis in patients with moderate prognosis brain metastases?

AIM: To compare the clinical utility of the Recursive Partitioning Analysis (RPA) and Graded Prognostic Assessment (GPA) in predicting outcomes for moderate prognosis patients with brain metastases. METHODS & MATERIALS: We reviewed 101 whole brain radiotherapy cases. RPA and GPA were calculated. Overall survival was compared. RESULTS: Sixty-eight patients had moderate prognosis. RPA patient characteristics for increased death hazard were ≤10 WBRT fractions or no surgery/radiosurgery. GPA patients had increased death risk with no surgery/radiosurgery or lower Karnofsky Performance Status. CONCLUSION: The indices have similar predicted survival. Patients scored by RPA with longer radiation schedules had longer survival; patients scored by GPA did not. This indicates GPA is more clinically useful, leaving less room for subjective treatment choices.

Availability of single-fraction palliative radiotherapy for cancer patients receiving end-of-life care within the Veterans Healthcare Administration.

BACKGROUND: Surveys demonstrate < 20% of radiation oncologists in the United States offer single-fraction palliative radiotherapy (RT) even though it is an acceptable standard of care. A study was conducted to investigate whether this held true for those practicing within the Veterans Healthcare Administration (VHA). METHODS: All radiation oncologists currently practicing at VHA medical centers were surveyed. Comparisons and associations of responses were evaluated by Fisher's exact test. RESULTS: The response rate was 90%. Half were full-time employees of the VHA, and the majority (70%) had thoroughly read guidelines on palliative RT for bone metastases recently published by either the American College of Radiology (ACR, 2009, 2012) or the American Society of Radiation Oncology (ASTRO, 2011). Single-fraction palliative RT for bone metastases had been prescribed by 76% of respondents, and 93% had prescribed a short course of ≤ 6 fractions. Respondents were less likely to have prescribed a single fraction for patients who had survival estimates of either > 6 months or > 12 months (66% versus 37%, p < 0.0001).Those not offering single-fraction palliative RT (24%) were more likely to be > 10 years out of training (37% versus 10%, p = 0.01), and to have worked in a private practice setting at some point in their career (36% versus 12%, p = 0.03). CONCLUSIONS: A majority of radiation oncologists within the VHA offer single-fraction therapy to their patients. These data ensure access to palliative RT is not limited within this health care system by a preference for prolonged treatment courses that may discourage patients and clinicians from seeking this care.

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 patient's 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 radiotherapy at the end of life: a critical review.

When delivered with palliative intent, radiotherapy can help to alleviate a multitude of symptoms related to advanced cancer. In general, time to symptom relief is measured in weeks to months after the completion of radiotherapy. Over the past several years, an increasing number of studies have explored rates of radiotherapy use in the final months of life and have found variable rates of radiotherapy use. The optimal rate is unclear, but would incorporate anticipated efficacy in patients whose survival allows it and minimize overuse among patients with expected short survival. Clinician prediction has been shown to overestimate the length of survival in repeated studies. Prognostic indices can provide assistance with estimations of survival length and may help to guide treatment decisions regarding palliative radiotherapy in patients with potentially short survival times. This review explores the recent studies of radiotherapy near the end of life, examines general prognostic models for patients with advanced cancer, describes specific clinical circumstances when radiotherapy may and may not be beneficial, and addresses open questions for future research to help clarify when palliative radiotherapy may be effective near the end of life.

External beam radiotherapy and bone metastases.

Management of bone metastasis is a multi-disciplinary effort that involves coordination between several medical specialties. External beam radiation therapy (EBRT) remains a powerful and efficient method of palliating pain and preventing skeletal complications from osseous metastasis. Various fractionation schemes, ranging from 8 Gy in a single dose to 30 Gy in 10 fractions, provide equivalent pain relief as demonstrated by dozens of randomized clinical trials. Toxicity profiles are well established and the treatment is generally well tolerated. Radiopharmaceuticals and high-dose, stereotactic radiation therapy are adjuncts to EBRT whose role is being elucidated through clinical trials. Multiple organizations have compiled guidelines and quality metrics to help refine the role of each modality in the management of painful osseous metastases.

The role of hypofractionated radiation in the management of non-osseous metastatic or uncontrolled local cancer.

Radiation therapy is often used to palliate symptoms caused by cancer. Short course, or "hypofractionated" palliative radiation therapy provides equivalent palliation in the setting of non-osseous metastasis or uncontrolled localized cancer while being more convenient and cost-effective than longer courses of radiation. Hypofractionated palliative radiation plays a role in the management of obstruction due to tumor, neurologic symptoms, pain caused by localized bulky disease, and bleeding in patients with primary tumors of the lung, head and neck, bladder, rectum, gynecologic malignancies, and metastasis to the liver, lung and brain. Hypofractionated palliative radiation is well tolerated with minimal and self-limited side effects. The side effects that do occur are generally limited to the body region treated and last from a few days to a few weeks.

ACR Appropriateness Criteria ® spinal bone metastases.

Abstract The spine is a common site of involvement in patients with bone metastases. Apart from pain, hypercalcemia, and pathologic fracture, progressive tumor can result in neurologic deterioration caused by spinal cord compression or cauda equina involvement. The treatment of spinal bone metastases depends on histology, site of disease, extent of epidural disease, extent of metastases elsewhere, and neurologic status. Treatment recommendations must weigh the risk-benefit profile of external beam radiation therapy (EBRT) for the particular individual's circumstance, including neurologic status, performance status, extent of spinal disease, stability of the spine, extra-spinal disease status, and life expectancy. Patients with spinal instability should be evaluated for surgical intervention. Research studies are needed that evaluate the combination or sequencing of localized therapies with systemic therapies including chemotherapy, hormonal therapy (HT), osteoclast inhibitors (OI), and radiopharmaceuticals. The roles of stereotactic body radiation therapy (SBRT) in the management of spinal oligometastasis, radioresistant spinal metastasis, and previously irradiated but progressive spinal metastasis are emerging, but more research is needed to validate the findings from retrospective studies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Whole brain radiotherapy for poor prognosis patients with brain metastases: predictably poor results.

BACKGROUND: Patients with brain metastases from solid tumors can be subdivided by characteristics into separate prognostic groups, such as the Radiation Therapy Oncology Group's Recursive Partitioning Analysis (RPA) or the Graded Prognostic Assessment (GPA). At our institution, patients falling into the poorest prognostic groups are often treated with whole brain radiotherapy (WBRT). OBJECTIVE: To determine if observed survival of poor prognosis patients treated with WBRT for brain metastases at our institution matches the survival predicted by RPA and GPA prognostic indices. METHODS: The charts of 101 consecutive patients with newly diagnosed brain metastases from solid tumors who received WBRT were retrospectively reviewed. We calculated each patient's RPA and GPA and compiled treatment and survival data. Observed median survival was compared to that predicted by the RPA and GPA prognostic indices. RESULTS: RPA III patients (n = 25) had a median survival of 2.4 months in our study. GPA 0.0-1.0 patients (n = 35) had a median survival of 2.4 months in our study. These values did not vary significantly from those predicted by the respective indices. LIMITATIONS: This is a retrospective analysis and subject to selection bias. CONCLUSION: Given the delivery time for WBRT and the potential side effects associated with the treatment, the predictably short overall survival in poor prognosis patients calls into question the value of WBRT in this patient subgroup.

ACR Appropriateness Criteria® follow-up and retreatment of brain metastases.

Multiple options for retreatment are available, which include whole-brain radiation therapy, stereotactic radiosurgery, surgery, chemotherapy, and supportive care. Size, number, timing, location, histology, performance status, and extracranial disease status all need to be carefully considered when choosing a treatment modality. There are no randomized trials examining the retreatment of brain metastases. Repeat whole-brain radiation has been examined in a single-institution experience, showing the potential for clinical responses in selected patients. Local control rates as high as 91% using stereotactic radiosurgery for relapses after whole-brain radiation are reported. Surgery can be indicated in progressive and/or hemorrhagic lesions causing mass effect. The role of chemotherapy in the recurrent setting is limited but some agents may have activity on the basis of experiences on a smaller scale. Supportive care continues to be an important option, especially in those with a poor prognosis. Follow-up for brain metastases patients is discussed, examining the modality, frequency of imaging, and imaging options in differentiating treatment effect from recurrence. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of the current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria® non-spine bone metastases.

Bone is one of the most common sites of metastatic spread of malignancy, with possible deleterious effects including pain, hypercalcemia, and pathologic fracture. External beam radiotherapy (EBRT) remains the mainstay for treatment of painful bone metastases. EBRT may be combined with other local therapies like surgery or with systemic treatments like chemotherapy, hormonal therapy, osteoclast inhibitors, or radiopharmaceuticals. EBRT is not commonly recommended for patients with asymptomatic bone metastases unless they are associated with a risk of pathologic fracture. For those who do receive EBRT, appropriate fractionation schemes include 30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, or a single 8 Gy fraction. Single fraction treatment maximizes convenience, while fractionated treatment courses are associated with a lower incidence of retreatment. The appropriate postoperative dose fractionation following surgical stabilization is uncertain. Reirradiation with EBRT may be safe and provide pain relief, though retreatment might create side effect risks which warrant its use as part of a clinical trial. All patients with bone metastases should be considered for concurrent management by a palliative care team, with patients whose life expectancy is less than six months appropriate for hospice evaluation. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR appropriateness criteria on metastatic bone disease.

Appropriate imaging modalities for screening, staging, and surveillance of patients with suspected and documented metastatic disease to bone include (99m)Tc bone scanning, MRI, CT, radiography, and 2-[(18)F]fluoro-2-deoxyglucose-PET. Clinical scenarios reviewed include asymptomatic stage 1 breast carcinoma, symptomatic stage 2 breast carcinoma, abnormal bone scan results with breast carcinoma, pathologic fracture with known metastatic breast carcinoma, asymptomatic well-differentiated and poorly differentiated prostate carcinoma, vertebral fracture with history of malignancy, non-small-cell lung carcinoma staging, symptomatic multiple myeloma, osteosarcoma staging and surveillance, and suspected bone metastasis in a pregnant patient. No single imaging modality is consistently best for the assessment of metastatic bone disease across all tumor types and clinical situations. In some cases, no imaging is indicated. The recommendations contained herein are the result of evidence-based consensus by the ACR Appropriateness Criteria((R)) Expert Panel on Musculoskeletal Radiology.

Management of metastatic spinal cord compression.

Spinal cord compression (SCC) from spinal metastasis is a common complication in cancer and if left untreated, permanent paraplegia or quadriplegia will occur. Timely diagnosis is crucial in preventing permanent neurologic damage. Once SCC is suspected, diagnostic imaging of the spine should be obtained to confirm diagnosis. Treatment consists of surgery, radiotherapy or a combination of both. Stereotactic body radiotherapy has also been incorporated into the management of SCC. The treatment decision should be made based on multiple factors, including tumor histology, retropulsion of bony fragments, performance status of the patient and status of extraspinal systemic disease. This review focuses on the pathophysiology, diagnosis and management of SCC.

Therapeutic guidelines for the treatment of bone metastasis: a report from the American College of Radiology Appropriateness Criteria Expert Panel on Radiation Oncology.

Bone metastases remain a therapeutic challenge because of the diversity of the problems they cause, the relative paucity of data regarding their treatment, and the necessity for management by a multidisciplinary palliative care team. The American College of Radiology convened an Appropriateness Criteria Expert Panel on Radiation Oncology for the treatment of bone metastasis to create representative clinical case scenarios and then rank the appropriate use of treatment modalities as well as the most reasonable radiotherapy dose schema and treatment planning methods. Here we present both the resulting Appropriateness Criteria and the rationale for making these decisions. The treatment recommendations are placed within the larger framework of the role of radiation in palliative care by discussing the efficiency of palliative radiotherapy schedules, cost effectiveness issues, and the need for additional research regarding the proper multidisciplinary care of patients with symptomatic bone metastasis.