The Role of Palliative Radiotherapy for Patients with Cancer John Childs Radiation Oncologist Auckland District Health Board 20 th June 2012

Principles of Pallative Treatment with Radiotherapy Ensure metastasis is cause of symptoms Account for needs and performance status of patient Establish clear outcome goal Communicate expected outcome Ensure minimal radiation side effects Account for treatment complexity

Bone Metastases Common cause of pain and other symptoms Bone metastases in 85% of people dying from lung, breast and breast cancer Less common thyroid, melanoma, kidney and bowel cancer (3% to 15%) Haematologic malignancy can be significant cause of bone pain (Myeloma and Lymphoma)

Bone Metastases: Prognosis Median survival is usually short despite advances in system therapy Lung cancer 6 months Breast and prostate (with bone metastases only) 2 to 4 years Indications for radiotherapy Median survival is usually short despite advances in system therapy Lung cancer 6 months Breast and prostate (with bone metastases only) 2 to 4 years Indications for radiotherapy Pain, difficulty with ambulation and immobility, hypercalcaemia, pathologic fractures, neurologic deficits, anxiety, depression, spinal cord or nerve root compression, and general deterioration of quality of life

Clinical Features: Bone Metastases Slowly progressive Insidious pain Often well localized Pain may be worse at night Worsen with weight bearing or ambulation May radiate to other areas (does not necessarily indicate nerve impingement because radicular pain can also be caused by spasm of muscles that originate or insert near the area of disease)

Bone Metastases: Goal of Radiotherapy Pain relief Complete 50% to 60% Overall 80% to 90% Preservation of function Maintain structural integrity Maintain quality of life Early intervention Minimise side effects of analgesics

Bone Metastases: Radiotherapy Schedules Various RT fractionation schedules 30 Gy in 10 fractions 20 Gy in five fractions single-fraction of 8 Gy Single fraction using 8 Gy Equal palliation Improved patient convenience and cost effectiveness compared Retreatment was necessary in approximately 20 percent

Bone Metastases: Radiotherapy Schedules The Evidence Three randomised trials comparing fractionated RT with single 8Gy Dutch multicenter 8Gy vs. 24Gy/6 Pain relief 69% and 72% Median time to response 3 weeks Retreatment 25% vs. 7% RTOG 8Gy vs. 30Gy/10 Pain relief 66% Retreatment 18% v. 9% British 8Gy vs. 20Gy vs. 30Gy 78% response rate Median time to response 1 month

Bone Metastases: Surgery Surgical fixation Prior to EBRT to decrease pain and facilitate rehabilitation in symptomatic bone metastases causing Fixation pathologic fracture involving the long bones or other weigh- bearing bones Prophylactic fixation to prevent pathologic fractures prior to EBRT. Inoperable fractures: EBRT may achieve pain relief alone

Bone Metastases: Other Approaches Stereotactic radiotherapy (SBRT): especially spinal and paraspinal tumours Radiopharmaceuticals: eg: strontium-89 [89Sr], samarium- 153 Bisphosphonates: Good evidence for breast and multiple myeloma. Current trials for prostate cancer. Hemibody Irradiation

Cerebral Metastases Very common site of metastases (autopsy studies 10% to 30%) Common primary sites are lung, breast and melanoma Increasing incidence in other cancers following chemotherapy Increased detection with MRI scanning

Prognostic Assessment Performance status Control of primary Age < 65 years I (Karnofsky Performance score [KPS] ≥70, controlled primary, age <65 years, brain metastasis only) 7.1 month II (not meeting requirements of classes I or III) 4.2 months III (KPS <70) 2.3 months RTOG studies

Corticosteroids Usual dose 4mg to 16mg daily Give with concurrent Ranitidine Usually improvement of PFS over first 7 days Reduce dose over 4 weeks Asymptomatic patients with limited oedema: reserve for neurologic symptoms

Management Whole Brain Radiotherapy Surgical resection Radiosurgery boost Post operative RT Stereotactic radiotherapy

Favourable Prognosis Surgery: Single metastasis in a surgically accessible location Limited number of metastases. Stereotactic RS: metastasis is smaller than 3 cm in a surgically inaccessible location, not suitable/declines more than one small metastasis Other disease stable WBRT or SRS post surgery Delay recurrence Impact on survival uncertain

Unfavourable Prognosis Whole Brain RT Improve neurologic deficits Prevent any further deterioration of neurologic function. Extent of improvement after WBRT directly related to the time from diagnosis to radiation therapy: early treatment associated with a better outcome Efficacy Neurologic symptoms improve in 70% Neurologic deficits improve in 40% to 50%

Dose Schedule Randomised trials have not shown significant differences with varying dose and fractions Common schedules are: 20Gy in 5 fractions 30 GY in 10 fractions 40 Gy in 15 fractions Approach depends on: Anticipated survival Clinical performance status

Stereotactic Radiosurgery Ability to treat surgically inaccessible areas of the brain, such as the brainstem Noninvasiveness and suitability for outpatient treatment Potential to treat multiple lesions Cost-effectiveness compared to neurosurgical resection

Prophylactic Cranial Radiotherapy Limited stage Small Cell Carcinoma Lung Cumulative incidence of brain metastases decreased 46% Absolute decrease in three-year cumulative incidence of brain metastases (33% versus 59%) Increase in the three-year survival rate from 15.3% to 20.7% Advanced Stage Small Cell Carcinoma Lung Benefits less clear The benefits of PCI must be balanced against the toxicity and potential impact on quality of life

Complications of Radiation Acute Complications Nausea/vomiting Hair loss Somnolence Change taste and smell Late Complications Most patients have a limited survival however with longer survival there is a risk for debilitating late complications. Leukoencephalopathy and brain atrophy, leading to neurocognitive deterioration and dementia Radiation necrosis, with symptoms related to the site of necrosis Normal pressure hydrocephalus, causing cognitive, gait and bladder dysfunction Neuroendocrine dysfunction, most commonly hypothyroidism Cerebrovascular disease

Carcinoma Lung: Superior Venacaval Obstruction Carcinoma lung most common cause (80%) Initial investigation and priority of treatment depends on severity of symptoms Radiotherapy: relief of symptoms 80% Most patients poor prognosis (<10%-15% survive 2 years)

Carcinoma Lung: superior venacaval obstruction Emergency management severe or rapidly progressive symptoms gross facial oedema and cerebral symptoms, or associated stridor Management High dose corticosteroid considered for palliative radiotherapy Other techniques ( venous and tracheobronchial stents, endobrachial laser or cryotherapy) Where there is local expertise appropriate for selected patients.

Carcinoma Lung Major Airway Obstruction with Stridor Severe symptoms require urgent treatment There are no randomised trials Palliative radiotherapy: 20Gy in 5 fractions or 30Gy in 10 fractions with high dose corticosteroids (grade c) Endobronchial therapy is an option (laser and brachytherapy) One randomised study no advantage over external beam: risk of major haemoptysis

Acute Complications of Radiotherapy Oesophagitis: dysphagia and dyspepsia Non productive cough L’Hermittes syndrome Skin reaction Lethargy and malaise

Late complications of Radiotherapy Pneumonitis (15%) Pulmonary fibrosis (30%) Oesophageal stricture, perforation or fistulae (1% -2%) Cardiac pericardial effusion, constrictive pericarditis, cardiomyopathy Spinal cord myelopathy (usually < 1%) Brachial plexopathy (<1%)