Joshua Jones MD, MA, FAAHPM

Perelman School of Medicine

University of Pennsylvania

Tracy Balboni MD, MPH, FAAHPM

Dana-Farber/Brigham and Women’s Hospital

Harvard Medical School

Best Practices for Palliative Radiotherapy

Parts 1 and 2 Objectives

1. Understand and perform the radiation oncologist’s role in palliative oncology

care, according to national guidelines (ASCO, Choosing Wisely, ASTRO Bone

Mets Guidelines, National Consensus Project)

2. Understand and apply in patient care key palliative care skills, e.g., pain

management skills, prognostication, communication skills

3. Understand and apply the evidence-based management principles to common

palliative scenarios: uncomplicated and complicated bone metastases,

reirradiation principles, palliation in head and neck cancers

For help with the CME questions, look out for the leap year frog…

Part 1. The Role of the Radiation Oncologist in Palliative CareJoshua Jones MD, MA, FAAHPM

Palliative Care: An Extra Layer of Support

Palliative care is specialized medical care for people living with a serious illness. This type of care is focused on providing relief from the symptoms and stress of a serious illness. The goal is to improve quality of life for both the patient and the family.

Palliative care is provided by a specially trained team of palliative care physicians, nurses, and other specialists who work together with a patient’s other doctors to provide an extra layer of support. It is appropriate at any age and at any stage in a serious illness, and it can be provided along with curative treatment.

https://www.capc.org/about/patient-and-family-resources/

• Improves quality of life

• Reduces symptom burden

• Reduces depression

• Increases patient and family satisfaction with care

• May improve length of survival

• May decrease burnout among other providers

• We all provide primary palliative care

Core Primary Palliative Care Skills for Radiation Oncologists• Palliative care should be available for

all patients with serious illness, at any age, at any stage to help across all processes of care

• Focus on comprehensive assessment of patient including goals and priorities

• Focus on support for families and caregivers

• Culturally inclusive care

• Communication among stakeholders

Eight domains of NCP:

• Structure and Processes of Care

• Physical Aspects of Care

• Psychological and Psychiatric Aspects of Care

• Social Aspects of Care

• Spiritual, Religious and Existential Aspects of Care

• Cultural Aspects of Care

• Care of People Nearing the End of Life

• Ethical and Legal Aspects of Care

What we will cover, part I…

• Pain management• In the context of the opioid crisis

• Prognostication• Challenges and importance

• Communication: Defining goals of care• Assessing Understanding

• Delivering a Headline

• Responding to Emotions

The Opioid Crisis

www.cdc.gov

Existing Pain Management Guidelines

• Most designed explicitly to guide management of non-cancer pain

• Promote non-medication based management

• Promote non-narcotic based medical therapies – acetaminophen, NSAIDs

• Caution judicious and safe practices when prescribing opioids

• How do these measures translate to managing cancer pain?

www.cdc.gov

An anecdote

• 67 year old man• Recent diagnosis of metastatic angiosarcoma

• Progression after first line systemic therapy

• Dramatic worsening of right shoulder pain

• Imaging shows lytic lesions in glenoid, large lytic lesion in surgical neck of right humerus

• Using oxycodone ER 10 mg BID, also using oxycodone 10 mg every 3 hours ATC

• Referred for palliative radiotherapy

• Next steps?

• Right shoulder pain improved, still required opioids, but fewer• Patient had progressive disease in spite of multiple subsequent systemic

therapies

• Complex course, support provided by medical oncology, radiation oncology, palliative care, but patient died

• 6 weeks later, the patient’s wife called…

The tension in prescribing opioids for cancer patients is real and growing

OPIOIDS ARE NECESSARY IN CANCER PAIN MANAGMENT• Many patients with cancer (up to

90%) have pain at some point during diagnosis

• Opioids are a mainstay for control of cancer-related pain

• Risk of cancer pain under-treatment

• NEED to ensure appropriate access to opioids for patients with cancer

OPIOIDS HAVE RISK EVEN FOR PATIENTS WITH ACTIVE CANCER• Risks associated with opioid

prescribing are real and seem to be escalating

• Risks of side effects, accidental overdoses or diversion

• How do we transition off opioids for patients in survivorship?

• NEED to protect public by mitigating risk of opioid prescribing

So, what do I NEED to know?Screen for pain.

Diagnose pain.

Assess risk.

Prescribe safely.

Educate patients.

Screening for Pain: Every Visit

PAIN SCREENING

Characterization of Symptoms

Differential Diagnosis

Pain Management (pharmacologic and non-pharmacologic)

+ s

cre

en

Repeat Screening (every visit)

Anticipated side effect or is ongoing workup necessary?

Routine re-assessment of symptom management during and

after treatment

After screening: pain diagnosis

• Is this an expected side effect of treatment (chemotherapy, radiotherapy, surgery)?

• Is the symptom responding as anticipated to usual management?

• Fully characterize the symptom:• Temporality (Onset, Duration, Course, Daily Fluctuation)• Location and radiation (pain)• Quality (patient descriptors – use their words); numeric scales• Interference with life• Exacerbating and alleviating factors• Modulating factors (psychological, spiritual distress, coping, cognitive impairment)• Full exam

How is a patient assessed for risk of aberrant behaviors associated with opioids?• Risk is a clinical judgment

• Many validated tools exist to assess risk of aberrant behaviors (misuse, diversion): ORT, SOAP-P, etc.

• Develop a standard departmental procedure

• Be sure to check Prescription Drug Monitoring Program (PDMP)

• If we don’t ask, we won’t see it…

Risk factors for aberrant behaviors

• Patients with a history of prescription, illicit drug, or alcohol dependence/substance abuse

• Patients who have a history of binge drinking or peers who binge drink

• Patients who have a family history of substance abuse

• Patients with a history of psychiatric disorder, including anxiety, depression, ADHD, PTSD, bipolar disorder, or schizophrenia

• Patients who have a history of sexual abuse victimization may be at increased risk for prescribed medication misuse/abuse

• Young age (<45 years)

• Patients with a history of legal problems or incarceration

https://www.nccn.org/professionals/physician_gls/pdf/pain.pdf

Prescription Drug Monitoring Programs (PDMPs)• All states except Missouri, District

of Columbia and Territory of Guam

• Includes all prescriptions regardless of method of payment

• More complete data on where patients are getting opioids

• SHOULD BE CHECKED FOR EVERY PATIENT GETTING A NEW OPIOID SCRIPT (+/- REFILLS)

• Know the rules in your state

Pain Management and the Opioid Epidemic. NAP. 2017.

Pain Management in Radiation Oncology

• Local and systemic treatments

• Adjuvants?• Infectious etiology? Fungal, bacterial, etc.

• Neuropathic component to the pain?• Consider gabapentin, pregabalin, duloxetine, tri-cyclics, etc.

• Inflammatory component to the pain?• Consider maximizing NSAIDs, corticosteroids?

• Excess irritation (secretions, reflux, diarrhea, urinary frequency, constipation, etc.)

• Consider aggressive management of other symptoms

Maximize non-opioids whenever possible.

• Adjuvant Analgesics & Co-Analgesics• Acetaminophen• NSAIDs• Neuropathic Agents

• Anti-depressants• Anti-convulsants

• Topical Agents• Capsaicins• NSAIDs• Lidocaine and others

• Alpha 2 Adrenoreceptor agonists• Anti-spasmodics• Corticosteroids*• Bisphosphonates/RANK-L Inhibitors• NMDA receptor antagonists• Cannabinoids

• For bone metastases, consider:• Corticosteroids (short term)• NSAIDs• Bisphosphonates/RANK-L inhibitors (take

longer to work)• Other interventions (surgery, vertebral

augmentation)

• For neuropathic pain, consider:• Anti-depressants (duloxetine, tri-cyclics)• Anti-convulsants (gabapentin, pregabalin)• Topical agents• Corticosteroids

• For visceral pain syndromes, consider:• Corticosteroids

*Be aware of high risk of side effects of steroids and need to ensure patients taper

http://www.pharmacytimes.com/publications/health-system-edition/2016/november2016/pain-in-patients-with-cancer; adapted from who.int

The WHO Cancer Pain Ladder

• Goal is to move toward opioids in step-wise fashion

• Try non-opioids first

• Add opioids when alternatives not working

• Titrate opioids as needed

Pain Management: Opioid Conversions• Account for incomplete cross tolerance when converting

• Methadone should only be used by experienced clinicians

https://www.nccn.org/professionals/physician_gls/pdf/pain.pdf

Opioid agreements, UDS and Naloxone

• Opioid agreements – not all rad onc clinics use them• Limit refills to one provider

• Need to know if a patient has signed an opioid agreement with another provider

• KEY: Who is going to manage pain for this patient?

• Urine Drug Screens• Utility to knowing what a patient is taking

• Can feel punitive

• Standard approach to UDS

• Naloxone• Opioid antagonist, used to reverse overdose, often prescribed with opioids now

Patient Education is critical, both on a national level and on an individual basis• National Programs

• FDA, CDC, HHS are working on ongoing programs

• Focus is on risks of opioids and mitigating risk

• Naloxone programs

• Prescriber education of patients and families• WE MUST EDUCATE EVERY PATIENT EVERY TIME

• Safe use

• Side effect management

• Safe storage

• Disposal

FDA ER/LA Patient Counseling Document

http://er-la-opioidrems.com/IwgUI/rems/pcd.action

• FDA ER/LA Opioid REMS program has specific opioid counseling document recommended for use

• Important to use this document or adapt to your own use

Opioid disposal – do not contribute to the epidemic by storing unneeded medications• FDA and DEA both provide detailed information on medication disposal on

their websites

• For opioids – generally flushing is optimal if no take back day is imminent –see list of medications that should be flushed:

• https://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/SafeDisposalofMedicines/ucm186187.htm#Flush_List

• National Take Back Days:• April 25, 2020• https://www.deadiversion.usdoj.gov/drug_disposal/takeback/index.html

Radiation Oncology Opioid Instructions (Penn)• Radiation Oncology Opioid Instructions

• Lock up *** to avoid unintentional exposures.

• Do not drive or operate machinery until familiar with the effects of this drug and/or while increasing the dose.

• you may be charged with a DWI if impaired while driving.

• chronic, stable doses of medication have not been associated with impairment unless combined with other sedating substances such as sleeping pills, anti-anxiety agents, or alcohol.

• do not combine with other sedating substances such as sleeping pills, anti-anxiety agents, or alcohol without the knowledge of your health care provider at HUP.

• Do not self-escalate or decrease the dose without first discussing with a qualified health care provider at HUP.

• Do NOT share this medication with others or use anyone else’s medications.

• Take *** exactly as prescribed. Do not cut, crush, snort, chew or in any other way modify the medication.

• Take a laxative such as Senokot or Miralaxdaily while taking opioids (unless contraindicated due to a previous medical condition).

• Notify your nurse or doctor if laxatives are ineffective (no bowel movement for more than 2 days OR hard/painful to pass bowel movements).

• Fentanyl patches: After removing, fold the sticky sides together and flush down the toilet.

• Dispose of unused *** at your local pharmacy (they may charge you several dollars) , at a take back day or flush down the toilet.

What do I need to do?

•Educate yourself.

•Screen for pain.

•Assess opioid risk.

•Prescribe safely.

•Educate patients.

Prognostication:How long do I have? Revisited…

Prognostication: Why Care?

• Impact on patient and family priorities and values about what is important

• Impact on clinical decision-making

• But there is significant uncertainty around prognosis

• AND it is difficult to talk about prognosis

• Patients think that we will discuss with them; we think they will ask

Physicians routinely overestimate prognosis

2000 BMJ article studied life expectancy estimated by physicians:

time remaining was overestimated by a factor of 5.3

more experienced physicians gave more accurate predictions

accuracy of prediction inversely proportional to length of doctor-patient relationship

Christakis et al. BMJ 2000.

Confirmatory studies in rad onc

Jones, et al. CA: J Clin, 2014.

We are not very good at prognostication

• Prospective study of 22 radiation oncology attendings’ accuracy in survival prediction

• Considered accurate if within appropriate range (0-6 mo, 6-12 mo, 12-24 moor >24 mo)

• 877 predictions for 689 patients

• 39.7% predictions were accurate (within range), 26.5% underestimates, 33.9% overestimates

• KPS remained best predictor of accuracy and survival, particularly for patients with short survival

• No impact of clinician experience on accuracy

• Better than data from the literature, but still not very accurate

Benson et al. Predicting Survival for Patients With Metastatic Disease. Red Journal, Jan 2020.

Many prognostic models exist in rad onc

GENERAL

• KPS and ECOG

BONE METASTASES

• Dutch Bone Mets

• Number of risk factors

• TEACHH model

• NEAT model

• BMETS

BRAIN METASTASES

• RPA

• DS-GPA

SPINAL CORD COMPRESSION

• Tomita Score

• Baur Score

• Rades Model

What might the future hold?

• BMETS Decision Support Tool

• Online decision-support tool using big data to personalize prognostic assessment and provide recommendations for communication and management

Provides individualizedprognosis- and evidence-based recommendations RT- and non-RT interventions

Displays an individualized predicted survival curve

Collects relevant patient-specific data to facilitate

ease of use

Treatment decision

Components of the DSP

Bone Metastases Ensemble Trees for Survival (BMETS)

• Uses 27 prognostic covariates and random survival forests to predict time from RT consultation to death

Patient Features

• Age

• Sex

• Race

• Karnofsky Performance Status

• White blood cell count

• Lymphocyte count

• Inpatient status

• Recent weight loss

Treatment Features

• Site of RT

• Concurrent palliative RT to other bone sites

• Concurrent palliative to non-bone sites

• On steroids

• On opiate medications

• Last systemic therapy type

• On system therapy in past month

• Prior surgery at RT site

Disease Features

• Primary cancer site

• Neuraxis compromise

• Time from cancer diagnosis

Other metastases to:

−Brain

−Lung

−Liver

−Adrenal

− Lymph nodes

− Soft tissue

− Other bone

− Other sites

Alcorn et. al., in review

Discussing prognosis

• What do patients want to know?• We NEED to ask

• If they want to know about time, consider• Ranges (hours to days, days to weeks, weeks to months, months to years…)

• Best Case/Worst Case Scenarios – what would it look like with or without XRT

• If they don’t want to know about time, consider other headlines• Functional status

• Uncertainty

Communication Skills for Rad Oncs in 8 minutes

Choosing Wisely: Palliative Care Referrals

ASTRO Choosing Wisely Campaign #8:“Don’t initiate non-curative radiation therapy without defining the goals of

treatment with the patient and considering palliative care referral.”

Choosingwisely.org

Earlier conversations about values and goals linked to better serious illness care • Increased goal-concordant care

• Improved quality of life / patient well-being

• Fewer hospitalizations

• More and earlier hospice care

• Better patient and family coping

• Several studies have correlated palliative RT with aggressive EOL care – is this a particularly vulnerable patient population?

Mack JCO 2010; Wright JAMA 2008; Chiarchiaro AATS 2015; Detering BMJ 2010; Zhang Annals 2009

Conversations are infrequent, late and limited• Infrequent

• Fewer than 1/3 of patients with end-stage diagnoses reported end-of-life (EOL) discussion with clinicians

• Late• In patients with advanced cancer, first EOL discussion 33 days before death

• 55% of initial EOL discussions occurred in hospital

• Limited• Conversations often fail to address key elements of quality discussions

Heyland DK Open Med 2009; Mack AIM 2012; Wright 2008

SERIOUS ILLNESS

CONVERSATION GUIDE:

A FRAMEWORK FOR

BEST

COMMUNICATION

PRACTICES

https://www.ariadnelabs.org/wp-content/uploads/sites/2/2017/05/SI-CG-2017-04-21_FINAL.pdf

DFCI Trial: Clinician and patient participants

• Cluster- randomized controlled trial in outpatient oncology

• 90 oncology clinicians (MDs, NPs, and PAs) volunteered and enrolled (72% participation rate)

• 278 patients with advanced cancer enrolled and randomized• 131 patients died

• Surprise question

Bernacki, et al. Effect of the Serious Illness Care Program in Outpatient

Oncology: A Cluster Randomized Clinical Trial. JAMA Int Med. Mar 2019.

DFCI Trial: Significant improvements in conversations• Of intervention and control patients who died (n= 131):

• Conversation Outcomes• More conversations (96% vs 79% p=0.005)

• Earlier conversations (143 days vs 71 days p<0.001)

• More accessible in EHR (61% vs 11% p<0.001)

Bernacki, et al. Effect of the Serious Illness Care Program in Outpatient

Oncology: A Cluster Randomized Clinical Trial. JAMA Int Med. Mar 2019.

DFCI Trial: Significant improvements in patient-centeredness of conversations• Significant increase in the intervention group in documentation

about: • Values and goals (89 vs 44%, p<0.001)

• Prognosis or illness understanding (91% vs 48% p<0.001)

• Life-sustaining treatments (63% vs. 32% p=0.004)

• Trend toward an increase in documentation about:• End of life care planning (80% vs. 68% p=0.08)

Bernacki, et al. Effect of the Serious Illness Care Program in Outpatient

Oncology: A Cluster Randomized Clinical Trial. JAMA Int Med. Mar 2019.

DFCI Trial: Significant improvements in patient-reported outcomes• Baseline

• No differences in moderate/severe anxiety (9.6% vs 9.0%, p=0.85) and depression (20.4% vs 19.3%, p=0.84) between intervention and control

• Two weeks post conversation:

• Proportion of patients with moderate/severe anxiety in intervention group half that of control (4.8% vs 11%, p=0.05)

• Proportion of patients with moderate/severe depression in intervention group half that of control (10.9% vs. 21.8%, p=0.03)

Bernacki, et al. Effect of the Serious Illness Care Program in Outpatient

Oncology: A Cluster Randomized Clinical Trial. JAMA Int Med. Mar 2019.

Summary

• Intervention results in clinical practice change:

• More and earlier serious illness conversations

• More accessible documentation in the EHR

• More patient-centered and comprehensive conversations

• Intervention significantly reduces moderate-severe anxiety and depression

• Lower levels of anxiety persist for 4 months after the intervention

• Patients have a positive experience and report enacting concrete behavioral

changes as a result of the serious illness conversation

Bernacki, et al. Effect of the Serious Illness Care Program in Outpatient

Oncology: A Cluster Randomized Clinical Trial. JAMA Int Med. Mar 2019.

My favorite part of SICP

1. Assess understanding

2. Ask permission

3. Three headlines to choose from:1. Time in ranges2. Uncertainty (gentlest)3. Function4. For Rad Onc, consider “We hope you have improvement with XRT, but

worry that you may have persistent symptoms

4. Explore hopes, worries, strengths, tradeoffs

5. Summarize and plan

Other tools exist: Vital Talk and…

• Curiosity approach: “Tell me more…”

• Ask, Tell, Ask

• Warning shots• Headlines (do not walk back!)

• Checklists• Acronyms: NURSE, SPIKES, SUPER,

REMAP, ADAPT

• Asking permission

• I wish statements• Pairing hope and worry

• Silence

• Best taught with methods other than powerpoint!

Responding to Emotions…

• Responding to emotion (NURSE):

• Name the emotion “It sounds like this has been frustrating…”

• Understand the emotion “It must be so hard to be in pain like that…”

• Respect (praise) patient “I am so impressed you have been able to…”

• Support the patient “The team and I will be here to help you with…”

• Explore the emotion “Tell me more about how … is affecting you…”

• Respond directly to patient/family response to receiving information. (“I can see this is upsetting…”)

Back, Mastering Communication, 2009.

Common Pitfalls with emotions• Physicians generally want to fix things! It is hard to sit with powerful

emotions.

• Be aware of potential detrimental responses:

The Emotional Hijacker/Terminator

• Don’t cry…

• Things are going to be okay

The “Vulcan”, only using cognitive skills

– It’s not your fault

The Strategist, only wanting to have an agenda

– Let’s talk next steps

Slide courtesy of K. Dharmarajan

Communication Pearls

1. Assess patient/family understanding

2. Deliver a HEADLINE

3. Respond to EMOTIONS (NURSE)

4. Assess values/priorities

5. Finalize a plan

Part 2. Evidence-Based Approaches to Common Clinical ScenariosTracy A. Balboni MD, MPH, FAAHPM

Part 2. Evidence-based management principles in common palliative scenarios

• Uncomplicated and complicated bone metastases

• Reirradiation principles

• Palliation in malignancies of head and neck

Complicated/Uncomplicate Mets: Scenario 1

• 59 yo M PS 1 with met adenocarcinoma of unknown primary

after presenting with T6 cord compression (pain only). Staging:

widespread bone, lung, nodal, liver metastases, including small

R humerus met

• Undergoes spine decompressive surgery→ RT 3Gy x 10

• Completes RT and about to start chemotherapy, notes 6/10 right

arm pain

• MRI: 3cm met in proximal diaphysis of right humerus

Case questions

1. How to define complicated vs uncomplicated bone metastases?

2. How to determine risk of pathological fracture?

3. Best fractionation scheme for RT when concern for fracture?

1. Complicated versus Uncomplicated

• Uncomplicated Bone Metastases:

1. No pathological (some also use impending) fracture

2. No cord compression (some use early MSCC and/or nerve root compression)

3. No prior radiation therapy

• Why uncomplicated vs complicated important?

• SF versus MF trials apply to uncomplicated bone metastases

• Do have dedicated trials for reirradiation, spinal canal compression which are

better applied to complicated setting, scant data in post-surgery long bone

setting

Is Case 1 complicated bone met? How do we determine impending fracture risk?

Key Evidence: Mirel’s Criteria Fracture Risk

Score 1 2 3

Site of lesion

Upper limb Lower limbTrochanteric region

Size of lesion

<⅓ of bone diameter

⅓-⅔ of bone diameter

>⅔ of bone diameter

Nature of lesion

Blastic Mixed Lytic

Pain Mild Moderate Functional

Mirels H. Metastatic disease in long bones: A proposed scoring system for diagnosing impending pathologic fractures. 1989. Clin Orthop Relat Res. 2003 Oct;(415 Suppl):S4-13.

Score Fracture risk* Recommendation

≤7 0-4%Safe to irradiate with minimal risk of fracture

8 15%Consider prophylactic fixation

≥9 >33%Prophylactic fixation indicated

irradiation.

Key Evidence: Spinal Instability Neoplasia Score

Assessment of Spinal Stability with SINS, includes

6 factors, summed to obtain score:

• 0-6 stable

• 7-12 intermediate

• 13+ unstable

Fourney et al. JCO 2011

Case continued

• Pt seen by orthopedic surgeon, discussion with med onc, rad onc,

given chemotherapy urgency and modest risk of fracture, RT alone

• What fractionation?

Dutch Bone Metastases Trial

Study Description

• RCT pts w/ bone mets (all except RCC/melanoma): 8Gy x 1 vs. 4Gy x 6

• Ineligible:

▪ Prior RT

▪ Path fractures (impending fracture were ELIGIBLE)

▪ MSCC

▪ Cervical spine mets

▪ RCC and melanoma

Steenland et al. Rad Onc, 52; 1999

Dutch Bone Metastases Trial

Results

• N=1171 pts

• Acute side effects: ND in SF/MF

• Pain CR+PR: ~71% in SF/MF groups

• Retreatment: 25% (SF) vs. 7% (MF), p<0.05

• Path fractures: 4% (SF) vs. 2% (MF), p<0.05 (denominator is all bone

sites treated, whether or not weight bearing)

DBMT: Analysis of Femur Path Fracture Cases

Results

• Of 1171 pts, 110 femur lesions with 14 fractures (13% rate)

• RFs examined: increasing pain, lesion size, circumferential cortical

involvement

• Key predictors of fx: size >3cm, circumferential cortical involve >50%

Van der Linden et al. JBJS, 86 (4) 2003

Bone Remineralization after RT

• RCT 170 bone mets pts (breast, lung,

prostate or RCC): 8Gy x 1 vs. 3Gy x 10

• ND in pain ORR (78% SF vs. 81% MF)

• Recalcification (CT scan at 6 months): 120%

(SF) vs. 173% (MF), p<0.001

Koswig et al. Strahlenther Onkol, 175 1999

0%

20%

40%

60%

80%

100%

120%

140%

160%

180%

200%

Single fraction Multi-fraction

Baseline percent calcification

Recommendation

• RT plan 4Gy x 6 → chemotherapy

• Shoulder pain resolved

• 6 months later notes increasing mid

back pain, worse while on treatment

table and at night

• MRI spine performed

Scenario 2: Malignant spinal canal compression

MRI spine: severe (grade 3) T8 cord compression w/ complete effacement of CSF, T8 included in prior RT

CT restaging: Progression of disease, CT - no spinal instability at T8 (SINS 5)

Prognosis: Estimated to be ~6 months (per Chow et al JCO 2008)

Malignant Epidural Spinal Canal Compression (MESCC) “Gold Standard” Data

Patchell et al. Lancet 2005: RCT of surgery + RT

vs. RT alone in 101 MESCC pts (RT: 3Gy x 10)

• Exclusion criteria: life expectancy ≤3 and/or

not surgery candidates

• DID NOT exclude unstable spines: 35% RT

alone; 40% surg+RT

• Greater ambulatory status after surgery+RT

vs. RT alone (84% vs. 57%, p=0.001)

• Surg assoc w/ improved survival (med 126

vs. 100 dys, p=0.03)

Figure. Kaplan-Meier estimates of length of time all study patients remained ambulatory after treatment

MESCC: Other Data Informing Role of Surgery

Rades et al. JCO 2010: Matched pair analysis of 108 surgery + RT pts vs. 216 RT alone pts

• Excluded pts with spinal instability

• Matching on 11 prognostic factors: age, gender, PS, primary tumor type, number of VBs

involved, other bone mets, other visceral mets, interval from dx to MSCC, ambulatory

status, time to developing motor deficits, RT regimen

• ND in ambulatory status post S+RT vs. RT alone (69% vs. 68%, p=0.99)

• ND in regaining ability to walk post S+RT vs. RT alone (30% vs. 26%, p=0.86)

• Limitations: may be residual selection bias

Rades et al. JCO, 28 (22), 2010

MESCC: Hypofrac RT in Poor Prognosis

SCORE-2 Trial (Rades et al JCO 2016):

203 poor prognosis (est median LE 3 mo)

MESCC pts randomized to 4Gy x 5 vs 3Gy x 10

• No difference in ambulatory function

(figure)

• Local PFS and OS at 3 and 6 months: no

difference

• mOS for entire cohort was 3.2 months

Data on SFRT for MESCC

SCORAD III: Hoskin et al. JAMA 2019

Non-inferiority multicenter RCT in UK/Australia, 8 Gy/1 vs 20 Gy/5 for MSCC, primary

endpoint ambulatory status at 8 weeks, within -11% non-inferior (in % with the ability

to ambulate)

• 688 patients enrolled, 66% ambulatory pre-RT

• 8 Gy/1 vs 20 Gy/5 at 2mo: ambulatory status preserved in 69.5% vs 73.3%, 90% CI

risk difference -11.85% to 4.28%

• Just missed reaching non-inferiority criteria

• Median OS for entire cohort ~3mo, no difference between arms

Principles of Spinal Re-RTNieder data (IJROBP 2004, 2005):

• 78 cases, 11 w/ radiation myelopathy (med 11 mos, range 4-25 mos)

• No RM cases seen w/ BEDGy2 ≤135.5

• RM cases seen w/ interval ≤2mos, BED individual course ≥102

• Risk scoring created based on BED (Gy2) each course, interval, cumulative BED

Factor 0 pts 1 pt 2 pts 3 pts 4 pts 5 pts 6 pts 7 pts 8 pts 9 pts

Cumulative BED

Gy2

<120 120.1-

130

130.1-

140

140.1-

150

150.1-

160

160.1-

170

170.1-

180

180.1-190 190.1-

200

>200

Interval<6mo X (4.5)

BED course

≥102Gy2

X (4.5)

• 5 mo or greater interval

• Cumulative Pmax to thecal

sac=70Gy/2Gy equivalent

(α/β=2 for cord)

• SBRT pmax comprises no

more than 50% of total nBED

Cord Tolerance in SBRT Spine ReRT

Principles of Spinal Re-RT

1. Keep cumulative BED Gy2 to ≤135.5

BED Gy(α/β) = n x d [1 + d/ (α/β)]where d = dose per fraction; n = number of fractions; α/β = 2 for spinal cord

2. No single course w/ BED ≥102Gy2

3. Re-RT interval ≥6 mos, if cord compromise imminent, can consider >2 mos

Scenario 2: MESCC Recommendation

• Dexamethasone 10mg x 1, 4mg q6hrs

• Discussed goals/hopes, wants to try “everything” to stay alive longer to be with

family for holidays, does not want surgery

• SF RT 8G x 1 → chemotherapy

• Myelopathy risk low (based on Nieder et al. data ~3%)

• Remained ambulatory, died 5 months later (in hospice for 6 days)

Scenario 3: Good prognosis bone metastases

• 62 yo woman w/ hx of DCIS of R breast (2004, s/p

BCT) progressive R hip pain (7/10) worse with

weight-bearing (10/10), non-ambulatory

• Work-up: bone only met disease with 8 x 9cm

right acetabular lesion, bx → met breast adenoca

(+/+/-)

• Prognosis is >1 year

• No surgical option (lesion too extensive), plasty

also not technically feasible

• How to optimize pain and disease control given

good life expectancy?

SBRT for Painful Non-spine Bone Metastases

Nguyen et al. JAMA Oncology 2019: Single institution,

phase II RCT, non-inferiority study of 160 pts with painful

bone mets randomized to SBRT (12-16Gy SF) vs. MFRT

(30Gy in 10fx); Primary endpoint pain response

• Pain Response(CR+PR) SBRT>MFRT:

- 2 weeks (62% vs. 36%, p=0.01)

- 3 months (72% vs. 49%, p=0.03)

- 9 months (77% vs. 46%, p=0.03)

• Local Control SBRT>MFRT

- 1 year (100% vs. 90.5%, p=0.01)

- 2 years (100% vs. 75.6%, p=0.01)

Recommendation and Clinical Scenario 4:

• SBRT on clinical trial (35Gy in

5 fractions)

• 3.5 years later develops

painful swelling in L maxillary

region, has lung, liver

metastases, prognosis ~6

months

Head and Neck Palliation

Varieties of regimens have been studied

• Short to intermediate course conventional regimens, eg: 4Gy x 5, Quad Shot (3.7Gy bid x

2 days repeated up to 3 cycles, q3-4 wk), 8Gy x 3, 3Gy x 10, 6Gy x 5, 2.4Gy x 16,

• SBRT regimens (eg, 35Gy in 5 fractions)

• Protracted higher dose (eg, 50-72Gy) regimens

Review is critical summary of data, with principles in RT palliative regimen selection being:

• Multi-D assessment

• Prognosis

• Consideration of other palliative therapies available and urgency of initiation

• Patient goals/values (larger goals and practical issues like travel, side effects)

Conclusions

1. Radiation oncologists play major role in palliative oncology care, outlined by

national guidelines, e.g., ASCO, Choosing Wisely, ASTRO Bone Mets Guidelines,

National Consensus Project

2. Radiation oncologists called upon to apply key generalist palliative care skills,

e.g., prognostication, pain management skills

3. Palliative RT is large proportion of care we provide, evidence-based

management principles guide palliative scenarios, e.g., uncomplicated and

complicated bone metastases, reirradiation principles, palliation in head and

neck cancers

Opioid Resources• Know your local resources

• Opioid use disorders• Pain management clinic• Palliative care clinic• Supportive oncology tumor board?• Substance use tumor board?

• Know the national resources• NCCN: https://www.nccn.org/professionals/physician_gls/pdf/pain.pdf• NIDA: https://www.drugabuse.gov/drugs-abuse/opioids• CDC: https://www.cdc.gov/vitalsigns/opioids/index.html• FDA: https://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm484714.htm• HHS: https://www.hhs.gov/opioids• NAM: http://nationalacademies.org/hmd/reports/2017/pain-management-and-the-

opioid-epidemic.aspx• CMS: https://www.cms.gov/Outreach-and-

Education/Outreach/Partnerships/Downloads/CMS-Opioid-Misuse-Strategy-2016.pdf