1. Suspecting Tumors, or Could it be cancer?
Donna E. Reece, M.D.
Princess Margaret Cancer Centre
University Health Network
Toronto, ON CANADA
07 February 2018

2. Background Low back pain is common
However, <1% have a serious cause (cancer, infection, fracture)1
1Henschke N et al. Arthritis Rhematol 2009; 60:

3. Case: 50 year old woman
Long-standing osteoporosis since age 32 with known compression fracture of T7 after moving furniture
Found to have light chain myeloma in 2006
CT scan of abdomen and pelvis performed for flank pain showed numerous small lytic lesions throughout the skeleton
Normal hemoglobin, creatinine, calcium
Normal serum protein electrophoresis
Serum free kappa level of 759 mg/L (normal mg/L )
Skeletal survey showed compression at T7, pathologic fracture and lytic lesion in L4; multiple "punched out“ lesions in the skull
Bone marrow biopsy showed sheets of malignant plasma cells

4. Multiple Myeloma What is it?
Cancer of bone marrow plasma cells (cells that make antibodies)
Intact or light chain component used as a “tumor marker”
Found in serum and/or urine
Serum or urine (24 hour) EP
Serum free light chain assay*
Second most common hematological malignancy
Median age 65 years
Key signs and symptoms
Anemia
Lytic bone damage
Renal failure
High serum calcium
Recurrent infections
*Not funded in outside labs in Ontario; must be ordered under hospital budget.

5. Multiple Myeloma What is it?
Tests to order for suspected myeloma:
Total serum protein and albumin
Serum protein electrophoresis (SPEP) –will detect a intact monoclonal Ab if over 1 g/L (80% of patients)
Serum immunofixation (IFE)- will identify the MoAb and can detect it if over 0.5 g/L
24 hour urine for total protein, electrophoresis (UPEP), and immunofixation –Will detect a monoclonal light chain (20%)
Serum free light chain assay—picks up excess kappa or lambda light chain if over g/L
Cancer of bone marrow plasma cells (cells that make antibodies)
Intact or light chain component used as a “tumor marker”
Found in serum and/or urine
Serum or urine (24 hour) EP
Serum free light chain assay*
Second most common hematological malignancy
Median age 65 years
Key signs and symptoms
Anemia
Lytic bone damage
Renal failure
High serum calcium
Recurrent infections
*Not funded in outside labs in Ontario; must be ordered under hospital budget.

6. Multiple Myeloma What is it?
Tests to order for suspected myeloma:
Total serum protein and albumin
Serum protein electrophoresis (SPEP) –will detect a intact monoclonal Ab if over 1 g/L (80% of patients)
Serum immunofixation (IFE)- will identify the MoAb and can detect it if over 0.5 g/L
24 hour urine for total protein, electrophoresis (UPEP), and immunofixation –Will detect a monoclonal light chain (20%)
Serum free light chain assay—picks up excess kappa or lambda light chain if over g/L
Electrophoresis
Cancer of bone marrow plasma cells (cells that make antibodies)
Intact or light chain component used as a “tumor marker”
Found in serum and/or urine
Serum or urine (24 hour) EP
Serum free light chain assay*
Second most common hematological malignancy
Median age 65 years
Key signs and symptoms
Anemia
Lytic bone damage
Renal failure
High serum calcium
Recurrent infections
*Not funded in outside labs in Ontario; must be ordered under hospital budget.

7. Multiple Myeloma What is it?
Tests to order for suspected myeloma:
Total serum protein and albumin
Serum protein electrophoresis (SPEP) –will detect a intact monoclonal Ab if over 1 g/L (80% of patients)
Serum immunofixation (IFE)- will identify the MoAb and can detect it if over 0.5 g/L
24 hour urine for total protein, electrophoresis (UPEP), and immunofixation –will detect a monoclonal light chain (20%)
Serum free light chain assay—picks up excess kappa or lambda light chain if over g/L
Cancer of bone marrow plasma cells (cells that make antibodies)
Intact or light chain component used as a “tumor marker”
Found in serum and/or urine
Serum or urine (24 hour) EP
Serum free light chain assay*
Second most common hematological malignancy
Median age 65 years
Key signs and symptoms
Anemia
Lytic bone damage
Renal failure
High serum calcium
Recurrent infections
Free Kappa mg/L
Free Lambda mg/L
Kappa/Lambda:
Serum free light chain (Freelite®) assay*
Antibody target
*Not funded in outside labs in Ontario; must be ordered under hospital budget.

8. Case: Imaging

9. Case: 50 year old woman, continued
She received induction chemotherapy and a stem cell transplant and entered a complete remission
Monthly IV pamidronate was given for 2 years, then q 3 months
She was monitored every 3 months with serum free light chain levels
Skeletal survey annually
She relapsed in 2014 and was treated with oral chemotherapy followed by a second stem cell transplant
In May 2016, she developed radicular pain down her right leg and an MRI of the spine was ordered
She was driving back to Sault Ste Marie when the MRI results were phoned to the MD

10. Case: Imaging New compression fracture at T6
with impending spinal cord compression

12. Key Points
She had the main risk factor for aggressively evaluating low back pain →prior hx of cancer
However, her cancer-related problem was not reflected by her symptoms
In this setting, the whole spine should be imaged, not just the area of concern (lumbosacral spine)
Her lumbar symptoms were related to degenerative disease
Immediate referral to neurosurgical facility important to maintain function
Patients with myeloma live many years now, and aggressive management of skeletal damage is critical to maintain quality of life

13. Background Suspecting tumors…
Tumors of the spine are more frequently metastatic (97%) rather than primary1
50-70% of cancer patients found to have spinal metastasis before death
Sources: prostate, breast, kidney, thyroid, lung
Acronym = “PBKTL”
GI cancers and melanoma as well
Hematologic malignancies are also potential causes
Multiple myeloma is a hematologic malignancy characterized by bone destruction and anemia
Lymphoma may occasionally present in bone
Thoracic/thoracolumbar (70%) and lumbosacral spine (20%) most common sites
1Lewandrowski KU, et al. Tumors of the Spine. Philadelphia: Elsevier Saunders; 2011;

14. Patterns of Bone Metastasis
Bone lesions may be lytic, blastic or mixed
Primarily blastic
Primarily lytic
Mixed
Prostate
Small cell lung
Hodgkin’s disease
Carcinoid
Medulloblastoma
POEMS syndrome
Multiple myeloma
Renal cell cancer
Non-small cell cancer
Thyroid cancer
Melanoma
Non-Hodgkin’s lymphoma
Langerhans cell histiocytosis
Breast cancer
GI cancers
Most squamous cell

15. Patterns of Bone Metastasis Imaging of the Spine
Lytic lesion
Blastic lesion

16. Bone is a dynamic organ……
Seeman E, et al. N Engl J Med. 2006;354: van Bezooijen RL, et al. Cytokine Growth Factor Rev. 2005;16:

17. Bone is a dynamic organ……
Osteoclasts mediate bone destruction, not tumor cells directly, in osteolytic metastasis
Seeman E, et al. N Engl J Med. 2006;354: van Bezooijen RL, et al. Cytokine Growth Factor Rev. 2005;16:

18. Bone is a dynamic organ……
New bone formation involved in osteoblastic metastasis
Seeman E, et al. N Engl J Med. 2006;354: van Bezooijen RL, et al. Cytokine Growth Factor Rev. 2005;16:

19. Suspecting malignancy….
Bone metastasis to the spine can cause
Pain
Pathologic fractures
Epidural spinal cord compression, including cauda equina syndrome
Cauda equina syndrome -- compression of nerve roots below spinal cord (i.e. L2) causing low back pain +/- radiation down legs, weakness of plantar flexion of the feet, bladder and rectal sphincter paralysis, impotence, sensory loss in dermatomal distribution of affected nerve roots
Hypercalcemia

20. Suspecting malignancy… Pain
Use of “red flag” symptoms suggested in some guidelines in the past
The goal was to identify patients at a higher risk of a dangerous cause of back pain
Could serve as indications for earlier imaging exams
Examples included: age ≥50, history of cancer, failure to improve by 1 month of therapy, unexplained weight loss, no relief with recumbency, insidious onset, sensory level, pain worse at night, fever, thoracic pain

21. Diagnostic Accuracy of ACP “Red Flags” for Spinal Malignancy: Meta-analysis
Only a prior history of cancer informative:
Post-test probability of 7% in primary care
Post-test probability of 33% in ER
Downie A, et al. BMJ 2013; 347:f7095.

22. Diagnostic Accuracy of Other “Red Flags” for Spinal Malignancy: Meta-analysis
Prevalence of spinal malignancy:
Primary care 0.5%
Secondary or tertiary setting 1.5%
Downie A, et al. BMJ 2013; 347:f7095.

23. Suggested Evaluation for Acute Low Back Pain
No hx of significant trauma
Signs or symptoms of cauda equina syndrome
(new urinary retention, fecal incontinence or saddle anesthesia)
Significant motor deficits
(progressive motor weakness or significant motor
deficits not localized to a single unilateral nerve root)
Yes
Emergent MRI and
consultation No
Yes
Discuss choice of imaging with
patient’s oncologist
Current or recent cancer history
(particularly breast, prostate, lung, thyroid, kidney, myeloma) No
Moderate to high risk of cancer
(multiple risk factors/symptoms, remote history of cancer, strong clinical suspicion)
Yes
Plain films and ESR (or CRP)
Plain film suggests
possible cancer
Plain film (-)
but ESR high
Evaluate for malignancy
MRI
Adapted from Wheeler SG et al. Evaluation of back pain in adults. UpToDate 2018.

24. Spine Imaging in Malignancy
Plain films
Poor sensitivity as screen for bone metastasis (at least 30% loss of bone density needed to see lytic lesion)
Can evaluate mechanical alignment of vertebra and screen for severe compression fracture
Also, bone survey remains the standard for screening for multiple myeloma
CT scans
Superior bony detail; can show lytic and blastic lesions before apparent on plain films
Good for diagnosing fracture or impending fracture
Can show soft tissue involvement
Can be helpful before surgery or XRT

25. Spine Imaging in Malignancy
MRI
More sensitive than CT for small lesions
Can show extent of tumor within bone
Useful to define extent of medullary and extraspinal disease of spine
Can distinguish benign and malignant causes of lesions
Gold standard for spinal cord compression, epidural disease or nerve root impingement
Disadvantages: sensitive to movement and metal artifact, not permitted with many implantable devices, can be problematic with claustrophobia
Bone scan
Skeletal scintigraphy with 99m-Tc MDP
Accumulates in areas of increased osteoblastic activity
Reasonably sensitive (79-86%) and specific (81-88%) ]
for bone metastases
NOT good for lytic lesions like myeloma or aggressive
lesions with rapid bone destruction

26. Other Indications for Imaging
No improvement in pain after 4-6 weeks of conservative therapy and risk factors for cancer
Plain films and ESR
Suspected compression fractures
Signs and symptoms
Sudden onset of pain with minimal or no trauma
Point tenderness
Girdle/belt/band-like pain
Muscle spasms
Can be osteoporotic or tumor-related
MRI can help distinguish these two possibilities

27. When to move beyond conservative approaches in a patient with back pain….
Should be based on:
Combination of clinical features
Strength of clinical suspicion
Consequences of delayed diagnosis

28. Thank you!
The PM Myeloma physicians, scientists, nurses and support staff
The PM Myeloma Research program nurses, coordinators, managers
The Myeloma Canada Research Network (MCRN)
Myeloma Canada
Bloom Chair for Myeloma Research
CCTG
TFRI collaboration with Dr. T. Reiman
Our myeloma patients and families